Utility of ANA in hospitalized patients with headache and suspected systemic autoimmune disease

Abstract

Objective
This study evaluates antinuclear antibody (ANA) test performance in identifying rheumatologic conditions as the source of the headache.


Background
ANA testing is widely used to screen for autoimmune diseases in patients with headaches, but its diagnostic utility remains unclear.


Methods
In this retrospective analytic, cross‐sectional study, 539 patients hospitalized with headache at Sheba Medical Center (2007–2022) underwent ANA testing. Data included demographics, ANA titers and patterns, C‐reactive protein levels, and rheumatologic diagnoses confirmed at discharge or follow‐up. Statistical analyses compared clinical features between groups with and without rheumatologic diagnoses.


Results

Rheumatologic diagnoses were confirmed in 9.6% (
n
 = 52). Affected patients were older (median 54.7 vs. 41.9 years,
p
 < 0.001), had higher ANA positivity (76.9% vs. 41.9%,
p
 < 0.001), and had elevated titers (
p
 = 0.003). Homogeneous (17.5% vs. 5.4%) and mixed (25.0% vs. 14.2%) staining patterns were more frequent in rheumatologic cases (
p
 = 0.02). C‐reactive protein levels lacked diagnostic utility except in vasculitis and giant cell arteritis. Notably, 83.6% of ANA‐positive patients had no rheumatologic diagnosis.



Conclusions
Whereas ANA positivity correlates with rheumatologic disease in patients with headache, its low positive predictive value limits utility as a standalone screening tool. Though age was a differentiator in ANA positivity, our findings support that ANA testing should be performed only when there is clinical suspicion for systemic autoimmune disease, regardless of patient age. Overuse may lead to false positives, unnecessary investigations, and resource strain. Clinical context rather than serology should guide autoimmune evaluation in headache management.