Cumulative Disease Damage and Anti-PM/Scl Antibodies Are Associated with a Heavy Burden of Calcinosis in Systemic Sclerosis.

OBJECTIVES
Ectopic calcification (calcinosis) is a common complication of systemic sclerosis, but a subset of systemic sclerosis 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.


METHODS
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 systemic sclerosis phenotypic classes. We used multinomial logistic regression to determine whether latent phenotypic classes and autoantibodies were independent risk factors for calcinosis burden.


RESULTS
29.4% (997/3388) of patients had calcinosis. 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 PH, ILD, cardiomyopathy, severe Raynaud's, gastrointestinal involvement, renal crisis, myopathy and/or tendon friction rubs) was associated with an increased risk of both a heavy burden (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).


CONCLUSIONS
Calcinosis burden is associated with cumulative systemic sclerosis-related tissue damage. Independent of disease severity, autoantibodies to PM/Scl are also associated with a heavy burden of calcinosis.