FEVER, COUGH AND RASH IN A TWELVE-YEAR-OLD TRAVELER

A 12-year-old boy was seen in consultation in early September in our outpatient infectious diseases subspecialty practice for 2 weeks of persistent fever and rash. He was in his usual vigorous state of health when school ended mid-June. With the start of his summer vacation he left Massachusetts to go to Arizona to visit relatives. While there he went swimming in an outdoor water park which had been closed the day before because of elevated water levels of Escherichia coli. Several days later there was a large dust storm in the desert where he was staying. He returned to Massachusetts in mid-July where he again went swimming, this time in a suburban pond. There he was bitten on the chest by a fish that broke the skin. As prophylaxis he received an adult use tetanus toxoid and diphtheria toxoid, absorbed, vaccine booster the following day. Three days later he traveled to a farm in Vermont where he cared for horses, chickens and goats. He also explored caves before returning home the last week of July. Around this time he began to experience nausea, fever and headaches, which recurred intermittently. By mid-August he had developed a fever to 103°F and was seen by his pediatrician. Laboratory evaluation at that time included a normal complete blood count, erythrocyte sedimentation rate, antinuclear antibody and negative Borrelia burgdorferi serology. He felt well for the next several days and his family left for a camping trip to Newfoundland. His adventures during this trip included eating wild game and drinking from a stream. By the third week of August a rash developed on the back of his right leg along with arthralgias involving his ankle, hand and knee. No frank joint swelling or erythema was noted at that time. Upon returning a week later he was seen again by his pediatrician and laboratory tests were performed which were again normal including rapid plasma reagin circle card test, Mycoplasma serology, throat culture, transaminases, creatinine, complete blood count, rheumatoid factor and an erythrocyte sedimentation rate of 41. A chest roentgenogram was also normal at that time. In the few days preceding his infectious consultation diseases visit, he developed pharyngitis, pleuritic chest pain and a dry cough. Our patient had a past medical history of testicular torsion, radius fracture, varicella and infectious mononucleosis. He was taking no medications and had no allergies. In the house where he was living there were several cats, dogs and fish. There were fleas in the house and he had in fact been bitten by them. Ticks also had been found on the dogs but our patient could recall no tick bites. There were no HIV risk factors. His vaccination status was up to date. Except for the skin findings, the physical examination was largely unremarkable. He was afebrile. Blood pressure, pulse and respirations were normal. He was in the 75th percentile for height and weight. He had mild upper abdominal tenderness but no palpable organomegaly. There were multiple circumferential areas of irregular erythema scattered across his trunk and extremities. Some had centers that resembled hematomas and others had a more target lesion appearance. Their diameters ranged from 1.5 to 6 cm. The erythema blanched and was not palpable. There was no mucous membrane involvement. Diagnostic testing was performed. Joseph I. Harwell, M.D.* Donna Fisher, M.D. Pediatric Infectious Diseases Division; Baystate Medical Center; Springfield, MA For denouement see p. 87. DENOUEMENT-CONTINUED FROM P. 81 Serology for Borrelia burgdorferi was strongly positive in this case with 3 of 3 IgM bands and 6 of 10 IgG bands on Western blot. This indicates a recent seroconversion (this test had been negative 2 weeks previously) by criteria recommended by the CDC wherein 2 of 3 IgM bands or 5 of 10 IgG bands are required to confirm an antibody response.1 Serologic studies were also sent for Epstein-Barr virus, parvovirus, Mycoplasma, Leptospira, Histoplasma, Coccidioides, Bartonella henselae and antistreptolysin O, which were all negative. Routine blood cultures were also negative. A 3-week course of doxycycline was prescribed with full resolution of symptoms. It is said that 90% of the diagnosis comes from the history. In this case the diagnosis is in the history but swimming in a sea of red herring. Our patient's primary symptoms were prolonged fever (3 weeks) and a rash that resembled erythema multiforme. Reviewing the history for possible explanations for these symptoms, we can start with the trip to Arizona. Coccidioides immitis, the cause of valley fever and endemic to the Southwest, can be associated with erythema multiforme.2 Infections with this organism may commonly occur after dust storms. An exposure history which includes a potentially contaminated water park, a waterborne traumatic injury and drinking from woodland streams suggests the possibility of Leptospira infection. Leptospirosis has recently been associated with an outbreak among triathletes swimming in a common contaminated lake source.3 Vaccination, particularly with diphtheria-pertussis, has been reported to cause erythema multiforme-like rash although not clearly found to have a causal relationship.2, 4 Because diphtheria was given along with the tetanus vaccine which our patient received, we could include this on our differential diagnosis although it seems coincidental. Histoplasma capsulatum infection can be acquired from spelunking as well as from exposure to chickens and other fowl. There is a strong association between histoplasmosis and erythema multiforme.2 Psittacosis may also be transmitted from chickens and can cause erythema multiforme.2 In addition to histoplasmosis and psittacosis, the multiple animal exposures in this case raise the possibility of other zoonotic infections. Specifically Francisella tularensis, or tularemia, can be contracted from horses and goats and is a reported cause of erythema multiforme.2 More mundane infections not associated with travel are even more strongly associated with the symptoms of fever, erythema multiforme-like rash, dry cough, pharyngitis and mild arthralgias. These include infection by Mycoplasma pneumoniae, group A streptococci, herpes simplex virus and a variety of other common viruses.2 Collagen vascular disorders, including lupus erythematosus and juvenile rheumatoid arthritis, are also known for producing this symptom complex.2, 5 B. burgdorferi is the spirochete that causes Lyme disease, a tick-borne infection endemic to the northeast but also found in mid-Atlantic, north central and far western United States as well as Europe. Carriage rates for ticks vary significantly by region with up to 65% of adult Ixodes scapularis ticks infected in concentrated foci in the northeast.6 Diagnosis of acute Lyme borreliosis is made by a combination of history of exposure and clinical findings. Serologic testing should be used to confirm cases in the stages beyond early infection. The illness occurs in stages of primary infection, dissemination and established late disease. Rash is the hallmark of primary and early disseminated disease with up to 90% of patients exhibiting this finding.6 Other findings include fatigue (54%), myalgia (44%), arthralgia (44%), headache (42%), fever (39%) and stiff neck (35%).6 Later manifestations can be extremely varied and include a variety of neurologic deficits, carditis and arthritis. Patients with a history of exposure and clinical findings consistent with disseminated and extracutaneous disease should undergo two step serologic testing with enzyme-linked immunosorbent assay or immunofluorescent assay followed by immunoblotting. In early stages, however, antibody testing may be negative and should not be used to confirm primary infection. The treatment of choice is doxycycline for varying durations depending on the organ system affected. Although probably equal in efficacy, penicillins and cephalosporins are not active against human granulocytic ehrlichiosis which may be present as a coinfection. With profound central nervous system disease some patients may require up to 1 month of intravenous therapy, typically with ceftriaxone. A vaccine has recently been approved for use in high risk individuals residing in or traveling to endemic areas. The vaccine has ∼75% efficacy for prevention of symptomatic infection after a three dose series.7 The vaccine is currently not approved for children younger than the age of 15 years, however, and the best prevention for this age group remains insect repellent and close surveillance for ticks. Our patient's rash at the time of presentation was rather atypical for Lyme disease and had the appearance more of erythema multiforme than of erythema migrans. Primary and secondary Lyme disease can have a variable appearance and can frequently be misdiagnosed or overdiagnosed.8 Borreliosis as a cause of biopsy-proved erythema multiforme has rarely been reported in the literature.9

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