1.2.4 Dermatomyositis

The incidence of dermatomyositis ranges from 2-9 per million with a F:M = 3:1. It is characterized by a bimodal age distribution, with two peaks of incidence in <10 years and from 30 to 60 years.

Dermatomyositis (DM) is a systemic inflammatory autoimmune disease classified among the idiopathic inflammatory myopathies. Dermatomyositis involves the skin with a characteristic eruption on the sun exposed areas, and muscles with a symmetric, proximal, extensor myopathy.

DM is an autoimmune disease, resulting from of an immune-mediated process triggered by outside factors (malignancy, drugs, infections) in genetically predisposed individuals (HLA class II). In adults, 15% are paraneoplastic, particularly genitourinary, ovarian and colon cancer. DM, with either or both cutaneous and muscle involvement, has been associated with drugs, including statins, fenofibrates and IFN-a. The pathogenesis of DM, like other idiopathic inflammatory myopathies, involves both the innate and the adaptive immune systems, and it is attributed to an antibody-mediated attack on endothelial cells, followed by complement-mediated destruction of capillaries and watershed ischemia of muscle fibers. Skin and muscle damage are due to toxicity from type I IFN-mediated pathways, in particular IFN-β. SARS-CoV-2 infection and vaccination may lead to new-onset dermatomyositis via autoimmunity due to interferon signaling, hyperinflammation and autoantibody induction.

Erythrocyte sedimentation rate and muscle enzymes, especially creatine kinase (CK), are elevated. Serum CK levels are elevated in 70-80% of patients; in 10% of those with normal CK, serum aldolase may be increased.

Anti-nuclear antibodies (ANA) can be positive but are a non-specific finding. In some cases, the anti- nuclear antibody test may be negative. Anti-extractable nuclear antigen antibodies (ENA) may indicate a severe course with pulmonary fibrosis. DM is associated with several myositis-specific antibodies. They include anti-amynoacil-tRNA synthetase (anti-synthetase) antibodies (>20%): Anti-Jo-1, anti-PL-12, anti-PL 7, etc. and a heterogeneous group of antibodies: anti-SRP (5%), anti-Mi2 (15%), anti-TIF-1γ (20- 40% in the classic form and in cases associated with malignancy), anti-NXP-2 (10-20%), anti-SAE (5%), anti-MDA5 (5-20%). The anti-Jo antibody is usually detected in patients with polymyositis (without skin lesions) and has been associated with a severe course and lung involvement. The titers of anti-Jo-. as well as those of anti-MDA5 and anti-SRP have been related to disease activity. MDA5 antibody has been associated with lung intersititial disease, skin ulcers, palmar papules and mechanic’s hands. Patients with anti-synthetase antibodies often have overlap syndromes with scleroderma.

Electromyography (EMG) shows polyphasic potentials. EMG of weak muscles shows increased insertional and spontaneous activity in the form of positive sharp waves and fibrillation potentials, or complex repetitive discharges along with early recruitment of small amplitude, short duration, polyphasic motor units. These findings are non-specific and can be seen in other myopathies. Skeletal muscle magnetic resonance imaging (MRI) can detect muscle necrosis, degeneration, and inflammation, and is characterized by increased signal intensity on short-tau inversion recovery, and sometimes more specific findings of abnormalities of fascia suggesting fasciitis. MRI and ultrasound of muscles may be sensitive enough to avoid muscle biopsy or can be used to identify the correct site where to perform a muscle biopsy.

The role of emerging imaging techniques like optical coherence tomography (OCT) and magnetic resonance imaging (MRI) is being investigated to aid in accurately assessing of inflammation and muscle damage.

Skin biopsy of the erythematous, scaling lesions of DM may reveal cell-poor interface dermatitis with a scanty mononuclear cell infiltrate, similar to lupus erythematosus. Epidermal atrophy, hydropic degeneration of basal keratinocytes, and dermal changes consisting of edema of the upper dermis, and interstitial mucin deposition are present. Direct immunofluorescence microscopy of lesional skin is usually negative, although granular deposits of immunoglobulins and complement in the epidermal basement membrane zone have been described in some patients. The histopathology of muscle biopsy in DM is characterized by muscle fiber degeneration and necrosis with lymphocytic infiltrates and obliterative vasculopathy. The characteristic abnormality is perifasicular atrophy, but it is present in only 50% of patients.

The course of DM is chronic. Spontaneous remission may occur in cases drug-induced or when an associated malignant tumour is successfully treated. In the absence of malignancy, prognosis is generally favourable, with 5-year survival rates ranging from 70-93%. Poor prognostic features are increased age, associated interstitial lung disease, cardiac disease, and late or previous inadequate treatment

The diagnosis is made on the clinical features. Laboratory investigations are aimed at documenting muscle damage and the autoimmune status. Adults should be evaluated for malignancy at diagnosis, followed by long-term surveillance.

Lupus erythematosus, mixed connective tissue disease (Sharp syndrome) and progressive systemic sclerosis may enter in differential diagnosis for the heliotrope rash or should be considered in case of overlap syndrome and/or lupus erythematosus. Gottron’s papules can be easily misdiagnosed with psoriasis and eyelid erythema and edema with eczema. Phototoxic and photoallergic eruptions for the photodistribution. Cutaneous T-cell lymphoma for the poikiloderma. Myopathy needs differential diagnosis with polymyositis, other inflammatory myopathies, muscular dystrophy, motor neuron disease, congenital myopathy, metabolic myopathy, mitochondrial myopathy, myasthenia gravis, myotonic dystrophy, and inclusion body myositis.

Treatment should be directed at the systemic disease, with the use of systemic corticosteroids (prednisone 1 mg/kg/day); in the case of resistant disease, it is indicated to start intravenous pulse corticosteroids plus a low dose of methotrexate or azathioprine. High-dose intravenous immunoglobulins are effectively used in cases where previous treatments are inappropriate. Immunosuppressant agents, such as cyclosporin A, mycophenolate mofetil and cyclophosphamide are considered in resistant cases. The ongoing research includes exploration of targeted therapies, like interferon pathway inhibitors (particularly anifrolumab), which aim to reduce inflammation and symptoms, as well as investigation into biological therapies, such as rituximab targeting B cells to decrease disease activity. Topical glucocorticoids are sometimes useful. Patients should avoid exposure to ultraviolet irradiation and aggressively use photoprotective measures, including broad-spectrum sunscreens.