What initial laboratory studies are recommended for someone with early disseminated Lyme (Lyme disease)?

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Last updated: May 8, 2025View editorial policy

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From the Guidelines

For early disseminated Lyme disease, I recommend ordering a two-tier serologic testing approach consisting of an enzyme immunoassay (EIA) or immunofluorescence assay (IFA) followed by a Western blot if the first test is positive or equivocal, as this approach has a sensitivity of 70%–100% and specificity of >95% for disseminated Lyme disease 1. When evaluating a patient with suspected early disseminated Lyme disease, it is essential to consider the potential involvement of multiple organ systems.

  • A complete blood count (CBC) and comprehensive metabolic panel (CMP) should be included to assess for systemic inflammation and organ function.
  • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) can help evaluate the inflammatory response.
  • If neurologic symptoms are present, cerebrospinal fluid analysis through lumbar puncture should be considered to check for antibodies and inflammatory markers.
  • An electrocardiogram (ECG) is important to evaluate for cardiac involvement, particularly AV block. It is crucial to note that serologic testing may initially be negative as antibodies take several weeks to develop, so clinical presentation remains important for diagnosis 1.
  • If symptoms strongly suggest Lyme disease despite negative initial testing, repeat serologic testing in 2-4 weeks may be warranted as the antibody response develops over time. The two-tier serologic testing approach is the recommended laboratory test in the United States for confirming the diagnosis of Lyme disease, especially in patients with disseminated disease 1.

From the Research

Initial Laboratory Studies for Early Disseminated Lyme

The following laboratory studies are recommended for someone with early disseminated Lyme:

  • Serum enzyme immunoassay (EIA) for antibody to Borrelia burgdorferi as the initial test 2, 3, 4
  • Supplementary IgG and IgM Western blotting of EIA-positive or -equivocal samples as the second-tier test 2, 3, 4
  • Alternatively, a multiplex immunoassay for VlsE1-IgG and pepC10-IgM antibodies can be used as a second-tier test, which has been shown to be equally specific but more sensitive than Western blotting for early-convalescent-phase disease 2
  • CXCL-13 in CSF is a promising new test for the improvement of the diagnosis of Lyme borreliosis 3

Considerations for Laboratory Testing

When interpreting serologic test results, it is essential to assess the patient's pretest probability of infection based on the probability of exposure and clinical findings 4

  • Two-tiered testing remains the gold standard in diagnosing Lyme disease, although new guidelines may be published soon 4
  • Limitations and pitfalls of serology include cross reactions, false IgM positivity, a seronegative window period at the early time of the infection, and serologic scars with a suspicion of reinfection 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Immunoserological Diagnosis of Human Borrelioses: Current Knowledge and Perspectives.

Frontiers in cellular and infection microbiology, 2020

Research

Appropriate laboratory testing in Lyme disease.

Cleveland Clinic journal of medicine, 2019

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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