Inappropriate ANA Serologic Testing Across Health Systems

Two recent studies presented at the American College of Rheumatology (ACR) Convergence 2022 conference evaluated ANA testing in the United States with some thought-provoking findings, confirming what many rheumatologists see in our clinical practice and referrals.

The first abstract was a population-based study (Abstract # 1278) which evaluated the trends of ANA testing in the United States over the past 20 years [1].  Hocaoglu et al evaluated all patients who underwent ANA testing between 2000 and 2019 in a region of the American Upper Midwest, excluding patients with systemic autoimmune disease.  There were 72,795 individuals who underwent over 134,000 ANA tests in this region over the testing period, with 96% of tests performed by ELISA method.  Interestingly, 46% of the total tests were repeated tests, with a mean time between repeated tests of only 2.7 years.  The study found high volume of ANA testing, with 12% of females and 6% of males in the population tested for ANA at least once over the study period, vastly disproportionate compared to prevalence of connective tissue diseases in this same region.  The authors comment that increased awareness of evidence-based reasons for ANA testing could lead to significant healthcare cost savings [1].

A second abstract by Wright et al developed a survey for Internal Medicine residents with questions related to ANA ordering and interpretation [2].  The study objective was to identify gaps in knowledge related to serologic testing, especially considering downstream financial burden of unwarranted ANA testing to patients and the healthcare system.  This was a small study with survey responses collected from 46 residents over a 2-week period in May 2022.  The data looked at practice habits in real-life and simulated scenarios as well as comfort with evaluation for connective tissue disease.

So what were the findings?  Interestingly, only 9% of the residents reported always being able to interpret a positive ANA.  The majority (67%) reported that when an ANA was ordered, less than half of the time their patient turned out to have a connective tissue disease.  Similarly 61% of residents stated they would order both an ANA and ENA panel initially, compared to 17% who would only order an ANA initially.  Slightly over 25% of respondents stated they would repeat ANA testing in a patient already known to have ANA-positive connective tissue disease, and 59% stated they would order ANA for non-specific symptoms such as fatigue, myalgia and back pain.  As rheumatologists are well-aware, ordering ANA for non-specific symptoms will yield many false positives given the high rate of incidental ANA positivity in the general population.  And similarly, once an ANA is positive, repeating the ANA has no utility in the clinical care of a patient with a known rheumatic autoimmune disease.

Taken together, these studies provide supportive evidence to observations noted by many rheumatologists: some primary care providers and other specialists are ordering ANA testing inappropriately, and many are not aware of appropriate indications to order ANA and ENA testing.  These findings suggest significant work is needed to develop curriculum to teach students, residents and even practicing internists and subspecialists on specific symptoms that raise probability of having connective tissue disease and warrant subsequent ANA testing.

During her coverage of several ANA-associated abstracts for RheumNow, Dr. Kathryn Dao stated an excellent take-home point from these studies for us as rheumatologists: “We have to do a better job training our medical students and residents about appropriate ANA and ENA testing, so they will not order or repeat these tests, unless absolutely necessary” [3].


[1] Hocaoglu M, Sanchez-Rodriguez A, Langenfeld H, Crowson C, Duarte-Garcia A. ANA Testing Practices in the United States: A Population-Based Study Between 2000 and 2019 [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). Accessed January 31, 2023.

[2] Wright J, Patel D. Are We Choosing Wisely? Results of a Survey of Internal Medicine Residents in a Single Center [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). Accessed January 31, 2023.

[3] RheumNow, Stop Ordering Repeat ANAs! [Video] (2022, November 14).