Is serology needed for diagnosis in patients with suspected Lyme disease?

Serology Testing in Lyme Disease Diagnosis

Serology testing is not needed for diagnosis in patients with erythema migrans (EM), but is recommended for patients with suspected Lyme disease who do not have the characteristic rash.

Diagnosis Based on Clinical Presentation

Erythema Migrans Present

• When a patient presents with erythema migrans (EM) and has a compatible epidemiologic and clinical history, the preferred means of diagnosis is visual inspection of the skin lesion without laboratory confirmation 1
• EM is the only manifestation of Lyme disease in the United States that is sufficiently distinctive to allow clinical diagnosis without laboratory testing 1
• Serologic testing is too insensitive in the acute phase (first 2 weeks of infection) to be helpful diagnostically, with many false negatives 1
• Patients with EM should be treated based on clinical findings alone 1

No Erythema Migrans

• For patients without EM but with suspected Lyme disease based on symptoms and exposure history, two-tiered serologic testing is recommended 1
• The recommended approach is a sensitive first test (ELISA or indirect fluorescent antibody test), followed by Western immunoblot testing to confirm equivocal or positive results 1
• For suspected Lyme neuroborreliosis, serum antibody testing is recommended rather than PCR or culture of cerebrospinal fluid or serum 1

Pretest Probability Considerations

• When determining whether to test for Lyme disease, clinicians must consider a patient's pretest probability 1
• The most crucial factor governing pretest probability is exposure history 1
• In areas where Lyme disease is not endemic, positive serologic results provide little diagnostic value for patients with no history of recent travel to endemic areas 1
• Even highly specific tests can show false-positive results when performed for patients with low pretest probability 1

Timing of Serologic Testing

• If serologic testing is performed in early disease and the initial result is negative, a convalescent-phase serum sample should be collected at least 2-3 weeks after the acute-phase sample 1
• Patients with early disseminated or late-stage disease usually have strong serologic reactivity 1
• Antibodies often persist for months or years after successfully treated or untreated infection, so seroreactivity alone cannot be used as a marker of active disease 1

Special Situations

Reinfection

• In cases of suspected reinfection, a detailed history and physical examination are essential as most patients will have EM 1
• For patients without EM, serologic analysis is still recommended but results should be interpreted with caution 1
• It may be helpful to conduct acute-phase and convalescent-phase serologic analysis to detect an increase in EIA titer or antibody bands that might indicate active infection 1

Neurologic Manifestations

• For suspected Lyme neuroborreliosis involving the CNS, if CSF testing is performed, simultaneous samples of CSF and serum should be obtained for determination of the CSF:serum antibody index 1
• Testing is recommended for patients with meningitis, painful radiculoneuritis, mononeuropathy multiplex, acute cranial neuropathies, or spinal cord inflammation with epidemiologically plausible exposure 1
• Testing is not recommended for typical amyotrophic lateral sclerosis, relapsing-remitting multiple sclerosis, Parkinson's disease, dementia, or new-onset seizures 1

Alternative Diagnostic Methods

• PCR can provide highly specific evidence of B. burgdorferi nucleic acid but has limited clinical utility due to low sensitivity and potential for contamination 1
• Synovial fluid PCR is >75% sensitive for Lyme arthritis and might be useful in conjunction with other analyses 1
• PCR of CSF has low sensitivity (38% for early neuroborreliosis) 1
• Culture of B. burgdorferi is possible but has limited diagnostic usefulness due to specialized medium requirements and protracted observation time 1

Common Pitfalls to Avoid

• Ordering serology for patients with typical EM, which is unnecessary and may lead to false negatives due to testing too early in disease course 1
• Testing patients with very low pretest probability, which increases the likelihood of false positive results 1
• Misinterpreting persistent antibodies as evidence of active infection, as antibodies can persist for months or years after successful treatment 1
• Failing to consider alternative diagnoses for EM-like lesions in non-endemic regions, such as Southern tick-associated rash illness (STARI) 1