Comprehensive Risk Profile of Gastrointestinal and Extra Articular Comorbidities in Ehlers-Danlos Syndrome: A Propensity-Matched Analysis of 118,256 Individuals

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. 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). 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). EDS patients exhibit heightened risk for GI, systemic and psychological comorbidities, highlighting the importance of multidisciplinary approaches for effective management.