Approach to Myositis Treatment
The treatment of myositis should follow a graded approach based on disease severity, with corticosteroids as the initial therapy for most patients, followed by steroid-sparing agents to minimize long-term complications. 1
Initial Diagnostic Workup
Laboratory Testing
- Muscle enzymes: CK, aldolase, transaminases (AST/ALT), LDH
- Inflammatory markers: ESR and CRP
- Autoantibody testing:
- Myositis-specific antibodies
- Anti-AChR and anti-striational antibodies (to rule out myasthenia gravis)
- Paraneoplastic autoantibodies (anti-TIF1γ, anti-NXP2) if pre-existing muscle symptoms
Additional Testing
- Urinalysis (to rule out rhabdomyolysis)
- Consider EMG, MRI, and/or muscle biopsy when diagnosis is uncertain
- Cardiac evaluation (troponin, ECG, echocardiogram) if myocardial involvement suspected
Treatment Algorithm by Severity
Grade 1 (Mild weakness with or without pain)
- Continue immunotherapy if applicable
- If CK/aldolase elevated with muscle weakness:
- Prednisone 0.5 mg/kg/day
- Acetaminophen or NSAIDs for myalgia if no contraindications
- Consider holding statins if patient is taking them
Grade 2 (Moderate weakness limiting instrumental ADLs)
- Hold immunotherapy temporarily
- Early referral to rheumatologist or neurologist
- If CK elevated (≥3× ULN):
- Prednisone 0.5-1 mg/kg/day
- NSAIDs as needed for pain
- Monitor for improvement
- Resume immunotherapy only when CK normalizes and symptoms resolve
Grade 3-4 (Severe weakness limiting self-care ADLs)
- Hold immunotherapy permanently if myocardial involvement
- Hospitalize patients with severe weakness, respiratory compromise, dysphagia, or rhabdomyolysis
- Urgent rheumatology/neurology consultation
- Initiate high-dose corticosteroids:
- Prednisone 1 mg/kg/day orally OR
- Methylprednisolone 1-2 mg/kg IV or higher-dose bolus for severe cases
- Consider additional therapies for severe or refractory disease:
- Plasmapheresis for acute or severe disease
- IVIG (note: slower onset of action)
- Immunosuppressants if no improvement after 2 weeks:
- Biologics (rituximab, TNFα or IL-6 antagonists)
- Synthetic DMARDs (methotrexate, azathioprine, mycophenolate mofetil)
Special Considerations
Dermatomyositis/Polymyositis
- Initial therapy: High-dose corticosteroids with concurrent steroid-sparing agent (methotrexate, azathioprine, or mycophenolate mofetil) 1
- For severe disease: Consider IV methylprednisolone, IVIG, cyclophosphamide, rituximab, or cyclosporine 1
Inclusion Body Myositis (IBM)
- Often less responsive to immunosuppressive therapy
- Consider 3-6 month trial of immunotherapy 2
- Focus on supportive care and physical therapy
Immune Checkpoint Inhibitor-Induced Myositis
- Higher risk of myocarditis and myasthenia gravis overlap
- More aggressive initial treatment approach
- May require permanent discontinuation of immunotherapy 1
Monitoring and Follow-up
- Regular assessment of muscle strength and function
- Monitor CK levels to assess treatment response
- For Grade 1: Complete examination and laboratory workup
- For Grade 2-4: Autoimmune myositis blood panel, EMG, MRI of affected joints
Pitfalls and Caveats
- Myositis with myocardial involvement or concurrent myasthenia gravis has high mortality rate and requires aggressive treatment 1
- Plasmapheresis immediately after IVIG will remove immunoglobulin, reducing efficacy 1
- Early recognition of immune-mediated myositis is critical to prevent permanent muscle damage
- Steroid-sparing agents should be considered early in treatment course to minimize corticosteroid-related complications
- Caution with rechallenging immunotherapy after myositis, especially with higher-grade toxicity 1
Differential Diagnosis Considerations
- Rule out other causes of muscle weakness:
- Drug-induced myopathies (statins)
- Metabolic myopathies
- Neuromuscular junction disorders
- Neuropathies
- Muscular dystrophies
By following this structured approach to myositis treatment based on severity grading, clinicians can optimize outcomes while minimizing treatment-related complications.