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

From the Guidelines

Testing for chronic Lyme disease should be approached with caution, and the recommended two-tier testing process, which includes an enzyme immunoassay (EIA) or immunofluorescence assay (IFA) followed by a Western blot test, should be used to confirm the diagnosis, as stated in the guidelines by the Infectious Diseases Society of America 1.

Key Points to Consider

• The two-tier testing process is the recommended approach for laboratory diagnosis of Lyme disease, with a sensitivity of 70%–100% for disseminated Lyme disease and a specificity of >95% during all stages of the disease 1.
• The diagnosis of chronic Lyme disease typically relies on a combination of clinical symptoms, potential exposure history, and ruling out other conditions with similar symptoms, rather than a single test result 1.
• Some specialty labs offer alternative tests like PCR, lymphocyte transformation tests, or CD57 natural killer cell counts, but these are not FDA-approved for Lyme diagnosis and may produce false positives 1.

Important Considerations for Testing

• The presence of erythema migrans, cranial nerve palsy, or papilledema can be helpful in differentiating Lyme meningitis from viral meningitis 1.
• Patients with neurologic Lyme disease should have a total body skin examination to look for a concurrent erythema migrans lesion and should be questioned to determine whether one had been present within the preceding 1–2 months 1.
• The use of intrathecal production of antibody to B. burgdorferi or amplification of B. burgdorferi DNA in CSF using PCR can be useful in selected cases, but few laboratories are capable of accurately performing these tests 1.

From the Research

Diagnostic Challenges

• Chronic Lyme disease is a rare condition caused by long-lasting and ongoing infection with the spirochete Borrelia burgdorferi (Bb) 2
• The most common manifestations are progressive encephalitis, myelitis, acrodermatitis chronica atrophicans with or without neuropathy, and arthritis 2
• Direct detection of Bb has low yield in most manifestations of chronic Lyme, while almost 100% of the cases are seropositive, that is, have detectable Bb IgG antibodies in serum 2

Laboratory Testing

• Detection of Bb antibodies only with Western blot technique and not with ELISA and detection of Bb IgM antibodies without simultaneous detection of Bb IgG antibodies should be considered as seronegativity in patients with long-lasting symptoms 2
• Patients with chronic Lyme in the nervous system (neuroborreliosis) have, with few exceptions, pleocytosis and production of Bb antibodies in their cerebrospinal fluid 2
• The use of Western blot and enzyme-linked immunosorbent assays can assist in the diagnosis of Lyme disease, but patients with discordant results should be carefully evaluated 3

Differential Diagnoses

• Strict guidelines should be applied in diagnostics of chronic Lyme, and several differential diagnoses, including neurological disease, rheumatologic disease, post-Lyme disease syndrome, chronic fatigue syndrome, and psychiatric disease, should be considered in the diagnostic workup 2
• Chronic Lyme disease is a poorly defined diagnosis that is usually given to patients with prolonged, unexplained symptoms or with alternative medical diagnoses 4
• Post-treatment Lyme disease syndrome (PTLDS) is a subset of chronic Lyme disease, characterized by non-specific symptoms that persist beyond 6 months after completion of therapy 5

Treatment

• Antibiotic treatment with administration route and dosages according to current guidelines are recommended for chronic Lyme disease 2
• Combination antimicrobial therapy or antibiotic courses longer than 4 weeks are not recommended 2
• A network meta-analysis found that oral amoxicillin, oral azithromycin, injectable ceftriaxone, and injectable cefotaxime were effective for treating Lyme disease, while cefuroxime and penicillin were safe for treating Lyme disease 6