Ms. M, aged 25, complained of red-tinged urine and severe swelling and pain in both thighs. One week earlier, she had participated in an aerobic “spinning” class. The room was air-conditioned, and she reported drinking about 750 cc of water during the 40-minute class. The next day, Ms. M noted severe pain in both thighs accompanied by swelling and bruising. Ibuprofen brought minimal relief. Five days later, her urine was reddish-brown.
Ms. M said she usually ran one to two miles once or twice weekly. She denied any history of severe myalgias or hematuria. No fever, rash, or arthralgias had preceded her current symptoms. Her medical history was negative. Except for the ibuprofen, she was taking no medications or supplements, including oral contraceptives, and she had no allergies. She denied tobacco or drug use and said she drank alcohol only occasionally.
1. EXAMINATION FINDINGS
Physical examination was unremarkable except for her significantly swollen thighs: Mid-thigh circumference was 52 cm on the left and 49 cm on the right. Both knees were swollen, the left more than the right, with normal patellar movement and no effusion. Active and passive ranges of motion in both hip and knee joints were restricted. Examination of her other joints was unremarkable. She was neurovascularly intact proximally and distally in the bilateral lower extremities, and she had 5/5 strength in the hip flexors and knee extensors.
2. LAB RESULTS
Pertinent laboratory results appear in Table 1. Ms. M also had 3+ blood on urine dipstick, with 2-3 RBCs per high-power field. Her serum myoglobin was 577 ng/mL (reference 25-58). A thyroid-stimulating hormone level was within normal limits. Urine toxicology screen and a pregnancy test were negative. Tests for syphilis and HIV were negative.
An x-ray of Ms. M’s knees demonstrated no bony abnormalities, acute fracture, or suprapatellar effusion. Venous Doppler ultrasound of the lower extremities revealed no thrombi. MRI of both thighs without contrast demonstrated increased T2 signal in both quadriceps muscles, consistent with myositis.
Elevated creatine kinase (CK), myoglobin, liver enzymes, and lactate dehydrogenase (LDH) pointed to rhabdomyolysis.
Rhabdomyolysis refers to the phenomenon of striated muscle necrosis, with release of intracellular pigments (i.e., myoglobin) and intracellular ions (i.e., potassium and phosphate anions) into the circulation. The major adverse clinical sequela of rhabdomyolysis is acute renal failure from pigment-induced injury.
The most common causes of rhabdomyolysis include prescription drugs (e.g., statins, antiretroviral medications, anti-psychotic medications) and illicit drugs (e.g., cocaine, PCP). Major trauma (especially involving crush injuries), seizures, and prolonged immobilization can also result in rhabdomyolysis.
Less common causes include congenital myopathies (e.g., Duchenne’s muscular dystrophy), metabolic myopathies (e.g., disorders of glycogenolysis, glycolysis, or lipid metabolism), and autoimmune myopathies (e.g., polymyositis). Rhabdomyolysis may also result from infection, endocrinopathies (i.e., hyperthyroidism), electrolyte disturbances (e.g., hypokalemia), hyperthermia, hypothermia, and heavy physical exertion.
Exertional nontraumatic rhabdomyolysis, such as Ms. M had, is a rare, but reported, phenomenon most often described in marathon participants or military recruits in basic training. Risk factors include lack of prior fitness training, sickle cell trait, dehydration, heat stress, and the concomitant use of drugs that increase risk of rhabdomyolysis (e.g., sympathomimetics).
Classic symptoms of rhabdomyolysis include weakness, myalgia, and gross hematuria. The most frequently involved muscles are those of the calves and lower back. General manifestations include fever, tachycardia, nausea, and vomiting. Other clinical manifestations depend on the etiology and include the adverse effects of the metabolic complications of rhabdomyolysis (e.g., fluid overload from renal failure or cardiac conduction abnormalities from electrolyte disturbances).
Rhabdomyolysis is usually suggested by the history and physical exam, although a high degree of clinical suspicion is necessary in cases such as Ms. M’s, which can be confused with delayed-onset muscle soreness. The most sensitive indicator of muscle injury is an elevation in CK, specifically the MM fraction; the degree of CK elevation is also prognostic, correlating with risk of developing renal failure. Other markers include aldolase, LDH, and aspartate aminotransferase. Serum and urine myoglobin are also elevated.
The gross hematuria observed in rhabdomyolysis is due to myoglobinuria. The classic finding is blood on urine dipstick with no concomitant microhematuria.
Diagnosis of the underlying condition is based on the history and physical exam. Metabolic conditions should be considered in patients with a history of recurrent rhabdomyolysis or excessive exertional muscle soreness since childhood.
Treatment is supportive and focuses on underlying causes. Aggressive hydration is essential to maintain adequate urine output and prevent pigment-induced injury to the renal tubules. Because myoglobin crystallizes in acidic environments, alkalinization of the urine has been advocated to prevent pigment deposition; similarly, forced diuresis with mannitol has been used to ensure adequate urine output. While no data suggest a benefit to either approach, a recent review did show a trend toward improved renal outcomes in patients with CK >30,000 units/L who were given bicarbonate.
In the majority of individuals who are able to handle high volumes and flow rates of fluid, aggressive administration of crystalloid (either normal saline or lactated Ringer’s) will likely prevent renal failure. In debilitated patients or patients with severe rhabdomyolysis, consider using bicarbonate to protect kidney function.
Ms. M was started on IV hydration with lactated Ringer’s at a rate of 200 cc/hr. By hospital day 2, her gross hematuria had resolved, and she was able to ambulate without significant pain. At the time of discharge on day 3, her mid-thigh circumference was 47 cm on the left and 46 cm on the right. She had full active and passive range of motion in the right hip and both knees, with only slightly restricted range of hip flexion on the left side.
The likelihood of recurrence in this patient is unclear. No specific measures have been shown to prevent exertional rhabdomyolysis, although proper fitness training and avoiding dehydration and heat stress are likely to be beneficial.
Dr. Harper is an intern at the University of Washington School of Medicine in Seattle, and Dr. Wong is an attending in internal medicine at New York-Presbyterian Hospital-Columbia in New York City.
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