Elsevier

The Lancet

Volume 371, Issue 9631, 28 June–4 July 2008, Pages 2201-2212
The Lancet

Seminar
Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood

https://doi.org/10.1016/S0140-6736(08)60955-1Get rights and content

Summary

Juvenile dermatomyositis, the most common inflammatory myopathy of childhood, is a rare systemic autoimmune vasculopathy that is characterised by weakness in proximal muscles and pathognomonic skin rashes. The length of time before the initiation of treatment affects presenting symptoms, laboratory measures, and pathophysiology. It also affects disease outcomes, including the development of pathological calcifications, which are associated with increased morbidity. Both genetic and environmental risk factors seem to have a role in the cause of juvenile dermatomyositis; HLA B8–DRB1*0301 ancestral haplotype is a strong immunogenetic risk factor, and antecedent infections and birth seasonality suggest that environmental stimuli might increase risk. Activation of dendritic cells with upregulation of genes induced by type-1 interferon (α) in muscle and peripheral blood seems to be central to disease pathogenesis. Treatment often includes combinations of corticosteroids, methotrexate, and other immunosuppressive agents. Disease outcome, if treatment is initiated early, is generally good. Randomised controlled trials are needed to define the most effective treatments.

Introduction

Juvenile dermatomyositis is a rare, often chronic, autoimmune disease with onset during childhood. It is a systemic vasculopathy characterised by symmetrical proximal muscle weakness, raised serum concentrations of muscle enzymes, and pathognomonic skin rashes that include the heliotrope rash over the eyelids and Gottron's papules over the extensor joint surfaces (figure 1). This disease is classified as one of the idiopathic inflammatory myopathies (table 1); the adult forms are more common.1, 2, 3, 4 In this Seminar, we will focus on juvenile dermatomyositis, but refer to other idiopathic inflammatory myopathies with juvenile onset where relevant. We review some important advances in the understanding of the causes, epidemiology, pathophysiology, clinical features, and treatment of idiopathic inflammatory myopathies in childhood.

Section snippets

Causes and epidemiology

The incidence of juvenile dermatomyositis in the USA is 3·2 per million children per year,5 which is similar to that in the UK.6 The average age at onset is 7 years, but 25% of patients are younger than 4 years at onset.7 In the USA, the ratio of girls to boys is 2·3 to 1,7 compared with 5 to 1 in the UK.6 Rash is the first symptom to be recognised in half the children and weakness is the first symptom in a quarter.8

Childhood idiopathic inflammatory myopathies, like other autoimmune diseases,

Pathological changes and pathophysiology

We have focused on new ideas about disease pathogenesis (figure 2) in juvenile dermatomyositis, and idiopathic inflammatory myopathies in general, rather than provide a complete review. Juvenile dermatomyositis is a vasculopathic condition.25 Typical histological changes in the muscle include swelling of the capillary endothelium with obliteration of the lumen, perifascicular atrophy, perivascular inflammation, muscle degeneration and regeneration, and the presence of tubuloreticular inclusions

Diagnostic criteria

Juvenile dermatomyositis is usually considered in the differential diagnosis either when erythematous rashes arise on the face or extremities or when acquired symmetrical muscle weakness is present. Many conditions might present similarly and should be considered in the differential diagnosis (table 2).43, 44 The diagnosis of juvenile dermatomyositis is mainly made through a constellation of clinical and laboratory tests, as applied in the 1975 criteria by Bohan and Peter.45, 46 Only two-thirds

Clinical features

In addition to proximal, usually progressive, muscle weakness and characteristic skin rashes (Gottron's papules or the heliotrope eyelid rash), the presenting features of juvenile dermatomyositis are protean (Figure 3, Figure 4,53, 54, 55, 56 panel). Nonetheless, some characteristic features deserve further discussion. Dystrophic calcification (figure 3D) occurs in up to 30% of patients.56, 57 The sites most frequently affected are pressure points: elbows, knees, digits, and buttocks.

Heterogeneity of childhood idiopathic inflammatory myopathies

Childhood idiopathic inflammatory myopathies can be divided into more homogeneous clinicopathological or serological subsets with distinctive epidemiology, and clinical, pathological, or prognostic features (Table 1, Table 3).1 Juvenile dermatomyositis is the most common subset, representing up to 85% of childhood idiopathic inflammatory myopathies.48, 53 The two other major subsets of idiopathic inflammatory myopathies are juvenile polymyositis, in which the characteristic rashes are absent,

Clinical course

Typically, children with myositis are followed up by serial examination of muscle strength, function, rash, other organs, and serum concentrations of muscle enzymes. However, tests for muscle enzymes are not very sensitive (more than 20% of patients have a normal creatine kinase concentration at diagnosis8) and frequently become normal with corticosteroid treatment even in active disease. Two international collaborative study groups have standardised and validated measures of disease activity

Treatment

Treatment for childhood idiopathic inflammatory myopathies have not been assessed in randomised controlled trials. Our best understanding of treatment comes from observational studies and clinical experience. Since the 1970s, standard treatment for juvenile dermatomyositis has been high-dose daily oral corticosteroids (eg, up to 2 mg/kg per day of prednisone, often in divided doses), which is continued until clinical and laboratory improvement are evident and then slowly reduced over at least a

Search strategy and selection criteria

We searched five databases: Medline (1950 to April week 4, 2007); Embase (1980 to week 18, 2007); Cinahl (1982 to May week 1, 2007); Evidence-Based Medicine Reviews (including the Cochrane Library); and Allied and Complementary Medicine (1985 to April, 2007). Any article on myositis in children was eligible for inclusion, with no restrictions on language or year of publication. The main search terms were “dermatomyositis”, “myositis”, “polymyositis”, “orbital myositis”, “overlap

References (138)

  • CM Artlett et al.

    Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies. Childhood Myositis Heterogeneity Collaborative Group

    Lancet

    (2000)
  • AM Reed et al.

    Chimerism in children with juvenile dermatomyositis

    Lancet

    (2000)
  • S Compeyrot-Lacassagne et al.

    Inflammatory myopathies in children

    Pediatr Clin North Am

    (2005)
  • AV Ramanan et al.

    Clinical features and outcomes of juvenile dermatomyositis and other childhood onset myositis syndromes

    Rheum Dis Clin North Am

    (2002)
  • LM Pachman

    Juvenile dermatomyositis. Pathophysiology and disease expression

    Pediatr Clin North Am

    (1995)
  • SL Bowyer et al.

    Childhood dermatomyositis: factors predicting functional outcome and development of dystrophic calcification

    J Pediatr

    (1983)
  • CH Spencer et al.

    Course of treated juvenile dermatomyositis

    J Pediatr

    (1984)
  • LG Rider

    Outcome assessment in the adult and juvenile idiopathic inflammatory myopathies

    Rheum Dis Clin North Am

    (2002)
  • JP Mitchell et al.

    Juvenile dermatomyositis presenting with anasarca: a possible indicator of severe disease activity

    J Pediatr

    (2001)
  • E Pope et al.

    Childhood acquired lipodystrophy: a retrospective study

    J Am Acad Dermatol

    (2006)
  • RA el-Azhary et al.

    Amyopathic dermatomyositis: retrospective review of 37 cases

    J Am Acad Dermatol

    (2002)
  • E Rivas et al.

    Macrophagic myofasciitis in childhood: a controversial entity

    Pediatr Neurol

    (2005)
  • C Sordet et al.

    Contribution of autoantibodies to the diagnosis and nosology of inflammatory muscle disease

    Joint Bone Spine

    (2006)
  • LA Love et al.

    A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups

    Medicine

    (1991)
  • EP Mendez et al.

    US incidence of juvenile dermatomyositis, 1995–1998: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Registry

    Arthritis Rheum

    (2003)
  • DP Symmons et al.

    The incidence of juvenile dermatomyositis: results from a nation-wide study

    Br J Rheumatol

    (1995)
  • LM Pachman et al.

    History of infection before the onset of juvenile dermatomyositis: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry

    Arthritis Rheum

    (2005)
  • LM Pachman et al.

    Juvenile dermatomyositis at diagnosis: clinical characteristics of 79 children

    J Rheumatol

    (1998)
  • GS Cooper et al.

    The role of genetic factors in autoimmune disease: implications for environmental research

    Environ Health Perspect

    (1999)
  • G Mamyrova et al.

    Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians

    Arthritis Rheum

    (2006)
  • LM Pachman et al.

    TNFalpha-308A allele in juvenile dermatomyositis: association with increased production of tumor necrosis factor alpha, disease duration, and pathologic calcifications

    Arthritis Rheum

    (2000)
  • LG Rider et al.

    Polymorphisms in the IL-1 receptor antagonist gene VNTR are possible risk factors for juvenile idiopathic inflammatory myopathies

    Clin Exp Immunol

    (2000)
  • ML Christensen et al.

    Prevalence of Coxsackie B virus antibodies in patients with juvenile dermatomyositis

    Arthritis Rheum

    (1986)
  • LJ Vegosen et al.

    Seasonal birth patterns in myositis subgroups suggest an etiologic role of early environmental exposures

    Arthritis Rheum

    (2007)
  • LM Pachman et al.

    New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis

    Arthritis Rheum

    (1997)
  • MJ Koch et al.

    Childhood polymyositis: a case-control study

    Am J Epidemiol

    (1976)
  • M Massa et al.

    Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis

    Arthritis Rheum

    (2002)
  • GC Topi et al.

    Dermatomyositis-like syndrome due to toxoplasma

    Br J Dermatol

    (1979)
  • G Mamyrova et al.

    Parvovirus B19 and onset of juvenile dermatomyositis

    JAMA

    (2005)
  • LM Pachman et al.

    Lack of detection of enteroviral RNA or bacterial DNA in magnetic resonance imaging-directed muscle biopsies from twenty children with active untreated juvenile dermatomyositis

    Arthritis Rheum

    (1995)
  • BQ Banker et al.

    Dermatomyositis (systemic angiopathy) of childhood

    Medicine

    (1966)
  • LR Wedderburn et al.

    International consensus on a proposed score system for muscle biopsy evaluation in patients with JDM, for potential use in clinical trials

    Arthritis Rheum

    (2007)
  • L Miles et al.

    Predictability of the clinical course of juvenile dermatomyositis based on initial muscle biopsy: a retrospective study of 72 patients

    Arthritis Rheum

    (2007)
  • Z Tezak et al.

    Gene expression profiling in DQA1*0501 children with untreated dermatomyositis: a novel model of pathogenesis

    J Immunol

    (2002)
  • EC Baechler et al.

    An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity

    Mol Med

    (2007)
  • CKC Li et al.

    MHC class I overexpression on muscles in early juvenile dermatomyositis

    J Rheum

    (2004)
  • P Englund et al.

    Interleukin-1alpha expression in capillaries and major histocompatibility complex class I expression in type II muscle fibers from polymyositis and dermatomyositis patients: important pathogenic features independent of inflammatory cell clusters in muscle tissue

    Arthritis Rheum

    (2002)
  • C Dorph et al.

    Signs of inflammation in both symptomatic and asymptomatic muscles from patients with polymyositis and dermatomyositis

    Ann Rheum Dis

    (2006)
  • K Nagaraju et al.

    Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction

    Arthritis Rheum

    (2005)
  • T Sugiura et al.

    Increased CD40 expression on muscle cells of polymyositis and dermatomyositis: role of CD40-CD40 ligand interaction in IL-6, IL-8, IL-15, and monocyte chemoattractant protein-1 production

    J Immunol

    (2000)
  • Cited by (341)

    • The clinical features of juvenile dermatomyositis: A single-centre inception cohort

      2022, Seminars in Arthritis and Rheumatism
      Citation Excerpt :

      The course of the disease in our patients is quite similar to our previous reports [2,24], and similar to that reported by other centers [4]. However, in one study done in Melbourne, the number of patients with polycyclic disease was considerably higher at 17.7% [8,19]. This likely reflects a difference in the way the term has been defined; for our definition we require a period of greater than 12 weeks in clinical and laboratory remission while off all medications before relapse.

    View all citing articles on Scopus
    View full text