What Causes Rhabdomyolysis?

Patient Presentation
A 6-year-old male came to the emergency room with rhinorrhea, fever, and malaise. He also had muscle aches and a cough that were getting worse for 2-3 days. Schoolmates had had similar problems. The past medical history was non-contributory. The pertinent physical exam showed an ill-appearing male with temperature of 101.8 degrees, and normal vital signs. Growth parameters were 25-50%. HEENT showed clear rhinorrhea and an erythematous pharynx. Chest showed some crackles at the right base. Heart had a normal S1, S2 without murmur. Abdomen was mildly tender diffusely that appeared more muscular. There was no hepatosplenomegaly or masses. Muscles were diffusely tender. There was no rash.

The laboratory evaluation included a complete blood count with a white blood count of 12.8 x 1000/mm² and some toxic vacuoles. A rapid strep test and rapid influenza test were negative. The radiologic evaluation of a chest radiograph showed a small infiltrate at the right base. The patient was diagnosed with community-acquired pneumonia but during discharge needed to urinate and produced brown-colored urine. The laboratory evaluation included a urinalysis that showed a specific gravity of 1.020, significant protein and no red blood cells. His liver function tests, protein and albumin were normal. Electrolytes were normal except for a potassium of 4.7 mg/dl, BUN of 35 mg/dl and creatinine of 2.1 mg/dl. His creatine kinase was 8735 U/L and the diagnosis of rhabdomyolysis was made. Over the next 12 hours, he was aggressively treated with intravenous fluids with bicarbonate, but developed oliguria. He also became more tachypnea and required oxygen, but did not develop any arrhythmias. He was started on ceftriaxone and azithromycin to treat for possible staphylococcus, streptococcus and mycoplasma. He then developed a pericardial effusion and was transferred to the intensive care unit. During his hospital stay he was diagnosed with Mycoplasma pneumoniae based upon polymerase chain reaction and IgM antibodies. His clinical course included developing pericarditis, myocarditis, oliguria without renal failure and hemolytic anemia in addition to the rhabdomyolysis. He recovered and was doing well 2 years later.

Discussion
Rhabdomyolysis was first described in 1881, and in 1941 a case series of crush victims from the Battle of Britain described rhabdomyolysis and subsequent acute renal failure.

Injury to the skeletal muscle that results in leakage of the intracellular content into the plasma defines rhabdomyolysis or literally the dissolution of the skeletal muscle. Causes of the initial injury are numerous (see below). Rhabdomyolysis in adults is classically described by muscle weakness, myalgia and dark urine. But this triad is not common in children. In a 2005 study of 210 children, 45% had myalgia, 38% had muscle weakness, and 3.6% had dark urine. Only 1 patient had all 3 symptoms. Other signs and symptoms include fever, nausea, emesis, abdominal tenderness and decreased reflexes.

Laboratory testing for rhabdomyolysis includes creatine kinase (CK) which usually rises within 12 hours, peaks at 24-36 hours and then decreases 35-40% per day. Therefore levels that are not decreasing after the appropriate time indicate continued insult. The peak CK may be predictive of acute renal failure. Urine myoglobin may be helpful when hematuria co-exists but is not as reliable as CK.

Treatment of the underlying cause is obviously important. Aggressive hydration with initial bolus hydration and then 2-3 times maintenance is usually recommended. Intravenous fluid with sodium bicarbonate to alkalinize the urine is often used. Mannitol may also be used for diuresis. Consultations with nephrology, genetics, rheumatology, surgery, critical care, and others can assist in managing the insult and the treatment of rhabdomyolysis. Dialysis is used to treat acute renal failure. Electrolyte abnormalities including hyperphosphatemia, hyperkalemia, hypocalcemia, hyperuricemia, hypoalbuminemia must be aggressive monitored for and managed. Other complications include disseminated intravascular coagulation, cardiac abnormalities, seizures and death.

Learning Point
The list of causes of rhabdomyolysis is extensive. In the pediatric population common causes are viral (especially Influenza A and B), trauma and connective tissue disease.
Causes of rhabdomyolysis include:

• Infectious
  • Bacterial
    • Bacillus cereus
    • Borrelia burgdorferi
    • Clostridium perfringens
    • Clostridium tetani
    • Francisella tularensis
    • Escherichia coli
    • Legionella
    • Leptospira
    • Mycoplasma
    • Staphylococcus epidermidis
    • Streptococcus
    • Salmonella
    • Vibrio family
  • Fungal
    • Aspergillus
    • Candida
  • Viral
    • Adenovirus
    • Cytomegalovirus
    • Echovirus
    • Epstein-Barr virus
    • Herpes family
    • Human immunodeficiency virus
    • Influenza A
    • Influenza B
    • Parainfluenza
    • West Nile virus
  • Parasite
    • Plasmodium
    • Rickettsia
  • Pyomyositis
  • Sepsis