When should Lyme disease serology be ordered and how should the results be interpreted?

From the Guidelines

Lyme disease serology should be ordered when a patient presents with symptoms consistent with Lyme disease and has potential exposure to ticks in endemic areas, following a two-tier approach with enzyme immunoassay (EIA) or immunofluorescence assay (IFA) and subsequent Western blot testing for confirmation, as recommended by current guidelines 1.

Key Considerations for Ordering and Interpreting Lyme Disease Serology

• The two-tiered serologic test has a sensitivity of ≈70%–100% and a specificity >95% for disseminated Lyme disease, but sensitivity is low (30%–40%) during early infection 1.
• Early Lyme disease (within 30 days of infection) may yield negative results as antibodies haven't developed yet, making clinical judgment crucial in these cases.
• For early localized disease with erythema migrans rash, treatment can begin without serologic confirmation.
• Positive IgM results are significant only within the first 30 days of symptoms, while IgG antibodies develop later and persist for years.
• False positives can occur with other spirochetal infections, autoimmune diseases, or prior Lyme exposure, and false negatives may happen with early antibiotic treatment or immunosuppression.
• Serologic tests cannot distinguish between active and past infections, so they should not be used to monitor treatment response, and repeat testing is generally unnecessary and potentially misleading in post-treatment follow-up 1.

Clinical Judgment and Interpretation

• Clinical judgment is essential in interpreting serology results, considering the patient's symptoms, exposure history, and potential for false positives or negatives.
• The presence of erythema migrans rash is a distinctive clinical sign that can allow for diagnosis without laboratory confirmation, but serology is necessary for other manifestations of Lyme disease.
• Understanding the limitations of serologic testing, including the window period and potential for false results, is crucial for accurate diagnosis and treatment.

Recommendations for Practice

• Follow current guidelines for two-tiered serologic testing, using EIA or IFA followed by Western blot testing for confirmation.
• Consider clinical judgment and patient history when interpreting serology results.
• Avoid unnecessary repeat testing in post-treatment follow-up, as antibodies may remain detectable for years despite successful treatment.

From the Research

When to Order Lyme Disease Serology

• Lyme disease serology should be ordered when a patient presents with symptoms compatible with Lyme disease, such as erythema migrans, fever, headache, or joint pain, and a history of exposure to ticks in an endemic area 2, 3.
• Serology testing is the primary laboratory tool employed to aid in diagnosing Lyme disease, particularly in cases where symptoms are nonspecific 2.
• The two-tiered algorithm, which includes an enzyme-linked immunosorbent assay (ELISA) followed by a Western blot test, is the recommended approach for optimizing specificity while maintaining high sensitivity 4, 3.

Interpretation of Lyme Disease Serology Results

• A positive result on the two-tiered test is considered diagnostic of Lyme disease, while a negative result does not rule out the disease, particularly in early stages 4, 3.
• The sensitivity of serology tests varies based on the duration of infection and the methodology used, with higher sensitivity in later stages of the disease 4, 3.
• The presence of specific antibodies, such as IgM and IgG, can be detected using ELISA, immunofluorescent assay (IFA), and immunoblot tests, with IgM antibodies typically indicating early infection and IgG antibodies indicating later infection 5.
• The modified two-tiered testing (MTTT) algorithm has been proposed as an update to the traditional two-tiered approach, with potential improvements in sensitivity and specificity 2.

Clinical Considerations

• Clinical and epidemiologic correlates should be carefully assessed before ordering serology tests, as false-positive results can occur in patients with other illnesses or a history of Lyme disease 3.
• The best indicator of stage 1 infection, erythema migrans, is presented in the majority of US cases and should prompt treatment without testing 3.
• Serology tests have limited application in early, localized infection, but are valuable in confirming extracutaneous infection 3.