The New England Journal of Medicine.
May 1, 2014.Teaching Topic
Lyme DiseaseE.D. Shapiro
Lyme disease, a zoonosis, is transmitted by certain ixodid ticks and is the most common reportable vectorborne disease in the United States, where it is caused only by the spirochete Borrelia burgdorferi sensu stricto (hereafter termed B. burgdorferi). In Europe and in Asia, B. afzelii, B. garinii, and other related species, in addition to B. burgdorferi, cause Lyme disease.
Clinical Pearls
Clinical Pearl What are the typical characteristics of erythema migrans?
The most common sign of Lyme disease is erythema migrans. Erythema migrans usually begins as a small erythematous papule or macule that appears at the site of the tick bite 1 to 2 weeks later (range, 3 to 32 days) and subsequently enlarges. The lesion may have centrally located vesicles or necrotic areas. Erythema migrans may be asymptomatic, mildly pruritic, or, in rare cases, painful; if untreated, lesions may become as large as 61 cm (2 ft) in diameter and may last for 3 to 4 weeks before resolving. Erythema migrans lesions may occur anywhere on the body surface, although common sites are the groin, axilla, waist, back, lower extremities, and, in children, the head and neck. Although reputed to have a bull’s-eye appearance, approximately two thirds of single erythema migrans lesions either are uniformly erythematous or have enhanced central erythema without clearing around it.
Clinical Pearl What are extracutaneous signs of disseminated Lyme disease?
Extracutaneous signs of disseminated Lyme disease that may occur, with or without erythema migrans, include neurologic conditions, such as cranial-nerve (particularly facial-nerve) palsy and meningitis that mimics aseptic meningitis, as well as carditis, which is most commonly manifested as heart block. Arthritis (most often affecting the knee) is a late sign of disseminated Lyme disease, occurring weeks to months after initial infection; it is seen in less than 10% of all cases, because most patients are treated and cured at an earlier stage of the illness.
Morning Report Questions
Q. How useful are serologic tests in the diagnosis of Lyme disease?
A. Serologic tests for the diagnosis of B. burgdorferi infection are generally of little use in patients with erythema migrans. Two-tier serologic testing for antibodies to B. burgdorferi is recommended (a quantitative test, usually an enzyme-linked immunosorbent assay [ELISA] of the concentration of antibodies to B. burgdorferi and, if results are positive or equivocal, a Western immunoblot); however, it has poor sensitivity in patients with erythema migrans during the acute phase (positive results in only 25 to 40% of patients without evidence of dissemination). Even in the convalescent phase after antimicrobial treatment, a substantial proportion of patients with erythema migrans (half of those without dissemination and a quarter of those with dissemination) do not have a positive test result. The sensitivity of two-tier testing is much better in patients either with early disseminated neurologic or cardiac Lyme disease (80 to 100%) or with late manifestations of Lyme disease such as arthritis (nearly 100%).
Q. What are the most appropriate antimicrobial agents for the treatment of early Lyme disease?
A. Randomized trials have assessed several different antimicrobial agents for the treatment of erythema migrans. In these trials, rates of cure (defined as complete resolution of signs and symptoms shortly after the completion of treatment) have been about 90% with doxycycline, amoxicillin, or cefuroxime axetil. With rare exceptions, patients who were not cured continued to have only nonspecific symptoms, such as fatigue or arthralgia. If a patient has a contraindication to all those drugs, macrolide antibiotics (e.g., azithromycin, clarithromycin, or erythromycin) are an option, but they are somewhat less effective, with cure rates of about 80%. First-generation cephalosporins, such as cephalexin, are not effective in treating Lyme disease.
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