What is the treatment for rhabdomyolysis (rhabdo) or inflammatory myopathy?

Treatment of Rhabdomyolysis vs Inflammatory Myopathy

The treatment approach fundamentally differs between rhabdomyolysis and inflammatory myopathy: rhabdomyolysis requires immediate aggressive fluid resuscitation (≥12L daily) to prevent acute kidney injury and correct life-threatening electrolyte abnormalities, while inflammatory myopathy demands immunosuppressive therapy with corticosteroids as the cornerstone of treatment. 1, 2

Distinguishing Between the Two Conditions

Rhabdomyolysis Presentation

• Muscle pain, weakness, and dark urine (myoglobinuria) with CK elevation >5 times upper limit of normal (typically >1,000 IU/L, often >10,000 IU/L in severe cases) 1, 3
• Urinalysis shows brown/cloudy urine positive for blood without RBCs, indicating myoglobinuria 1
• Acute onset following identifiable triggers: trauma/crush injury, extreme exertion, medications (especially statins), toxins, prolonged immobilization, or heat exposure 1, 3
• Hyperkalemia, hyperphosphatemia, hypocalcemia, and metabolic acidosis are common 1, 3

Inflammatory Myopathy Presentation

• Progressive proximal muscle weakness (difficulty standing, lifting arms) with or without pain, developing over weeks to months 2
• CK elevation is present but weakness is the dominant feature, not acute pain 2
• Autoantibodies may be positive (ANA, anti-Jo-1, anti-SRP, anti-Mi-2) 2, 4
• EMG shows myopathic changes; muscle biopsy demonstrates inflammatory infiltrates 2
• Extramuscular manifestations may include interstitial lung disease, characteristic rashes (in dermatomyositis), or mechanic's hands 2

Critical pitfall: Inflammatory myopathy can present with severe rhabdomyolysis and renal failure, creating diagnostic confusion. If CK remains persistently elevated despite adequate fluid resuscitation, or if weakness predominates over pain, screen with ANA and ESR to identify underlying autoimmune myopathy. 4

Treatment of Rhabdomyolysis

Immediate Management (First 24 Hours)

1. Aggressive Intravenous Fluid Resuscitation

• Initiate immediately with ≥12L daily of isotonic crystalloid (normal saline or lactated Ringer's) to achieve urine output of 300 mL/hour 1, 5
• For severe rhabdomyolysis (CK >15,000 IU/L): administer >6L fluid resuscitation 1
• For moderate cases: 3-6L per day is typically sufficient 1
• Early fluid resuscitation is critical—delayed treatment significantly increases acute kidney injury risk 1, 6
• This aggressive regimen results in large positive fluid balance, which is well tolerated in young, carefully monitored patients 5

2. Discontinue Causative Agents

• Immediately stop statins, NSAIDs, and any implicated medications or supplements (red yeast rice, creatine monohydrate, wormwood oil, licorice, Hydroxycut) 1, 2
• Avoid succinylcholine in perioperative settings 1

3. Electrolyte Management

• Monitor potassium closely and correct hyperkalemia emergently (can cause life-threatening cardiac arrhythmias) 1, 3
• Perform serial electrolyte measurements including calcium, phosphorus, and magnesium 1
• Obtain arterial blood gas to assess for metabolic acidosis 1

4. Compartment Syndrome Surveillance

• Monitor for pain, tension, paresthesia, paresis (early signs); pulselessness and pallor indicate irreversible damage 1
• Perform early fasciotomy if compartment pressure >30 mmHg or differential pressure (diastolic BP - compartment pressure) <30 mmHg 1

Therapies NOT Recommended

• Bicarbonate administration does not improve outcomes and is conditionally recommended against 6
• Mannitol does not reduce acute renal failure or dialysis need and is conditionally recommended against 6
• Loop diuretics lack strong evidence for benefit 3

Pain Management

• Acetaminophen 500-1000 mg is the preferred first-line analgesic (onset 15-30 minutes, maximum 4-6 grams daily) to avoid nephrotoxic NSAIDs 1
• Avoid all NSAIDs (ibuprofen, naproxen, diclofenac, ketorolac) due to renal toxicity in patients already at high AKI risk 1
• For severe pain unresponsive to acetaminophen: use opioids (oral morphine 20-40 mg for opioid-naive patients) 1
• If GFR <30 mL/min: fentanyl or buprenorphine are safest opioid choices 1

Monitoring and Disposition

• Repeat CK, creatinine, electrolytes, and urinalysis every 6-12 hours until CK trending downward 1, 3
• Cardiac monitoring with ECG and troponin if severe rhabdomyolysis (to detect cardiac involvement) 1
• Most patients require hospital admission; consider discharge only if CK <5,000 IU/L, normal renal function, no electrolyte abnormalities, and reliable follow-up 3

Treatment of Inflammatory Myopathy (Polymyositis/Dermatomyositis)

Initial Corticosteroid Therapy

Adults:

• Begin prednisone 1 mg/kg/day (maximum 60-80 mg/day) as monotherapy 2
• Continue high-dose for 2-4 weeks until strength improves and CK normalizes 2
• Taper gradually: reduce by 10-20% of current dose every 2-4 weeks over 6-12 months 2

Children with Juvenile Dermatomyositis:

• Prednisone 2 mg/kg/day (maximum 60 mg/day) 2
• Add subcutaneous methotrexate 15 mg/m² weekly from onset as key component of treatment 2
• Follow consensus taper: reduce by 10-20% every 2-4 weeks once dosage reaches 0.5 mg/kg 2

Severe or Refractory Disease

For life-threatening presentations (severe weakness, dysphagia, respiratory involvement, or rhabdomyolysis):

• IV methylprednisolone 500-1000 mg/day (10-30 mg/kg/day in children) for 1-3 days 2
• IVIG 1 g/kg divided over 1-2 days, repeated monthly for 1-6 months if inadequate response to steroids 2
• Consider plasmapheresis for acute severe disease or poor corticosteroid response 2

Second-Line Immunosuppressive Agents

For steroid-refractory disease or to enable steroid-sparing:

• Methotrexate 7.5-15 mg weekly (oral or subcutaneous) demonstrates equal improvement to cyclosporine with better tolerability 2
• Azathioprine 1-3 mg/kg/day as alternative steroid-sparing agent 2
• Mycophenolate mofetil for maintenance therapy if symptoms persist after 4 weeks 2

For severe interstitial lung disease or refractory myositis:

• Cyclophosphamide 0.6-1.0 g/m² IV every 4 weeks for 3-6 months (occasionally extended to 12 months) 2
• Administer with mesna (40% of cyclophosphamide dose) and aggressive hydration (2-3L within 24 hours) to prevent hemorrhagic cystitis 2
• Monitor white blood cell count at nadir (8-14 days post-infusion) to avoid counts <3.0 x 10⁹/L 2

Rituximab for refractory disease:

• Two doses of 1000 mg IV separated by 2 weeks (adults) or 375 mg/m² weekly for 4 weeks 2
• The Rituximab in Myositis trial showed 83% favorable response rate in refractory patients 2
• Screen for hepatitis B/C, latent tuberculosis, and obtain baseline immunoglobulin levels before administration 2

Calcineurin inhibitors (reserved for severe refractory cases):

• Cyclosporine 3.0-3.5 mg/kg/day or tacrolimus, monitoring trough levels to avoid renal toxicity 2

Monitoring During Treatment

• Serial CK, muscle strength testing, and functional assessments every 2-4 weeks 2
• Screen for steroid complications: glucose, blood pressure, bone density 2
• For cyclophosphamide: CBC at nadir, urinalysis for hemorrhagic cystitis 2
• For rituximab: monitor for progressive multifocal leukoencephalopathy (maintain high suspicion for JC virus reactivation with any CNS symptoms) 2

Special Consideration: Statin-Associated Autoimmune Myopathy

• Rare necrotizing myopathy with persistent CK elevation, muscle weakness, and anti-HMGCR antibodies despite statin discontinuation 2
• Requires permanent statin cessation AND immunosuppressive therapy (corticosteroids ± additional agents) 2
• Refer to neuromuscular specialist for muscle biopsy confirmation and management 2

When Inflammatory Myopathy Presents as Rhabdomyolysis

If rhabdomyolysis persists despite adequate fluid resuscitation (CK remains elevated >48-72 hours):

• Obtain ANA, ESR, CRP, and myositis-specific antibodies 4
• Consider muscle biopsy if autoantibodies positive or clinical suspicion high 4
• Initiate corticosteroids (prednisone 1 mg/kg/day) if inflammatory myopathy confirmed, while continuing supportive care for rhabdomyolysis 4, 7
• Transition to steroid-sparing agent (methotrexate) for long-term control 4

This dual presentation requires both immediate fluid resuscitation to prevent renal failure AND prompt immunosuppression to address the underlying inflammatory process. 4, 7