Calcinosis develops in an estimated 40% of patients with Juvenile Dermatomyositis (JDM). Conflicting studies have not definitively identified actionable risk factors or demonstrated that patients with calcinosis have unique clinical features. Diverse therapies are used to treat calcinosis, but there are limited data on the use of biologic agents apart from small case series. Using a large patient registry, we aimed to identify patients at risk for calcinosis, distinguish clinical phenotypes, and examine treatment history with biologic agents.

Methods:

The Childhood Arthritis and Rheumatology Research Alliance (CARRA) created a multi-site registry for pediatric rheumatologic diseases, enrolling patients from 2010 to 2015. We performed cross-sectional analysis of baseline data in all JDM patients. We compared those with any history of calcinosis to those with no history, in respect to demographics, disease features, patient-reported outcome measures and treatment with biologic agents. The difference of symptom onset date and first rheumatology visit was used to calculate duration of symptoms prior to treatment. Differences between patients with and without calcinosis were analyzed with t-test or Wilcoxon Rank Sum tests for continuous variables as appropriate, while comparisons for categorical variables used Chi-square or Fisher’s Exact tests as appropriate. Statistically significant measures at the alpha level of 0.05 on univariate analyses were included in multivariate logistic regression modeling.

Results:  

Of 652 JDM patients, 601 contained requisite data on calcinosis. Females accounted for 71% of patients. The majority (83%) were Caucasian, 13% African-American, while 15% identified as Hispanic. Mean age of JDM disease onset was 6.6 years. In total, 84 patients (14%) had a history of calcinosis. This history was associated with skin ulcerations (p=0.0005), lipodystrophy (p<0.0001) and contractures (p<0.0001). Patients with cardiac, lung or gastrointestinal disease, individually or combined, did not show a significant association. Calcinosis patients also had higher CHAQ (p=0.0034), HRQOL (p=0.011) and global assessment scores, with the strongest correlation for parent/patient reported global scores (p<0.0009, 13.7%). In multivariate analysis, differences in the distribution of proportions retained significance in patients with calcinosis for measures of delayed time to treatment (OR 1.5, CI 1.3-1.8), male gender (OR 1.75, CI 1.02-3.03), and African-American race (OR 2.5, CI 1.3-4.8). Those with calcinosis were also more likely to have received IVIG (OR 1.9, CI 1.1-3.3), rituximab (OR 4.6, CI 1.8-11.4) and anti-TNF therapy (OR 2.7 CI 1.006-7.5).

Conclusion:  

In this registry, one of the largest JDM and calcinosis cohorts, patients with a history of calcinosis are more likely to have received certain biologic agents than those without. Affected patients were also more likely to be male, of African ancestry and have longer symptom duration before treatment. These features should be considered risk factors and encourage screening measures. Patients with lipodystrophy, skin ulcerations or contractures should raise similar concern.