Pathophysiology of inflammatory and autoimmune myopathies

SummaryThe main subtypes of inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion-body myositis (sIBM). The review provides an update on the main clinical characteristics unique to each subset, including fundamental aspects on muscle pathology helpful to assure accurate diagnosis, underlying immunopathomechanisms and therapeutic strategies. DM is a complement-mediated microangiopathy leading to destruction of capillaries, distal hypoperfusion and inflammatory cell stress on the perifascicular regions. NAM is an increasingly recognized subacute myopathy triggered by statins, viral infections, cancer or autoimmunity with macrophages as the final effector cells mediating fiber injury. PM and IBM are characterized by cytotoxic CD8-positive T cells which clonally expand in situ and invade MHC-I-expressing muscle fibers. In IBM, in addition to autoimmunity, there is vacuolization and intrafiber accumulation of degenerative and stressor molecules. Pro-inflammatory mediators, such as gamma interferon and interleukin IL1-β, seem to enhance the accumulation of stressor and amyloid-related misfolded proteins. Current therapies using various immunosuppressive and immunomodulating drugs are discussed for PM, DM and NAM, and the principles for effective treatment strategies in IBM are outlined.In this issueInflammatory or necrotizing myopathies, myositides and other acquired myopathies, new insight in 2011Benveniste O et al., Paris, FranceObservations on the classification of the inflammatory myopathiesHilton-Jones D, Oxford, United KingdomPathogenic aspects of dermatomyositis, polymyositis and overlap myositisGherardi RK, Créteil, FranceSporadic inclusion-body myositis: conformational multifactorial aging-related degenerative muscle disease associated with proteasomal and lysosomal inhibition, endoplasmic reticulum stress, and accumulation of amyloid-β42 oligomers and phosphorylated tauAskanas V et al., Los Angeles, USAPathophysiology of inflammatory and autoimmune myopathiesDalakas MC, Athens, GreeceMyositis or dystrophy? Traps and pitfallsBenveniste O et al., Paris, FranceTherapy of polymyositis and dermatomyositisMarie I, Rouen, France