Background/Purpose: ANA positivity is a frequent finding in pediatric rheumatology referrals, but infrequently reflects underlying autoimmune disease. Earlier studies found that most ANA positive patients without a diagnosis at referral seldom progressed to develop clinical autoimmunity. However, these studies predated the widespread use of electronic health records (EHR) and were limited to patients followed by pediatric rheumatology, restricting long-term outcome assessment. Modern data describing the extended clinical course of ANA positive children across healthcare settings are lacking. This study addresses this gap by leveraging EHR data to evaluate ANA based referrals and their progression to autoimmune disease over time.

Methods: This study utilized a retrospective chart review of all new patient referrals to a single pediatric rheumatology center in California from July 2015 through June 2017. Eligible patients were those referred with an ANA as either a part of, or the sole reason, for referral. Patients were excluded with preexisting rheumatologic diagnoses, second opinions, and hospital follow up appointments. Demographic characteristics, laboratory data, and eventual autoimmune diagnoses were manually abstracted from the available EHR records through August of 2025. 

Results: A total of 720 new referrals to pediatric rheumatology were reviewed from July 2015 through June 2017. In 178 referrals (24.7%) were for ANA related reasons. Of these, 10 patients (5.6%) received a rheumatologic diagnosis at the initial evaluation. Over a median duration of 98 months of available EHR records, 11 patients (6.2%) subsequently developed an autoimmune disease, including Crohn’s disease (1), Hashimoto’s thyroiditis (1), ITP (1), PsA (3), RA (1), SLE (2), and UCTD (2). Among all ANA based referrals, SLE was diagnosed in only 3 patients, 1 at presentation and 2 later in adulthood.

Conclusion: In this single-center cohort with over 8 years of EHR-based follow-up, most children referred for a positive ANA without clinical features of autoimmunity remained healthy. Autoimmune disease occurred in 11.8% of referrals—5.6% at presentation and 6.2% developing later—indicating that ANA positivity can have clinical relevance in a minority of cases. These findings reaffirm that ANA positivity is generally benign in pediatric populations, while providing updated long-term data on progression in otherwise “benign” referrals. The results underscore the value of selective ANA testing, appropriate longitudinal monitoring, and thoughtful referral triage, particularly given the ongoing pediatric rheumatology workforce shortage.

Overall Development of Autoimmune Disease

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/are-you-positive-about-this-positive-ana-referral-outcomes-for-ana-based-referrals-to-pediatric-rheumatology-and-subsequent-disease-development/