What laboratory tests are used to diagnose late-stage Lyme (Lyme) disease?

From the Guidelines

For late Lyme disease, the recommended laboratory testing is a two-tier approach consisting of an initial enzyme immunoassay (EIA) or immunofluorescence assay (IFA), followed by a Western blot test if the first test is positive or equivocal, as this approach has a high specificity (>95%) and sensitivity (70%–100%) for disseminated Lyme disease 1.

Key Considerations

• In late-stage Lyme disease, IgG antibodies are typically present at high levels, making serologic testing more reliable than in early disease.
• Both IgM and IgG Western blots may be performed, but IgG is more important for late disease diagnosis.
• The C6 peptide ELISA is another option that may be used as a standalone test or as part of the two-tier approach.
• PCR testing of synovial fluid can be helpful in cases of Lyme arthritis, though it has limited sensitivity.
• Cerebrospinal fluid analysis may be necessary for suspected neuroborreliosis, looking for intrathecal antibody production and elevated protein levels.

Important Notes

• Antibodies can persist for years after successful treatment, so these tests cannot distinguish between active infection and past exposure.
• Clinical correlation with symptoms is essential for proper diagnosis of late Lyme disease.
• Novel 2-tiered algorithms, such as a 2-tiered EIA approach, have been proposed to improve early diagnosis of Lyme disease, but further research is still needed to determine their validity for late disease diagnosis 1.

From the Research

Lab Tests for Late Lyme Disease

• The two-tiered antibody testing approach is commonly used for diagnosing Lyme disease, including late Lyme disease 2, 3, 4.
• This approach typically involves an initial enzyme immunoassay (EIA) followed by a Western blot test 2, 3.
• For late Lyme disease, the two-tiered approach has been shown to have 100% sensitivity 2.
• Alternative testing strategies, such as the use of a C6 peptide EIA, have also been evaluated and may offer similar or better sensitivity than the traditional two-tiered approach 2, 5, 3.
• A multiplex immunoassay using VlsE1-IgG and pepC10-IgM antibodies has been shown to be equally specific and more sensitive than Western blotting for diagnosing late Lyme disease 5.
• The choice of lab test for late Lyme disease may depend on various factors, including the patient's clinical presentation and the availability of testing options 4.

Specific Lab Tests

• The C6 peptide EIA has been shown to be a sensitive and specific test for late Lyme disease, with a sensitivity of 100% in some studies 2, 3.
• The VlsE1-IgG and pepC10-IgM multiplex immunoassay has been shown to be a promising alternative to traditional testing approaches, with improved sensitivity and specificity 5.
• Western blotting remains a commonly used test for diagnosing Lyme disease, including late Lyme disease, although it may have limitations in terms of sensitivity and specificity 2, 3, 4.

Test Performance

• The sensitivity and specificity of lab tests for late Lyme disease can vary depending on the testing approach and the patient population being studied 2, 5, 3, 4.
• In general, the two-tiered approach and alternative testing strategies, such as the C6 peptide EIA and multiplex immunoassay, have been shown to have high sensitivity and specificity for diagnosing late Lyme disease 2, 5, 3, 4.