What laboratory tests are recommended for diagnosing Lyme (Lyme disease)?

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Last updated: May 5, 2025 • View editorial policy

From the Guidelines

For suspected Lyme disease, a two-tiered serologic analysis consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting, is the recommended laboratory test in the United States. This approach is necessary to confirm the diagnosis, but proper interpretation depends on symptoms and timing of illness 1. The sensitivity of 2-tiered testing is low (30%–40%) during early infection, while the antibody response is developing, but increases to 70%–100% for disseminated Lyme disease 1.

Key Considerations

  • Patients who have a lesion consistent with erythema migrans and live in or have traveled to Lyme-endemic areas can be given a diagnosis without laboratory testing 1.
  • For all other patients, laboratory testing is necessary to confirm the diagnosis, and the 2-tiered serologic analysis is the recommended approach 1.
  • The use of other diagnostic tests for Lyme disease, such as PCR testing of joint fluid, has limited utility for other manifestations, and blood cultures are not routinely used for Lyme diagnosis.

Laboratory Tests

  • Enzyme-linked immunoassay or immunofluorescence assay as the initial screening test
  • Reflexive immunoblotting to confirm the diagnosis if the initial test is positive or equivocal
  • IgM and IgG Western blots for early Lyme disease (less than 30 days of symptoms)
  • Only IgG Western blot for late Lyme disease (more than 30 days) to avoid false positives due to persistent IgM 1.

From the Research

Labs to Order for Lyme Disease

To diagnose Lyme disease, several laboratory tests can be ordered, including:

  • Enzyme-linked immunosorbent assay (ELISA) for immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against Borrelia burgdorferi 2, 3, 4, 5, 6
  • Western blot test to confirm the presence of antibodies against B. burgdorferi 2, 6
  • Peptide ELISA based on the borreliacidal antibody epitope of B. burgdorferi OspC 2
  • ELISA with recombinant antigens of B. burgdorferi, such as p41-G, OspC, and OspF 6

Interpretation of Test Results

The interpretation of test results is crucial in diagnosing Lyme disease. The sensitivity and specificity of the tests vary, and a combination of tests may be necessary to confirm the diagnosis. For example:

  • The peptide ELISA based on the OspC epitope has been shown to be highly sensitive and specific for early Lyme disease 2
  • The ELISA with recombinant antigens has been shown to be sensitive and specific for detecting IgM and IgG antibodies against B. burgdorferi 6
  • The Western blot test is often used to confirm the presence of antibodies against B. burgdorferi, but it may not be as sensitive as other tests 2, 6

Additional Considerations

When ordering labs for Lyme disease, it is essential to consider the following:

  • The stage of the disease, as different tests may be more appropriate for different stages 5
  • The presence of other infections or diseases that may cause cross-reactivity with Lyme disease tests 3, 6
  • The use of vaccines, such as the OspA vaccine, which may affect the interpretation of test results 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.