Evaluation of Recurrent Rhabdomyolysis
For patients with recurrent rhabdomyolysis, you must investigate for an underlying genetic or metabolic muscle disorder, as repeated episodes indicate this is not simply an exertional or acquired cause. 1, 2
When to Suspect an Underlying Genetic Disorder
Recurrent episodes are the primary red flag that distinguishes pathologic from physiologic rhabdomyolysis. Specifically investigate for genetic causes when patients present with: 2, 3
- Multiple episodes of rhabdomyolysis (more than one episode warrants investigation) 2
- History of exercise intolerance beyond what is expected for their conditioning level 2, 3
- Positive family history of neuromuscular disorders or unexplained muscle symptoms 2
- Severity of episodes that exceeds the expected response to the exercise or trigger performed 3
- Persistently elevated serum CK between episodes with no identified cause after initial neurological workup 1
Structured Diagnostic Algorithm for Recurrent Cases
Initial Etiology-Specific Testing
Medication and supplement review is mandatory as the first step: 4
- Discontinue statins immediately (particularly those metabolized by CYP3A4) 4
- Stop all dietary supplements including red yeast rice (contains lovastatin), creatine monohydrate, wormwood oil, licorice, and Hydroxycut 4
- Review for drug interactions that increase myopathy risk 4
Genetic and Metabolic Workup
Refer for malignant hyperthermia susceptibility testing in cases of: 1
- Exertional rhabdomyolysis with recurrence 1
- Persistently raised serum CK after neurological evaluation 1
- Idiopathic hyperCKemia 1
Autoimmune evaluation should include: 4, 1
- ANA, ASMA, and ANCA if autoimmune myositis is suspected 4, 1
- Consider referral to neurology specializing in neuromuscular disorders for potential autoimmune myopathy 5
Advanced neuromuscular testing may include: 1
- EMG and MRI to differentiate inflammatory myositis from other causes 1
- Genetic testing for hereditary muscle enzyme defects (metabolic myopathies, mitochondrial disorders) 2, 6
Infectious and Systemic Causes
Viral studies if viral myositis is clinically suspected 4, 1
Endocrine and metabolic screening for: 6
Core Laboratory Monitoring During Evaluation
Serial measurements should track: 4, 1
- Creatine kinase (CK) levels - the diagnostic gold standard 7, 8
- Complete electrolyte panel (potassium, calcium, phosphorus, magnesium) to assess for hyperkalemia and other abnormalities 4, 1
- Renal function tests (BUN, creatinine) to monitor for acute kidney injury 1
- Serum myoglobin (prognostic gold standard, though shorter half-life than CK) 1, 7
Urinalysis looking for: 4
Additional testing based on severity: 4, 1
- Liver function tests to assess hepatic involvement 4, 1
- Coagulation studies to evaluate for disseminated intravascular coagulation 4, 1
- Arterial blood gas for metabolic acidosis in severe cases 4, 1
- ECG and cardiac troponin to rule out cardiac involvement 1
Critical Pitfalls to Avoid
Do not dismiss recurrent episodes as simply "overtraining" - this pattern demands genetic investigation even in athletes. 2, 3
Do not restart statins without completing the genetic workup, as statin-associated autoimmune myopathy can persist even after drug discontinuation. 4, 5
Do not overlook SLCO1B1 gene mutations which increase statin-induced rhabdomyolysis risk and may guide future medication decisions. 4
Monitor for compartment syndrome in any acute episode with early signs of pain, tension, paresthesia, and paresis (late signs of pulselessness and pallor indicate irreversible damage). 4, 1
Risk Stratification for Acute Kidney Injury
Patients with CK >16,000 IU/L have significantly increased risk of acute renal failure. 2
In crush syndrome cases, CK >75,000 IU/L is associated with >80% risk of acute kidney injury. 1
Mortality rate is approximately 10% overall but significantly higher with acute renal failure. 2