Myopathies inflammatory

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

The myopathy associated with chronic alcohol abuse has also been associated with increased free-radical activity (Martin and Peters, 1985) as have various other toxicity syndromes affecting muscle, such as cocaine toxity (Kloss et al., 1983). Little work appears to have been undertaken on the possible role of free radicals in the inflammatory myopathies, although, by analogy with other inflammatory disorders, this is likely to be an area worthy of further study. 

Human creatine kinase -MM MAK33 IgGl Cardiac disease, mitochondrial disorders, inflammatory myopathies, myasthenia, polymyositis, McArdle s disease, NMJ disorders, muscular dystrophy, ALS, hypo and hyperthyroid disorders, central core disease, acid maltase deficiency, myoglobinuria, rhabdomyolysis, motor neuron diseases, A. thaliana A. thaliana 2S2 seed storage protein SP + 0.02-0.4% TSP of fresh leaf extract (10-12% TSP of intercellular fluid) 52... 

Miller, F.W., Inflammatory Myopathies Polymyositis, Dermatomyositis, and Related Conditions, in Arthritis and Allied Conditions —A Textbook of Rheumatology (15th Edition), Koopman, W. and Moreland, L., Eds., 2004 chap. 75 (volume 2), ppl593-1620. 

Pain, muscular weakness, cramps and ease of fatigue are the most usual symptoms of muscular disease. In most cases, it is diseases of the vascular or nervous system or problems with the processes providing energy within the muscle that are responsible for clinical problems with muscles. Other clinical problems include the muscular dystrophies, myotonic disorders, inflammatory myopathies and disorders of neuromuscular transmission (see Walton, 1996). The best known is Duchenne muscular dystrophy. 

Unlabeled Uses Treatment of biliary cirrhosis, chronic acfive hepatitis, glomerulonephritis, inflammatory bowel disease, inflammatory myopathy, multiple sclerosis, myasthenia gravis, nephrotic syndrome, pemphigoid, pemphigus, polymyositis, systemic lupus erythematosus... 

The effectiveness of immunosuppressive drugs in autoimmune disorders varies widely. Nonetheless, with immunosuppressive therapy, remissions can be obtained in many instances of autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, type 1 diabetes, Hashimoto s thyroiditis, and temporal arteritis. Improvement is also often seen in patients with systemic lupus erythematosus, acute glomerulonephritis, acquired factor VIII inhibitors (antibodies), rheumatoid arthritis, inflammatory myopathy, scleroderma, and certain other autoimmune states. 

An 87-year-old man developed progressive proximal limb weakness 1 year after starting leuprolide therapy for prostate cancer (60). Electromyography showed a moderately severe non-inflammatory myopathy without evidence of fiber necrosis or associated biochemical changes. Within 6 months after stopping leuprolide he was able to resume his usual activities. 

Clinical Use. Azathioprine (Imuran) is a cytotoxic agent that is structurally and functionally similar to certain anticancer drugs, such as mercaptopurine.22,30 Azathioprine is primarily used to prevent the rejection of transplanted organs, especially in patients with kidney transplants. Azathioprine may also be used to suppress immune responses in a wide range of other conditions, such as systemic lupus erythematosus, dermatomyositis, inflammatory myopathy, hepatic disease, myasthenia gravis, and ulcerative colitis. As presented in Chapter 16, azathioprine is also used as an antiarthritic disease-modifying agent. 

Similar serum enzyme elevations are found in polymyositis (A3, B4a, B20, D2, D17, E5, H7, KIO, M15, M18, Pl, P4, P5, P7, R15, S15, S26, T8, W12, W19), a nonspecific inflammatory myopathy sometimes associated with neoplastic disease but in general related to the collagen diseases and likewise responsive to corticosteroid therapy. The condition occurs at all ages in both sexes, may be acute or insidious with perhaps a normal erythrocyte sedimentation rate, may or may not be painful, or may be accompanied by an erythematous rash (dermatomyositis). Characteristically the earliest appearance of weakness is in the muscles of the pelvic... 

A previously healthy 63-year-old man, who had taken quinidine gluconate 972 mg/day for 9 months, developed diffuse edematous erythema on the extensive surfaces of the hands, arms, and face, with marked accentuation over the joints. His nail-fold capillaries were dilated and the shoulder abductors were shghtly weak. His erythrocyte sedimentation rate was shghtly raised (29 mm/hour) and there was a positive ANA titer (1 640) with a speckled pattern. There were no antibodies to Sm, ribonucleoprotein, SSA or SSB antigens, or histones. There was no evidence of inflammatory myopathy on electromyography, and a skin biopsy showed a mild, superficial, perivascular, lymphocytic inflammation with positive direct immunofluorescence for IgG and IgM at the dermoepidermal junction. There was no evidence of malignancy. All these abnormalities resolved rapidly after quinidine withdrawal. 

Myositis, autoimmune. Rare systemic inflammatory myopathies, including primary polymyositis, primary dermatomyositis, myositis associated with malignancy, childhood dermatomyositis, and myositis with multisystem autoimmune disease (e.g. mixed connective tissue disease, systemic sclerosis). Autoantibodies against aminoacyl-tRNA synthetases (e.g. anti-Jo-1), signal recognition particle (e.g. anti-SRP54), nuclear helicase (anti-Mi-2), tRNA and tRNA-protein complexes (e.g. anti-Mas), and translation factor (anti-KJ) have been described as myositis specific. 

Rider LG, Artlett CM, Foster CB, Ahmed A, Neeman T, Chanock SJ, Jimenez SA, Miller FW, for the Childhood Myositis Heterogeneity Collaborative Study Group (2000) Polymorphisms in the IL-1 receptor antagonist gene VNTR are responsible risk factors for juvenile idiopathic inflammatory myopathies. Clin Exp Immunol, 121 47-52. 

A variety of debilitating diseases, such as rheumatoid arthritis, inflammatory myopathies, cancers, and a variety of immunological diseases are treated with the classic synthetic glucocorticoids, dexamethasone, and prednisone. However, long-term treatment with these drugs often leads to serious side effects such as fat redistribution, diabetes, vascular necrosis, and osteoporosis. There is currently an intense effort to identify new small molecules that are able to differentially modulate GR to retain the beneficial effects of glucocorticoids and reduce the incidence of unwanted side effects [10]. 

Dalakas, M.C. Retroviruses and Inflammatory Myopathies in Humans and Primates. 

Musculoskeletal A toxic non-inflammatory myopathy has been attributed to mesala-zine [101 ]. 

Lee CS, Chen TL, Tzen CY, et al. Idiopathic inflammatory myopathy with diffuse alveolar damage. CUn Rheumatol 2002 21 391 396. 

The idiopathic inflammatory myopathies are rare with a frequency of 6 to 10 per million population (223). DM is the most common at all ages, affecting both children and adults and women more than men. PM is usually encountered after the second decade (223). The clinical and serological expression of these myopathies varies considerably according to ethnicity. Pulmonary complications result from both direct and indirect injury, with respiratory muscle dysfunction and ILD, the most frequent specific manifestations (Table 1) (1,2,223,225). Lung involvement is frequent in PM/DM and is increasingly recognized as a frequent source of morbidity and the major cause of mortality (26,226-230). 

Table 3 Main Antibodies Associated with Idiopathic Inflammatory Myopathies s s... 

Symptomatic ILD significantly shortens survival in patients with inflammatory myopathies, whereas asymptomatic ILD does not (26). In a case series of 70 patients with PM/DM-ILD, survival was 85.8%, 74.4%, and 60.4% at one, three, and five years, respectively (237), with similar findings subsequently reported (234). Deaths are mainly lung related (234,237). However, mortality ranges from 50% to 100% in patients with acute ILD despite intensive immunosuppression (24-26,228,234,241,253). Mortality is higher with an acute presentation, neutrophilic alveolitis, an initial FVC <60%, or DLco <45%, but does not vary with anti-Jo 1 antibody status (228,234,241,253). In Asian studies, ILD is more refractory to therapy and outcome is worse in DM than in PM, and most importantly, in CADM (26,256). Complete resolution of ILD may occur with underlying OP or NSIP (23,234) and, surprisingly, in a patient with UIP (234). Resolution is observed in 19%, improvement in 56%, and deterioration in 25% (234). Relapses may occur when treatment is tapered (23,234,239). 

Troyanov Y, Targoff IN, Tremblay JL, et al. Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies analysis of 100 French Canadian patients. Medicine (Baltimore) 2005 84 231-249. 

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