Antinuclear antibody (ANA) testing in primary care. The test is positive what now? A two-phase observational study of UK primary care.

Abstract

The ANA-associated diseases are rare autoimmune diseases (including Systemic lupus erythematosus [SLE], Sjögren's, Scleroderma, autoimmune hepatitis). Interpretation of ANA-tests is difficult, it is frequently positive in patients who do not appear to have an associated disease. In those who are ANA-positive we suspect there are features that can help distinguish those who will later develop disease. To understand the characteristics of those tested, and in those who have positive features associated with disease development. Two phase study: 1) A case control study to examine characteristics of those tested. Cases defined as having had an ANA-test performed regardless of result, matched to controls who have never had an ANA test. 2) A cohort study of ANA-tested cases. In those who are ANA-positive, exposures (from literature, clinicians, and patients) will be used to predict the outcome ANA-associated disease. Phase 2: 888,179 patients have at least one ANA-test performed: positive 22,587 (2.54%), negative 21,908 (2.47%), unknown 843,684 (94.99%).ANA-tested cohort. HR if positive: ANA-disease 5.15 (4.89 to 5.43); All-cause mortality 1.20 (1.16 to 1.24); CV mortality 1.20 (1.14 to 1.27) (adjusted HR (95% CI)).ANA-positive cohort. At 3 years 10.0% (9.7 to 10.5%) and at 20 year 15.7% (16.5 to 14.9% (95% CI) develop ANA-associated disease. HR for Female 2.29 (1.96 to 2.68); <55 years 1.53 (1.37 to 1.71) (adjusted HR (95% CI). Defining the test result is difficult. However, there is clear differentiation between the positive and negative/unknown cohorts. Positive-test status is associated with ANA-disease development and mortality. If ANA-positive, most of those who will develop disease are diagnosed soon after testing; male gender and advanced-age reduce the risk of ANA-diseases.