Toxic myopathies

Genetic testing

NCV/EMG

Laboratory

Imaging

Biopsy

-

+++

+

+

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Fig. 28. Steroid-induced myopathy. A Proximal leg atrophy in a patient with chronic steroid use. B Fat redistribution around the upper torso and neck

Distribution/anatomy

Time course Onset/age

Clinical syndrome

Usually proximal muscles are involved, although in severe necrotizing myopathies with rhabdomyolysis, all muscles may be affected

The time course is variable, depending on the type of toxic agent Can occur at any age

There is appearance of neuromuscular symptoms after exposure to a specific medication or toxin. There may be an acute episode, with rhabdomyolysis or the disorder may develop over months. The clinical presentations include a focal myopathy, acute painful or painless weakness, chronic painful or painless weakness, myalgia alone, or CK elevation alone. In severe cases, toxic myopathy may be associated with myoglobinuria, inflammation of the muscle, muscle tenderness and myalgia. In cases of mitochondrial or vacuolar damage, the myalgia is usually painless. Steroids cause type 2 fiber atrophy that is painless (Fig. 28). Necrotic myopathies may be due to acute alcohol exposure, amiodarone, chloroquine, cocaine, emetine, clofibrate, heroin, combined neuromuscular blocking agents and steroids, perhexilline, and statins (HMG CoA reductase inhibitors). Other causes of muscle injury in necrotic myopathies include crush injuries occurring in comatose or motionless patients who are taking drugs for addiction. In cocaine-induced myopathy there may be ischemia or impaired oxidative phosphorylation. In the vacuolar myopathies there is accumulation of autophagic (lysosomal) vacuoles. This type of toxic myopathy is observed with amiodarone, chloroquine, colchicine, and vincris-

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Fig. 29. Necrotizing alcoholic myopathy showing degenerating fibers (arrow), and regenerating fibers (arrow head)

Fig. 30. Colchicine myopathy. Empty vacuoles are observed throughout the muscle, but with no inflammation tine. The second type of vacuolar myopathy is seen with hypokalemic agents including thiazides, and amphotericin B. Mitochondrial defects are seen with anti-HIV agents that inhibit nucleoside or nucleotide reverse transcriptase and deplete mitochondrial DNA. The resulting accumulation of abnormal mitochondria results in formation of "ragged red fibers". Zidovudine (AZT) is associated with mitochondrial changes, and sometimes with inflammation. Type 2 atrophy is absorbed in steroid myopathy. Chronic alcohol use is also associated with similar changes. Another type of toxic myopathy, is the inflammatory toxic myopathy - these have similar clinical features to dermatomyo-sitis. Typically D-penicillamine is associated with an inflammatory myopathy. A perivascular inflammation may be observed with phenytoin, procainamide, hydralazine, L-dopa, and streptokinase. Eosinophilic myositis and fasciitis associated with L-tryptophan is probably due to an allergic reaction.

A range of mechanisms lead to necrosis in toxic myopathies including damage Pathogenesis to the muscle membrane, the presumed cause of myopathy observed with statin drugs. Other causes of muscle injury in necrotic myopathies include crush injuries occurring in comatose or motionless patients, particularly taking drugs of addiction, and ischemia/impaired oxidative phosphorylation - as might be observed in cocaine-induced myopathy.

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