Inflammatory Muscle Disease

Abstract

The main types of idiopathic inflammatory myopathies (IIM) are dermatomyositis (DM), polymyositis (PM), overlap myositis which includes the anti-synthetase syndrome, immune-mediated necrotizing myopathy (IMNM), and sporadic inclusion body myositis (sIBM). Major clinical and laboratory manifestations of IIMs are proximal muscle weakness, skin manifestations (Gottron’s sign, heliotropic rash, mechanic’s hands, and calcinosis cutis), lung involvement, elevated muscle enzymes, as well as myositis-specific and/or myositis-associated autoantibodies. These autoantibodies can be biomarkers for certain disease features: (a) anti-PM/Scl for interstitial lung disease (ILD), inflammatory arthritis, Raynaud’s phenomenon (RP), mechanic’s hands and overlap manifestations with systemic sclerosis (sclerodactyly, telangiectasias, esophageal reflux disease, subcutaneous edema, puffy hands, and calcinosis); (b) anti-U1snRNP for myositis in the context of mixed connective tissue disease (MCTD); (c) anti-Ku for overlap myositis with other autoimmune systemic diseases; (d) anti-Ro52 frequently co-occur with anti-Jo1 antibodies and connote an increased risk for severe ILD; (e) antibodies to aminoacyl-tRNA synthetases (anti-Jo1, anti-PL7, anti-PL12, anti-OJ, anti-EJ, anti-KS, anti-Zo, anti-SC, anti-JS, and anti-YRS) for the subtype of anti-synthetase syndrome characterized by mechanic’s hands, arthritis, ILD, and RP; (f) anti-SRP (signal recognition particle), for severe muscle and heart involvement; (g) anti-HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) for statin use-related necrotizing myopathy; (h) anti-MDA5 (melanoma differentiation-associated gene 5) for amyopathic myositis with ILD; and (i) anti-cN1A (cytosolic 5′ nucleotidase 1A) for sIBM. Paraneoplastic myositis is characterized by autoantibodies to TIF-1 (transcriptional intermediary factor 1) antigen. In terms of histopathology, DM is characterized by prominent perivascular and perifascicular inflammation, PM by endomysial inflammation, and sIBM by a combination of inflammation and degeneration of muscle fibers with internal rimmed vacuoles. IMNM is considered a macrophage-mediated inflammatory process. Scattered necrotic muscle fibers surrounded by sparse inflammatory cells (predominantly lymphocytes) are characteristic. Endocrine conditions (Cushing’s disease, thyroid dysfunction, and diabetes mellitus) as well as genetic abnormalities (mitochondrial myopathies) induce muscle diseases, which have to be distinguished from IIMs. Furthermore, recently a distinct nosological entity has been described, which encompasses patients who present radiological and/or histological features of interstitial pneumonia along with clinical manifestations that could suggest an autoimmune process but do not meet established criteria for a particular connective tissue disease. These patients are categorized as having interstitial pneumonia with autoimmune features (IPAF). Follow-up of these patients is necessary for possible evolution to a definite autoimmune disease.