Objective To determine whether the pattern of skin involvement can predict clinical features, risk of restrictive lung disease (RLD) and survival in a large scleroderma (SSc) cohort.

Methods Demographic and clinical data collected over 30 years from 2205 patients with SSc were retrospectively analysed after subdividing subjects into four subtypes based on pattern of skin fibrosis: type 0 (no skin involvement), type 1 (limited to metacarpophalangeal joints), type 2 (distal to elbows/knees) and type 3 (proximal to elbows/knees). Clinical features associated with skin subsets were identified by regression analyses. Kaplan–Meier and Cox proportional hazards models were used to compare time to RLD and survival across subtypes.

Results The presence and severity of RLD were positively associated with skin subtype (p<0.001). RLD prevalence incrementally ranged from 51.9% in type 0 to 76.7% in type 3 (p<0.001). Type 2 SSc exhibited a distinct phenotype with intermediate risk for RLD relative to type 1 (higher, p<0.001) and type 3 (lower, p<0.001) and a unique autoantibody profile, with a prevalence of anticentromere antibodies lower than type 1 (28.9% vs 44.1%, p=0.001) and of anti-topoisomerase I antibodies similar to type 3 (32.8% vs 28.7%, p=0.38). These autoantibodies were also found to be significant negative (OR=0.33, p<0.001) and positive (OR=1.6, p=0.01) predictors of RLD risk, respectively. Mortality was also intermediate in type 2 patients relative to type 3 (p=0.0003) and type 1 (p=0.066).

Conclusions These data suggest that the current classification subdividing SSc into limited and diffuse cutaneous subtypes misclassifies an intermediate group of patients exhibiting unique autoantibody profile, disease course and clinical outcomes.