How should I interpret serological test results for Lyme disease, and when should I consider referral to a specialist?

Guideline-aligned answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

Posted: 14 August 2025 Guideline-Aligned (High Confidence) Clinically Reviewed
Dr Kola Tytler MBBS CertHE MBA MRCGPClinical Lead • iatroX

Serological test results for Lyme disease should be interpreted as follows: a positive or equivocal ELISA test should be followed by an immunoblot test for confirmation, and treatment may be started while awaiting results if there is high clinical suspicion .

If the ELISA is negative but symptoms persist, review the patient's history and consider alternative diagnoses; if Lyme disease is still suspected within 4 weeks of symptom onset, repeat the ELISA after 4–6 weeks, or perform an immunoblot test if symptoms have lasted 12 weeks or more .

A positive immunoblot test confirms Lyme disease, and treatment with antibiotics should be initiated .

If the immunoblot is negative, regardless of ELISA results, but symptoms persist, consider referral to a specialist for further assessment, additional testing (such as synovial fluid analysis or lumbar puncture), or to explore alternative diagnoses .

If the immunoblot is negative and symptoms have resolved, no treatment is required .

Referral to a specialist should also be considered in cases with focal symptoms or neurological, cardiac, or dermatological features, or if there is diagnostic uncertainty .

Educational content only. Always verify information and use clinical judgement.

How should I interpret serological test results for Lyme disease, and