BY DAVID DIAZ; JONATHAN HAVERTY, DO; & JORGE DIAZ, DO
A previously healthy 20-year-old woman presented to the emergency department with three days of bilateral thigh pain. The pain had initially started in a focal area of the anterior aspect of the lower thighs bilaterally. The next day, her pain had progressed to involve a larger area of her thighs, and she noticed redness and swelling in the same area.
She had difficulty walking and bending her legs due to the pain. She said no other muscle groups were involved and she had never experienced this before. The patient had no history of vigorous physical activity or trauma, illicit drug use, recent travel, and insect bites. She had no other symptoms or history other than a recent URI, which had resolved a week earlier.
Her vital signs were unremarkable, and she was well-appearing and in no distress. The anterior aspect of the thighs bilaterally was tender with mild swelling and erythema. Her legs were symmetric, and no joint involvement was apparent. She had intact sensation and pulses distally and only mildly diminished quad strength bilaterally, but the exam was limited due to pain.
On a hunch, a creatine kinase level was ordered and came back with a surprising result of 33,000 U/L. We then ordered a urinalysis, liver panel, CBC, basic metabolic panel, pregnancy test, and urine toxicology screen for drugs of abuse. The urine was described by the lab as clear, yellow, and dipstick positive for moderate heme with only one RBC/HPF.
The liver panel showed an elevated AST (322 U/L), ALT (92 U/L), and LDH (533 U/L) with normal bilirubin levels. The urine toxicology screen was negative. Serum potassium, BUN, and creatinine were normal. The patient was diagnosed with rhabdomyolysis of unknown etiology.
She was admitted, treated with hydration, and monitored for renal function and potassium. The inpatient team ordered a viral panel that was positive for adenovirus and echovirus, which could indicate a recent viral infection (consistent with her previous URI), but no convalescent titers were ordered to confirm this. Her workup for rheumatologic causes, inflammatory myopathies, and endocrinopathies was negative. Rheumatology was consulted and concluded that the cause of rhabdomyolysis was most likely viral myositis.
Her CK levels peaked to 44,100 U/L on her second day of admission, and then declined to less than 10,000 U/L by day four when she was discharged. Her hospital course was uneventful, and she did not develop any severe complications or renal sequelae of rhabdomyolysis.
Rhabdomyolysis is characterized by skeletal muscle breakdown with leakage of muscle contents, including myoglobin, sarcoplasmic elements, and electrolytes into the circulation. (N Engl J Med 2009;361:62:72.) Some of the most common causes of rhabdomyolysis include trauma, immobilization, strenuous exercise, recent surgery, sepsis, hyperthermia, drugs, toxins, metabolic and electrolyte disorders, myopathies, and infections (viral and bacterial). Rhabdomyolysis has many causes, all thought to share a common final pathophysiologic process.
The mechanism of skeletal muscle injury is thought to be secondary to increased intracellular calcium caused by depletion of ATP or by direct injury to the plasma membrane. This increase in intracellular calcium leads to persistent muscle contraction and activation of calcium-dependent proteases and phospholipases that lead to irreparable cellular injury and eventually myocyte necrosis. (N Engl J Med 2009;361:62:72.)
Patients may manifest symptoms as a result of this pathologic process, which include the classic triad of muscle pain, weakness, and dark urine although up to 50 percent of patients may not report any muscular symptoms. (Medicine [Baltimore] 1982;61:141.)
Muscle pain when present is typically noted in the proximal muscle groups such as the thighs and shoulders. (Eur J Intern Med 2007;18:90.) Other clues to the diagnosis include electrolyte abnormalities, acute kidney injury, elevations in the creatine kinase and other muscle enzymes, and urinalysis that is heme-positive but with minimal or absent RBCs.
Diagnosis of rhabdomyolysis is typically made with a history of acute muscular illness with marked elevations in serum CK, typically five times the upper limit of normal with or without characteristic urinary findings. Elevations in serum CK levels are highly variable at presentation, ranging from 1,500 to more than 100,000 U/L, with the mean peak CK typically around 10,000 to 25,000 U/L. (Medicine [Baltimore] 2005;84:377.) Other laboratory values, such as AST, ALT, LDH, aldolase, and uric acid, may also be elevated.
Prompt diagnosis of rhabdomyolysis is critical to identify patients at risk for developing severe complications, including AKI, compartment syndrome, disseminated intravascular coagulation, or severe electrolyte derangements that could lead to cardiac arrhythmias. AKI is one of the most common complications of rhabdomyolysis with a reported incidence ranging from 13 percent to approximately 50 percent of patients. (N Engl J Med 2009;361:62:72.) The incidence of AKI in rhabdomyolysis was noted to be highest in patients who had used illicit drugs, alcohol, or experienced trauma. (Medicine [Baltimore] 2005;84:377.)
The pathophysiological mechanisms responsible for acute kidney injury seen in rhabdomyolysis is thought to be multifactorial including ischemia due to renal vasoconstriction, renal tubular injury caused by myoglobin-induced oxidative injury, and distal tubule obstruction due to precipitation of myoglobin-Tamm-Horsfall protein complexes. Interestingly, the precipitation of the myoglobin-Tamm-Horsfall protein complexes is accelerated by the presence of acidic urine, and myoglobin's nephrotoxic effects are clinically insignificant unless the urine is acidic. (N Engl J Med2009;361:62:72.) The utility of alkalinization of urine for treating rhabdomyolysis-induced AKI is controversial. Nonetheless, the mainstay of treatment for rhabdomyolysis includes aggressive fluid resuscitation to prevent AKI, correction of electrolyte abnormalities, and monitoring for other complications such as compartment syndrome.
Our patient's case was a rather unusual presentation of rhabdomyolysis. She had no history of trauma or strenuous exercise, urine toxicology was negative, and her history did not fit with that of a typical case of rhabdomyolysis. She had no apparent inciting event leading to her diagnosis other than a recent URI, and if it weren't for the chance CK ordered, this case might have been missed.
This case also highlights some important clinical pearls regarding rhabdomyolysis: Presentations of this illness can be highly variable, the inciting event leading to rhabdomyolysis may not always be obvious, and up to 50 percent of cases don't present with the classic triad of muscle pain, weakness, and dark urine. It makes sense to have a high level of suspicion and a low threshold to order a creatine kinase level.
Dr. David Diaz is a fourth-year medical student at the UCSF School of Medicine in San Francisco. Dr. Haverty is a first-year resident in the Hofstra-Northwell Emergency Medicine Residency at the Donald and Barbara Zucker School of Medicine in Hempstead, NY, and Dr. Jorge Diaz is an associate clinical professor of emergency medicine at the David Geffen School of Medicine, UCLA, and an emergency physician at Olive View-UCLA Medical Center in Sylmar, CA.