The Connective Tissue and Diseases Section began studying inflammatory myopathies (polymyositis, dermatomyositis, and related diseases) some years ago in an attempt to understand the relationship of autoantibodies to autoimmune disease. These diseases seemed to offer the best example of autoimmune diseases associated with highly specific disease-related autoantibodies and evidence of a viral etiology. They are very uncommon and hence relatively less studied than other autoimmune diseases, and they are very debilitating and hence in need of improved therapy. In order to attract patients here to allow more detailed clinical, immunological, genetic, and viral studies, we began doing trials of therapy and have completed a number of such studies. They are among the very few published controlled trials in this difficult to treat family of illnesses. The past year saw the publication of a long-running controlled trial on the use of more aggressive cytotoxic regimens for patients with myositis unresponsive to standard therapy. The favorable experience with the combination of methotrexate and azathioprine has led to adoption of this regimen by others. A trial of the purine analog, flurodeoxyadenosine, has been analyzed, and the results accepted for publication. This trial was uncontrolled, but the favorable responses in patients unresponsive to conventional treatment support the view that a controlled trial should be done. A pilot trial of the anti-thyroid drug methimazole has been continued and the treatment regimen intensified and prolonged. This trial was undertaken to make use of an unexpected property of the drug which was discovered by Dr. Leonard Kohn of NIDDK and Dr. Dinah Singer of NCI: that it can down-regulate MHC. Patients with active myositis are receiving a 6-month trial, with muscle biopsies being performed for research purposes at the beginning and 3 months into therapy. The level of mRNA of MHC I & II in muscle tissue and simultaneously-obtained peripheral blood monocytes is measured by Northern analysis. Patients are assessed carefully clinically, and the presence of inflammation in the quadriceps is measured by MRI. The MRI analysis will employ a computer-based measure of tissue edema on the STIR image which has been developed with the Radiology Department of the Clinical Center. A description of this technique will appear in the journal Magnetic Resonance Imaging in the coming months. The only protocol currently accepting myositis patients is for methimazole. The results in the fludarabine trial suggest that a controlled trial is warranted, perhaps after additional dose-finding experience. A decision on further clinical trials has not yet been made. Dr. Lisa Rider has continued to examine patients with juvenile myositis at the Clinical Center and to lead a collaborative group of pediatric rheumatologists throughout the country and in Canada in a thorough clinical and laboratory description of the disease. Dr. Frederick Miller is examining patients with silicone implant- associated myositis and a similar control group of women with silicone implants who are free of connective tissue diseases in an attempt to determine whether or not the myositis differs from ordinary myositis clinically, immunologically, or biochemically, and whether or not those who develop it differ from the control group in any recognizable way. Both Dr. Rider and Dr. Miller are former members of ARB who now work at CBER, FDA and are volunteers in the ARB clinic.
