What are the pertinent questions to ask a patient with nontraumatic rhabdomyolysis?

Essential History Questions for Nontraumatic Rhabdomyolysis

When evaluating a patient with suspected nontraumatic rhabdomyolysis, immediately inquire about medication use (particularly statins), recent exercise patterns, substance use, and symptoms of muscle injury to identify the underlying cause and guide urgent management. 1, 2

Medication and Supplement History

Prescription Medications

• Ask specifically about statin use (atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin), as these are the most common drug-related cause of rhabdomyolysis, with an incidence of 1.6 per 100,000 patient-years 1, 2
• Inquire about recent dose increases or new statin prescriptions, as risk increases with higher dosages 2
• Ask about concomitant medications that interact with statins through CYP3A4 inhibition or transporter inhibition (BCRP, OATP1B1/OATP1B3, P-gp), including cyclosporine, gemfibrozil, tipranavir plus ritonavir, glecaprevir plus pibrentasvir, azole antifungals, and macrolide antibiotics 2
• Document use of fibrates (particularly gemfibrozil), colchicine, or lipid-modifying doses of niacin (>1 gram/day), as these significantly increase rhabdomyolysis risk when combined with statins 2

Over-the-Counter Products and Supplements

• Ask about dietary supplements associated with rhabdomyolysis risk, including red yeast rice (contains lovastatin), creatine monohydrate, wormwood oil, licorice, and Hydroxycut 1, 3
• Inquire about grapefruit juice consumption, as intake exceeding 1.2 liters daily increases statin-related rhabdomyolysis risk 2
• Document all over-the-counter medications, herbal supplements, and performance-enhancing products 4

Exercise and Physical Activity History

Recent Exercise Patterns

• Ask about novel or unaccustomed exercise, particularly sudden increases in intensity or duration, as exertional rhabdomyolysis commonly follows unaccustomed physical activity 1
• Inquire specifically about the timing of exercise relative to symptom onset, noting that creatine kinase peaks 24-120 hours after the exercise event, not immediately 1
• Document whether the patient recently returned from injury or changed training programs, as transition periods carry higher risk 1
• Ask about dancing, prolonged standing, or other sustained physical activities that may not be perceived as "exercise" but can trigger rhabdomyolysis 5

Environmental Conditions

• Inquire about exercise in hot or humid conditions, as hyperthermia increases rhabdomyolysis risk 6
• Ask about adequate hydration during and after physical activity 3

Substance Use History

Alcohol and Illicit Drugs

• Document alcohol consumption patterns, as alcoholic myopathy is a common cause of nontraumatic rhabdomyolysis 7
• Ask about recreational drug use, including cocaine, methamphetamine, ecstasy (MDMA), ketamine, and heroin, using an open and nonjudgmental approach 4, 7
• For injection drug users, inquire about needle-sharing practices and sources 4

Medical History and Risk Factors

Underlying Medical Conditions

• Ask about hypothyroidism, particularly uncontrolled hypothyroidism, as this is a significant risk factor for statin-induced and other forms of rhabdomyolysis 2
• Document history of renal impairment or chronic kidney disease, which increases rhabdomyolysis risk 2
• Inquire about diabetes mellitus, as this is a patient-specific risk factor 1
• Ask about sickle cell trait or disease, as these patients have unique susceptibility to exertional rhabdomyolysis and impaired ability to concentrate urine 5
• Document history of liver disease or substantial alcohol consumption, as these increase risk of hepatic injury from medications 2

Prior Episodes and Family History

• Ask about previous episodes of rhabdomyolysis, as recurrent episodes suggest an underlying genetic or metabolic disorder 1, 8
• Inquire about childhood history of exercise intolerance, muscle cramps, or early fatigue 1, 8
• Document family history of neuromuscular disorders, metabolic myopathies, or unexplained muscle problems 1, 8
• Ask about family history of malignant hyperthermia or adverse reactions to anesthesia 1

Symptom Characterization

Classic Triad (Present in <10% of Cases)

• Ask about muscle pain (myalgia), particularly in large muscle groups such as thighs, calves, and lower back 9, 8
• Inquire about muscle weakness or difficulty with movement 9, 8
• Ask specifically about dark urine (tea-colored, cola-colored, or brown), which indicates myoglobinuria 9, 8

Associated Symptoms

• Document presence of muscle stiffness, cramping, or tenderness 1
• Ask about severe fatigue beyond what would be expected from the activity level 1
• Inquire about fever or malaise accompanying muscle symptoms 2
• Ask about abdominal pain, nausea, or vomiting 5

Infectious and Inflammatory Triggers

Recent Illnesses

• Ask about recent viral infections, as viral myositis can trigger rhabdomyolysis 1, 7
• Inquire about bacterial infections or sepsis 2, 7
• Document any recent febrile illnesses 7

Vascular and Ischemic Causes

• Ask about symptoms suggesting arterial occlusion or limb ischemia, including sudden onset of severe pain, pallor, pulselessness, or paresthesias 7
• Inquire about prolonged immobilization or compression of muscle groups 10

Metabolic and Endocrine Factors

• Ask about symptoms of electrolyte disorders, including severe dehydration, excessive sweating, or inadequate fluid intake 2
• Document recent major surgery, trauma, sepsis, or shock, as these acute conditions increase risk of renal failure secondary to rhabdomyolysis 2
• Inquire about uncontrolled epilepsy or recent seizures 2, 10

Common Pitfalls to Avoid

• Do not rely solely on the classic triad of myalgia, weakness, and dark urine, as this is present in fewer than 10% of patients with rhabdomyolysis 8
• Do not dismiss mild or atypical symptoms, as rhabdomyolysis can present with variable clinical features 9
• Do not overlook sickle cell trait in African American patients with exertional rhabdomyolysis, as microscopic hematuria may mask underlying myoglobinuria 5
• Do not assume that absence of recent trauma rules out significant muscle injury, as nontraumatic causes are diverse and frequently overlapping 9, 7
• Do not fail to ask about all supplements and over-the-counter products, as patients may not consider these "medications" 1, 3