Dermatoniyositis and polymyositis

Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies. The major manifestation of the myositis is proximal muscle weakness. Thirty percent to 40% of adults and 95% of children have cutaneous manifestations (DM) that include: (1) Gottron's papules; (2) the heliotrope suffusion around the eyes, associated with periorbital edema; (3) poikiloderma, often photosensitive; and (4) nailfold changes including erythema, telangiectasia, and depletion or abnormality of the nailfold capillaries, visible with magnification. In juvenile DM, calcinosis is often seen in skin, subcutaneous tissue, or muscle. DM and PM are systemic diseases, and manifestations outside the skin and muscle may occur. Fever, weight loss, arthritis, and Raynaud's phenomenon are seen in some cases. Interstitial lung disease may develop, as well as lung involvement from ventilatory failure or aspiration. Cardiac involvement may include arrhythmias, heart block, and congestive heart failure. Dysphagia may result from myositis of the pharyngeal muscles or from decreased lower esophageal motility. In about 20% to 25% of adults with DM, and less commonly with PM, there is an associated malignancy. The nature of the association is not known, and the increased frequency of malignancy in PM/DM has not been statistically established. The relative frequency of different tumors is similar to that in the general population, but ovarian tumors may be more frequent. In some cases, there may be a relationship of activity of the myositis to that of the malignancy. In adults with PM/DM, a careful baseline screening is important, and any abnormalities should be pursued. Risk of malignancy is higher in older patients with DM, but without connective tissue overlap, who have a poor response to treatment or have a previous malignancy. Diagnostic criteria include proximal muscle weakness, elevated muscle enzymes, typical findings on electromyography and muscle biopsy, and characteristic cutaneous lesions. Measurement of creatine kinase is commonly used to assist in monitoring disease activity, as well as to support the diagnosis. Electromyography can document the presence of a myopathy and help to exclude neuropathies. Muscle biopsy can provide the strongest evidence for establishing a diagnosis. Mononuclear cell infiltration, necrosis, degeneration, and regeneration are seen. Perimysial inflammation with perifascicular atrophy is characteristic of DM, while endomysial infiltration is more common in PM. Vasculopathy with endothelial cell damage and capillary loss is characteristic of DM. Cutaneous histopathology can show compatible changes but cannot establish the diagnosis. Vacuolar changes in the basal layer, basement membrane thickening, epidermal atrophy, dermal edema with increased mucin, and a mononuclear cell infiltrate at the dermal-epidermal junction are seen. Immunofluorescence does not show specific findings. Other conditions that may cause a clinically similar myopathy must be excluded, including infections (with human immunodeficiency virus [HIV], human T-cell leukemia virus type I [HTLV-1], Toxoplasma, and other agents), inclusion body myositis, congenital or metabolic myopathies, drug effects, endocrine disorders, and others. Autoimmunity is clearly involved in the pathogenesis of PM and DM, but the factors leading to the autoimmune response have not been identified. Genetic influences are important, as demonstrated by an increased frequency of HLA-DR3. Viruses are most commonly suspected as possible triggering factors, especially picornaviruses and retroviruses. Other possibilities include Toxoplasma, drugs or toxins, and malignancy. Recent studies of the phenotypes of mononuclear cells infiltrating muscle biopsies have revealed that T-cell cytotoxicity against muscle fibers appears to be an important mechanism of muscle injury in PM but not DM. Vasculopathy associated with deposition of activated complement in the muscle vessels appears to be important in DM. Autoantibodies to nuclear and cytoplasmic antigens are common in PM/DM. A group of myositis-specific antibodies are directed at aminoacyl-tRNA synthetases, of which the most common is anti-histidyl-tRNA synthetase (anti-Jo-1), found in 20% of PM/DM patients. Antisynthetases are associated with a high frequency of interstitial lung disease, arthritis, and Raynaud's phenomenon. Anti-Mi-2, another myositis-specific antibody, is directed at an unidentified nuclear antigen. When present, it is strongly associated with cutaneous involvement. Ninety-five percent of patients with anti-Mi-2 have DM, while 15% to 20% with DM have anti-Mi-2. Several autoantibodies, including anti-PMScl, anti-Ku, anti-UIRNP, and anti-U2RNP, have been associated with myositis-scleroderma overlap syndrome. The myositis-specific antibodies may be helpful in diagnosis and in identifying significant patient subgroups and have implications for etiology and pathogenesis. The treatment of the myositis is generally initiated with corticosteroids, in adults usually prednisone, 60 to 80 mg/d. Immunosuppressive agents, most often azathioprine or methotrexate, are used in up to 25% of patients, usually for steroid resistance or severe steroid side effects. Case reports have described success with cyclosporin in resistant cases. The skin disease may persist despite control of the myositis, and hydroxychloroquine has been useful in such cases. With current treatment, the prognosis of PM/DM has improved and morbidity is decreased, with an 80% 5-year survival rate. Malignancy, interstitial lung disease, and cardiac disease contribute to mortality. Those with a long delay before initiation of treatment have less chance of recovering full strength.