Why might a false positive serologic test for Lyme disease occur?
• Adequately treated patients may remain seropositive for many years after an infection is eradicated. Furthermore, individuals who live in endemic areas are more likely to have had a subclinical infection in the past and may also be seropositive.
• Antibodies directed toward other spirochetes may cross-react to the Borrelia antigen(s) used in ELISA. This scenario should be considered in a patient with over 1 month of nonspecific symptoms and a positive IgM ELISA, but a negative IgG ELISA (since patients with Lyme disease should develop an IgG response within this time period). This can occur in syphilis, leptospirosis, tick-borne relapsing fever, or with exposure to Treponema denticola (a spirochete found in the oral cavity) during a dental procedure.
• Cross-reactivity may occur in other conditions including granulocytic anaplasmosis, Helicobacter pylori infections, bacterial endocarditis, and autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis.
• Nonspecific polyclonal B-cell activation in Epstein–Barr virus, cytomegalovirus, and malaria may also produce cross-reactive antibodies.
• The use of unvalidated methods for interpretation of Western blots may lead to false-positive results. This may be due to an erroneous scoring of a faint band, more often an issue with IgM blots than IgG blots.
Due to these limitations, Lyme testing should only be used to confirm the diagnosis in patients with a compatible clinical presentation and should be avoided as a screening method in patients who have multiple vague complaints.