The serum CK concentration may be elevated or normal. The muscle biopsy shows elements of both myopathic and neuropathic disease, with the special feature in muscle of rimmed vacuoles on the Gomori trichrome stain that are more central in the muscle fibers than those seen with inclusion body myositis. The mechanism of the muscle damage is unknown but is probably attributable to the drug’s interference with tubulin, a protein required for the polymerization of microtubules in muscle and nerve. Weakness resolves in a matter of days or weeks when the drug is discontinued, but the neuropathic features may remain.
Other drugs that cannot be compactly summarized but may produce a toxic myopathy or neuromyopathy include amiodarone, chloroquine, and hydroxychloroquine as mentioned in Chap. 41.
Alcohol Myopathy (See Also Chap. 41)
Several forms of muscle weakness have been ascribed to alcoholism. In one type, a painless and predominantly proximal weakness develops over a period of several days or weeks in the course of a prolonged drinking bout and is associated with severe degrees of hypokalemia (serum levels <2 mEq/L). The urinary excretion of potassium is not significantly increased, and depletion is probably the result of vomiting and diarrhea. In addition, serum levels of liver and muscle enzymes are markedly elevated. Biopsies from severely weakened muscles show single-fiber necrosis and vacuolation. Treatment consists of the administration of potassium chloride intravenously (about 120 mEq daily for several days), after which oral administration suffices. Strength returns gradually in 7 to 14 days, and enzyme levels return to normal concomitantly.
A more dramatic myopathic syndrome, occurring acutely at the height of a prolonged drinking bout and appropriately termed acute alcoholic myopathy, is manifest by severe pain, tenderness, and edema of the muscles of the limbs and trunk, accompanied in severe cases by renal damage (see Hed et al). Hypokalemia is not implicated. The myonecrosis is generalized in some patients, and remarkably focal in others. A swollen, painful, tender limb or part of a limb may give the appearance of a deep venous thrombosis or lymphatic obstruction. Myonecrosis is reflected by high serum levels of CK and aldolase and the appearance of myoglobin in the urine, leading in the most severe cases to fatal myoglobinuric renal failure. Indeed, in a general hospital, alcoholism is one of the most common causes of rhabdomyolysis and myoglobinuria, rivaled only by status epilepticus and trauma. Some patients recover within a few weeks, but others require several months, and relapse during another drinking spree occurs frequently. Restoration of motor power occurs with muscle regeneration but may be hindered by polyneuropathy and other syndromes of neuromuscular disability associated with alcoholism. Haller and Drachman have produced rhabdomyolysis in rats by subjecting the animals to a brief fast following a 2to 4-week exposure to alcohol, suggesting that a similar mechanism may be operative in alcoholic individuals.
Perkoff and his associates described what is presumably a third form of acute muscular disorder in alcoholics, characterized by severe muscular cramps and diffuse weakness in the course of a sustained drinking bout. They noted a number of biochemical abnormalities in these patients, as well as in asymptomatic alcoholics who had been drinking heavily for a sustained period before admission to the hospital: elevated serum levels of CK, myoglobinuria, and a diminished rise in blood lactic acid in response to ischemic exercise. The status of this syndrome and its relation to the conventional acute alcoholic myopathy are unclear to us.