Global 
Deutschland Esophagus to Small Intestine
Aliment Pharmacol Ther. 2026;63(8):1151-1161
Comprehensive risk profile of gastrointestinal and extra articular comorbidities in Ehlers-Danlos syndrome: A propensity-matched analysis of 118,256 individuals
Background: Ehlers-Danlos syndrome (EDS) comprises inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It links to systemic comorbidities, including gastrointestinal (GI) disorders, but hitherto large-scale data remain limited. We aimed to evaluate the prevalence of GI, systemic and psychological comorbidities in EDS patients versus propensity score-matched controls, using a comprehensive research network database.
Design: This was a retrospective, propensity-matched analysis (2005–2023) utilising the TriNetX network. We identified EDS patients (excluding Marfan’s syndrome). Propensity score matching (1:1) generated balanced cohorts for age, sex and baseline characteristics. Comorbidities were analysed via prevalence rates and odds ratios (ORs) with 95% confidence intervals (CIs).
Results: Matched cohorts included 59,128 pairs. Among GI disorders, gastroesophageal reflux disease was most common in EDS (18.4%, OR = 1.5, 95% CI: 1.4–1.5, p < 0.001), followed by constipation (12.4%, OR = 1.8, 95% CI: 1.7–1.9, p < 0.001), irritable bowel syndrome (7.3%, OR = 2.6, 95% CI: 2.5–2.8, p < 0.001) and gastroparesis (4.7%, OR = 8.2, 95% CI: 7.3–9.2, p < 0.001). Psychiatric conditions showed heightened prevalence of anxiety (26.1%, OR = 1.8, 95% CI: 1.7–1.8, p < 0.001) and depression (18.7%, OR = 1.3, 95% CI: 1.2–1.3, p < 0.001). Systemic comorbidities included postural orthostatic tachycardia syndrome (13.2%, OR = 899.7, 95% CI: 483.8–1673.0, p < 0.001), chronic pain (7.9%, OR = 7.0, 95% CI: 6.4–7.6, p < 0.001), migraines (19.7%, OR = 2.5, 95% CI: 2.4–2.6, p < 0.001) and fibromyalgia (9.5%, OR = 1.7, 95% CI: 1.6–1.8, p < 0.001).
Conclusion: EDS patients exhibit heightened risk for GI, systemic and psychological comorbidities, highlighting the importance of multidisciplinary approaches for effective management.
DOI: 10.1111/apt.70506