Objective. To assess survival and incidence of organ-based complications in a large single-center cohort of unselected systemic sclerosis (SSc) patients, and to explore predictors of survival and clinically significant pulmonary fibrosis (PF) and pulmonary hypertension (PH).Methods. The study cohort consisted of 398 consecutive SSc patients, followed up for up to 15 years. Cox proportional hazards analysis with demographic, clinical, and laboratory characteristics as predictor variables was used to develop prediction models for pulmonary complications and survival.Results. The overall survival estimate at the end of followup was 57% among patients with limited cutaneous SSc (lcSSc) and 50% among patients with diffuse cutaneous SSc (dcSSc) (P ‫؍‬ 0.017). We found that greater age at disease onset, dcSSc, lower diffusing capacity for carbon monoxide (DLCO), lower hemoglobin levels, higher serum creatinine levels, and the presence of PH or cardiac involvement were independent predictors of worse survival. Over the entire followup period, 42% of dcSSc patients and 22% of lcSSc patients developed clinically significant PF (P < 0.001). The variables that predicted clinically significant PF development were dcSSc, greater age at onset, lower forced vital capacity and DLCO, and the presence of anti-topoisomerase I antibody, while the presence of anticentromere antibody was protective. There was no difference in cumulative incidence of PH between the 2 subsets-24% in lcSSc and 18% in dcSSc (P ‫؍‬ 0.558). Incidence rates were 1-2% per year. The PH prediction model demonstrated that greater age at onset, increase in serum creatinine levels, lower DLCO, and the presence of anti-RNA polymerase III or anti-U3 RNP antibodies were associated with increased risk of PH, while antitopoisomerase I antibody positivity reduced the hazard.Conclusion. Our study provides data on longterm outcome of SSc and the timing and frequency of major organ complications. The predictive models we present could be used as clinical tools for patient risk stratification and could facilitate cohort enrichment for event-driven studies.

Our results confirm the overexpression of IL-6 in dcSSc and support the potential of IL-6 as a surrogate marker for clinical outcome in this disease. The data also provide rationale for clinical studies targeting IL-6 trans-signalling as a potential antifibrotic therapy for SSc.

The pathogenetic role of autoantibodies in systemic sclerosis (SSc) remains unclear, but these autoantibodies have been established as strong predictors of disease outcome and the pattern of organ complications in patients with this condition. The three most frequently observed types of SSc-specific autoantibody-anti-centromere antibodies, anti-topoisomerase antibodies and anti-RNA polymerase III antibodies-are found in over 50% of patients; the presence of each is generally exclusive of the others. Although a lot less frequently observed, antibodies directed against U3RNP and Th/To are also specific for scleroderma, whereas anti-Pm/Scl, anti-Ku and anti-U1RNP antibodies are seen mainly in patients with overlap syndromes. Up to 11% of patients with SSc can test negative for antinuclear antibodies. Strong links exist between autoantibody specificities and disease presentation and outcome, which make autoantibodies essential assessment tools in patients with SSc.

Objective To describe the associations between autoantibodies, clinical presentation, and outcomes among patients with systemic sclerosis (SSc) in order to develop a novel SSc classification scheme that would incorporate both antibodies and the cutaneous disease subset as criteria. Methods Demographic and clinical characteristics, including cutaneous subset, time of disease and organ complication onset, and autoantibody specificities, were determined in a cohort of SSc subjects. Survival analysis was used to assess the effect of the autoantibodies on organ disease and death. Results The study included 1,325 subjects. Among the antibody/skin disease subsets, anticentromere antibody–positive patients with limited cutaneous SSc (lcSSc) (n = 374) had the highest 20‐year survival (65.3%), lowest incidence of clinically significant pulmonary fibrosis (PF) (8.5%) and scleroderma renal crisis (SRC) (0.3%), and lowest incidence of cardiac SSc (4.9%), whereas the frequency of pulmonary hypertension (PH) was similar to the mean value in the SSc cohort overall. The anti–Scl‐70+ groups of patients with lcSSc (n = 138) and patients with diffuse cutaneous SSc (dcSSc) (n = 149) had the highest incidence of clinically significant PF (86.1% and 84%, respectively, at 15 years). Anti‐Scl‐70+ patients with dcSSc had the lowest survival (32.4%) and the second highest incidence of cardiac SSc (12.9%) at 20 years. In contrast, in anti‐Scl‐70+ patients with lcSSc, other complications were rare, and these patients demonstrated the lowest incidence of PH (6.9%) and second highest survival (61.8%) at 20 years. Anti–RNA polymerase antibody–positive SSc patients (n = 147) had the highest incidence of SRC (28.1%) at 20 years. The anti–U3 RNP+ SSc group (n = 56) had the highest incidence of PH (33.8%) and cardiac SSc (13.2%) at 20 years. Among lcSSc patients with other autoantibodies (n = 295), the risk of SRC and cardiac SSc was low at 20 years (2.7% and 2.4%, respectively), while the frequencies of other outcomes were similar to the mean values in the full SSc cohort. Patients with dcSSc who were positive for other autoantibodies (n = 166) had a poor prognosis, demonstrating the second lowest survival (33.6%) and frequent organ complications. Conclusion These findings highlight the importance of autoantibodies, cutaneous subset, and disease duration when assessing morbidity and mortality in patients with SSc. Our novel classification scheme may improve disease monitoring and benefit future clinical trial designs in SSc.