Clinical characteristics and risk factors for calcinosis cutis in systemic sclerosis: insights from the EUSTAR database

Objectives: Calcinosis Cutis (CaC) represents one of the most frequent and disabling non-lethal manifestations in systemic sclerosis (SSc). Our objectives were to evaluate 1) associations of CaC with SSc clinical characteristics and 2) identify risk factors for CaC development. Methods: EUSTAR database-registered SSc patients with available information on their CaC status were included. We compared baseline patient characteristics (with vs without CaC at baseline) and investigated predictors of CaC development for 5 and 10 years (in those without baseline CaC) with logistic regression analyses. Results: 7,114 SSc patients were included. At baseline, 11.9% had CaC. Among 1,010 and 997 patients without baseline CaC, 40% and 46% developed CaC within 5 years and 10 years, respectively. Patients with CaC were more frequently female, had longer disease duration, higher modified Rodnan Skin Score, telangiectasia, digital ischaemia, late capillaroscopy patterns, joint contractures, tendon friction rubs, gastrointestinal involvement (all p< 0.001), pulmonary arterial hypertension (PAH) (p= 0.02), joint synovitis, and renal crisis (both p= 0.04). CaC patients had a higher frequency of anti-centromere and anti-PM/Scl antibody positivity (p< 0.001; p= 0.03, respectively).Predictors for the development of CaC at 5 years included longer disease duration (OR 1.04), cardiac involvement (OR 1.63), late capillaroscopy pattern (OR 1.70), telangiectasia (OR 1.92), digital ulcers (OR 2.60), and PAH (OR 2.10). Predictors at 10 years included longer disease duration (OR 1.03), diffuse cutaneous SSc (OR 1.51), female gender (OR 1.85), telangiectasia (OR 1.92), and digital ulcers (OR 2.92). Conclusions: CaC is common and progressive; clinical risk factors may provide insights into the pathogenesis.