The major causes of myopathy are drugs, toxins, metabolic disturbances, inflammatory syndromes, endocrinopathies, infections, and muscle dystrophies. I. Toxin and drug-induced myopathy
A. Steroid myopathy. The insidious onset of proximal muscle weakness in a patient on steroids should suggest steroid myopathy. Myopathy can occur while a patient is on low or high doses of steroids, frequently after a recent increase in dose.
The duration of steroid treatment does not correlate with the time of onset. Patients with steroid myopathy frequently have at least two other steroid side effects, such as osteoporosis, cushingoid facies, hyperglycemia, hypertension, or psychiatric disorders. Concomitant hypokalemia is usually not seen. Inflammation is not present.
1. Laboratory studies. Serum muscle enzymes—creatine kinase (CK), aldolase, and aspartate aminotransferase (AST, previously known as SGOT)—are not increased; urinary creatinine excretion, however, is increased.
EMG studies generally are not helpful. Muscle biopsy in patients with Cushing's syndrome has shown predominantly type 2 fiber atrophy, but biopsy in steroid myopathy has yielded conflicting results and has not been helpful.
2. Treatment is to reduce the steroid dose as much as possible or to discontinue the drug.
B. Hypokalemic myopathy. Any drug or pathologic condition causing hypokalemia can cause muscle weakness. Several drugs have been implicated, some with better substantiation than others; those usually implicated are diuretics and cathartics. Hypokalemia can also exacerbate muscle weakness due to other types of myopathies.
1. An acute syndrome of muscle pain, tenderness, and weakness of proximal and axial muscles may be seen. More generalized weakness can also occur.
Serum muscle enzymes are elevated, and muscle biopsy may show vacuolar myopathy, with or without fiber necrosis and regeneration. EMG may show myopathic changes. Reflexes may be depressed or absent.
2. Chronic hypokalemia can result in a painless proximal or generalized myopathy, also with depressed or absent reflexes. As in the acute syndrome, serum muscle enzymes are elevated, and muscle biopsy shows vacuolar myopathy. Diagnosis is based on demonstration of hypokalemia and identification of the offending drug.
3. Treatment is restoration of a normal serum potassium level.
C. Alcoholic myopathy. Alcohol has been shown to be a direct hepatotoxin; proof of its muscle toxicity still rests largely on clinical interpretations. Three types of myopathy are caused by alcohol.
1. Acute. This form presents with cramps and, at times, with fulminant rhabdomyolysis and myoglobinuria, which usually occur together with swelling and tenderness of proximal muscles. Muscle enzymes are markedly elevated. Muscle biopsy shows necrosis and phagocytosis with little regeneration. Recovery occurs with abstinence.
2. Chronic. This form is least common and may occur even in the absence of a history of the acute clinical variety, described in the preceding section. Proximal muscles are weak, atrophied, and mildly tender. Unless alcoholic neuropathy is also present, distal muscle strength remains intact. Muscle enzymes are moderately elevated, and EMG shows myopathic changes. The lower extremities are affected prominently, with both atrophy and tenderness. Histopathologic findings include fiber necrosis, a mild increase in fibrous tissue, focal fat infiltration, a large variability in muscle fiber size, and regeneration of fibers.
3. Subclinical. In this form, muscle enzyme elevation occurs without clinical weakness and may be common in confirmed alcoholics. Diagnosis of alcoholic myopathy is based on the standard tests mentioned previously (enzymes, EMG, and muscle biopsy), but it should be remembered that a coexistent peripheral neuropathy caused by nutritional deficiency or another toxin may be present.
D. Drug-induced rhabdomyolysis and myoglobinuria. Features include severe muscle pain with swelling and tenderness, markedly elevated serum muscle enzymes, and gross (dark red-brown) pigmenturia. The urine is positive by "dipstick" (benzidine or orthotolidine). If hemolysis is suspected, the urine is reddish, the serum is pink, and a low serum haptoglobin is present. Immunoassays and electrophoresis can definitely differentiate hemoglobin and myoglobin and, in doubtful instances, should be performed. Renal failure is the worst consequence of myoglobinemic states. Emphasis from the outset should be placed on maintaining urinary output with furosemide and mannitol, as needed. Other acute laboratory abnormalities are hypocalcemia and hyperkalemia. Several drugs and toxins can induce acute rhabdomyolysis, including cocaine, illicit heroin mixtures, amphetamines, alcohol, some antimalarial drugs, anesthetics, and other drugs that cause hypokalemia. Lipid-lowering agents (e.g., lovastatin and other "statins," gemfibrozil) can also produce this syndrome. Other causes of myoglobinuria include McArdle disease, phosphofructokinase (PFK) deficiency, exertion, crush injury, prolonged pressure, injury during surgery, immobilization resulting from neurologic disorders, ischemia, and malignant hyperthermia syndrome.
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