Can Lyme Disease Cause a Positive ANA Test?
Yes, patients with Lyme disease can have a positive antinuclear antibody (ANA) test, though this is not a routine or expected finding and should not be used to diagnose or exclude Lyme disease.
Evidence for ANA Positivity in Lyme Disease
The relationship between Lyme disease and ANA positivity has been documented in clinical research, though it remains an uncommon and non-specific finding:
A 1991 study found that sera positive for Lyme antibodies had an increased frequency of positive ANA tests compared to controls, suggesting that Lyme infection may trigger antinuclear antibody production 1
A case report documented a 12-year-old patient with Lyme arthritis who had an ANA titer of 1:80, demonstrating that ANA positivity can occur in confirmed Lyme disease cases 2
Recent research has shown an association between ANA seropositivity in fibromyalgia patients and Borrelia-specific T lymphocyte reactivity, with ANA-positive patients showing significantly higher T cell responses to Borrelia burgdorferi (mean 5.60 vs 1.77, p < 0.05) 3
A 2016 review confirmed that positive ANA tests may be seen with both acute and chronic infections, including Lyme disease, particularly when ANA testing is used as an initial screen in patients with non-specific symptoms 4
Clinical Implications and Diagnostic Pitfalls
The presence of a positive ANA should not alter the standard diagnostic approach to Lyme disease, which relies on two-tiered serologic testing (EIA/IFA followed by Western blot) rather than autoantibody panels 5, 6, 7:
False-positive Lyme titers can occur in patients with autoimmune diseases, creating diagnostic confusion when both ANA and Lyme serology are positive 6
The 1991 study found that ANA did not markedly interfere with Lyme assay performance, with only 1 of 53 ANA-positive sera showing false-positive Lyme results—no different from controls 1
However, the reverse may be true: Lyme antibodies may interfere with ANA testing, potentially causing false-positive ANA results 1
When to Test for Lyme Disease (Not Based on ANA)
Testing for Lyme disease should be based on objective clinical findings and epidemiologic exposure, never on the presence of a positive ANA alone 5, 6, 7:
Strong indications include: lymphocytic meningitis, cranial neuropathy (especially facial palsy), radiculoneuritis, acute myocarditis/pericarditis with appropriate exposure, or large joint arthritis in endemic areas 5, 6, 7
Testing should be avoided in patients with nonspecific symptoms, isolated psychiatric illness, typical presentations of ALS/MS/Parkinson's/dementia, or those lacking tick exposure in endemic regions 5, 6, 7
Erythema migrans (a gradually expanding annular lesion >5 cm) should be diagnosed clinically and treated immediately without serologic testing in endemic areas 7
Key Clinical Caveat
A positive ANA in a patient with suspected Lyme disease does not confirm, exclude, or alter the diagnosis—the standard two-tiered Lyme testing algorithm must still be followed based on appropriate clinical and epidemiologic criteria 5, 6, 7. The ANA positivity may simply reflect immune dysregulation triggered by the infection or may be an incidental finding, as approximately 20% of the general population has a positive ANA without autoimmune disease 8.