Cumulative disease damage and anti-PM/Scl antibodies are associated with a heavy burden of calcinosis in systemic sclerosis.

Abstract

Ectopic calcification (calcinosis) is a common complication of SSc, but a subset of SSc patients has a heavy burden of calcinosis. We examined whether there are unique risk factors for a heavy burden of calcinosis, as compared with a light burden or no calcinosis. We reviewed the medical records of all patients in the Johns Hopkins Scleroderma Center Research Registry with calcinosis to quantify calcinosis burden using pre-specified definitions. We performed latent class analysis to identify SSc phenotypic classes. We used multinomial logistic regression to determine whether latent phenotypic classes and autoantibodies were independent risk factors for calcinosis burden. Of all patients, 29.4% (997/3388) had calcinosis, and 13.5% (130/963) of those with calcinosis had a heavy burden. The latent phenotypic class with predominantly diffuse skin disease and higher disease severity (characterized by pulmonary hypertension, interstitial lung disease, cardiomyopathy, severe RP, gastrointestinal involvement, renal crisis, myopathy and/or tendon friction rubs) was associated with an increased risk of both a heavy burden [odds ratio (OR) 6.92, 95% CI 3.66, 13.08; P < 0.001] and a light burden (OR 2.88, 95% CI 2.11, 3.95; P < 0.001) of calcinosis compared with the phenotypic class with predominantly limited skin disease. Autoantibodies to PM/Scl were strongly associated with a heavy burden of calcinosis (OR 17.31, 95% CI 7.72, 38.81; P < 0.001) and to a lesser degree a light burden of calcinosis (OR 3.59, 95% CI 1.84, 7.00; P < 0.001). Calcinosis burden is associated with cumulative SSc-related tissue damage. Independent of disease severity, autoantibodies to PM/Scl are also associated with a heavy burden of calcinosis.