Diagnosis of lyme disease

American Family Physician,  July 15, 2005  by Daniel L. Depietropaolo,  John H. Powers,  James M. Gill,  Andrew J. Foy

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The use of serologic testing and its value in the diagnosis of Lyme disease remain confusing and controversial for physicians, especially concerning persons who are at low risk for the disease. The approach to diagnosing Lyme disease varies depending on the probability of disease (based on endemicity and clinical findings) and the stage at which the disease may be. In patients from endemic areas, Lyme disease may be diagnosed on clinical grounds alone in the presence of erythema migrans. These patients do not require serologic testing, although it may be considered according to patient preference. When the pretest probability is moderate (e.g., in a patient from a highly or moderately endemic area who has advanced manifestations of Lyme disease), serologic testing should be performed with the complete two-step approach in which a positive or equivocal serology is followed by a more specific Western blot test. Samples drawn from patients within four weeks of disease onset are tested by Western blot technique for both immunoglobulin M and immunoglobulin G antibodies; samples drawn more than four weeks after disease onset are tested for immunoglobulin G only. Patients who show no objective signs of Lyme disease have a low probability of the disease, and serologic testing in this group should be kept to a minimum because of the high risk of false-positive results. When unexplained nonspecific systemic symptoms such as myalgia, fatigue, and paresthesias have persisted for a long time in a person from an endemic area, serologic testing should be performed with the complete two-step approach described above.

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Lyme disease is a systemic illness resulting from infection with the spirochete Borrelia burgdorferi. (1) According to the Centers for Disease Control and Prevention (CDC) definition for reportable cases of Lyme disease, the annual number of cases increased from 7,943 in 1990 to 17,730 in 2000. (2,3) The disease is most prevalent in children two to 15 years of age and in adults 30 to 59 years of age. (3) Figure 1 (4) shows the endemicity of Lyme disease in areas of the United States.

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Lyme disease is associated with a variety of signs that may present at different stages of the infection. The stages include early localized, early disseminated, and late chronic (Table 1). (5) The most common symptoms include skin and musculoskeletal involvement. In endemic areas, about 18 percent of infected persons present with only nonspecific systemic symptoms. (6) Early diagnosis is crucial because untreated infection can result in advanced disease involving the heart, nervous system, or joints. (7)

Clinical Presentation

The onset of clinical manifestations of Lyme disease typically occurs within seven to 10 days after a tick bite, with a reported range of one to 36 days. (8) Most patients (60 to 80 percent) develop the early, localized form of Lyme disease, which is characterized by erythema migrans and influenza-like symptoms. (9) Research suggests that erythema migrans most commonly presents as a centrifugally expanding, erythematous annular patch (10) (Figure 2). However, a recent observational cohort study (11) reported that in highly endemic areas, early erythema migrans mainly presented as homogeneous or central redness rather than a peripheral erythema with partial central clearing.

[FIGURE 2 OMITTED]

Clinical manifestations of Lyme disease in children resemble those in adults. The most common manifestation in children is erythema migrans rash followed by arthritis, facial nerve palsy, aseptic meningitis, and carditis. (3) Lyme meningitis has been reported in children with facial nerve palsy. (12) As in adults, Lyme meningitis may be subtle and usually occurs without meningismus. When compared with children with viral meningitis, children with Lyme meningitis have presented with much lower rates of fever but with similar rates of headache, neck pain, and malaise. (13)

Coinfection of patients (10 percent) with other tick-borne illnesses, such as human granulocytic ehrlichiosis, caused by Babesia microti and rickettsial-like pathogens, has been reported. (14) Co-infected patients commonly present with a prolonged influenza-like illness that fails to respond to antiborrelial therapy.

The most widely accepted guidelines for the diagnosis of Lyme disease are those from the American College of Physicians (ACP), (15) which were based on the 1990 CDC surveillance criteria (Table 2). (16) Because of the limitations of laboratory testing for Lyme disease, diagnosis is based primarily on clinical findings. (7,9,17,18) An algorithm for the diagnosis of Lyme disease is presented in Figure 3.

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Laboratory Tests

The host antibody response to B. burgdorferi infection develops slowly, and only one half of patients with early-stage Lyme disease will have a positive serology. The immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies appear two to four and four to six weeks, respectively, after the onset of erythema migrans and peak at six to eight weeks. Although IgM usually declines to very low levels after four to six months of illness, IgG remains present at low levels despite successful treatment. (18) Therefore, physicians should evaluate the significance of a serologic result in the context of the patient's epidemiologic history.