In a single section from a biopsy sample, there may be only necrosis and phagocytosis of individual muscle fibers without infiltrates of inflammatory cells, or the reverse may be observed. However, in serial sections, muscle necrosis is shown to be adjacent to inflammatory infiltrates. Repeated attacks of a necrotizing myositis exhaust the regenerative potential of the muscles so that fiber loss, fibrosis, and residual thin and large fibers in haphazard arrangement may eventually impart a dystrophic appearance. For all these reasons, the pathologic picture can be correctly interpreted only in relation to clinical and other laboratory data. Guidelines for the interpretation of the muscle biopsy reflecting these comments, a critical step in correct diagnosis of the inflammatory myopathies, are given in the review by Dalakas and Hohlfeld.
Even more distinctive of DM are microvascular changes in muscle. Endothelial alterations (tubular aggregates in the endothelial cytoplasm) and occlusion of vessels by fibrin thrombi may be appreciated, with associated zones of infarction. The same vascular changes underlie the lesions in the connective tissue of skin, subcutaneous tissue, and gastrointestinal tract when they are present. The perifascicular muscle fiber atrophy had in the past been attributed to an ischemic process set up by capillary occlusion, but recent evidence suggests otherwise (see Greenberg and Amato).
All attempts to isolate an infective agent in the inflammatory myopathies have been unsuccessful. Several electron microscopists observed virus-like particles in muscle fibers, but a causative role has not been proved. A polymyositic illness has not been induced in animals by injections of affected muscle as it has in models of several other inflammatory neurologic conditions. Nevertheless, the notion that an autoimmune mechanism is operative in PM and DM is supported by the association of these disorders with a number of the more clearly established autoimmune diseases enumerated earlier in this chapter. Further evidence of an autoimmune nature is given by the presence of specific autoantibodies in nearly half of cases, as also described earlier.
Immunopathologic studies have substantiated an autoimmune mechanism and suggested that PM, DM, and necritizing myositis can be distinguished from one another on the basis of their immunopathologic characteristics. In DM, immune complexes, IgG, IgM, complement (C3), and membrane-attack complexes are deposited in the walls of venules and arterioles, indicating that the immune response is directed primarily against intramuscular blood vessels (Whitaker and Engel; Kissel et al). Such a response is lacking in PM (and in IBM, discussed further on). Engel and Arahata have demonstrated a difference between the two disorders on the basis of the subsets and locations of lymphocytes that make up the intramuscular inflammatory aggregates. However, the deposition of these complexes may be a secondary event as our colleagues Greenberg and Amato propose. In PM, there are a large number of activated T cells, mainly of the CD8 class, whereas B cells are sparse. Moreover, T cells, accompanied by macrophages, enclose and invade nonnecrotic muscle fibers. In DM, very few fibers are affected in this manner, and the percentage of B cells at all sites is significantly higher than it is in PM. Engel and Arahata interpreted these differences as indicating that the effector response in DM is predominantly humoral, whereas in PM the response is composed of cytotoxic T cells, clones of which have been sensitized to a yet undefined antigen on the muscle fiber. The current understanding of immunopathogenesis is summarized in the review by Dalakas (2015).