Pathophysiology of inflammatory and autoimmune myopathies

Inflammatory Muscle Diseases

“…CD8+ T cells (termed the MHC-CD8 complex) is useful for confirming the diagnosis and for ruling out disorders with nonimmune inflammation, as seen in some muscular dystrophies. 2,3,5,17,25 In necrotizing autoimmune myositis, there are abundant necrotic fibers invaded or surrounded by macrophages (Fig. 2E and 2F).…”

“…Muscle biopsy is most useful when the biopsy site is properly chosen (i.e., in a muscle that does not have clinical signs of advanced or end-stage disease but is also not minimally affected), the specimen is processed at an experienced laboratory, and the findings are interpreted in the context of the clinical picture. [1][2][3]24,25 In dermatomyositis, the inflammation is perivascular and is most prominently located in the interfascicular septae or the periphery of the fascicles. The muscle fibers undergo necrosis and phagocytosis -often in a portion of a muscle fasciculus or the periphery of the fascicleowing to microinfarcts that lead to hypoperfusion and perifascicular atrophy.…”

“…The muscle fibers undergo necrosis and phagocytosis -often in a portion of a muscle fasciculus or the periphery of the fascicleowing to microinfarcts that lead to hypoperfusion and perifascicular atrophy. [1][2][3][4][5] Perifascicular atrophy, which is characterized by layers of atrophic fibers at the periphery of the fascicles, often with perivascular and interfascicular infiltrates, is diagnostic of dermatomyositis (or of overlap myositis, when the skin changes are absent or transient) [1][2][3][4][5]10,24,25 (Fig. 1A).…”

“…Lymphocytic infiltrates are sparse, and MHC class I up-regu- lation is often prominent beyond the necrotic fibers. 3,4,6,14,25 Necrotizing autoimmune myositis is most often mediated by specific antibodies against SRP or HMGCR (see the Glossary), often with complement deposits on capillaries. 15,16 Inclusion-body myositis has all the inflammatory features of polymyositis, including the CD8-MHC complex, but in addition has chronic myopathic changes with increases in connective tissue and in the variability in fiber size, autophagic vacuoles that have walls lined internally with material that stains bluish-red with hematoxylin and eosin or modified Gomori trichrome (Fig.…”

“…In dermatomyositis, complement C5b-9 membranolytic attack complex is activated early (before the destruction of muscle fibers is evident) and deposited on the endothelial cells, leading to necrosis, reduction of the density of endomysial capillaries, ischemia, and musclefiber destruction resembling microinfarcts [1][2][3][4][5][6]24,25,34 ; the remaining capillaries have dilated lumens to compensate for the ischemia 2,3,25 ( Fig. 1A through 1D).…”