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Background: Antinuclear antibodies (ANA) are autoantibodies related to autoimmune diseases but may also present in healthy people. Measuring ANA in an ambulatory setting may be inappropriately ordered as some patients may exhibit clinical features with significant serologic findings but not meet criteria for diagnosis of ANA-related systemic autoimmune diseases. Prompt referral to specialty clinic may be delayed by improper screening. To help improve referral practices, we conducted a retrospective study to uncover pertinent characteristics of ANA+ patients that predict higher likelihood of systemic lupus erythematosus (SLE) diagnosis. Objectives: To describe characteristics of ANA+ patients that predict higher odds of SLE diagnosis. Methods: We reviewed electronic medical records of 288 patients with ANA+ polyarthralgia who were referred by their PCP to the Yale Lupus Clinic (YLC) from 2020 to 2023. We excluded 91 patients diagnosed with the following: Sjogren's syndrome (n=15), drug-induced lupus (n=1), cutaneous lupus (n=7), and APS (n=4). Patients with sarcoidosis, Crohn's disease, psoriasis, and ulcerative colitis were also excluded (n=64). The remaining 197 patients were divided into 3 groups based on their final diagnosis at the YLC: without connective tissue disease (No CTD), undifferentiated connective tissue disease (UCTD), and diagnosed with SLE based on 2019 EULAR/ACR classification criteria. The mean number of days from referral before consultation at YLC was counted. ANA titer was divided into ≤1:160 and ≥1:160. Erythrocyte sedimentation rate (ESR) was categorized based on the Westergren method. A multinomial logistic regression analysis was done (SPSS version 29.0.1.0 (171)) to generate a model that could help predict the likelihood of UCTD or SLE diagnosis. Incorporated "Predictor" variables were age, sex, race, body mass index (BMI), ANA titer, ESR and CRP. Results: Of the 3 groups, 122 (42.4%) were No CTD, 36 (12.5%) were UCTD and 39 (13.5%) were SLE patients. The number of days from referral to consult to YLC were similar among the 3 groups. No CTD (73.7%) and UCTD (69.4%) patients were found to have lower ANA titers compared to patients with SLE (64.1%) with higher ANA titers. 53.8% of SLE patients presented with elevated ESR. All 3 cohorts exhibited mild to high increases in CRP. Extractable nuclear antigen antibodies (ENA) were positive in 8 (6.56%) and 6 (17%) patients in No CTD and UCTD, respectively. In the SLE group, 64% were positive for multiple ENA, mainly, dsDNA, anti-SSA, anti-Sm and anti-U1RNP. Multinomial regression analysis was done to investigate possible predictors of UCTD and SLE diagnosis using the No CTD group for reference. Significant predictors that had the most contribution to the model included age (p = 0.021), ANA titer (p p = 0.002). Only CRP was found to have a significant contribution to predicting diagnosis of UCTD (p = 0.020), while significant predictors for SLE diagnosis included age (p = 0.023), ANA titer (p = 0.004), and ESR (p = 0.0010). Notably, the effect size of ESR was much larger than other predictors of SLE diagnosis. Conclusion: The turn-around time for the 3 cohorts in this study from when they were referred by their primary care provider until they were seen in the specialty clinic were similar. Among them, 42.4% were classified as No CTD patients referred to the YLC. This implies inefficiency in our referral system in allocating ANA+ patients to our specialty clinic. Therefore, novel methods of evaluating and determining referral necessity have been explored. Testing for ANA titer has been used as a tool for initial evaluation where a positive result would entail further investigation. In our study, we did not find an ANA pattern that is unique in patients with SLE when compared to those with No CTD and UCTD. However, our logistic regression analysis suggests higher CRP levels are predictive of UCTD, while elevated ESR, high ANA titer, and younger age were predictive of a final diagnosis of SLE. These findings suggest careful consideration of these clinical variables could help guide clinicians and triage services to refer to the specialty clinic more appropriately than solely relying on ANA positivity. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.
Par‐Young et al. (Sat,) studied this question.