What is the initial step in testing for Lyme disease?

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Last updated: June 24, 2025View editorial policy

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From the Guidelines

The initial step in testing for Lyme disease is a two-tier blood testing approach, starting with an enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) test, as recommended by the most recent guidelines 1. This approach is based on the fact that the diagnosis of Lyme disease is primarily clinical, and serologic testing provides valuable supportive diagnostic information in patients with endemic exposure and objective clinical findings that indicate later-stage disseminated Lyme disease 1. The two-tier testing consists of an initial EIA or ELISA test, followed by a Western blot test to confirm the diagnosis by identifying specific antibodies. It's essential to note that these tests may not be reliable in the very early stages of infection (first few weeks) as antibodies take time to develop. Some key points to consider when testing for Lyme disease include:

  • Testing should be considered for patients with symptoms consistent with Lyme disease and potential exposure to ticks in endemic areas.
  • Early symptoms typically include a characteristic expanding rash called erythema migrans (often resembling a bull's-eye), fever, fatigue, headache, and muscle and joint aches.
  • In some cases, especially when the classic rash is present and there's a history of tick exposure in an endemic area, physicians may diagnose and treat Lyme disease based on clinical presentation without waiting for test results, as stated in the guidelines 1. The sensitivity of the two-tiered testing is low (30%–40%) during early infection, but it increases to 70%–100% for disseminated Lyme disease, with a high specificity (>95%) during all stages of the disease 1.

From the Research

Initial Step in Testing for Lyme Disease

The initial step in testing for Lyme disease involves a clinical evaluation, which is then supported by serologic testing using a 2-step process 2, 3.

Serologic Testing Process

  • The first step is based on a high sensitivity ELISA test 3
  • The second step involves confirming positive results from the ELISA test with a more specific Western blot assay 3

Importance of Clinical Evaluation

Clinical evaluation is crucial in the diagnosis of Lyme disease, as it relies on the recognition of signs and symptoms, such as erythema migrans, flu-like syndrome, and arthritis, in the setting of travel to or residence in an endemic area 2, 4.

Geographic Considerations

It is also important to consider the geographic location of the patient, as Lyme disease is more common in certain areas, such as the northeastern United States, Wisconsin, Minnesota, and Michigan 2.

Co-Infections

In some geographic areas, patients may be co-infected with other pathogens, such as Babesia, Ehrlichia, and Anaplasma, which are transmitted by the same Ixodes ticks that transmit Borrelia burgdorferi 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Tick borne illness-Lyme disease.

Disease-a-month : DM, 2018

Research

Lyme disease: review.

Archives of medical science : AMS, 2012

Research

Lyme disease: clinical manifestations, diagnosis, and treatment.

Seminars in arthritis and rheumatism, 1991

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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