What laboratory tests are recommended for a Lyme disease (Lyme) panel?

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Last updated: March 13, 2025View editorial policy

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From the Guidelines

For a Lyme disease panel, I recommend ordering a two-tier testing approach starting with an enzyme immunoassay (EIA) or immunofluorescence assay (IFA) as the initial screening test, followed by a Western blot test to confirm the diagnosis, as supported by the most recent guidelines 1.

Recommended Laboratory Tests

The two-tier testing approach is the recommended laboratory test for confirming the diagnosis of Lyme disease. This approach includes:

  • Enzyme-linked immunoassay (EIA) or immunofluorescence assay (IFA) as the initial screening test
  • Western blot test to confirm the diagnosis if the initial test is positive or equivocal

Specific Tests

Specific tests that can be used in the two-tier testing approach include:

  • ELISA test for antibodies to Borrelia burgdorferi
  • Western blot tests for both IgM and IgG antibodies
  • C6 peptide ELISA as an alternative confirmatory test in some cases

Important Considerations

It's essential to note that:

  • Antibodies may not be detectable in early infection (within the first few weeks)
  • Patients with the characteristic erythema migrans rash should be treated empirically without waiting for test results
  • PCR testing of joint fluid may be helpful in cases of Lyme arthritis, though it's not routinely used for initial diagnosis
  • Interpretation of test results should always consider clinical presentation and exposure history, as false positives and negatives can occur 1.

From the Research

Laboratory Tests for Lyme Disease

The following laboratory tests are recommended for a Lyme disease panel:

  • Two-tiered testing approach, which includes an enzyme-linked immunoassay (EIA) or immunofluorescence assay (IFA) as the first tier, followed by Western blotting (WB) as the second tier 2, 3, 4
  • Modified two-tiered (MTT) algorithms, which have been shown to improve the sensitivity of testing in early disease while maintaining high specificity 3
  • Use of a whole-cell sonicate enzyme immunoassay (EIA) as the first tier, followed by a VlsE C6 peptide EIA as the second tier 5
  • Serologic assays, which are recommended for laboratory confirmation of Lyme disease, with a sensitivity that depends on the stage of infection and ranges from 30% in early localized disease to near 100% in late-stage disease 6

Test Characteristics

The characteristics of the recommended tests are:

  • Sensitivity: varies depending on the test and stage of infection, but can be as low as 30% in early localized disease and as high as 100% in late-stage disease 2, 3, 6
  • Specificity: generally high, but can be affected by factors such as seropositivity in the population due to immunization with the Lyme disease vaccine and the emergence of new Borrelia species that cause Lyme disease-like illnesses 2, 3
  • Positive predictive value: varies depending on the test and population being tested, but can be as high as 70% for the two-EIA algorithm 5

Testing Algorithms

The recommended testing algorithms are:

  • Standard two-tiered (STT) algorithm, which includes an EIA or IFA as the first tier, followed by WB as the second tier 2, 3, 4
  • Modified two-tiered (MTT) algorithms, which have been shown to improve the sensitivity of testing in early disease while maintaining high specificity 3
  • Two-EIA algorithm, which uses a whole-cell sonicate EIA as the first tier, followed by a VlsE C6 peptide EIA as the second tier 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.

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