Identification of Clinical Features and Autoantibodies Associated With Calcinosis in Dermatomyositis

Abstract

IMPORTANCE Prior studies have estimated that up to 20% of adults with dermatomyositis (DM) have calcinosis, which can lead to significant morbidity. Identification of risk factors may provide a better understanding of the pathogenesis and ultimately therapy for this difficult clinical problem. Risk factors for calcinosis in adults with DM have not been extensively studied. OBJECTIVES To determine the prevalence of calcinosis and to identify associated clinical features in a cohort of extensively phenotyped adults with DM. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study of 126 patients diagnosed as having DM from January 1, 2006, through January 1, 2013, was performed. Patients were adults (≥18 years of age) attending the Stanford University Medical Center clinic. MAIN OUTCOMES AND MEASURES Calcinosis, defined as the presence of calcium deposition in the skin and subcutaneous tissues on physical examination. RESULTS Fourteen patients (11.1%) had calcinosis, with the extremities most commonly involved. Patients with vs those without calcinosis had a longer disease duration (median, 6.9 years; range, 2.4–18.1; vs median, 3.9 years; range, 0.2-19.2 years; P = .003) and more fingertip ulcers (50.0% vs 9.3%, P < .001). An association between calcinosis and both interstitial lung disease and anti–MDA-5 autoantibodies was identified, but this association did not persist in multivariate models that adjusted for fingertip ulcers. Fingertip ulcers and disease duration were strongly associated with calcinosis in all multivariate models, independent of the underlying autoantibody present. Autoantibodies to NXP-2 were associated with calcinosis (odds ratio, 15.52; 95% CI, 2.01-119.90), whereas anti–transcriptional intermediary factor 1-γ antibodies were protective (odds ratio, 0.2; 95% CI, 0.01-0.99) in multivariate analyses that adjusted for fingertip ulcers and other covariates. CONCLUSIONS AND RELEVANCE Calcinosis was a relatively uncommon clinical feature in our cohort of adults with DM. Our data suggest that calcinosis is positively associated with longer disease duration, fingertip ulcers, and NXP-2 autoantibodies and negatively associated with transcriptional intermediary factor 1-γ antibodies. A common vascular mechanism may underlie the development of both calcinosis and fingertip ulcers in patients with DM.

Distinctive cutaneous and systemic features associated with antitranscriptional intermediary factor-1γ antibodies in adults with dermatomyositis

“…22 Mechanisms that drive calcinosis are not well understood, and it is likely that they are not related to the classic inflammatory activity that we traditionally recognize and may be related to the vasculopathy seen in DM disease. 27 …”

Cutaneous Manifestations in Dermatomyositis: Key Clinical and Serological Features—a Comprehensive Review

“…Forty-three percent of anti-NXP2-positive patients developed calcinosis. In US patients with adult-onset DM, this antibody was strongly associated with calcinosis in multivariate analysis (OR 15.52, 95 % CI 2.01-119.90) [42]. In an Italian study of adult DM/PM, heliotrope rash (P=0.01) and calcinosis (P=0.09) were found to be more frequent in patients with anti-MJ antibodies, which were the most frequent specificity [43].…”

The Clinical Features of Myositis-Associated Autoantibodies: a Review

“…Other disease associations include muscle contractures, atrophy and worse function status [68]. Data suggests that anti-NXP2 is also associated with calcinosis in adult DM (personal observation) [71][72][73]. In a recent study, 11 % had calcinosis overall, associated independently with disease duration, fingertip ulcers, as well as anti-NXP2 [71].…”