Idiopathic inflammatory myopathies

Idiopathic inflammatory myopathies (IIMs), except for sporadic inclusion body myositis (sIBM), present with subacute symmetrical weakness of the limb girdle muscles, an elevated serum creatine kinase activity, and inflammatory cells in the muscle biopsy (necrotizing autoimmune myopathy being an exception). In dermatomyositis, additional skin abnormalities are found. IIMs are nowadays subclassified into the following categories: (1) dermatomyositis (DM), including (1a) classic dermatomyositis, which may be associated with connective tissue disorders (CTDs) and malignancy, (1b) juvenile dermatomyositis, and (1c) clinical amyopathic dermatomyositis; (2) polymyositis (PM) encompassing (2a) classical PM and (2b) nonspecific or overlap myositis, associated with CTD; (3) autoimmune necrotizing myopathy, associated with malignancy, statin use and CTD; and (4) sporadic IBM, sometimes associated with CTDs. These conditions result from chronic immune activation after exposure to environmental risk factors in individuals with a predisposing genetic background. A strong association of autoantibodies with distinct clinical phenotypes and prognosis is found in patients with myositis. Inflammatory myopathies, sporadic IBM excluded, are amenable to immunosuppressive and immunomodulation therapies. The prognosis of IIM is not well known since long-term outcome and prognostic factors vary widely. Disease-related mortality rates in PM and DM are at least 10%. In DM mortality is attributed to cancer and pulmonary complications. Juvenile dermatomyositis has a low mortality rate. Because chronic immunosuppressive therapy is associated with significant side-effects, and many patients remain (partially) refractory to treatment, novel therapeutic agents that are safe and effective are needed.