What are the causes of rhabdomyolysis?

Causes of Rhabdomyolysis

Rhabdomyolysis is caused by a wide variety of conditions that damage skeletal muscle, with the most common causes being medications/toxins, trauma, excessive muscle activity, and metabolic disorders. 1, 2

Major Categories of Causes

1. Medications and Toxins

• Statins: Can cause myopathy and severe rhabdomyolysis, especially at higher doses or when combined with other medications 3
  • Cerivastatin (withdrawn from market) had 16-80 times higher risk of fatal rhabdomyolysis compared to other statins 3
  • Red yeast rice supplements (containing lovastatin) 3
• Illicit drugs: Cocaine is strongly associated with rhabdomyolysis 4
• Other medications:
  • Fibrates (especially when combined with statins)
  • Cyclosporine
  • Macrolide antibiotics
  • Certain antifungal drugs
  • Niacin 3
• Dietary supplements:
  • Wormwood oil
  • Licorice
  • Creatine monohydrate
  • Hydroxycut 3

2. Trauma and Compression

• Direct muscle injury
• Crush injuries
• Prolonged immobilization
• Compartment syndrome
• Surgical procedures (especially with prolonged positioning) 3, 5

3. Excessive Muscle Activity

• Intense exercise
• Seizures
• Status epilepticus
• Delirium tremens 2

4. Metabolic and Endocrine Disorders

• Electrolyte abnormalities (hypokalemia, hypophosphatemia)
• Diabetic ketoacidosis
• Hypothyroidism
• Hyperthyroidism 2

5. Genetic/Inherited Disorders

• Glycogen storage diseases
• Fatty acid oxidation disorders
• Mitochondrial myopathies
• Muscular dystrophies 1, 6, 7

6. Infections

• Viral (influenza, HIV, EBV)
• Bacterial (Legionella, Streptococcus)
• Fungal infections 2, 6

7. Temperature-Related

• Hyperthermia
• Malignant hyperthermia
• Heat stroke
• Hypothermia 2

8. Other Causes

• Ischemia/hypoxia of muscle
• Prolonged seizures
• Alcohol abuse
• Systemic inflammatory conditions 7, 8

Clinical Pearls and Pitfalls

• Multiple factors: In approximately 60% of cases, multiple factors contribute to rhabdomyolysis 8
• Recurrence risk: Highest in patients with underlying genetic muscle disorders (10% of cases) 8
• Diagnostic challenge: Only about half of patients present with the classic triad of myalgias, weakness, and dark urine 6
• Drug interactions: Risk of statin-induced rhabdomyolysis increases significantly when combined with fibrates, particularly gemfibrozil 3
• Compartment syndrome: Consider urgent surgical consultation for fasciotomy if suspected, as benefits decrease significantly if delayed beyond 8 hours 1
• Urine testing limitations: Urine myoglobin testing is positive in only 19% of cases, so a negative test does not exclude rhabdomyolysis 8

Diagnostic Approach

1. Laboratory testing:

   • Serum creatine kinase (CK) >10 times upper limit of normal
   • Urinalysis for myoglobinuria
   • Electrolytes, BUN, creatinine
   • ECG to assess for cardiac complications 1

2. For recurrent cases or suspected genetic causes:

   • Detailed family history
   • Consider genetic panels for metabolic myopathies
   • Muscle biopsy may be indicated 1, 6

Early recognition and aggressive hydration are crucial to prevent acute kidney injury, which occurs in approximately 15-33% of patients with rhabdomyolysis 5, 8.