What are the diagnostic tests for Lyme disease (Lyme borreliosis)?

From the Guidelines

Lyme disease testing should be considered for patients with symptoms consistent with Lyme disease and a history of potential tick exposure in endemic areas, following a two-step process with enzyme immunoassay (EIA) or immunofluorescence assay (IFA) and Western blot test for confirmation, as recommended by the Infectious Diseases Society of America (IDSA) 1.

Key Considerations

• Testing is most useful in later stages of infection when antibodies have had time to develop, usually 2-6 weeks after infection 1.
• Patients with the characteristic bull's-eye rash (erythema migrans) can be treated empirically without testing, as antibodies may not be detectable in early infection 1.
• False negatives can occur if testing is done too early, while false positives may result from cross-reactivity with other conditions 1.
• The IDSA recommends against routine testing for Lyme disease in patients with typical amyotrophic lateral sclerosis, relapsing-remitting multiple sclerosis, Parkinson’s disease, dementia or cognitive decline, or new-onset seizures, unless there is epidemiologic evidence of exposure to ticks infected with B. burgdorferi 1.

Diagnostic Approach

• The two-step testing process involves an initial EIA or IFA, followed by a Western blot test if the initial result is positive or equivocal 1.
• The Western blot test should only be performed if the initial EIA is reported as positive or equivocal, and should include both IgM and IgG antibodies for the first 4 weeks of illness 1.
• The presence of erythema migrans, cranial nerve palsy, or papilledema can help differentiate Lyme meningitis from viral meningitis, and laboratory testing is required to confirm the diagnosis 1.

Treatment

• For early Lyme disease, doxycycline 100mg twice daily for 10-14 days is typically prescribed for adults, with alternative antibiotics including amoxicillin or cefuroxime 1.
• Patients should understand that a negative test doesn't necessarily rule out Lyme disease if clinical suspicion is high, especially in early infection, and treatment decisions should be based on clinical judgment and epidemiologic evidence 1.

From the Research

Lyme Disease Testing Methods

• The Western blot technique is used as a serodiagnostic confirmation test for Lyme borreliosis, analyzing the humoral immune response to Borrelia burgdorferi 2.
• The Centers for Disease Control and Prevention (CDC) recommends a 2-tiered serologic testing algorithm for the evaluation of patients with suspected Lyme disease, which includes a screening enzyme immunoassay (EIA) or an immunofluorescence assay (IFA) that reflexes to IgM and IgG immunoblots 3.
• Standard 2-tier testing (STTT) has been the primary diagnostic test for Lyme disease since 1995, but a modified 2-tier test strategy using 2 EIAs has been approved by the Food and Drug Administration, offering a faster, less expensive, and more sensitive assay compared with STTT 4.

Accuracy of Diagnostic Tests

• A systematic review and meta-analysis of North American research found that the Immunetics® C6 B. burgdorferi ELISA™ and the two-tier approach have superior specificity compared to proposed replacements, and the CDC recommended western blot algorithm has equivalent or superior specificity over other proposed test algorithms 5.
• Direct detection methods, culture and PCR of tissue or blood samples, were not as sensitive or timely compared to serological testing 5.
• A study evaluating the modified two-tiered testing method for diagnosis of Lyme disease in children found that conventional two-tiered testing (CTTT) and modified two-tiered testing (MTTT) results agreed in most cases, with MTTT providing a promising alternate Lyme disease testing strategy for children 6.

Interpretation of Test Results

• The early immune response in Lyme borreliosis is triggered mainly by the flagellin, and interpretation criteria for blot positivity in early-stage borreliosis are primarily based on the presence of the 21 kDa band and the semiquantitatively recorded intensity of the 41 kDa band 2.
• In the diagnosis of late-stage infection, blot positivity relies on the presence of the 94 kDa, 39 kDa, 31 kDa, 30 kDa and 21 kDa bands 2.
• The CDC's established guidelines recommend the use of a 2-tiered serologic testing algorithm for the evaluation of patients with suspected Lyme disease, which includes a screening enzyme immunoassay (EIA) or an immunofluorescence assay (IFA) that reflexes to IgM and IgG immunoblots 3.