Functional Gastrointestinal Disease In Patients with Rheumatoid Arthritis: Disease Activity, Functionality, and Quality of Life

Abstract

Objectives

Rheumatoid arthritis (RA) is an autoimmune disease characterised by systemic inflammation, with gastrointestinal symptoms being among the most common extra-articular manifestations. Functional gastrointestinal disorders (FGIDs), which occur in the absence of an organic cause, are reported more frequently in patients with autoimmune diseases. This study investigated the rate of FGIDs in RA patients, its relationship with RA disease activity, and its effect on the quality of life of RA patients.

Patients and Methods

All RA patients completed the Rome IV questionnaire, the Short Form 12 (SF-12), and the Health Assessment Questionnaire (HAQ) to assess disease and general health. The Disease Activity Score (DAS 28), the number of tender and swollen joints, and acute-phase reactant levels were used to assess disease activity, with results recorded together with demographic data.

Results

Of the 115 RA patients, 54.8% had FGIDs, with the most common type being functional dyspepsia (FD) (39.1%). Other diagnoses included irritable bowel syndrome (16.5%), functional constipation (13.9%), and functional diarrhoea (7.8%). Patients with FGIDs had higher DAS28 scores compared to those without (median 3.77 [interquartile range: 2.68] vs. 2.96 [1.99]; p=0.017). After applying the Bonferroni correction for multiple tests (corrected significance level p<0.0042), we found that correlations between functional constipation and functional dyspepsia and quality of life outcomes were not statistically significant.

Conclusion

FGIDs are common among RA patients and are associated with more severe symptoms and reduced quality of life. Their management may involve various strategies.

Keywords

functional gastrointestinal disorders - disease activity - quality of life - rheumatoid arthritis

Schlüsselwörter

funktionelle gastrointestinale Störungen - Rheumatoide Arthritis - Krankheitsaktivität - Lebensqualität

Publication History

Received: 20 September 2025

Accepted: 07 October 2025

Article published online:
27 January 2026

• References

• 1 Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet 2016; 388: 2023-2038
• 2 Lin YJ, Anzaghe M, Schülke S. Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis. Cells 2020; 9: 880
• 3 Cojocaru M, Cojocaru IM, Silosi I. et al. Extra-articular Manifestations in Rheumatoid Arthritis. Maedica (Bucur) 2010; 5: 286-291
• 4 Conforti A, Di Cola I, Pavlych V. et al. Beyond the joints, the extra-articular manifestations in rheumatoid arthritis. Autoimmun. Rev. 2021; 20: 102735
• 5 Togashi T, Ishihara R, Watanabe R. et al. Rheumatoid Factor: Diagnostic and Prognostic Performance and Therapeutic Implications in Rheumatoid Arthritis. J Clin Med 2025; 14: 1529
• 6 Asai S, Takahashi N, Nagai K. et al. Influence of Gastrointestinal Symptoms on Patient Global Assessment in Patients with Rheumatoid Arthritis. SN Comprehensive Clinical Medicine 2020; 2: 619-626
• 7 Black CJ, Drossman DA, Talley NJ. et al. Functional gastrointestinal disorders: advances in understanding and management. Lancet 2020; 396: 1664-1674
• 8 Holtmann G, Shah A, Morrison M. Pathophysiology of Functional Gastrointestinal Disorders: A Holistic Overview. Dig Dis 2017; 35: 5-13
• 9 Drossman DA, Richter J, Talley NJ. et al. The functional gastrointestinal disorders: Diagnosis, pathophysiology and treatment. 1994. Boston: Little Brown;
• 10 Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology 2016; S0016-5085: 00223-00227
• 11 Sha H, Zhu W. Unveiling causal pathways in autoimmune diseases: a multi-omics approach. Autoimmunity 2025; 58: 2480594
• 12 Ford AC, Talley NJ, Walker MM. et al. Increased prevalence of autoimmune diseases in functional gastrointestinal disorders: case–control study of 23 471 primary care patients. Alimentary pharmacology and therapeutics 2014; 40: 827-834
• 13 Koloski N, Jones M, Walker MM. et al. Population based study: atopy and autoimmune diseases are associated with functional dyspepsia and irritable bowel syndrome, independent of psychological distress. Aliment Pharmacol Ther 2019; 49: 546-555
• 14 Aletaha D, Neogi T, Silman AJ. et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62: 2569-2581
• 15 Hansen IMJ, Andreasen RA, Hansen MNB. et al. The Reliability of Disease Activity Score in 28 Joints–C-Reactive Protein Might Be Overestimated in a Subgroup of Rheumatoid Arthritis Patients, When the Score Is Solely Based on Subjective Parameters. J Clin Rheumatol 2017; 23: 102-106
• 16 Prevoo ML, van 't Hof MA, Kuper HH. et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheu 1995; 38: 44-48
• 17 Felson DT, Anderson JJ, Boers M. et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum 1993; 36: 729-740
• 18 Ware JE, Kosinski M, Keller SD. SF-12: How to Score the SF-12 Physical and Mental Health Summary Scales. 1995. Boston: The Health Institute, New England Medical Center;
• 19 Soylu C, Kütük B. Reliability and Validity of the Turkish Version of SF-12 Health Survey. Turkish Journal of Psychiatry 2022; 33: 108-117
• 20 Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol 1982; 9: 789-793
• 21 Senerdem N, Gül A, Koniçe M. et al. The use of two different Health Assessment Questionnaires in Turkish rheumatoid arthritis population and assessment of the associations with disability. Clin Rheumatol 1999; 18: 33-37
• 22 Lacy BE, Pimentel M, Brenner DM. et al. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am J Gastroenterol 2021; 116: 17-44
• 23 Kalkan EA, Kalkan Ç, Barutcu S. et al. Prevalence and Determinants of Gastrointestinal Manifestations in Patients with Selected Rheumatologic Diseases. Turk J Gastroenterol 2022; 33: 576-586
• 24 Daraei M, Afshari A, Alesaeidi S. et al Evaluation of the Prevalence of Irritable Bowel Syndrome in Patients with Rheumatoid Arthritis. Journal of Iranian Medical Council 2022; Volume 5: 4
• 25 Jin J, Cai X, Rao P. et al. Microbiota and immune dynamics in rheumatoid arthritis: Mechanisms and therapeutic potential. Best Pract Res Clin Rheumatol 2025; 39: 102035
• 26 Kim HJ, Jung JY, Kim JW. et al. Impact of disease-related indicators on pain measures in rheumatoid arthritis: a biopsychosocial perspective. J Rheum Dis 2025; 32: 38-47
• 27 Cao Y, Fan D, Yin Y. Pain Mechanism in Rheumatoid Arthritis: From Cytokines to Central Sensitization. Mediators Inflamm 2020; 2076328
• 28 Cervero F. Central sensitization and visceral hypersensitivity: Facts and fictions. Scandinavian Journal of Pain 2014; 5: 49-50
• 29 Xinyi Y, Runrun Z, Xinchang W. The gut-joint axis: Genetic evidence for a causal association between gut microbiota and seropositive rheumatoid arthritis and seronegative rheumatoid arthritis. Medicine 2024; 103 p e37049
• 30 Koloski NA, Talley NJ, Boyce PM. The impact of functional gastrointestinal disorders on quality of life. Am J Gastroenterol 2000; 95: 67-71
• 31 Myasoedova E, Talley NJ, Manek NJ. et al. Prevalence and Risk Factors of Gastrointestinal Disorders in Patients with Rheumatoid Arthritis: Results from a Population-Based Survey in Olmsted County, Minnesota. Gastroenterol Res Pract 2011; 745829
• 32 Suares NC, Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol 2011; 106: 1582-1591 quiz 1581, 1592