Diagnosis

Clinical Description: Lyme disease most often presents with a characteristic "bull's-eye" rash, erythema migrans, accompanied by nonspecific symptoms such as fever, malaise, fatigue, headache, muscle aches (myalgia), and joint aches (arthralgia).

The incubation period from infection to onset of erythema migrans is typically 7 to 14 days but may be as short as 3 days and as long as 30 days.

Some infected individuals have no recognized illness (asymptomatic infection determined by serological testing), or manifest only non-specific symptoms such as fever, headache, fatigue, and myalgia.

Lyme disease spirochetes disseminate from the site of the tick bite by cutaneous, lymphatic and blood borne routes. The signs of early disseminated infection usually occur days to weeks after the appearance of a solitary erythema migrans lesion. In addition to multiple (secondary) erythema migrans lesions, early disseminated infection may be manifest as disease of the nervous system, the musculoskeletal system, or the heart. Early neurologic manifestations include lymphocytic meningitis, cranial neuropathy (especially facial nerve palsy), and radiculoneuritis. Musculoskeletal manifestations may include migratory joint and muscle pains with or without objective signs of joint swelling. Cardiac manifestations are rare but may include myocarditis and transient atrioventricular blocks of varying degree.

B. burgdorferi infection in the untreated or inadequately treated patient may progress to late disseminated disease weeks to months after infection. The most common objective manifestation of late disseminated Lyme disease is intermittent swelling and pain of one or a few joints, usually large, weight-bearing joints such as the knee. Some patients develop chronic axonal polyneuropathy, or encephalopathy, the latter usually manifested by cognitive disorders, sleep disturbance, fatigue, and personality changes. Infrequently, Lyme disease morbidity may be severe, chronic, and disabling. An ill-defined post-Lyme disease syndrome occurs in some persons following treatment for Lyme disease. Lyme disease is rarely, if ever, fatal.

Image: Western Blot (IgG) Serodiagnostic Testing. (View enlarged image.)

Diagnosis: The diagnosis of Lyme disease is based primarily on clinical findings, and it is often appropriate to treat patients with early disease solely on the basis of objective signs and a known exposure. Serologic testing may, however, provide valuable supportive diagnostic information in patients with endemic exposure and objective clinical findings that suggest later stage disseminated Lyme disease. When serologic testing is indicated, CDC recommends testing initially with a sensitive first test, either an enzyme-linked immunosorbent assay (ELISA) or an indirect fluorescent antibody (IFA) test, followed by testing with the more specific Western immunoblot (WB) test to corroborate equivocal or positive results obtained with the first test. Although antibiotic treatment in early localized disease may blunt or abrogate the antibody response, patients with early disseminated or late-stage disease usually have strong serological reactivity and demonstrate expanded WB immunoglobulin G (IgG) banding patterns to diagnostic B. burgdorferi antigens. Antibodies often persist for months or years following successfully treated or untreated infection. Thus, seroreactivity alone cannot be used as a marker of active disease. Neither positive serologic test results nor a history of previous Lyme disease assures that an individual has protective immunity. Repeated infection with B. burgdorferi has been documented. B. burgdorferi can be cultured from 80% or more of biopsy specimens taken from early erythema migrans lesions. However, the diagnostic usefulness of this procedure is limited because of the need for a special bacteriologic medium (modified Barbour-Stoenner-Kelly medium) and protracted observation of cultures. Polymerase chain reaction (PCR) has been used to amplify genomic DNA of B. burgdorferi in skin, blood, cerobro-spinal fluid, and synovial fluid, but PCR has not been standardized for routine diagnosis of Lyme disease.

References:

Clinical Description:

Bujak DI, Weinstein A, Dornbush RL. Clinical and neurocognitive features of the post Lyme syndrome. J Rheumatol 1996;23:1392-1397.

Gaudino EA, Coyle PK, Krupp LB. Post-Lyme syndrome and chronic fatigue syndrome. Neuropsychiatric similarities and differences. Arch Neurol 1997;54:1372-1376.

Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med 1990;323:1438-1444.

Rahn DW. Natural history of Lyme disease. In: Rahn DW, Evans J, eds. Lyme disease, Philadelphia: American College of Physicians, 1998;35-48.

Shadick NA, Phillips CB, Logigian EL, et al. The long-term clinical outcomes of Lyme disease. Ann Intern Med 1994;121:560-567.

Steere AC, Levin RE, Molloy PJ et al. Treatment of Lyme arthritis. Arthritis Rheum 1994;37:878-888.

Diagnosis:

Berger BW, Johnson RC, Kodner C, Coleman L. Cultivation of Borrelia burgdorferi from erythema migrans lesions and perilesional skin. J Clin Microbiol 1992;30:359-361.

Brettschneider S, Bruckbauser H, Klugbauer K, Hofmann H. Diagnostic value of PCR for detection of Borrelia burgdorferi in skin biopsy and urine samples from patients with skin borreliosis. J Clin Microbiol 1998;36:2658-2665.

Centers for Disease Control and Prevention. Recommendations for Test Performance and Interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Aug 11, 1995;44:590-591.
(Also available in PDF format [214 KB, 16 pages].)

Dressler F, Whelan JA, Reinhart BN, Steere AC. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis 1993;167:392-400.

Johnson, BJ, Robbins KE, Bailey RE, et al. Serodiagnosis of Lyme disease: accuracy of a two-step approach using a flagella-based ELISA and immunoblotting. J Infect Dis 1996;174:346-353.

Nocton JJ, Dressler F, Rutledge BJ, et al. Detection of Borrelia burgdorferi by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med 1994;44:1203-1207.

Nowakowski J, Schwartz I, Nadelman RB, et al. Culture-confirmed infection and reinfection with Borrelia burgdorferi. Ann Intern Med 1997;127:130-132.

Tugwell P, Dennis DT, Weinstein A, et al. Clinical guideline 2: laboratory evaluation in the diagnosis of Lyme disease. Ann Intern Med 1997; 127:1109-1123.

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This page last reviewed November 14, 2003

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