Systemic inflammation and extra-articular manifestations in rheumatoid arthritis: a cross-sectional study

Frontiers in Medicine, 2026

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DOI 10.3389/fmed.2026.1814238
Data confidence 70 medium
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Abstract

Background Rheumatoid arthritis (RA) is a bodywide inflammatory condition that produces additional symptoms outside the joints that make the disease more severe and lead to patient disability and death. This research investigated various factors associated with the presence of extra-articular manifestations in RA patients. Methods The cross-sectional study was conducted from 2023 to 2025 and assessed 299 adult patients who received RA confirmation. Clinical assessments, laboratory tests, and instrumental results were evaluated for extra-articular manifestations, and univariable and multivariable logistic regression analyses were performed to examine these relationships. Results: Extra-articular manifestations were present in 278 patients (93%). Patients with extra-articular manifestations were older ( p = 0.039) and more frequently had disability (76% vs. 48%, p = 0.004). They also demonstrated higher levels of systemic inflammation, including C-reactive protein (median 20 vs. 11 mg/L, p = 0.015), erythrocyte sedimentation rate (36 vs. 21 mm/h, p < 0.001), rheumatic factor (92 vs. 55.2 IU/mL, p < 0.001), and higher antinuclear antibodies index values (1.5 vs. 0.43, p = 0.023). In the multivariable model, ESR remained independently associated with extra-articular manifestations (adjusted OR = 1.18, p < 0.001), while elevated white blood cell count was inversely associated (adjusted OR = 0.07, p = 0.001). Conclusions: Extra-articular manifestations in rheumatoid arthritis are most strongly associated with sustained systemic inflammation, as reflected by ESR, underscoring the importance of monitoring chronic inflammatory burden and the need for longitudinal studies to clarify causality and therapeutic implications.