Causal Effects of Inflammatory Arthritis Subtypes on Fibromyalgia: A Comprehensive Mendelian Randomization Study.

PURPOSE: Fibromyalgia (FM) is a chronic pain disorder characterized by widespread musculoskeletal pain and central sensitization, often co-occurring with inflammatory arthritis (IA) in clinical presentation. While observational studies suggest a higher prevalence of FM among IA patients, the causal relationship between IA and FM remains uncertain due to potential confounding factors and the possibility of reverse causation.

PATIENTS AND

METHODS

We employed a two-sample Mendelian randomization (TSMR) approach to evaluate the causal effect of nine IA subtypes on FM, utilizing genetic summary data from large-scale genome-wide association studies (GWAS) encompassing up to 201,581 participants (exposure: IA phenotypes) and 168,378 participants (outcome: FM). The primary analysis was conducted using the Inverse-Variance Weighted (IVW) method, with sensitivity analyses assessing robustness and pleiotropy.

RESULTS

MR analysis revealed significant causal links between several IA subtypes and FM. Rheumatoid arthritis (OR 1.105, 95% CI 1.020-1.198), enteropathic arthritis (OR 1.207, 95% CI 1.123-1.299), Juvenile Idiopathic Arthritis (OR 1.307, 95% CI 1.183-1.445), and other IA subtypes showed an increased risk of FM (all p<0.0001). Psoriatic arthritis demonstrated no significant association with FM (OR 1.006, 95% CI 0.909-1.112, p=0.911). Sensitivity analyses confirmed no significant heterogeneity and consistent results, despite minor horizontal pleiotropy observed in MR-Egger regression.

CONCLUSION

This study provides genetic evidence supporting a causal relationship between IA subtypes and an increased risk of FM. However, no significant causal link was found between psoriatic arthritis and FM. These findings emphasize the role of immune-mediated inflammation in FM pathogenesis and highlight the differential impact of various IA subtypes on FM risk.