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Lyme disease is caused by the spirochete Borrelia burgdorferi. The spirochete is transmitted to humans through the bite of Ixodes species ticks. Endemic areas for Lyme disease in the United States (US) correspond with the distribution of 2 tick species, Ixodes dammini (Northeastern and upper Midwestern US) and Ixodes pacificus (West Coast US). In Europe, Ixodes ricinus transmits the spirochete.
Lyme disease exhibits a variety of symptoms that may be confused with immune and inflammatory disorders. Inflammation around the tick bite causes skin lesions. Erythema chronicum migrans (ECM), a unique expanding skin lesion with central clearing that results in a ring-like appearance, is the first stage of the disease. Any of the following clinical manifestations may be present in patients with Lyme disease: arthritis, neurological or cardiac disease, or skin lesions. Neurologic and cardiac symptoms may appear with stage 2 and arthritic symptoms with stage 3 of Lyme disease. In some cases, a definitive distinction between stages is not always seen. Further, secondary symptoms may occur even though the patient does not recall having a tick bite or a rash.
According to the manufacturer’s package insert, early antibiotic treatment of Lyme disease can resolve clinical symptoms and prevent progression of the disease to later stages. However, the early administration of antibiotics may suppress the antibody response to levels that are undetectable by current laboratory tests.(4)
The Second National Conference on the Serologic Diagnosis of Lyme Disease (1994) recommended that laboratories use a 2-test approach for the serologic diagnosis of Lyme disease. Accordingly, specimens are first tested by the more sensitive EIA. An immunoblot assay is used to supplement positive or equivocal Lyme (EIA). An immunoblot identifies the specific proteins to which the patient's antibodies bind. Although there are no proteins that specifically diagnose Borrelia burgdorferi infection, the number of proteins recognized in the immunoblot assay is correlated with diagnosis.
Culture or PCR of skin biopsies obtained near the margins of ECM are frequently positive. In late (chronic) stages of the disease, serology is often positive and the diagnostic method of choice. PCR testing also may be of use in these late stages if performed on synovial fluid or cerebrospinal fluid.
Diagnosing Lyme disease
IgM assay is useful for confirming stage 1 (acute) Lyme disease.
IgG assay is useful for confirming stage 2 and stage 3 Lyme disease.
IgM antibodies to Borrelia burgdorferi may be detectable within 1 to 2 weeks following the tick bite; they usually peak during the third to sixth week after disease onset, and then demonstrate a gradual decline over a period of months. IgM antibody may persist for months even though antimicrobial agents are given. The IgM assay is more likely to be useful during early disease, and should only be tested during the first 4 to 6 weeks after disease onset.
Negative specimens typically demonstrate antibodies to less than 2 of the 3 significant Borrelia burgdorferi proteins. Additional specimens should be submitted in 2 to 3 weeks if Borrelia burgdorferi exposure has not been ruled out.
Individuals who have recently seroconverted due to infection with Borrelia burgdorferi may display incomplete banding patterns, but may develop increased reactivity (both in band intensity and number) when followed for a period of 4 to 6 months.
Serum IgG is detected as early as 2 weeks after onset of disease. Significant concentrations of antibody and immunoblot banding patterns for Borrelia burgdorferi can be found years after onset.
Normal specimens and false-positive EIA specimens generally have antibodies to 4 or fewer proteins. Except for early patients, antibodies from patients with Lyme disease generally bind to 5 or more proteins.
For persons who have received recombinant OspA vaccine and who are not infected with Borrelia burgdorferi, an intense band representing antibody to the OspA protein (band 30) should be visible on the immunoblot.
The immunoblot should not be used as a screening assay. In addition, immunoblot may be negative in specimens that are weakly-positive by EIA, or in patients with early Lyme disease.
Test results should be used in conjunction with clinical evaluation and information related to tick exposure.
A negative test result does not necessarily rule out current or recent infection. The specimen may have been drawn before demonstrable antibody developed. Patients with early disease often have serum antibody titers below the diagnostic threshold for several weeks following disease onset.
Test results from immunosuppressed patients and pregnant women may be difficult to interpret.
Positive test results may not be valid in persons who have received blood or blood product transfusions within the past several months.
Antibiotic therapy administered early in the first-stage of disease may suppress the antibody response to the point that diagnostic threshold levels are never attained.
False-positive reactions may occur with patients with other spirochetal diseases (syphilis, yaws, pinta, relapsing fever, or leptospirosis), influenza, autoimmune disorders, multiple sclerosis, or amyotrophic lateral sclerosis.
1. Dressler F, Whalen JA, Reinhardt BN, Steere AC: Western blotting in the serodiagnosis of Lyme disease. J Infect Dis 1993;167(2):392-400
2. Brown SL, Hansen SL, Langone JJ: Role of serology in the diagnosis of Lyme disease. JAMA 1999;282:62-66
3. Anonymous: Lyme disease-United States, 1995. MMWR Morb Mortal Wkly Rep 1996;June 14;45(23):481-484
4. Package insert: Viramed Biotech AG-Borrelia B31 IgG ViraStripe, Viramed Biotech AG, Steinkirchen, Germany, 2009