Effectiveness of Rituximab Therapy on Severe Calcinosis in 4 Children with Juvenile Dermatomyositis

Abstract

Background: Calcinosis is an important sequela of JDM which may cause significant morbidity and mortality. There is no standard curative treatment for calcinosis but different agents were used with variable efficacy. We report the favorable outcome of rituximab on severe calcinosis in 4 JDM patients and present their clinical data. Patients and Methods: A retrospective chart review of 4 children with JDM and severe calcinosis who received rituximab for relapsing or polycyclic JDM course. Diagnosis and follow up of calcinosis was clinically and by X-ray. Review data included: age of patients at onset of JDM symptoms and diagnosis, clinical and laboratory criteria at diagnosis, disease course and duration of follow up. Data about calcinosis onset, sites, severity and its progression were also included. Further data about rituximab therapy included: dosage, side effects, other treatment used before, during or after this drug and outcome and duration of follow up of calcinosis after therapy. Results: 4 patients (2 male, 2 female), interval between onset of symptoms and diagnosis was 6 -12 months, course of JDM was polycyclic or relapsing, duration of follow up was 5 -7 years. Calcinosis was severe causing ulceration, recurrent skin infections and joint limitation. It was not improving despite treatment with different DMARDs and/or bisphosphonates, colchicine and warfarin. Reason to start rituximab was inadequate disease control with conventional DMARDs. All patients received steroids and more than one DMARD before starting rituximab and were continued thereafter, follow up after rituximab was 3 to 5 years. All patients had improvement in disease activity and frequency of admission especially due to complications of calcinosis. One patient had complete clearance of calcinosis for the last 5 years. Others had significant improvement in calcinosis with no new lesions, decreased sites and density and decreased calcinosis related contractures. There were no serious side effects to rituximab. Conclusion: Our study showed the favorable effect of rituximab in treatment of calcinosis in 4 patients with JDM-associated severe calcinosis when it was used with other conventional DMARDs.

Treatment of calcinosis cutis in systemic sclerosis and dermatomyositis: A review of the literature

“…33,34 From the results of studies, the partial response rate ranged from 0/6 (0%) 34 to 100% in 3 studies including 3 to 9 patients. 31,32,35 The complete response rate ranged from 0% 29,33,34 to 100% in a study of 3 SSc patients. 31 In studies, the relapse rate was 0% with a follow-up of 12 to 60 months.…”

“…Our literature search identified citations; reports for 30 studies 10,20, were included in this systematic review (Figure 1), including RCTs, 20,30 11 prospective cohort studies 31,32,36,[43][44][45][46][47][48]51,53 and 17 retrospective studies. 10,[26][27][28][29][33][34][35][37][38][39][40][41][42]49,50,52 The sample size ranged from 3 to 78 patients, for a total of 288 patients (SSc=108, adult DM=66, juvenile DM=90, and DM or SSc but unspecified diagnosis=24).…”

“…The partial response rate ranged from 0/12 (0%) 29 to 9/14 (64%). 28 No complete responses were reported in the 3 studies and no adverse events were reported in the study of Vayssairat et al 10 Rituximab: Rituximab was used in 7 studies (SSc=18, adult DM=9, juvenile DM=32) including 3 prospective studies, [31][32][33] 3 retrospective studies 29,34,35 and one RCT versus placebo…”

“…31 In studies, the relapse rate was 0% with a follow-up of 12 to 60 months. 31,35 Adverse events were assessed in 3 studies and included localized bacterial infection of the calcinosis (n=2), moderate acute infusionrelated events (n=1), and intestinal perforation 2 weeks after a combination of rituximab and pulse methylprednisolone infusions (n=1).…”

“…Indeed, although one study of 6 juvenile DM patients did not reported improvement, 34 most studies showed at least partial response, including 3 with 100% partial response. 31,32,35 Moreover, 3 studies reported at least one patient with complete response. 30,31,35 TNF-α inhibitors, particularly infliximab, may have a beneficial effect on calcinosis cutis in juvenile DM, but their use should be carefully scrutinized in SSc because of reports of severe exacerbation of pulmonary fibrosis associated with their use.…”