Central sensitization partially mediates the relationship between obesity and functional impairment across fibromyalgia and related rheumatic disorders

Abstract Background Obesity is increasingly recognized as an important contributor to chronic pain and disability, yet its relationship with central sensitization and symptom burden across rheumatic diseases remains incompletely characterized. While elevated body mass index (BMI) has been associated with worse outcomes in fibromyalgia (FM), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), few studies have evaluated these relationships simultaneously using multidimensional symptom measures and central sensitization assessments. Methods We conducted a cross-sectional analysis of prospectively collected baseline data from Ohio State University (recruitment 2018–2025) and the University of Texas at Austin (recruitment beginning September 2020). Participants had fibromyalgia (FM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or were healthy controls. When both the Revised Fibromyalgia Impact Questionnaire (FIQR) and Symptom Impact Questionnaire (SIQR) were completed, FIQR was retained under the study harmonization rule. Models adjusted for age, sex, race, diagnosis, and study site. Results The baseline cohort comprised 1240 participants (FM 843, RA 194, SLE 127, healthy controls 76). The adjusted continuous-BMI FIQR/SIQR model included 918 observations and estimated a 4.13-point increase in symptom impact per standard-deviation higher BMI (95% CI 2.83–5.43; p < 0.001). Compared with normal BMI, the adjusted difference for obesity class II/III was + 10.24 points. In 873 complete cases with FM, RA, or SLE, the adjusted indirect BMI–FIQR/SIQR association through CSI was 1.206 (bootstrap 95% CI 0.36–2.02), accounting for 28.5% of the total association. These cross-sectional associations do not establish a causal pathway. Conclusions Higher BMI was associated with greater symptom impact and worse functional outcomes across rheumatic diagnostic groups. CSI statistically accounted for part of the BMI–symptom-impact association, but causal mediation cannot be established from cross-sectional data. Key Points • Increasing BMI was independently associated with greater disability, pain burden, and reduced physical functioning across fibromyalgia, rheumatoid arthritis, and systemic lupus erythematosus. • Central sensitization partially mediated the relationship between obesity and functional impairment. • The strongest obesity-related associations involved physical function, pain severity, and fibromyalgia-related disability, supporting a transdiagnostic pattern across inflammatory and non-inflammatory rheumatic disorders • Obesity may represent a modifiable upstream contributor to central sensitization and disability.