Elena Moraitis

Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study

IntroductionThe aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM).MethodsSerum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist).ResultsAnti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease.ConclusionsAnti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed.

Childhood Infections and Trauma as Risk Factors for Stroke

Stroke is as common as brain tumor in children. The etiology of childhood arterial ischemic stroke (AIS) appears to be multifactorial, resulting from the interaction between genetic predisposition and environmental triggers. The risk factors for AIS in children are markedly different from the atherosclerotic risk factors in adults. Trauma and infections have been identified as associations in previous studies and are exposures of particular interest because of their increased prevalence in the children. The aim of this review article is to provide an overview of the research studies that have addressed the role of infections and trauma in pediatric AIS.

Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile Dermatomyositis Shown by Marginal Structural Modeling

In patients with severe or refractory juvenile dermatomyositis (DM), second‐line treatments may be required. Cyclophosphamide (CYC) is used to treat some connective tissue diseases, but evidence of its efficacy in juvenile DM is limited. This study was undertaken to describe clinical improvement in juvenile DM patients treated with CYC and model the efficacy of CYC treatment compared to no CYC treatment.

Infantile-onset LMNA-associated Muscular Dystrophy Mimicking Juvenile Idiopathic Inflammatory Myopathy.

To the Editor: Juvenile idiopathic inflammatory myopathy (JIIM) refers to a group of rare chronic autoimmune conditions. Juvenile dermatomyositis (JDM) is the most common JIIM. The hallmarks of JDM are characteristic cutaneous features and proximal muscle weakness; however, adermatitic forms have been described. Polymyositis presents with both proximal and distal muscle weakness, muscle atrophy, and similar degrees of dysphagia, arthritis, and contractures1. Although magnetic resonance imaging (MRI) is widely used, muscle biopsy remains a critical tool in the diagnosis of JIIM, especially in atypical cases1. Recently, LMNA -associated congenital muscular dystrophy (LMNA-CMD) has been reported as a novel and severe form of laminopathy with secondary inflammatory changes mimicking inflammatory myopathies2,3. Mutations in the LMNA gene encoding lamin A/C are responsible for multiple disease phenotypes4. Some of them may present early in life as a congenital muscular dystrophy2,3. ### Patient We report the case of a 26-month-old girl, first child of non-consanguineous parents, who was referred to our department based on a history of progressive muscle weakness with raised creatine kinase (CK) and a muscle biopsy showing marked inflammation. There was no family history of neuromuscular or autoimmune diseases. She was born by normal uncomplicated delivery; no reduced fetal movements were described by the mother during pregnancy. By 1 year of age, she was … Address correspondence to Dr. E. Moraitis, Rheumatology Department, Great Ormond Street Hospital for Children, Great Ormond Street, London, WC1N 3JH, UK. E-mail: elena.moraitis.13{at}ucl.ac.uk

Sub-phenotyping of juvenile dermatomyositis: can it assist clinical decisions?

Juvenile Dermatomyositis (JDM) is a rare serious disease (affecting 2-3 million children/year) presenting with rash and proximal muscle weakness. Serious complications can include calcinosis, GI ulceration, interstitial lung disease (ILD) and even death. It is becoming clear that JDM is a heterogeneous condition. Dividing JDM into sub-phenotypes would allow better prediction of disease severity and more targeted treatments. We have identified novel auto-antibodies in subtypes of JDM that may correlate with specific phenotypes.

PReS-FINAL-2130: Antibodies to MDA5 correlate with a distinct phenotype in children with juvenile dermatomyositis, including higher risk of lung involvement and ulcerative skin disease

Myositis specific autoantibodies (MSA), exclusively found in patients with Idiopathic Inflammatory Myopathies can be detected in approximately 60% of children with JDM. Anti-MDA5 antibodies, a subgroup of MSA, appear to be associated with clinically amyopathic myositis, rapidly progressive interstitial lung disease (RP-ILD) and a poor prognosis in adult East Asian dermatomyositis patients. Small studies in Japanese children with JDM have suggested similar disease phenotype. This contrasts dramatically with findings in predominantly Caucasian US adult populations where anti-MDA5 has been associated with a distinct cutaneous phenotype and no association with RP-ILD has been found.

PReS-FINAL-2130-A: Effectiveness of intravenous cyclophosphamide in severe or refractory juvenile dermatomyositis - a national cohort study UK and Ireland

Evidence suggests that early and aggressive treatment in Juvenile Dermatomyositis (JDM) improves outcome and prevents complications. Cyclophosphamide has been used as a second-line agent in the treatment of severe or refractory JDM. Published data on the effectiveness of cyclophosphamide in JDM are limited to a previous small case series and case reports.