A Case of Fever and Rash After a Tick Bite

Abstract

A 55-year-old man who lived in rural Indiana with a history of diabetes mellitus type 2 presented to the Emergency Department in May with 5 days of headache, fever to 104 °F, diffuse myalgias, and generalized weakness. He frequently performed yardwork. He had noticed a tick on his arm 10 days before that he removed with tweezers. He reported that it was not engorged. Three weeks prior to presentation, he went camping in the forest and slept in a cabin. He had frequent contact with his 3-year-old granddaughter who had a recent febrile upper respiratory illness.

A 55-year-old man with a history of diabetes mellitus type 2 presented to the Emergency Department (ED) in May with 5 days of headache, fever to 104 °F, diffuse myalgias, and generalized weakness. He denied neck stiffness or photophobia. He also denied confusion, nausea, or vomiting.

The patient lived in rural Indiana. He frequently performed yardwork, and he had noticed a tick on his arm 10 days before. He removed the tick with tweezers and reported that it was not engorged. Three weeks prior to presentation, he went camping in the forest and slept in a cabin. He had a pet dog. He also had frequent contact with his 3-year-old granddaughter who had a recent febrile upper respiratory illness. For his diabetes he took metformin.

On physical examination, temperature was 38.7 °C, blood pressure 92/60 mmHg, heart rate 123 beats per minute, and respiratory rate 18 breaths per minute. In general, he appeared diaphoretic and uncomfortable. His cardiac exam revealed an irregularly irregular rhythm, pulmonary exam was clear, and abdominal exam was benign. He was alert and oriented, and his neurologic exam was grossly within normal limits. He had negative Kernig’s and Brudzinski’s signs.

In the ED, he received a dose of intravenous (IV) ceftriaxone, after which he developed an acute, diffuse, erythematous petechial rash on his trunk and extremities, including the palms of his hands (Fig. 40.1). Complete blood count showed a white blood cell (WBC) count of 8900/μL with 78% neutrophils and 14% bands, hemoglobin of 14.6 g/dL, and platelets of 25,000/μL (normal range,150,000–450,000/μL). His complete metabolic panel (electrolytes, liver tests, creatinine, and blood urea nitrogen) was unremarkable. A lumbar puncture was deferred due to thrombocytopenia and concerns for bleeding. Computed tomography (CT) of the head and magnetic resonance imaging (MRI) scan of the brain were unremarkable. An electrocardiogram (EKG) revealed that he was in atrial fibrillation. The patient became increasingly hypotensive, and he was intubated and mechanically ventilated, started on vasoactive agents, and transferred to the medical intensive care unit.

Fig. 40.2.

Ticks that transmit in the United States: (a) American dog tick (Dermacentor variabilis); (b) Rocky Mountain wood tick (Dermacentor andersoni); (c) brown dog tick (Rhipicephalus sanguineus). Source: Centers for Disease Control and Prevention. http://www.cdc.gov/ticks/geographic_distribution.html (Accessed on May 2, 2017)

Fig. 40.1.

Photograph of rash on patient’s palm

Microbiology studies drawn on admission are shown in Table 40.1. While he had positive serum IgG for cytomegalovirus (CMV) and Epstein Barr virus (EBV), indicating prior infection with these viruses, the rest of his microbiology results did not reveal a diagnosis. He was empirically treated with vancomycin, aztreonam, levofloxacin, acyclovir, and doxycycline to cover broadly for possible meningitis, encephalitis, and rickettsial disease. β-Lactam antibiotics were avoided as it was thought that ceftriaxone might have caused his rash. Five days into his admission, his platelet count had improved to 120,000/μL, and a lumbar puncture was deemed safe and performed. It showed a total cell count of 18 cells/μL, with 10 WBC/μL, 8 red blood cells/μL, 14% neutrophils, 68% lymphocytes, and 16% monocytes. Protein was 54 mg/dL (normal range, <45 mg/dL), and glucose 106 mg/dL. In the cerebrospinal fluid (CSF), enterovirus polymerase chain reaction (PCR), herpes simplex virus (HSV) 1 and 2 PCR, varicella zoster virus (VZV) PCR, and West Nile virus (WNV) antibodies were negative.

Table 40.1.

Patient’s admission microbiology test results

Microbiology test (blood/serum unless noted)	Result
Blood culture	Negative
Urine culture	Negative
Human immunodeficiency virus (HIV) antibody	Negative
Respiratory viral panela	Negative
Rickettsia rickettsii IgM, IgG	Negative
Rickettsia typhi IgM, IgG	Negative
Anasplasma phagocytophilum IgM, IgG	Negative
Ehrlichia chaffeensis IgM, IgG	Negative
Lyme disease (Borrelia burgdorferi) EIA	3.21 Lyme index units (normal range < 0.75)
Lyme Western blot IgM, IgG	Negative
Cytomegalovirus (CMV) IgM	Negative
CMV IgG	Positive
Epstein Barr virus (EBV) IgM	Negative
EBV IgG	Positive

^aPolymerase chain reaction test for the following pathogens: adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus OC43, coronavirus NL63, human metapneumovirus, human rhinovirus/enterovirus, influenza A, influenza A/H1, influenza A/H1–2009, influenza A/H3, influenza B, parainfluenza 1, parainfluenza 2, parainfluenza 3, parainfluenza 4, respiratory syncytial virus (RSV), Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae

The differential diagnosis for fever in a patient with a petechial rash includes meningococcemia, Rocky Mountain spotted fever (RMSF) and other rickettsial diseases, drug reaction, parvovirus B19 infection (fifth disease), and infectious mononucleosis (Table 40.2). The patient’s history of tick bite raises the concern for RMSF, human granulocytic anaplasmosis, or monocytic ehrlichiosis. This patient’s severe illness and rash involving the palms is more characteristic of RMSF than ehrlichiosis.

Table 40.2.

Differential diagnosis of fever and maculopapular and petechial rash

Disease	Pathogen
Infectious
Rocky Mountain spotted fever	Rickettsia rickettsii
Murine typhus	Rickettsia typhi
Ehrlichiosis	Ehrlichia chaffeensis, Ehrlichia ewingii
Anaplasmosis	Anaplasma phagocytophilum
Scarlet fever	Group A Streptococcus
Meningococcemia	Neisseria meningitidis
Disseminated gonococcal disease	Neisseria gonorrhoeae
Fifth disease	Parvovirus B19
Roseola	Human herpesvirus-6 (HHV-6)
Enteroviral disease	Coxsackie virus, echovirus, etc.
Infectious mononucleosis	Epstein-Barr virus (EBV) infection
Mycoplasma pneumonia	Mycoplasma pneumoniae
Leptospirosis	Leptospira spp.
Noninfectious
Kawasaki disease
Drug reaction
Thrombotic thrombocytopenic purpura (TTP)
Stevens-Johnson syndrome
Toxic shock syndrome

One week after his initial presentation, the rickettsial serology was repeated and this time revealed a positive RMSF IgM titer (>1:256) with a negative IgG. Based on this result, he was diagnosed with RMSF. His antibiotics were narrowed to only doxycycline. He gradually recovered and was discharged to an acute rehabilitation facility.

Rocky Mountain Spotted Fever (RMSF)

RMSF is a tick-borne zoonosis caused by transmission of to a human via the bite of an infected tick. The primary vector in the United States (US) is the American dog tick (Dermacentor variabilis), but the pathogen is also transmitted by the Rocky Mountain wood tick (Dermacentor andersoni) and the brown dog tick (Rhipicephalus sanguineus). RMSF occurs throughout the United States, but, despite its name, cases predominantly occur in the Midwest and Southeast [1].

The mean incubation period between exposure and onset of symptoms is 7 days, with a range of 2–14 days [2]. RMSF cases follow a seasonal pattern, with 90% of infections occurring between April and September. Clinical signs and symptoms include fever, myalgias, severe headache, as well as nausea, vomiting, and abdominal pain. A characteristic petechial or maculopapular rash that starts around the wrists and ankles and may involve the palms and soles appears 2–5 days after the onset of fever. Less common clinical presentations include myocarditis, pneumonia, acute kidney injury, and neurologic manifestations. RMSF often causes severe illness, with a case fatality rate of 5–10%.

The diagnosis of RMSF is based onclinical signs and symptoms in a patient with possible tick exposure. Treatment should not be delayed while awaiting laboratory confirmation of the diagnosis. Laboratory abnormalities include mild hepatic transaminitis, thrombocytopenia, hyponatremia, and mild lymphocytic pleocytosis in the CSF [3]. Immunohistochemistry performed on skin biopsy at rash onset may be useful to confirm a diagnosis. RMSF serology typically becomes positive 7–10 days after symptom onset. A fourfold increase in serum antibody titers or a convalescent titer >1:64 is diagnostic. There is possible cross-reaction between RMSF titers and other spotted fever group rickettsioses, especially Rickettsia parkeri, which is transmitted by the Gulf Coast tick Amblyomma maculatum, may have an eschar at the site of tick bite and usually causes a mild illness. The treatment of choice for RMSF is oral doxycycline 100 mg twice per day for 5–7 days, continuing at least 2–3 days after the patient defervesces. Chloramphenicol is an alternative treatment only used in cases of severe doxycycline allergy or during pregnancy if the illness is mild, but chloramphenicol is associated with increased mortality, is also associated with adverse effects, and is ineffective against other severe tick-borne infections in the differential diagnosis, i.e., human granulocytic anaplasmosis and human monocytic ehrlichiosis.

Key Points/Pearls

• Rocky Mountain spotted fever (RMSF) is a severe tick-borne zoonosis caused by and transmitted by various ticks including the American dog tick, the Rocky Mountain wood tick, and the brown dog tick.

• Typical symptoms include fever and severe headache followed 2–5 days later by a maculopapular or petechial rash that starts around the wrists or ankles and may involve the palms and soles; skin biopsy may confirm the diagnosis when immunohistochemistry identifies Rickettsia rickettsii within the endothelium.

• The diagnosis of RMSF should be made clinically; serologic studies become positive 7–10 days after onset of symptoms.

• The treatment of choice for RMSF is doxycycline, even in children and during pregnancy.

• Severe rickettsioses to consider in the United States are RMSF, human granulocytic anaplasmosis, and human monocytic ehrlichiosis; in other regions of the world, Mediterranean spotted fever, epidemic typhus, and scrub typhus also can cause severe illness.

• In severely ill patients with fever and rash, one should consider the possibility of rickettsioses and the possible indication of adding doxycycline.