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Idiopathic inflammatory myopathy, a category encompassing polymyositis, dermatomyositis, and a number of other disorders, is very uncommon, but has been the focus of intense study in the Arthritis and Rheumatism Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases for the past several years. We describe the clinical picture, stressing the need for biopsy to ensure correct diagnosis. It is especially important to recognize the treatment-resistant variant, inclusion body myositis. The extraskeletal manifestations, particularly the cardiopulmonary, oropharyngeal, gastrointestinal, and endocrine involvement, are described. The cardiopulmonary involvement, especially interstitial lung disease, arrhythmias, and cardiac failure, may dominate the clinical picture. The known causes are varied, and include drugs, toxins, and some infectious agents, however, in most cases a cause cannot yet be identified. Circumstantial evidence suggests that picornaviruses may initiate some cases in humans, and a very similar disease in mice caused by a picornavirus is actively under study. Studies of autoantibodies and cellular immune function support a central role for disordered immunity in the pathogenesis. The myositis-specific autoantibodies, especially those directed at certain enzymes important in protein synthesis (the aminoacyl-transfer RNA synthetases), are found in a clinically distinct subset of patients. Although most patients respond initially to corticosteroids, cytotoxic drugs are sometimes added when steroid toxicity or refractoriness develops. We describe several newer therapies under study for such cases and outline future directions in research.

Denture cream contains zinc, and chronic excessive use may result in hypocupremia and serious neurologic disease.

Objective-Because studies suggest that ultraviolet radiation (UVR) modulates myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine if UVR may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the United States.Methods-We assessed the relationship between surface UVR intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 myositis patients from referral centers in the U.S. Myositis autoantibodies were detected by validated immunoprecipitation assays. Surface UVR intensity was estimated from UV index data collected by the U.S. National Weather Service.Results-UVR intensity was associated with the relative proportion of patients with dermatomyositis (odds ratio [OR] 2.3, 95% confidence interval [CI] 0.9-5.8) and with the proportion of patients expressing anti-Mi-2 autoantibodies (OR 6.0, CI 1.1-34.1). Modeling of these data showed that these associations were confined to women (OR 3.8, respectively) and suggests that gender influences UVR effects on autoimmune disorders. Significant associations were not seen in men, nor were UVR levels related to the presence of anti-synthetase or anti-signal recognition particle autoantibodies.Conclusion-This first study of the distribution of myositis phenotypes and UVR exposure in the United States showed that UVR may modulate the clinical and immunologic expression of autoimmune disease in women. Further investigation of the mechanisms by which these effects are produced may give insights into pathogenesis and suggest therapeutic or preventative strategies.Current evidence suggests that autoimmune diseases result from environmental exposures in genetically susceptible individuals and ultraviolet radiation (UVR) is an environmental exposure of increasing interest (1). Beyond UVR's recognized association with skin cancer are other immunomodulatory effects possibly related to the development of immune- Furthermore, studies suggest that UVR regulates levels of the dermatomyositis-specific Mi-2 autoantigen via protein translational effects (4).The idiopathic inflammatory myopathies (IIM) are acquired systemic autoimmune conditions that share chronic muscle weakness due to chronic muscle inflammation. The two major clinical groups, dermatomyositis (DM) and polymyositis (PM), are distinguished by the presence of photosensitive pathognomonic rashes in DM (5). These two forms of IIM share some genetic risk factors but differ in others and appear to have distinct pathogeneses (5). Categorizing myositis patients by the presence or absence of myositis-specific autoantibodies (MSA) results in more homogenous groups in terms of epidemiology, clinical presentations, genetics and prognoses (5). MSA include autoantibodies directed against aminoacyl-tRNA synthetases (anti-synthetases), the signal recognition particle (anti-SRP), and autoantibodies that react with a 240 kD protein called chromodomain helicase DNA bi...

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Results. In contrast to European American patients with IIM, African American patients with IIM, in particular those with polymyositis, had no strong disease associations with HLA alleles of the 8.1 ancestral haplotype; however, African Americans with dermatomyositis or with anti-Jo-1 autoantibodies shared the risk factor HLA-DRB1*0301 with European Americans. We detected novel HLA risk factors in African American patients with myositis overlap (DRB1*08) and in African American patients producing anti-signal recognition particle (DQA1*0102) and anti-Mi-2 autoantibodies (DRB1*0302). DRB1*0302 and the European American-, anti-Mi-2-associated risk factor DRB1*0701 were found to share a 4-amino-acid sequence motif, which was predicted by comparative homology analyses to have identical 3-dimensional orientations within the peptide-binding groove.Conclusion. These data demonstrate that North American IIM patients from different ethnic groups have both shared and distinct immunogenetic susceptibility factors, depending on the clinical phenotype. These findings, obtained from the largest cohort of North American minority patients with IIM studied to

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