Comparative analysis of extra-articular manifestations in seronegative and seropositive rheumatoid arthritis patients: a 6-year retrospective study in a tertiary care center.

objectiveExtra-articular manifestations in rheumatoid arthritis (RA) are associated with poorer prognosis and reduced quality of life. However, these manifestations have been far more studied in seropositive than in seronegative RA, particularly in the MENA region. This study aims to examine and compare the prevalence and types of extra-articular manifestations in seropositive versus seronegative RA.

methodsRetrospective cohort study conducted at the American University of Beirut Medical Center (2018-2024). The target population consists of patients with RA, whether seropositive or seronegative, diagnosed based on the 2010 (ACR) classification criteria. Comparison between groups was performed using chi-square and T test; Pearson's correlation coefficient (r) was utilized for correlation analyses, and ANOVA was used to compare group means.

resultsAmong 634 patients with RA, 282 (44.9%) had extra-articular manifestations. Of these, 210 (74.5%) were seropositive, and 72 (25.5%) were seronegative. Notably, upon examining the serological groups, the prevalence of ExRA was 49.3% among seronegative patients compared to 43.03% among seropositive patients. Baseline characteristics were similar between seropositive and seronegative RA groups in age (mean 51 ± 11), sex (83-89% female), smoking status, BMI, and age at diagnosis, with seropositive patients having longer disease duration (p < 0.001). Fibromyalgia was more common in seronegative RA (25% vs 12%, p = 0.008), while osteoarthritis was more frequent in seropositive RA (10% vs 1.4%, p = 0.019). Most patients (≈90%) had 1-2 extra-articular features. Anemia (54.3%) and sicca syndrome (41.1%) were the most prevalent. Nearly all patients received conventional DMARDs, while biologics and advanced therapies were more frequently used in seropositive RA.

conclusionSeronegative RA patients showed distinct patterns in both extra-articular features, comorbidities profiles, and treatment approach. Extra-articular manifestations were slightly more common in seronegative patients, suggesting that this subgroup may still carry a relevant systemic burden. Unlike most prior studies that examined serostatus among patients with extra-articular disease, our study assessed the prevalence of these manifestations within each serological category. Key Points • Sicca symptoms, Raynaud's phenomenon, and osteoporosis were significantly more common in seronegative RA. • Anemia and sicca symptoms were the most common extra-articular manifestations. • Biologic and advanced therapies were more frequently used in seropositive RA, likely reflecting greater systemic severity.