A Woman With Muscle Pains and Dark Urine

An 18-year-old woman presented with acute renal failure. She had been at a church youth function at which the activities required running. She subsequently suffered exhaustion and muscle cramps. Later that night the cramping became severe, and her urine became dark, which she thought was from blood, and she was taken to the hospital. She denied similar episodes in the past but did recall a long history of exercise intolerance with severe cramping. Exercise also caused shortness of breath, and she had been diagnosed with asthma as a child. She had not engaged in much physical activity since then.

Current medications included phenergan and an unnamed over-the-counter decongestant. Social history was negative for tobacco or drug use. She lived with her parents, and her family history was negative for neurologic diseases.

Physical examination revealed an obese girl whose general examination was unremarkable. Higher cortical function and cranial nerve testing were normal. Motor examination showed profound weakness of 2/5 throughout. She complained of severe pain with passive movements of the extremities. Sensory examination was normal. Reflexes were 1+ in the arms and knees, 2+ in the ankles; they were symmetrical.

What is the Differential Diagnosis?

This patient presented with a severe paralyzing illness and diffuse muscle pains. The pigmenturia is against a disorder of neuromuscular transmission. Neuropathies, such as Guillain–Barré syndrome, can present with pain, severe weakness, and areflexia, but this patient had normal reflexes. Another possibility is porphyria, which presents in a similar manner to Guillain–Barré syndrome but with pigmenturia. The muscle pain with exercise intolerance and normal reflexes are rather atypical for neuropathy and most likely represent primary myopathy.

The symptoms are indicative of rhabdomyolysis, and the history of exercise intolerance is suggestive of a metabolic myopathy, such as in the glycogenosis, including phosphorylase kinase, myophosphorylase, phosphoglycerate mutase, phosphofructokinase, lactate dehydrogenase, and β-enolase deficiencies. Typically, these patients report a history of difficulty with high-intensity exercise such as running. Diseases of fatty acid transport, such as carnitine palmitoyltransferase deficiency, can also present with exercise intolerance but usually only during prolonged exercise or fasting. Sustained exercise intolerance and the ability to perform only brief bursts of exercise are symptoms that help to differentiate this disorder from disorders of glucose metabolism.

Mitochondrial disorders should be considered, as they may present with rhabdomyolysis. The possibility of an inflammatory myopathy seems unlikely given the patient’s long history of exercise intolerance without previous overt muscle weakness, although rhabdomyolysis may be the initial presentation of an inflammatory myopathy. Drug ingestion (including alcohol), thyroid disease, and uremia and electrolyte imbalances are also conditions to consider.

What Diagnostic Testing should be Performed Next?

Her serum creatine kinase (CK) level was elevated at 40,893 IU/L (normal, <200 IU/L); aspartate transaminase was 455 IU/L (normal, 0–40 IU/L); alanine transaminase, 306 IU/L (normal, 30–65 IU/L); creatinine, 9.4 mg/dL (normal, <1.5 mg/dL); and blood urea nitrogen, 102 μg/dL (normal, <20 μg/dL). She therefore required hemodialysis, and this gradually normalized. Testing for thyroid-stimulating hormone, antinuclear antibodies, human immunodeficiency virus, and hepatitis A, B, and C were all negative. Her urinalysis showed dark urine ( Fig. 91-1 ) that was positive for “blood,” but had only eight RBCs. However, a test for myoglobin in the urine was positive.

An exercise test was not performed.

What is Rhabdomyolysis?

She was diagnosed as having rhabdomyolysis , a term that means destruction of skeletal muscle, and this is caused by a variety of mechanisms, such as trauma, toxins, infections, or metabolic derangements ( Table 91-1 ).

Table 91-1

Causes of Myoglobinuria

Modified from Bertorini TE. Myoglobinuria, malignant hyperthermia, neuroleptic malignant syndrome and serotonin syndrome. Neurol Clin . 1997;15(3):649–671.

Metabolic exhaustion

Excessive exercise in healthy persons

Seizures, delirium, tetanus, and strychnine

Heat stroke

Cold exposure

Metabolic myopathies, particularly during exercise: carnitine palmityl transferase deficiency, very-long-chain acyl–CoA deficiency, myoadenylate deaminase deficiency, mitochondrial disease, and glycogen storage diseases (phosphorylase, phosphofructokinase, phosphorylase kinase, phosphoglycerate mutase, phosphoglycerate kinase, and lactate dehydrogenase deficiencies)

Malignant hyperthermia

Neuroleptic malignant syndrome, serotonin syndrome

Diabetic acidosis

Ischemic (coma, arterial occlusion)

Trauma (crush syndrome)

High-voltage shock

Myopathies, nonmetabolic

Dystrophinopathies

Infectious myositis (influenza virus, HIV, toxic shock, bacterial infections, e.g., clostridium, legionnaires’ disease)

Autoimmune myositis (dermatomyositis, polymyositis)

Toxins, abuse substances

Alcohol

Lysergic acid diethylamide

Cocaine

Plasmoid

Methadone

Heroin

Phencyclidine

Amphetamines

Envenomations (e.g., wasps, spiders, and snakes)

Cicuta

Haff disease

Medications

Cholesterol-lowering drugs

Hypokalemia-causing drugs (e.g., diuretics, amphotericin B), licorice

Azidothymidine

Salicylate overdose

Azathioprine

Theophylline

Lithium

Epsilon aminocaproic acid

Fluid, electrolyte imbalance

Hypokalemia

Hypernatremia

Hyponatremia

Hypophosphatemia

Hyperosmolar states

Water intoxication

CoA , Coenzyme A; HIV , human immunodeficiency virus.

Rhabdomyolysis leads to leakage of muscle contents including the oxygen-binding protein myoglobin, and thus the terms myoglobinuria and rhabdomyolysis are used interchangeably.

Rhabdomyolysis was apparently recorded first in the Bible in the Book of Numbers, wherein it states that the Israelites became ill after eating quail which had probably fed on hemlock seeds.