Dermatomyositis (ORPHA:221)
A rare idiopathic inflammatory myopathy (IIM) characterized by evocative skin lesions, muscle involvement with symmetrical proximal muscle weakness, and specific histological features. The clinical subtypes are defined by the presence of myositis-specific antibodies (anti-Mi2, anti-NXP2, anti-TIF1-γ, anti-MDA5, or anti-SAE antibodies) and are associated with specific clinical phenotypes and prognosis.
Epidemiology
Annual incidence is estimated between 1/125,000-1,000,000, and prevalence between 1/10,000-50,000. Dermatomyositis (DM) is more common in women than in men (2:1).
Clinical description
Onset is generally in adulthood, in some cases earlier (Juvenile DM). The classical skin findings are of periorbital heliotrope rash and Gottron's papules, photodistributed violaceous erythema and poikiloderma, and periungual telangiectasias. Symmetrical proximal muscle weakness subsequently develops over weeks or months, with severity depending on antibody type. Anti-Mi2 DM (5-20% of DM patients) and anti-TIF1-gamma DM (15-25%) present a moderate to severe proximal muscle weakness with classical skin lesions. Anti-NXP2 DM (15-25%) presents specifically subcutaneous edema and calcinosis. Anti- SAE DM (5%) presents classical skin lesions with mild or no muscle involvement. Anti-MDA5 DM (5-20%) present with classical skin lesions, ulcerations, mechanic's hands, arthritis, pulmonary involvement, and no or mild muscle involvement. Pulmonary manifestations ranges from aspiration pneumonia to a severe life-threatening rapidly progressive interstitial lung disease (ILD). DM may involve other systems (cardiac, articular, gastro-intestinal). About one third of DM patients develop malignancy, often within 0 to 3 years before or after disease onset (breast and ovarian cancers in women, and lung and prostate cancer in men).
Etiology
Although the etiology is not fully understood, it is suggested to be associated with certain HLA regions, genes implicated in other autoimmune diseases, and triggers such as infections or cancer. The interferon (IFN) pathways play a key role in DM physiopathology, especially type I IFNs, and an IFN signature has been detected in blood sample, muscle and skin tissues.
Diagnostic methods
Diagnosis is based on the characteristic clinical and laboratory (elevated serum creatine kinase and presence of myositis-specific antibody) findings, as well as myopathic findings on electromyography (EMG). It is generally confirmed by muscle biopsy showing inflammatory infiltrates around blood vessels and perifascicular atrophy.
Differential diagnosis
The differential diagnoses include other inflammatory myopathies, muscular dystrophies of late onset, as well as adult-onset nemaline myopathy, proximal myotonic myopathies, systemic lupus erythematosus, pityriasis rubra pilaris, lichen planus, and polymorphous light eruption.
Management and treatment
Treatment aims to eliminate inflammation and restore muscle performance. Initial treatment includes high-dose corticosteroids, followed by tapering to an appropriate maintenance dose. Immunosuppressive agents (methotrexate, azathioprine, and mycophenolate mofetil) are frequently used in combination. Intravenous immunoglobulin or intravenous methylprednisolone may be used in severe cases. For patients with rapidly progressive ILD a specific approach must be discussed (cyclophosphamide, calcineurin inhibitors). Physical therapy is also recommended. Topical corticosteroid, tacrolimus, and hydroxychloroquine 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. Pulmonary involvement should be evaluated with high resolution computed tomography and pulmonary function tests, and suspected cardiac involvement with echocardiography. Skin lesion severity should be evaluated with the CDASI (Cutaneous Dermatomyositis Disease Area and Severity Index). Age-appropriate cancer screening is recommended at diagnosis and in cases of relapse within 3 years or refractory disease.
Prognosis
Prognosis is sometimes poor and depends on patient response to treatment, severity of disease manifestations and comorbidities (notably, cancer and pulmonary involvement). Increased cancer risk is associated with age > 50 years, male sex, and presence of specific DM autoantibodies: anti-TIF1-y > anti-NXP2 > anti-Mi2. The anti-MDA5 subgroup is associated with 20% mortality due to rapidly progressive ILD.

                            Last update: 
                            February 2021


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