What is the diagnostic test for Lyme disease arthritis?

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Last updated: July 31, 2025View editorial policy

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Diagnostic Testing for Lyme Disease Arthritis

The recommended diagnostic test for Lyme disease arthritis is two-tiered serologic testing consisting of an enzyme-linked immunoassay (EIA/ELISA) or immunofluorescence assay (IFA) as the first tier, followed by a Western immunoblot if the first tier is positive or equivocal. 1, 2

Diagnostic Algorithm for Lyme Arthritis

  1. Two-tiered serologic testing:

    • First tier: ELISA or IFA (detects both IgM and IgG antibodies)
    • Second tier: Western immunoblot (only if first tier is positive/equivocal)
      • For suspected Lyme arthritis (late disease), IgG Western blot is sufficient 1
      • IgG Western blot is considered positive if ≥5 of 10 specific bands are present (18,21-24,28,30,39,41,45,58,66,93 kDa) 2
  2. Synovial fluid analysis (adjunctive testing):

    • PCR testing of synovial fluid has >75% sensitivity for Lyme arthritis 1
    • Synovial fluid typically shows:
      • Mild-to-moderate inflammation
      • Median leukocyte count of ~24,250 leukocytes/mm³
      • Predominance of granulocytes 1

Interpretation and Clinical Correlation

  • All patients with Lyme arthritis should be seropositive by two-tier testing that includes an ELISA and IgG immunoblot 1
  • In a seropositive patient, a positive PCR test on synovial fluid adds increased diagnostic certainty 1
  • Important caveat: Positive PCR results from joint fluid in a seronegative patient should be regarded with skepticism 1

Clinical Features of Lyme Arthritis

  • Lyme arthritis is typically monoarticular or oligoarticular, predominantly affecting the knee 1, 3
  • Large knee effusions out of proportion to pain are characteristic 1
  • Intermittent episodes of joint inflammation may spontaneously resolve after weeks to months if untreated 1

Common Pitfalls to Avoid

  1. Do not rely on PCR or culture alone for diagnosis - these have limited sensitivity and should be used as adjuncts to serologic testing 1

  2. Do not interpret fewer bands on Western blot as positive:

    • A positive IgG Western blot requires ≥5 of 10 specific bands
    • Interpreting fewer bands as positive leads to false positives 1, 2
  3. Do not perform Western blot without first-tier EIA/ELISA:

    • Following the two-tier protocol is essential for accurate diagnosis 2
    • Western blot should only be performed if the first-tier test is positive/equivocal 2
  4. Do not test patients with low pretest probability:

    • Testing has poor positive predictive value in patients without:
      • Travel to/residence in endemic areas
      • Known tick exposure
      • Compatible clinical symptoms 2

For Lyme arthritis specifically, the two-tiered serologic testing approach has excellent sensitivity (70-100%) and specificity (>95%) since it represents late disseminated disease when antibody responses are well-developed 1, 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Lyme Disease Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Lyme Arthritis.

Infectious disease clinics of North America, 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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