Is Anti-NXP2 Autoantibody a Risk Factor for Calcinosis and Poor Outcome in Juvenile Dermatomyositis Patients? Case Series.

Natasa Toplak,Angelo Ravelli,Silvia Rosina,Cassyanne L Aguiar,Tomas Dallos,Oz Rotem Semo,Raju Khubchandani,Pallavi Pimpale Chavan,Anjali Patwardhan

doi:10.3389/fped.2021.810785

Abstract

Juvenile dermatomyositis (JDM) has a wide spectrum of clinical presentations. In the last decade, several myositis-specific antibodies have been identified in patients with JDM and connected with specific organ involvement or specific clinical picture. It has been published that the presence of anti-NXP2 autoantibodies presents a risk for calcinosis in patients with JDM. We aimed to investigate the prevalence of calcinosis and response to the treatment in JDM patients with anti-NXP2. In a retrospective, multinational, multicenter study, data on 26 JDM (19 F, 7 M) patients with positive anti-NXP2 were collected. The mean age at disease presentation was 6.5 years (SD 3.7), the median diagnosis delay was 4 months (range 0.5–27 months). Patients were divided into two groups (A and B) based on the presence of calcinosis, which occurred in 42% of anti-NXP2 positive JDM patients (group A). Four patients already had calcinosis at presentation, one developed calcinosis after 4 months, and 6 developed calcinosis later in the disease course (median 2 years, range 0.8–7.8). The differences in laboratory results were not statistically significant between the groups. The mean age at disease presentation (5.2/7.5 years) trended toward being younger in group A. Children with calcinosis were treated with several combinations of drugs. In four cases, rituximab and, in one case, anti-TNF alpha agents were used successfully. Disease outcome (by evaluation of the treating physician) was excellent in four, good in two, stable in two, and poor in three patients. None of the patients from group B had a poor disease outcome. In conclusion, JDM patients with anti-NXP2 are prone to develop calcinosis, especially if they present with the disease early, before 5 years of age. The development of calcinosis is associated with worse disease outcomes. The combination of several immunomodulatory drugs and biologic drugs can stop calcinosis progression; however, there are no evidence-based therapies for treating calcinosis in JDM patients.

Highlights

Juvenile dermatomyositis (JDM) has a spectrum of clinical presentations, from mild forms of myositis and skin changes with a monocyclic course to very severe forms with vital organ involvement and late complications, including calcinosis and lipodystrophy (1)
In our case series study, 42% of JDM patients with positive antiNXP2 presented with calcinosis or developed calcinosis during the disease course
Patients with calcinosis trended toward being younger at disease presentation and had a more severe disease course and worse outcome than patients who did not develop calcinosis despite anti-NXP

Summary

Introduction

Juvenile dermatomyositis (JDM) has a spectrum of clinical presentations, from mild forms of myositis and skin changes with a monocyclic course to very severe forms with vital organ involvement and late complications, including calcinosis and lipodystrophy (1). Among different MSA, anti-NXP2 and anti-PM/Scl are most commonly associated with calcinosis in JDM and the adult form of dermatomyositis. TIF1γ and MDA5 MSA were risk factors for calcinosis (3, 4). Calcinosis is one of the major complications of JDM and is found in 20–40% of patients (5, 6). It has been published that young age at disease presentation, regardless of MSA, presents a risk for calcinosis in patients with JDM (7). The presence of anti-NXP2 increases the risk of calcinosis across all ages (7). MSA are associated with disease severity, worse functional status, and persistent disease activity (9)

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