What initial testing is recommended for a patient presenting with concern for Lyme (Lyme disease) arthritis?

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From the Guidelines

For suspected Lyme arthritis, I recommend a two-tier testing approach starting with an enzyme-linked immunosorbent assay (ELISA) to detect antibodies against Borrelia burgdorferi, followed by a Western blot test if the ELISA is positive or equivocal, as outlined in the 2016 guidelines for laboratory diagnosis of Lyme disease 1. This approach is supported by the most recent and highest quality study, which emphasizes the importance of proper interpretation of laboratory tests in the context of symptoms and timing of illness. Some key points to consider when interpreting test results include:

  • The sensitivity of two-tiered testing is low (30%–40%) during early infection, but increases to 70%–100% for disseminated Lyme disease 1
  • Specificity is high (>95%) during all stages of disease 1
  • Patients typically develop antibodies within 4-6 weeks after infection, so testing too early may yield false negatives
  • If clinical suspicion remains high despite negative serology, consider repeating tests in 2-4 weeks Additionally, synovial fluid analysis may be helpful to rule out other causes of arthritis, including crystal analysis and culture, as recommended by the 2020 guidelines for the prevention, diagnosis, and treatment of Lyme disease 1. It is essential to perform testing before initiating antibiotics to avoid false negative results. The diagnosis of Lyme arthritis relies on both clinical presentation (typically monoarticular or oligoarticular arthritis affecting large joints, especially the knee) and laboratory confirmation of B. burgdorferi infection, as symptoms alone are not specific enough for definitive diagnosis.

From the Research

Initial Testing for Lyme Arthritis

To diagnose Lyme arthritis, the following initial testing is recommended:

  • Enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies against Borrelia burgdorferi 2, 3, 4
  • Western blot analysis to confirm the results of the ELISA, particularly when there are low antibody titers 2, 3, 4
  • Synovial fluid analysis, including PCR for B. burgdorferi, to detect the presence of the bacteria in the joint fluid 5

Interpretation of Test Results

The interpretation of test results is crucial in diagnosing Lyme arthritis:

  • A positive ELISA result should be confirmed by Western blot analysis 2, 4
  • IgG antibody levels of 200 IU/ml or higher may be sufficient to detect antibodies to B. burgdorferi, and a confirmatory immunoblot may be omitted 4
  • The presence of IgM antibodies may indicate early infection, while IgG antibodies may indicate later stages of infection 2, 3

Clinical Considerations

Clinical considerations are essential in diagnosing Lyme arthritis:

  • A thorough medical history and physical examination should be performed to rule out other causes of arthritis 5
  • The clinical presentation of Lyme arthritis may vary, but it often presents as chronic knee monoarthritis 5
  • The sensitivity of synovial fluid PCR for B. burgdorferi may be low, and a negative result does not rule out the diagnosis 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Lyme arthritis in Western Europe: a multicentre retrospective study.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2022

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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