A distinct gastrointestinal symptom profile characterizes clinically relevant fatigue in systemic sclerosis

Objective: To identify the specific gastrointestinal (GI) symptoms associated with clinically relevant fatigue in systemic sclerosis (SSc), beyond the established association between overall GI involvement and fatigue. Methods: We conducted a cross-sectional study including consecutive patients with SSc fulfilling the 2013 ACR/EULAR classification criteria. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) scale, with clinically relevant fatigue defined as a score ≤ 30. Demographic, clinical, laboratory, and organ involvement data were collected. Individual GI symptom domains (GERD, dysphagia, bloating, diarrhea and constipation), together with the Medsger GI severity score, were analyzed. Bivariate analyses and multivariable logistic regression analyses were performed to evaluate symptom-specific associations with clinically relevant fatigue. Results: Among 115 patients, clinically relevant fatigue was observed in 42 (36.5%). Patients with FACIT-Fatigue ≤ 30 more frequently reported GERD (90.5% vs 60.3%), dysphagia (40.5% vs 16.4%), bloating (66.7% vs 15.1%), and diarrhea (28.6% vs 11.0%) (all p < 0.05). No statistically significant between-group differences were detected in the available objective disease measures. In the primary Firth penalized logistic regression model, bloating (OR 9.11, 95% CI 3.53–25.71) and GERD (OR 4.08, 95% CI 1.29–15.44) were associated with clinically relevant fatigue. Dysphagia showed a directionally consistent but less precise association. In a continuous-outcome sensitivity analysis, GERD, dysphagia, and bloating were associated with lower FACIT-Fatigue scores. Conclusions: Clinically relevant fatigue in SSc was associated with a distinct profile of patient-reported GI symptoms, particularly bloating and GERD. These findings provide a more granular characterization of fatigue-related GI burden in SSc. (Table presented.)