Michael A. Gerber
Lyme disease is the most commonly reported vector-borne illness in the United States, accounting for more than 95% of such cases. It is caused by the spirochete, Borrelia burgdorferi, which is transmitted to humans through the bite of an Ixodes tick.1,2
More than 90% of the cases of Lyme disease are reported from 10 states located along the northeastern and mid-Atlantic seaboard and in the upper north-central regions of the United States. Sixty-one percent of the reported cases occur in children 5 to 14 years of age.3 The principal risk factor for acquiring Lyme disease in endemic areas is residence in suburban or rural areas that are wooded or overgrown with brush and infested by infected vector ticks. The ticks that can transmit Lyme disease (Ixodes scapularis, also known as the black-legged or deer tick, in the eastern United States, and Ixodes pacificus, also known as the western black-legged tick, in the western United States) are found in wooded areas, high grasses, marshes, gardens, and beach areas. Humans acquire B burgdorferi from infected ticks at the time the tick takes a blood meal.
Lyme disease is not spread by person-to-person contact or by direct contact with infected animals. Although transplacental transmission of B burgdorferi has been reported, the effect of such transmission on the fetus remains uncertain. Available data suggest that congenital Lyme disease occurs only very rarely, if at all.4 Transmission in breast milk has not been documented. Although B burgdorferi can survive in stored blood for several weeks, the risk for transfusion-acquired Lyme disease appears to be minimal.
The clinical manifestations of Lyme disease depend on the stage of the disease—early, localized disease; early, disseminated disease; or late disease.1,2 The most common manifestation of early, localized Lyme disease, erythema migrans, appears 3 to 30 days (but typically within 7-10 days) after a tick bite at the site of the bite.1,2 Erythema migrans begins as a red macule or papule and usually expands over days to weeks to form a large, annular, erythematous lesion that is at least 5 cm and as much as 70 cm in diameter (median of 15 cm). The rash may be uniformly erythematous, or it may appear as a target lesion with variable degrees of central clearing (eFig. 267.1 ). It can vary greatly in shape and, occasionally, may have vesicular or necrotic areas in the center. Erythema migrans is usually asymptomatic, but may be pruritic or painful and accompanied by systemic symptoms such as fever, malaise, headache, myalgias, and arthralgias.
The most common manifestation of early, disseminated Lyme disease is multiple erythema migrans.1,2,5 The secondary skin lesions, which usually occur from 3 to 5 weeks after the tick bite, consist of multiple annular erythematous lesions similar to, but usually smaller than, the primary lesion. Other common manifestations of early, disseminated Lyme disease are cranial nerve palsies, especially facial nerve palsy, and meningitis.5,6 Carditis, which is usually manifested by various degrees of heart block, although rare, may also occur at this stage. Systemic symptoms such as myalgias, arthralgias, headache, and fatigue are common in the early, disseminated stage.
Late Lyme disease is characterized by arthritis, which is usually monoarticular or oligoarticular, that affects the large joints, particularly the knee.7 The arthritis occurs weeks to months after the initial infection. Although the affected joint is typically swollen and tender, the intense pain associated with a septic arthritis is usually not present. Encephalitis, encephalopathy, and polyneuropathy are also manifestations of late Lyme disease but are rare in children.6
For patients who present with the characteristic lesion of erythema migrans, the diagnosis should be based on the clinical presentation alone. For patients who do not have erythema migrans, the diagnosis also should be based on clinical findings, but with support from laboratory testing.8,9 Methods for identifying the presence of B burgdorferi in a patient (eg, culture, antigen detection, histopathology) have poor sensitivity and/or specificity and may require invasive procedures (eg, skin biopsy) to obtain an appropriate specimen for testing. Laboratory confirmation usually depends on serologic testing for antibodies to B burgdorferi.
Unfortunately, serologic tests for Lyme disease have not been adequately standardized. In addition, antibodies to B burgdorferi are not detectable in most patients with early, localized Lyme disease. Furthermore, some patients who are treated with antimicrobial agents early in the course of their disease never develop antibodies to B burgdorferi. However, most patients with early, disseminated Lyme disease, and virtually all patients with late Lyme disease, have antibodies to B burgdorferi.8,9 As with other infections, once such antibodies develop, they may persist for many years despite cure of the disease. Consequently, tests for antibodies should not be used to assess the success of treatment.
Because of the lack of specificity of the EIA, a two-test approach is recommended for confirming the diagnosis of B burgdorferi infection. Sera that are positive or equivocal by a sensitive EIA should be tested by a standardized Western immunoblot for the presence of antibodies to proteins specific for B burgdorferi; those that are negative by a sensitive EIA do not require immunoblot testing.8,9
A major problem in diagnosing Lyme disease is the widespread practice of ordering serologic tests in patients with only nonspecific symptoms (eg, fatigue, arthralgia) who have a low pretest probability of having Lyme disease. Almost all positive serologic test results in such patients are false positives. Patients with Lyme disease almost always have specific signs (eg, erythema migrans, facial nerve palsy, arthritis), and although nonspecific symptoms commonly accompany these specific signs, nonspecific symptoms are almost never the only clinical manifestation of Lyme disease.
Table 267-1 lists the recommended treatment for Lyme disease in children. Doxycycline is the drug of choice for treatment of early, localized disease in children 8 years of age and older.9 Amoxicillin is recommended for those children younger than 8 years and for those children who cannot tolerate doxycycline. Cefuroxime axetil is an alternative first-line therapy for early Lyme disease. Because of their lower efficacy, macrolide antibiotics should be reserved for patients who are unable to take or who are intolerant of doxycycline, amoxicillin, and cefuroxime axetil.9 Most experts treat persons with early, localized Lyme disease for 14 days. Overall, clinical response to therapy is prompt, and erythema migrans resolves within several days of initiating therapy. Treatment of erythema migrans almost always prevents development of later stages of Lyme disease.9
Table 267-1. Recommended Treatment of Lyme Disease in Children
The optimal duration of antimicrobial therapy for the various stages of Lyme disease is not well established, but there is no evidence that children with any manifestation of Lyme disease benefit from either prolonged (>4 weeks) or repeated courses of either orally or parenterally administered antimicrobial agents.9-11
The long-term prognosis for children who are treated with appropriate antimicrobial therapy for early or late stages of Lyme disease is excellent.5,9,12 The most common reason for a lack of response to appropriate antimicrobial therapy for Lyme disease is misdiagnosis (ie, the patient actually does not have Lyme disease).10 Approximately 10% of adults and less than 5% of children with Lyme arthritis develop inflammatory joint disease that does not respond to antimicrobial agents and typically affects one knee for months to years. Because of the increased frequency of certain HLA-DR4 alleles in these patients, an autoimmune mechanism has been proposed.
It is not uncommon for children with early Lyme disease to have persistence of vague, nonspecific symptoms after completing an appropriate course of antimicrobial therapy. The persistence of such symptoms is not an indication of treatment failure. Within 6 months of completing the initial course of antimicrobial therapy, these vague, nonspecific symptoms will resolve without additional antimicrobial therapy. For those unusual patients who have persistent symptoms more than 6 months after the completion of antimicrobial therapy, an attempt should be made to determine whether these symptoms are the result of active infection, a postinfectious phenomenon, or another illness.9-11
The best currently available method for preventing Lyme disease is to avoid tick-infested areas in areas where Lyme disease is endemic. If this is not possible, a number of measures may help decrease the risk that ticks will attach and subsequently transmit infection.1,2,9 Frequent visual inspection of skin and clothing may help identify ticks before attachment. Transmission of B burgdorferi from infected ticks usually requires a prolonged duration of attachment (≥48 hours). Therefore, careful inspection and prompt removal of ticks can substantially reduce the risk of Lyme disease. Use of protective clothing may interfere with tick attachment, and wearing light-colored clothing may facilitate the recognition of ticks. Application of tick and insect repellents that contain DEET (N,N-diethyl-m-toluamide) to the skin provides additional protection and is safe when used according to product label instructions. Repellent sprays containing permethrin are also effective when applied to clothing. Routine use of antimicrobial agents to prevent Lyme disease following a deer tick bite, even in highly endemic areas, is not recommended.9Serologic testing for Lyme disease at the time of a recognized tick bite is also not recommended.9A Lyme disease vaccine was licensed in 1999 for persons 15 to 70 years of age, but was withdrawn from the market in 2002, reportedly because of poor sales.