The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes

Abstract

The aim of this review is to summarize recent advances in the understanding of the clinical and autoantibody phenotypes, their associated outcomes, and the pathogenesis of the juvenile idiopathic inflammatory myopathies (JIIMs). The major clinical and autoantibody phenotypes in children have many features similar to those in adults, and each has distinct demographic and clinical features and associated outcomes. The most common myositis autoantibodies in JIIM patients are anti-p155/140, anti-MJ, and anti-MDA5. Higher mortality has been associated with overlap myositis as well as with the presence of anti-synthetase and anti-MDA5 autoantibodies; a chronic illness course and lipodystrophy have been associated with anti-p155/140 autoantibodies; and calcinosis has been associated with anti-MJ autoantibodies. Histologic abnormalities of JIIMs detectable on muscle biopsy have also been correlated with myositis-specific autoantibodies; for example, patients with anti-MDA5 show low levels of inflammatory infiltrate and muscle damage on biopsy. The first genome-wide association study of adult and juvenile dermatomyositis revealed three novel genetic associations, BLK, PLCL1, and CCL21, and confirmed that the human leukocyte antigen region is the primary risk region for juvenile dermatomyositis. Here we review the well-established pathogenic processes in JIIMs, including the type 1 interferon and endoplasmic reticulum stress pathways. Several novel JIIM-associated inflammatory mediators, such as the innate immune system proteins, myeloid-related peptide 8/14, galectin 9, and eotaxin, have emerged as promising biomarkers of disease. Advances in our understanding of the phenotypes and pathophysiology of the JIIMs are leading to better tools to help clinicians stratify and treat these heterogeneous disorders.

Cutaneous and Systemic Findings Associated With Nuclear Matrix Protein 2 Antibodies in Adult Dermatomyositis Patients

“…Severe edema and/or anasarca has also been reported in juvenile DM patients, with the largest series showing 20 of 21 (95%) with myalgia, 11 of 18 (61%) with dysphagia, and 7 of 21 (33%) with calcinosis . Furthermore, up to 70% of these patients (7/10) had gastrointestinal ulcerations , a finding that has also been associated with anti–NXP‐2 antibodies .…”

Characteristics and outcome of children with juvenile dermatomyositis in Cape Town: a cross-sectional study

“…Certain immune phenotypes associated with presence of anti-MJ autoantibodies, found in 12–23 % of JIIM patients, have been associated with higher risk of occurrence of calcinosis and severer disease [25]. It is not known if black African children have higher prevalence of these immune phenotypes thus putting them at greater risk for calcinosis.…”

The IgG2 Isotype of Anti–Transcription Intermediary Factor 1γ Autoantibodies Is a Biomarker of Cancer and Mortality in Adult Dermatomyositis

“…Other reported risk factors for cancer in adult DM, i.e., older age, male sex, and cutaneous necro sis, have also been identified in anti TIF1γ-positive adult DM (10,(16)(17)(18)(19). Anti TIF1γ autoantibodies are also found in 30-40% of patients with juvenile DM, without any association with cancer (8,13,20).…”