What tests should be ordered for a patient after a tick bite to diagnose Lyme disease?

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Last updated: June 11, 2025View editorial policy

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From the Guidelines

For diagnosing Lyme disease after a tick bite, a two-tier testing approach is recommended, starting with an enzyme immunoassay (EIA) or immunofluorescence assay (IFA), followed by a Western blot test if the initial result is positive or equivocal, as supported by the most recent guidelines 1. This approach is crucial for accurately diagnosing Lyme disease, especially in patients who do not present with the characteristic erythema migrans rash. The two-tier testing strategy helps in reducing false positives and improving diagnostic accuracy. It is also important to note that for patients with a clear clinical presentation of erythema migrans in endemic areas, laboratory testing may not be necessary, and treatment can be initiated based on clinical judgment alone 1. Additionally, for patients presenting with neurological symptoms, further testing such as cerebrospinal fluid analysis may be warranted to confirm the diagnosis of neurologic Lyme disease. The timing of testing is critical, as antibodies may not be detectable until 2-4 weeks after the tick bite, and early antibiotic treatment can prevent antibody development, potentially leading to false-negative results 1. Therefore, a thorough clinical assessment and consideration of the patient's history and the endemic area are essential in determining the need for and interpretation of diagnostic tests for Lyme disease. Key points to consider include:

  • The two-tier testing approach for diagnosing Lyme disease
  • Clinical diagnosis without laboratory testing for patients with erythema migrans in endemic areas
  • The importance of timing in testing due to the development of antibodies
  • The potential impact of early antibiotic treatment on test results
  • The consideration of neurological symptoms for further diagnostic evaluation.

From the Research

Diagnostic Tests for Lyme Disease

To diagnose Lyme disease after a tick bite, the following tests can be ordered:

  • Enzyme-linked immunosorbent assay (ELISA) 2
  • Western blot 2, 3
  • Immunetics® C6 B. burgdorferi ELISA™ 2
  • Two-tier serological test protocol 2, 4
  • Direct detection methods, such as culture or PCR of tissue or blood samples 2

Test Interpretation

When interpreting test results, it is essential to consider the pretest probability of Lyme disease 3. Laboratory testing is recommended only in patients whose pretest probability of Lyme disease is 0.20 to 0.80 3. If the pretest probability is less than 0.20, testing will result in more false-positive results than true-positive results; a negative test result in this situation effectively rules out the disease 3.

Clinical Diagnosis

Diagnosis of Lyme disease is usually made clinically, based on clinical manifestations and adjunctive laboratory testing 5, 6. The disease has three stages, each with specific clinical features:

  • Early localized infection: erythema migrans, fever, malaise, fatigue, headache, myalgias, and arthralgias 5
  • Early disseminated infection: neurologic, musculoskeletal, or cardiovascular symptoms and multiple erythema migrans lesions 5
  • Late disseminated infection: intermittent swelling and pain of one or more joints (especially knees) 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Laboratory evaluation in the diagnosis of Lyme disease.

Annals of internal medicine, 1997

Research

Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease.

MMWR. Morbidity and mortality weekly report, 2019

Research

Diagnosis and treatment of Lyme disease.

Mayo Clinic proceedings, 2008

Research

Lyme disease: diagnosis and treatment.

Current opinion in rheumatology, 2020

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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