What is the most effective diagnostic test for Lyme disease?

From the Guidelines

The most effective diagnostic test for Lyme disease is the 2-tiered serologic analysis, which consists of an enzyme-linked immunoassay (EIA) or immunofluorescence assay (IFA) followed by reflexive immunoblotting.

Key Points

• The sensitivity of 2-tiered testing is low (30%–40%) during early infection, but increases to 70%–100% for disseminated Lyme disease 1.
• The specificity of 2-tiered testing is high (>95%) during all stages of disease 1.
• The first-tier test measures the overall antibody response (typically IgM and IgG) of a patient to B. burgdorferi antigens, with EIA being the most commonly used method 1.
• The use of other diagnostic tests for Lyme disease is limited, and clinicians should only use FDA-cleared diagnostic tests 1.

Diagnostic Approach

• Patients with a lesion consistent with erythema migrans (EM) and a history of exposure to Lyme-endemic areas can be diagnosed without laboratory testing 1.
• For all other patients, laboratory testing is necessary to confirm the diagnosis, and the 2-tiered serologic analysis is the recommended approach 1.
• Clinicians should consider the patient's history, timeline of symptoms, and pretest probability when ordering and interpreting the test result 1.

Clinical Guidelines

• The Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) recommend testing for Lyme disease in patients with acute disorders such as meningitis, radiculoneuritis, or cranial neuropathies, and epidemiologically plausible exposure to ticks infected with B. burgdorferi 1.
• Routine testing for Lyme disease is not recommended for patients with typical amyotrophic lateral sclerosis, relapsing-remitting multiple sclerosis, Parkinson’s disease, dementia or cognitive decline, or new-onset seizures 1.

From the Research

Diagnostic Tests for Lyme Disease

The most effective diagnostic test for Lyme disease is a topic of ongoing research and debate.

• The standard two-tiered (STT) algorithm, which includes an enzyme-linked immunoassay (EIA) or immunofluorescence assay (IFA) followed by Western blotting (WB), has been the primary diagnostic test for Lyme disease since 1995 2.
• However, the STT algorithm has low sensitivity in early infection, and there are drawbacks associated with the WB use in practice 3.
• Modified two-tiered (MTT) algorithms have been shown to improve the sensitivity of the testing in early disease while maintaining high specificity 3.
• A study comparing MTT algorithms with the STT algorithm found that all MTT algorithms had higher sensitivities than STT algorithms and were highly specific 3.
• Rapid diagnostic tests (RDTs) have also been evaluated, but their performance was found to be below that of laboratory-based diagnostics 4.
• The choice of diagnostic test may depend on the patient's pretest probability of infection, and two-tiered testing remains the gold standard in diagnosing Lyme disease 5.
• New technologies examining early immune responses to Borrelia burgdorferi have the potential to diagnose Lyme disease in the first weeks of infection when existing serologic testing is not recommended due to low sensitivity 2.
• Evidence-based comparisons of different diagnostic assays have been made to select the most appropriate screening assay for diagnosis of Lyme disease 6.