Clinical Course and Development of Rheumatological Diseases in Individuals With Asymptomatic Rheumatoid Factor Positivity: A Retrospective Cohort Study

Abstract

Objective: The clinical significance of asymptomatic rheumatoid factor (RF) positivity remains incompletely understood. This study evaluated 2-year clinical outcomes and predictive factors for disease progression in individuals with asymptomatic RF positivity. Methods: This retrospective cohort study included 88 asymptomatic RF-positive individuals followed up at 6-month intervals for 2 years. Baseline anti–cyclic citrullinated peptide (anti-CCP), antinuclear antibody, and hepatitis B/C serologies were analyzed. Statistical methods included Spearman correlation, univariate logistic regression with Firth correction, and 1-sided Fisher exact testing. Results: The mean (SD) age was 51.5 (14.9) years; 67 (76.1%) were female. Within 2 years, rheumatologic diseases developed in 14 participants (15.9%): rheumatoid arthritis (RA; n = 7), Sjögren disease (n = 5), systemic lupus erythematosus (n = 1), and undifferentiated connective tissue disease (n = 1). Baseline HBsAg positivity was 8.0% (n = 7). Anti-CCP positivity strongly predicted RA progression (median-unbiased OR, 237.0; 95% CI, 18.7-3004.8; P < .001), with an 87.5% (7/8) positive predictive value. Elevated RF levels correlated significantly with overall rheumatological disease (P = .04) and specifically RA (P = .03). No meaningful correlations emerged between RF levels and age, erythrocyte sedimentation rate, C-reactive protein, or HBsAg status. Conclusions: Asymptomatic RF positivity carries a substantial 2-year risk (15.9%) for developing rheumatic conditions, predominantly RA and Sjögren disease. Anti-CCP positivity and elevated RF titers are strong predictors of progression. Regular clinical follow-up may enable earlier detection and intervention, though larger prospective studies are needed.