Juvenile dermatomyositis (ORPHA:93672)
An early-onset form of dermatomyositis (DM), a systemic, autoimmune inflammatory muscle disorder with vasculopathy, characterized by proximal and symmetrical muscle weakness, evocative skin lesions, and systemic manifestations. Vasculopathy occurs in the skin, muscle (mainly in the perifascicular area), and sometimes in the intestinal tissue.
Epidemiology
Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy of childhood, with an annual incidence of 1/250,000-500,000 children. Females are affected more frequently than males (2-5:1 ratio).
Clinical description
Onset of juvenile dermatomyositis (JM) is on average between 5 to 14 years of age. Patients commonly have the signs of DM, i.e symmetrical proximal muscle weakness and erythematous rash (heliotrope rash, Gottron papules, erythema in sun-exposed areas), that is sometimes pruritic, along with cutaneous vasculitis and ulcerations, calcinosis of soft tissue (20-40%), and vasculopathy affecting the digestive tract (with bowel ischemia and/or infarction, abdominal pain, and melena). Muscle weakness variably impairs physical function. Commonly reported signs also include myalgia and arthralgia. Other associated extramuscular features include dysphagia, sometimes dysphonia, hoarseness, pneumonitis, cardiac manifestations (conduction defects, myocarditis, dilated cardiomyopathy), Raynaud's phenomenon and inflammatory arthritis. Specific clinical and histological characteristics are described according to myositis-specific antibody presence. Calcinosis is associated with a younger age at disease onset and positivity for anti-NXP2 antibody. Macrophage activation syndrome, a severe sometimes life-threatening condition, is described in some children. Unlike adult-onset DM, there is no association between malignancy and anti-TIF1-γ antibody positivity. The rare reported malignancies include lymphoma and leukemia.
Etiology
The pathogenesis of JDM has been partially elucidated and is associated with certain HLA regions (different associations compared to adult onset DM) as well as several triggers such as infections. The interferon (IFN) pathways play a key role, especially type I IFNs and an IFN signature has been detected in muscle fibers, and endothelial cells.
Diagnostic methods
Diagnosis is based on the clinical signs and magnetic resonance imaging (MRI) of muscle. Muscle and skin involvements should be evaluated with specific standardized tools. Muscle biopsy and electromyographic testing may also be used, especially in case of atypical JDM. Muscle enzymes (creatine kinase) may be elevated. In JDM, 65% of the patients have myositis-specific antibodies with different prevalence compared to adult onset DM (20-25% with anti-TIF1-γ, 18-20% with anti-NXP2, 4-10% with anti-Mi2). Lung and cardiac involvement should be assessed at diagnosis.
Differential diagnosis
Differential diagnosis in JDM may include mitochondrial myopathies, infectious myopathies, other forms of inflammatory myopathies, particularly autoimmune necrotizing myopathy, as well as Duchenne muscular dystrophy or Becker muscular dystrophy, systemic lupus erythematosus, and juvenile idiopathic arthritis. Monogenic interferonopathies, such as proteasome-associated autoinflammatory syndrome and STING-associated vasculopathy with onset in infancy syndrome, may mimic JDM.
Management and treatment
The aim of treatment is to reduce long-term morbidity and to restore physical function. High-dose corticosteroids are the mainstay of treatment, with dose tapering after a few weeks of therapy depending on patient response. Methotrexate may also be used, and for severe disease, intravenous methylprednisolone (IVMP). In case of refractory disease, other immunosuppressive treatments may be prescribed. Physical therapy is important to maintain or restore muscle strength. Topical corticosteroids and tacrolimus have been used to treat skin manifestations. Patients should avoid direct UV light and use high-factor sunscreen. There is no validated treatment for calcinosis.
Prognosis
The course of JDM is highly variable: 30-50% patients go into remission within 2 to 3 years, whilst others have a cyclic course marked by relapse or an ulcerative or chronic disease course. Treatment is generally effective, with very low mortality rates (less than 4%). The disorder may however be associated with significant morbidity (calcinosis, persistent muscle weakness, skin and muscle atrophy).

                            Last update: 
                            March 2021


                            - Expert reviewer(s): 
                            Dr Céline ANQUETIL  - Pr Olivier BENVENISTE