Systemic Sclerosis in the Elderly. Comparison of Disease Manifestation, Comorbidities, and Survival in Geriatric Systemic Sclerosis

Objectives Systemic sclerosis (SSc) is a heterogeneous autoimmune rheumatic disease characterized by widespread vascular dysfunction, immune dysregulation, and progressive fibrosis affecting the skin and internal organs. Although SSc may occur across the lifespan, it most commonly presents between the third and fifth decades of life. Increasing recognition of disease onset in older adults has prompted investigation into whether geriatric-onset systemic sclerosis represents a distinct clinical and prognostic entity. This study aimed to delineate the epidemiologic, clinical, and prognostic characteristics of late-onset systemic sclerosis (LoSSc; diagnosis ≥65 years) compared with early-onset disease (EoSSc; diagnosis <65 years) within the Toronto Scleroderma Program cohort. Methods A total of 2,303 patients fulfilling ACR/EULAR classification criteria for SSc were included, comprising 1,976 EoSSc and 327 LoSSc cases. The primary outcome was all-cause mortality from the time of diagnosis, while secondary outcomes included disease-specific manifestations, comorbidity burden, and functional status. Relative risks (RR) with 95% confidence intervals (CI) were calculated for clinical and serological features. Survival analyses were performed using Kaplan-Meier estimates and Cox proportional hazards modeling to identify independent predictors of mortality. Results LoSSc patients exhibited distinct clinical characteristics compared with those with earlier onset disease. They were significantly less likely to demonstrate esophageal dysmotility (RR 0.91, 95% CI 0.85–0.97), digital ulcers (RR 0.65, 95% CI 0.53–0.81), or anti-Scl-70 antibody positivity (RR 0.68, 95% CI 0.51–0.91), suggesting a lower prevalence of classic fibrotic and vasculopathic features. In contrast, LoSSc patients demonstrated a higher prevalence of pulmonary arterial hypertension (RR 1.59, 95% CI 1.33–1.89) and a substantially greater burden of age-associated comorbidities, including coronary artery disease, systemic hypertension, diabetes mellitus, hyperlipidemia, peripheral vascular disease, malignancy, stroke, and atrial fibrillation. Functional impairment was also more pronounced, with LoSSc patients more frequently classified as NYHA class II or higher (RR 1.50, 95% CI 1.17–1.92). The risk of multimorbidity was strikingly elevated, with LoSSc patients demonstrating a 27-fold increased likelihood of having 6 or more comorbid conditions. Survival analyses revealed significantly higher mortality in LoSSc at one, 5, and 10 years post-diagnosis (Figure 1). Late-onset disease was an independent predictor of mortality (adjusted HR 4.51, p<0.0001), even after adjustment for key confounders including sex, cardiovascular comorbidities, interstitial lung disease, pulmonary hypertension, renal crisis, and malignancy. Figure 1. Kaplan Meier survival curves comparing people with SSc diagnosed at age 65 or older (Late-onset Systemic Sclerosis, LoSSc) and those diagnosed before 65 years (Early-onset Systemic Sclerosis, EoSSc). Conclusion These findings indicate that LoSSc constitutes a clinically and prognostically distinct phenotype, characterized by increased comorbidity, higher cardiopulmonary complications, and reduced survival. Tailored approaches to screening, management, and prognostication are warranted for older adults with systemic sclerosis.