During the early stages of Lyme disease, the diagnosis is best made clinically by recognizing the characteristic rash, a singular lesion of erythema migrans, because antibodies against B burgdorferi are not detectable in most people within the first few weeks after infection. During the first 4 weeks of infection, seroDiagnostic Tests are insensitive and are not recommended generally. Although cultures of a biopsy specimen of the perimeter of the skin lesion often yield the organism, cultures of Borrelia species (which require special media) are not available commercially and are not recommended. Diagnosis in patients with early disseminated disease who have multiple lesions of erythema migrans also is made clinically. Diagnosis of early disseminated disease without rash or late Lyme disease should be made on the basis of clinical findings and serologic test results. Some patients who are treated with antimicrobial agents for early Lyme disease never develop antibodies against B burgdorferi ; they are cured and are not at risk of late disease. Most patients with early disseminated disease and virtually all patients with late disease have antibodies against B burgdorferi . Once such antibodies develop, they persist for many years and perhaps for life. Consequently, tests for antibodies should not be used to assess the success of Treatment. The results of serologic tests for Lyme disease should be interpreted with careful consideration of the clinical setting and the quality of the testing laboratory.
A 2-step approach is recommended for serologic diagnosis of B burgdorferi . First, a quantitative screening test for serum antibodies should be performed using a sensitive enzyme immunoassay (EIA) or immunofluorescent antibody assay (IFA). Serum specimens that yield positive or equivocal results then should be tested by a standardized Western immunoblot for presence of antibodies to B burgdorferi ; serum specimens that yield negative results by EIA or IFA should not be tested further by immunoblot. Immunoblot test should not be performed if EIA test result is negative or instead of an EIA; positive immunoblot results likely would not be attributable to Lyme disease. When testing to confirm early disseminated disease without rash, immunoglobulin (Ig) G and IgM immunoblot assays should be performed. To confirm late disease, only an IgG immunoblot assay should be performed, because false-positive results may occur with the IgM immunoblot. In people with symptoms lasting longer than 1 month, a positive IgM test result alone (ie, negative IgG test) is likely to represent a false-positive result and should not be the basis on which to diagnose Lyme disease. A positive result of an IgG immunoblot test requires detection of antibody ("bands") to 5 or more of the following: 18, 23/24, 28, 30, 39, 41, 45, 60, 66, and 93 kDa polypeptides. A positive test result of IgM immunoblot requires detection of antibody to at least 2 of the 23/24, 39, and 41 kDa polypeptides. Two-step testing is needed, because EIA and IFA may yield false-positive results because of the presence of antibodies directed against spirochetes in normal oral flora that cross-react with antigens of B burgdorferi or to cross-reactive antibodies in patients with other spirochetal infections (eg, syphilis, leptospirosis, relapsing fever), certain viral infections (eg, varicella, Epstein-Barr virus), or certain autoimmune diseases (eg, systemic lupus erythematosus).
A licensed serologic test that detects antibody to a peptide of the immunodominant conserved region of the variable surface antigen vlsE of B burgdorferi appears to have equivalent specificity and sensitivity compared with the 2-step protocol. Polymerase chain reaction (PCR) testing (using a laboratory with excellent quality procedures) has been used to detect B burgdorferi DNA in joint fluid. Urinary antigen detection has no role in diagnosis.
Suspected central nervous system Lyme disease can be confirmed by demonstration of intrathecal production of antibodies against B burgdorferi . However, interpretation of results of antibody tests of cerebrospinal fluid is complex, and physicians should seek the advice of a specialist experienced in management of patients with Lyme disease to assist in interpreting results.
The widespread practice of ordering serologic tests for patients with nonspecific symptoms, such as fatigue or arthralgia, who have a low probability of having Lyme disease or because of parental pressure, is discouraged. Almost all positive serologic test results in these patients are false-positive results. In areas with endemic infection, subclinical infection and seroconversion also can occur, and the patient's symptoms merely are coincidental. Patients with acute Lyme disease almost always have objective signs of infection (eg, erythema migrans, facial nerve palsy, arthritis). Nonspecific symptoms commonly accompany these specific signs but almost never are the only evidence of Lyme disease.
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