Unveiling the landscape of systemic sclerosis in Egypt: a comprehensive national multicenter analysis of the Egyptian EUSTAR cohort

Abstract Background and objectives Systemic sclerosis (SSc) is a heterogeneous and debilitating multi-system autoimmune disease characterized by widespread microvascular vasculopathy and progressive multi-organ fibrosis. While localized cohorts have been described, there is a critical need for a standardized, national-scale multicenter validation to fully capture the epidemiological and phenotypic characteristics of SSc in Egypt. This study aimed to delineate the nationwide clinical, serological, and functional landscape of systemic sclerosis across Egypt utilizing the standardized EUSTAR registry framework across major geographic referral centers. Methods A multi-center, retrospective registry-based review was conducted on 354 Egyptian SSc patients enrolled within the international EUSTAR database. Longitudinal and cross-sectional data were extracted across standardized registry parameters, including detailed demographics, clinical subsets (LeRoy criteria), comprehensive organ system involvement (evaluated via high-resolution computed tomography [HRCT], echocardiography, and nailfold capillaroscopy [NFC]), autoantibody profiles, and patient-reported quality-of-life indices (HAQ-DI and L-PF questionnaires). Results The cohort demonstrated a prominent female predominance (89.3%) with a mean overall age of disease onset of 37.6 + 13.5 years. Limited cutaneous SSc was the most frequent phenotype (53.1%), though an exceptionally high rate of diffuse cutaneous SSc was documented (42.2%). Marked microvascular severity was evidenced by a high prevalence of active digital ulcers (56.7%), a history of digital gangrene (10.8%), and a dominant “active” capillaroscopic microangiopathy pattern (47.8%). Visceral organ involvement was highly pervasive: gastrointestinal reflux and dysphagia affected 78.7% and 75.4% of patients, respectively, while Gastric Antral Vascular Ectasia (GAVE) was remarkably frequent at 20.9%. Objective interstitial lung disease (ILD) was confirmed on HRCT in 46.8% of evaluated patients ( n = 47/101), with ground-glass opacification documented in 70.4%, and an echocardiographic high probability of pulmonary hypertension (PH) was documented in 11.8% ( n = 40/342 valid cases). Serological evaluation revealed a highly robust seropositive footprint with elevated rates of anti-Scl70 (51.0%) and anti-centromere (55.6%) autoantibodies. Symptomatic inflammatory arthritis was reflected by a moderate mean disease activity index (DAS28-ESR: 4.4 + 1.3). Conclusion The national Egyptian SSc phenotype is characterized by an significant microvascular burden, an elevated diffuse cutaneous subset rate, and widespread gastrointestinal and active inflammatory pulmonary involvement. The cohort exhibits a unique serological signature featuring highly robust autoantibody positivity and significant systemic inflammation, highlighting the urgent need for targeted national screening algorithms and specialized therapeutic access.