Pathophysiology of inflammatory and autoimmune myopathies

The 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 issue

Inflammatory or necrotizing myopathies, myositides and other acquired myopathies, new insight in 2011

Benveniste O et al., Paris, France

Observations on the classification of the inflammatory myopathies

Hilton-Jones D, Oxford, United Kingdom

Pathogenic aspects of dermatomyositis, polymyositis and overlap myositis

Gherardi RK, Créteil, France

Sporadic 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 tau

Askanas V et al., Los Angeles, USA

Pathophysiology of inflammatory and autoimmune myopathies

Dalakas MC, Athens, Greece

Myositis or dystrophy? Traps and pitfalls

Benveniste O et al., Paris, France

Therapy of polymyositis and dermatomyositis

Marie I, Rouen, France