Selected Infectious Diseases

Key Points.

Lyme disease, the leading cause of vector-borne infectious illness in the United States, is associated with three distinct clinical stages: early localized, early disseminated, and late disseminated.

“Food-borne illness” refers to an acute onset of symptoms, ranging from vomiting, diarrhea, and abdominal pain/cramping to potential life-threatening complications, caused by the ingestion of contaminated food. Onset and duration of symptoms vary, depending on the specific cause.

Distinguishing between diseases associated with foreign travel can be difficult since many present with fever associated with constitutional symptoms such as headache, myalgias, malaise, anorexia, and vomiting/diarrhea.

Young children with infectious mononucleosis are often asymptomatic, although they may present with low-grade fever, pharyngitis, lymphadenopathy, splenomegaly, malaise, rash, headache, anorexia, nausea, chills, and myalgias.

Selected Diagnoses

• Tick-borne illnesses

  • Lyme disease
  • Ehrlichiosis

• Food-borne illness

• Diseases associated with foreign travel

• Infectious mononucleosis

• Severe acute respiratory syndrome

Discussion of Individual Diagnoses

Tick-borne Illnesses

Lyme Disease

Lyme disease is the leading cause of vector-borne infectious illness in the United States, with 23,000 cases reported in 2002. It is caused by the spiral-shaped bacterium Borrelia burgdorferi. The bacterium is transmitted to humans via the bite of an infected deer tick, of which there are two types: the western black-legged tick (Ixodes pacificus), causing disease on the Pacific coast, and the black-legged tick (Ixodes scapularis), causing disease in the northeastern and north-central United States. The reservoirs for these ticks are the white-footed mouse and deer. Transmission is based on the length of attachment of the tick, with low risk of transmission associated with less than 24 to 48 hours of attachment. Lyme disease is commonly found in the northeastern mid-Atlantic and midwestern portions of the United States, as well as several counties in northwestern California. Outside the United States, the disease can be found in Spain, France, Austria, Germany, Russia, and Japan. Clinical manifestations of Lyme disease may present year-round, with a higher incidence during late spring to summer (May to August).

CLINICAL PRESENTATION

Lyme disease is associated with three distinct clinical stages: early localized, early disseminated, and late disseminated (Table 71-1 ). Clinical findings are based on time from the initial exposure (bite of the infected tick). The classic rash of Lyme disease is erythema migrans (EM), commonly found on the head or neck in young children or the extremities of older children. The lesion begins as a small red maculae or papule at or adjacent to the site of the bite, which enlarges in an annular centrifugal fashion to approximately 10 to 15 cm in diameter, resembling a “bull's eye.” EM is commonly associated with nonspecific symptoms such as fever, fatigue, malaise, headache, myalgias, and arthralgias. EM, found in only two thirds of humans bitten by an infected tick, appears typically 14 days after the initial exposure. The rash and constitutional symptoms are typically self-limited and not dependent on treatment with antibiotics.

Table 71-1.

Clinical Findings and Treatment^* in Lyme Disease

Stage (Time from Initial Exposure)	Treatment†
Early Localized (7–14 days)
Erythema migrans	Amoxicillin 50 mg/kg/day divided bid or
	Doxycycline‡ 100 mg bid × 14–21 days
Early Disseminated (days to weeks)
Multiple erythema migrans	Amoxicillin (as above) × 21–28 days
Neurologic
Cranial neuropathy (Bell's palsy)	Amoxicillin (as above) × 21–28 days
Radiculoneuritis	Amoxicillin (as above) × 21–28 days
Aseptic meningitis/encephalitis	Ceftriaxone 75–100 mg/kg/day ×
	14–28 days or 30–60 days depending on clinical response
Cardiac
Myopericarditis	Ceftriaxone (as above) × 14–21 days
Atrioventricular block	Cardiology consult
Cardiomegaly	Cardiology consult
Musculoskeletal
Arthralgias	Supportive care
Myalgias	Supportive care
Late Disseminated (weeks to months)
Arthritis	Amoxicillin (as above) × 28 days
Chronic polyneuropathy	Supportive care
Chronic encephalopathy§	Supportive care

^*Treatment for Lyme disease may have different recommendations from different sources; consultation with an infectious disease expert should be considered.

^†Cefuroxime axetil or erythromycin can be used for penicillinallergic patients.

^‡Only in children 8 years or older.

^§Sleep disturbance, fatigue, mood changes, concentration difficulty, and memory loss.

If untreated, early disseminated Lyme disease may occur weeks to months following initial exposure. Of those cases that progress, 20% develop neurologic manifestations (cranial neuropathy, radiculoneuropathy, aseptic meningitis/encephalitis),¹ 10% develop cardiac manifestations (myopericarditis, atrioventricular [AV] block, or cardiomyopathy), and 20% develop multiple EM. The most common cranial neuropathy associated with Lyme disease is Bell's palsy (peripheral VII nerve palsy), which may be unilateral or bilateral. While commonly confused with viral meningitis, Lyme meningitis is more often associated with Bell's palsy, papilledema, longer duration of symptoms prior to lumbar puncture, lack of fever at time of diagnosis, and cerebrospinal fluid (CSF) pleocytosis (especially neutrophils).²

Late disseminated Lyme disease is associated with oligoarthritis (most common manifestation), chronic polyneuropathy, and chronic encephalopathy (commonly manifesting as sleep disturbance, fatigue, mood changes, concentration difficulty, memory loss).³ The arthritis associated with late disseminated disease is often limited to large weight-bearing joints.⁴

The diagnosis of Lyme disease can be made clinically, serologically, or by polymerase chain reaction (PCR) (Table 71-2 ). The clinical diagnosis can be made simply by identifying the classic EM rash, or by identifying one clinical manifestation (arthritis, cranial neuropathy, AV block, aseptic meningitis, or radiculoneuritis) and isolation of or serologic evidence of B. burgdorferi infection. Enzyme-linked immunosorbent assay (ELISA) or Western blot techniques, both of which detect immunoglobulin M (IgM) and immunoglobulin G (IgG), are serologic tests that can confirm the diagnosis. In Lyme disease, IgM peaks approximately 4 weeks and IgG approximately 6 weeks after initial exposure. The Centers for Disease Control and Prevention recommends the use of ELISA as the initial screening test, and confirmation with the Western blot if the ELISA is positive (due to cross reactivity on ELISA of Epstein-Barr virus [EBV], parvovirus, syphilis, systemic lupus erythematosus, and juvenile rheumatoid arthritis).⁵ PCR may also be used to amplify DNA of Borrelia burgdorferi in blood, CSF fluid, and synovial fluid. Other laboratory tests, such as complete blood count, erythrocyte sedimentation rate, aspartate aminotransferase (AST), and complement factors (C3/C4), may help to support the diagnosis of Lyme disease. The differential diagnosis of Lyme disease can be found in Table 71-3 .

Table 71-2.

Diagnosis of Lyme Disease

Erythema migrans or at least one manifestation (arthritis, cranial neuropathy, AV block, aseptic meningitis, radiculoneuritis) and isolation or serologic evidence of Borellia burgdorferi infection

Serologic evidence

Perform enzyme-linked immunosorbent assay (ELISA) first

If positive, confirm with Western immunoblot

Polymerase chain reaction (PCR)—may be used on blood, CSF fluid, or synovial fluid

Supportive

Elevated WBC count, sedimentation rate, AST, complement C3/C4

Joint fluid with 25,000–125,000 WBCs/mm3 with polymorphonuclear predominance

CSF with mild pleocytosis (<1000 cells) and neutrophil predominance

Abbreviations: AST, aspartate aminotransferase; AV, atrioventricular; CSF, cerebrospinal fluid; WBC, white blood cell.

Table 71-3.

Differential Diagnosis of Lyme Disease

Musculoskeletal

Fibromyalgia

Chronic fatigue syndrome

Viral illness (infectious mononucleosis)

Bell's Palsy

Trauma

Ramsay Hunt syndrome

Local invasion from suppurative mastoiditis or otitis media

Mumps, varicella, or enterovirus neuritis

Guillain-Barré syndrome

Brainstem tumor

Sarcoidosis

Aseptic Meningitis

Coxsackievirus

Enterovirus

Echovirus

Poliovirus

Arthritis

Septic

Reactive

Juvenile rheumatoid

Parvovirus

Traumatic

Rheumatic fever

MANAGEMENT

Early localized Lyme (EM) can be treated with oral antibiotics for 14 to 21 days (see Table 71-1). Children from an endemic area presenting with constitutional symptoms without EM and a documented tick bite may be tested for Lyme and treated prophylactically. While most experts do not recommend performing a lumbar puncture on children with Bell's palsy and suspected Lyme disease who are otherwise well appearing, clinical evidence of meningitis or encephalitis does warrant a lumbar puncture, with cerebrospinal fluid sent for PCR analysis, hospitalization of the child, and intravenous antibiotics for 30 to 60 days. Cardiac manifestations of Lyme disease require hospitalization of the child, intravenous antibiotics, and cardiology consultation. Oligoarthritis associated with Lyme disease should be confirmed by either serologic or PCR analysis and treated with oral antibiotics for 28 days. Chronic polyneuropathy and chronic encephalopathy require neurologic consultation. It is recommended that all complicated cases of Lyme disease be referred to either a pediatric infectious disease or rheumatology specialist.

Children presenting with a deer tick attached to the skin should have it removed promptly. Ticks should be removed with either tweezers or fingers shielded with rubber gloves, grasping the tick as close to the skin as possible and pulling with steady, even pressure without squeezing or crushing the body of the tick. Prophylactic antibiotic treatment has not traditionally been recommended in the case of an attached tick since the transmission rate is low (<10%), but a recent prospective study found that 200 mg of doxycycline was effective in preventing EM in adults living in hyperendemic areas who had removed an attached deer tick within the prior 72 hours. However, this regimen is unproven in children and has the potential for significant side effects in those less than 8 years of age. Therefore, it cannot be routinely recommended.^{6, 7}

Ehrlichiosis

Human ehrlichiosis is caused by the bite of an infected tick. In the United States, the lone star tick (Amblyonmma americanum), the black-legged tick (Ixodes scapularis), and the western black-legged tick (Ixodes pacificus) are known vectors. The four species known to cause disease in humans are Ehrlichia chaffeensis, phagocytophila, equi, and, most recently, ewingii. ⁸ Erlichiae are small, gram-negative bacteria that invade leukocytes, causing two clinically similar illnesses: human monocytic ehrlichiosis (reported from the southeastern and south-central United States) and human granulocytic ehrlichiosis (reported from Wisconsin and Minnesota).8, 9, 10

CLINICAL PRESENTATION

Disease caused by Ehrlichia species occurs more frequently in the spring and summer months, especially between April and September. Although rates of ehrlichiosis increase with age, there have been reported cases of severe and fatal infections in children and young adults. The incubation of Ehrlichia is 5 to 10 days after the initial tick bite. Infected humans may be asymptomatic, or may exhibit constitutional symptoms such as fever (>38°C), headache, malaise, myalgias, nausea, vomiting, diarrhea, cough, photophobia, arthralgias, confusion, and rash. The rash associated with ehrlichiosis occurs in 60% of infected children, and can be described as macular, maculopapular, or petechial, occurring on the face, trunk, and extremities, or rarely (<10%) on the palms or soles. If untreated, ehrlichiosis may progress to more severe illness: meningoencephalitis, seizure, coma, cardiomyopathy, adult respiratory distress syndrome, respiratory failure, disseminated intravascular coagulation, and renal failure. The mortality rate is 2% to 3%.8, 9, 10

The diagnosis of human ehrlichiosis can be made on clinical suspicion, but is confirmed by blood smear (demonstrating the organisms by Giemsa staining or Diff-Quick methods), serologic testing (indirect immunofluorescence), PCR, or blood culture. Serologic testing may not be useful in the first week as IgM and IgG levels increase during the second week of illness. Laboratory findings associated with ehrlichiosis include leukopenia (60%), thrombocytopenia (70%), elevated liver enzymes (85%), and hyponatremia less than 130 mEq/L (40%). Differential diagnosis of ehrlichiosis includes Rocky Mountain Spotted Fever, meningococcal infection, subacute bacterial endocarditis, secondary syphilis, idiopathic thrombocytopenic purpura, gonococcemia, and neoplastic disease.8, 9, 10

MANAGEMENT

Antibiotics should not be withheld pending diagnostic studies in children with clinical suspicion for human ehrlichio-sis. Doxycycline (4.4 mg/kg per day divided twice a day, maximum daily dose 200 mg) for children ages 8 years or older should be given by either the oral or the intravenous route and continued for at least 3 days after the defervescence of the fever, for a minimum of 5 to 10 days. The use of doxycycline may be considered in children less than 8 years of age in consultation with an infectious disease expert, recognizing the potential for significant side effects. Children who are toxic appearing, have severe constitutional symptoms, or have severe illness (adult respiratory distress syndrome, meningoencephalitis, renal failure, disseminated intravascular coagulation, coma, cardiomyopathy) should be admitted to the hospital for supportive care. Consultation with pediatric infectious disease and critical care specialists should be considered.

Food-borne Illness

“Food-borne illness” refers to an acute onset of symptoms caused by the ingestion of contaminated food. The etiology of contamination in food may be infectious agents such as bacteria, bacterial toxins, or viruses, or noninfectious causes, such as poisons or chemicals. Onset and duration of symptoms vary, depending on the specific cause.¹¹

CLINICAL PRESENTATION

The clinical manifestations of food-borne illness caused by infections depend on whether an enterotoxin or cytotoxin is released by the etiologic organism.¹² Enterotoxins, which can be formed prior to ingestion or while in the intestine, cause symptoms without penetrating the intestinal mucosa, leading to watery diarrhea, usually without leukocytes (Table 71-4 ). Cytotoxins cause destruction of the lining of the intestinal mucosa, resulting in bloody diarrhea with leukocytes, and may invade lymphatic tissue, causing systemic symptoms (Table 71-5 ). An infectious etiology not caused by either an enterotoxin or cytotoxin is Clostridium botulinum. Symptoms include descending weakness and paralysis within 4 days of the ingestion of contaminated canned foods, such as mushrooms, smoked fish, or vegetables. Symptoms result from the absorption of botulinum toxin by the intestine, which blocks the release of acetylcholine at the neuromuscular junction. Treatment may require respiratory support in an intensive care setting.

Table 71-4.

Enterotoxins Causing Food-borne Illness

Agent	Source	Incubation (hr)	Clinical Manifestations*	Treatment
Staphylococci	Improperly stored meats, bakery, dairy	2–6	Intense vomiting and watery diarrhea, abdominal cramps, low-grade fever	Supportive
Bacillus cereus	Contaminated grains, meats, vegetables	1–6	Intense vomiting, abdominal cramps	Supportive; vancomycin or ciprofloxacin if invasive
		8–16	Diarrhea and abdominal cramps
Clostridium perfringens	Inadequately cooked meats and poultry	8–20	Abdominal cramps and diarrhea; vomiting and fever are rare	Supportive
Vibrio cholerae	Contaminated water and food (shellfish)	8–24	Profuse “rice” watery diarrhea for 3–5 days without abdominal cramps or fever	Tetracycline or doxycycline (shortens duration of symptoms)
Vibrio parahaemolyticus	Raw or improperly cooked seafood	8–24	Profuse watery diarrhea for 3–5 days	Tetracycline or doxycycline (shortens duration of symptoms)
Enterotoxic Escherichia coli	Contaminated meats, cheese, salads	8–18	Watery diarrhea ± vomiting or abdominal cramping	Supportive
Giardia lamblia	Contaminated water	2–3 days	Mild bloody diarrhea ± abdominal cramping for possibly more than 1 wk, ± anorexia	Metronidazole

^*Clinical manifestations for less than 2 days unless noted.

Table 71-5.

Cytotoxins Causing Food-borne Illness

Agent	Source	Incubation (hr)	Clinical Manifestations	Treatment
Salmonella	Beef, poultry, dairy, eggs, fish, reptiles	12–30	Abrupt onset of moderate to large amount of diarrhea becoming bloody ± abdominal pain or vomiting or low-grade fever	Intravenous cephalosporin if bacteremic, <3 mo of age, or immunosuppressed
Shigella	Potato, egg salad; lettuce, raw vegetables	12–30	Abrupt onset of bloody diarrhea, tenesmus, abdominal cramps lasting 3–7 days	Bactrim or ampicillin if severe disease, dysentery, or immunosuppressed
Campylobacter jejuni	Undercooked chicken or cattle	3–5 days	Foul-smelling, watery then bloody diarrhea ± abdominal cramps for 5–8 days, ± fever	Azithromycin or erythromycin (shortens duration of symptoms)
Yersinia enterocolitica	Contaminated pork or milk	4–6 days	Acute abdominal pain, fever, diarrhea	Bactrim or gentamycin (decreases duration of fecal excretion)
Escherichia coli O157:H7	Food or water contaminated with cow feces	3–5 days	Severe bloody diarrhea with painful abdominal cramps and low-grade fever; hemolytic-uremic syndrome in 3%–5%	Supportive
Entamoeba histolytica	Contaminated food or water	12–24	Sudden onset of bloody diarrhea with vomiting or abdominal cramps possibly lasting for more than a week	Metronidazole

Enterotoxins, which produce symptoms within 4 to 6 hours of ingestion, include Staphylococcus aureus and Bacillus cereus. Cytotoxin-induced illness requires ingestion of organisms that must then multiply and invade the mucosa of the gastrointestinal tract. For this reason, patients often develop symptoms more than 6 to 12 hours after the food is ingested. Cytotoxins are more likely to produce fever, bloody diarrhea, and severe systemic symptoms.

For the most part, diagnosis is made clinically. However, a majority of food-borne illness can be diagnosed by routine stool culture or specialized staining, microscopic analysis for ova and parasites, or detection of toxin in the stool. Prior to laboratory results, history, such as onset and duration of symptoms, frequency and consistency of vomiting and/or diarrhea, presence of abdominal cramping, or systemic symptoms, will provide some clues to the etiology of the illness in the emergency department. Also important is the type of food ingested prior to symptoms, recent travel history, and similar symptoms in close contacts.

Physical examination should focus on the state of hydration as well as other potential life-threatening complications, such as neurologic, respiratory, hepatic, and renal failure. Laboratory studies, such as complete blood count, blood culture, or serum electrolyte analysis, may be helpful to determine the extent of systemic involvement. Stool cultures should be reserved for cases of bloody diarrhea, severe abdominal pain, immunocompromised or very young hosts, or toxic-appearing infants and children. Stool analysis for ova and parasites should be considered in cases of prolonged incubation or duration of symptoms. Some infectious causes, such as Yersinia, may mimic appendicitis, and therefore radiologic studies may be required to rule out an acute abdomen. In pediatric patients, two potential complications that should be looked for are Guillain-Barré syndrome (associated with Campylobacter infection) and hemolytic-uremic syndrome (associated with Escherichia coli O157:H7) (see Chapter 47, Peripheral and Neuromuscular Disorders; and Chapter 88, Renal Disorders).¹³

MANAGEMENT

While a majority of cases of food-borne illness can be managed at home without any specific therapy, some children require hospitalization, intravenous hydration therapy, and antibiotics (see Tables 71-4 and 71-5; see also Chapter 72, Vomiting and Diarrhea, for additional information on food-borne illness).

Diseases Associated with Foreign Travel

Distinguishing between diseases associated with foreign travel can be difficult since many present with fever associated with constitutional symptoms such as headache, myalgias, malaise, anorexia, and vomiting/diarrhea. Therefore, history of recent travel to endemic areas should point to a possible diagnosis.

Typhoid fever, caused by ingestion of contaminated water or food with Salmonella typhi, is endemic to India and Africa. Malaria, caused by the bite of an infected mosquito transmitting a species of Plasmodium, is endemic to sub-Saharan Africa, Southeast Asia, and India. Dengue fever, caused by the bite of an infected mosquito (Aedes aegypti), is endemic to the Caribbean and Central and South America.

The clinical features and complications associated with these selected diseases are varied and often overlap (Table 71-6 ). Management includes diagnosis by clinical suspicion, followed by supportive care and antibiotics if indicated. Intensive care hospitalization is necessary if complications are present. Consultation with a pediatric infectious disease specialist is also suggested.14, 15, 16, 17

Table 71-6.

Selected Infections Associated with Foreign Travel

Disease	Initial Symptoms	Complications	Diagnosis	Treatment
Typhoid fever	Fever increase over 2–3 days, headache, malaise, cough, rose spots. After 1st week: coma, abdominal distention, “pea soup” diarrhea, respiratory distress	Intestinal hemorrhage, intestinal perforation, acute renal failure, myocarditis, DIC	Stool culture for Salmonella; serologic tests (ELISA); elevated ESR, PT/PTT, LFTs; hyponatremia, hypokalemia, anemia	Ciprofloxacin, chloramphenicol, cefotaxime, ampicillin
Malaria	Paroxysms of fever, chills, sweats; flulike symptoms, vomiting and diarrhea, febrile seizures, meningitis, anemia, jaundice	Toxicity, high fever, dehydration, severe anemia, seizure/coma, pulmonary edema, renal failure, shock, bleeding diathesis	Blood smear (thick/thin); serologic tests (ELISA)	Chloroquine, quinine, quinidine, mefloquine, halofantrine
Dengue fever	Fever, headache (frontal/retro-orbital), generalized macular rash, bone pain, nausea/vomiting, anorexia, cutaneous hyperesthesias	Dehydration, bleeding diathesis, DIC, shock, myocarditis, encephalopathy, liver failure	Serologic tests (ELISA); leukopenia, thrombocytopenia; elevated BUN, LFTs	Supportive care

Abbreviations: BUN, blood urea nitrogen; DIC, disseminated intravascular coagulation; ELISA, enzyme-linked immunosorbent assay; ESR, erythrocyte sedimentation rate; LFTs, liver function tests; PT, prothrombin time; PTT, partial thromboplastin time.

Infectious Mononucleosis

Clinical Presentation

Infectious mononucleosis is caused by Epstein-Barr virus (EBV), a member of the herpesvirus family. Infection is transmitted via contact with oropharyngeal secretions. While commonly asymptomatic in young children, adolescents and young adults often pre-sent with low-grade fever, pharyngitis, lymphadenopathy, and splenomegaly after an incubation of 4 to 6 weeks. Other constitutional symptoms associated with EBV include malaise, rash, headache, anorexia, nausea, chills, and myalgias. Rare complications of EBV infections include pancreatitis, cholecystitis, myocarditis, myositis, glomerulonephritis, encephalitis, transverse myelitis, and cranial nerve palsies (Table 71-7 ). Spontaneous splenic rupture occurs in 1% to 2% of cases of infectious mononucleosis. The differential diagnosis of infectious mononucleosis includes rubella, Toxoplasma gondii, adenovirus, human immunodeficiency virus, cytomegalovirus, human herpesvirus-6, and Stevens-Johnson syndrome.

Table 71-7.

Clinical Manifestations of Infectious Mononucleosis

Early Findings

Classic triad

Fever

Pharyngitis (exudative or nonexudative)

Lymphadenopathy (bilateral posterior cervical)

Rash (generalized maculopapular)

Late Findings

Hepatomegaly/splenomegaly

Jaundice

Palatal petechiae

Chronic fatigue

Rare Findings

Pancreatitis

Cholecystitis

Myocarditis

Myositis

Glomerulonephritis

Encephalitis

Transverse myelitis

Cranial nerve palsies

Unique to EBV

Bilateral upper lid edema

Uvular edema

The diagnosis of infectious mononucleosis can be made either by clinical suspicion or serologic testing.¹⁸ Heterophile antibodies are typically present in 75% of older children and adolescents by the end of the first week of symptoms, and in 90% by the third week of symptoms. In children younger than 10 years, there is a 10% to 15% false-negative rate for detecting heterophile antibodies. EBV antigens can also be detected to determine stage of illness. Laboratory studies supportive of EBV include elevated transaminase levels, relative lymphocytosis (>60%) with greater than 10% atypical lymphocytes, mild to moderate leukocytosis (12,000 to 20,000 cells/μl), mild thrombocytopenia, and elevated erythrocyte sedimentation rate.

Management

Treatment of infectious mononucleosis is supportive. Several studies have demonstrated some effectiveness of corticosteroids in reducing the pain associated with pharyngitis.^{19, 20} In children and young adults with spenomegaly, close follow-up (at least 3 weeks from the beginning of symptoms) is required with their primary care physician. Those who participate in contact sports or extreme activities should refrain over this time period.²¹

Severe Acute Respiratory Syndrome

Severe acute respiratory syndrome (SARS), caused by a member of the Coronaviridae virus family, produces a flulike illness that may progress to life-threatening complications, such as pneumonia, respiratory failure, or death.²² Thought to be originally from the Guangdong providence in southern China when 305 cases of atypical pneumonia occurred there in February 2003, subsequent outbreaks have seen the illness spread to Asia, Canada, and the United States. The mortality rate has been estimated at 10%. A detailed clinical case definition of SARS may be found at www.cdc.gov/ncidod/sars/.

Clinical Presentation

After an incubation period of 2 to 10 days, patients present with constitutional symptoms such as fever (>100.4°F), headache, myalgias, fatigue, chills, anorexia, and diarrhea, followed in 2 to 7 days with nonproductive cough, dyspnea, and progressive hypoxemia. Mechanical ventilation may be necessary in patients with respiratory failure. Chest radiographs demonstrate pneumonia (focal interstitial or generalized patchy infiltrates) after a week of symptoms. Lymphopenia develops in 70% to 90% of infected patients. Other laboratory findings associated with SARS include leukopenia, thrombocytopenia, mild hyponatremia and hypokalemia, elevated liver enzymes, and elevated creatine kinase.

The diagnosis of SARS can be made in patients with both (1) radiologic confirmation of pneumonia or acute respiratory distress syndrome of unknown etiology and (2) one of the following risk factors 10 days before onset of illness: travel to mainland China, Hong Kong, or Taiwan or close contact with an ill person with history of recent travel to those areas; health care or laboratory worker in close contact with patient with suspected SARS; or involvement in cluster of cases of atypical pneumonia. Other serologic testing is necessary, but should be at the recommendation of local and state health departments.

Management

Patients with a suspicion of SARS should be admitted to a critical care unit for supportive care. Respiratory droplet precautions should be instituted. Controversy exists regarding the efficacy of corticosteroids or ribavirin in the treatment of patients with SARS.²³