What is the recommended treatment and management approach for a patient diagnosed with myositis?

Treatment and Management of Myositis

For patients with myositis, initiate high-dose corticosteroids immediately based on disease severity (prednisone 0.5-1 mg/kg/day for moderate disease, 1 mg/kg/day or IV methylprednisolone 1-2 mg/kg for severe disease), combined with early steroid-sparing immunosuppression (methotrexate, azathioprine, or mycophenolate mofetil) to prevent irreversible muscle damage and allow corticosteroid tapering. 1, 2, 3

Initial Assessment and Risk Stratification

Critical first steps:

• Assess for true muscle weakness (not just pain-limited movement) - proximal muscle weakness indicates inflammatory myositis requiring aggressive treatment, whereas pain without weakness suggests polymyalgia-like syndrome with different management 1, 2, 4

• Immediately evaluate for cardiac involvement by obtaining troponin and ECG, as myocardial involvement is potentially fatal and requires permanent discontinuation of any causative agents plus aggressive immunosuppression 1, 2, 4

• Measure creatine kinase (CK) levels - markedly elevated CK (≥3× upper limit of normal) confirms inflammatory myositis and guides treatment intensity 1, 4

• Screen for rhabdomyolysis with urinalysis for myoglobinuria, as this is life-threatening 4

• Check additional muscle enzymes (aldolase, AST, ALT, LDH) and inflammatory markers (ESR, CRP) 1, 2, 4

• Examine skin for dermatomyositis features (Gottron papules, heliotrope rash, shawl sign) 2

Treatment Algorithm Based on Disease Severity

Grade 1 (Mild): Mild stiffness/pain, no weakness

• Continue any causative therapy if applicable 1
• Initiate acetaminophen and/or NSAIDs for analgesia if no contraindications 1, 3
• If CK elevated, initiate prednisone 0.5 mg/kg/day 2, 3
• Obtain complete rheumatologic workup: ANA, RF, anti-CCP, myositis-specific antibodies 1, 2
• Monitor ESR and CRP 1

Grade 2 (Moderate): Moderate weakness/pain limiting instrumental activities of daily living

• Hold any causative therapy (e.g., immune checkpoint inhibitors) 1
• Initiate prednisone 0.5-1 mg/kg/day if CK ≥3× upper limit of normal 1, 2
• Concurrently start steroid-sparing agent: methotrexate (15-20 mg/m² weekly), azathioprine (2-3 mg/kg/day), or mycophenolate mofetil (2-3 g/day divided) 1, 3, 4
• Early referral to rheumatologist or neurologist 1, 2
• Consider permanent discontinuation of causative therapy if objective findings present (elevated enzymes, abnormal EMG, abnormal MRI, or positive biopsy) 1
• Taper prednisone after 3-4 weeks if symptoms improve 1
• Escalate to Grade 3 management if no improvement after 4 weeks 1

Grade 3-4 (Severe): Severe weakness limiting self-care activities

• Permanently discontinue any causative therapy 1
• Consider hospitalization for severe weakness, respiratory compromise, dysphagia, or rhabdomyolysis 1, 2
• Urgent referral to rheumatologist and/or neurologist 1, 2

Corticosteroid regimen:

• Initiate prednisone 1 mg/kg/day orally for standard severe cases 1, 2
• For severe compromise (weakness severely limiting mobility, cardiac involvement, respiratory compromise, dysphagia): methylprednisolone 1-2 mg/kg IV or pulse therapy 500-1000 mg/day for 3-5 days 1, 3, 4

Additional immunosuppression:

• Consider plasmapheresis for acute or severe disease (faster onset than IVIG) 1, 4
• Consider IVIG therapy (note: plasmapheresis immediately after IVIG will remove immunoglobulin) 1, 4
• Add other immunosuppressants (rituximab, TNF-α antagonists, IL-6 antagonists) if symptoms worsen or no improvement after 2 weeks 1
• Consider methotrexate, azathioprine, or mycophenolate mofetil for maintenance if symptoms and CK do not resolve after 4-6 weeks 1, 4

Management of Refractory Disease

• Rituximab is the preferred biologic for refractory myositis, particularly effective in patients with certain myositis-specific autoantibodies 3, 4, 5
• Alternative biologics: TNF-α or IL-6 antagonists (tocilizumab) 1, 4
• IL-6 inhibition caution: can cause intestinal perforation (extremely rare); avoid in patients with colitis or GI involvement 1
• Cyclosporine 3-5 mg/kg/day in divided doses for refractory cases 3

Critical Pitfalls to Avoid

Cardiac involvement:

• Myocardial involvement has high mortality and requires permanent discontinuation of causative agents 1, 4
• Always check troponin and ECG - consider echocardiogram or cardiac MRI if any cardiac symptoms present 2, 4
• Cardiologist involvement is essential when cardiac biomarkers elevated or ECG abnormal 2

CK elevation interpretation:

• Not all CK elevations require corticosteroids - exercise-induced muscle damage can produce CK >10,000 U/L without requiring treatment 4
• Distinguish true myositis from exercise-related elevation by clinical context and presence of weakness 4

Rechallenge considerations:

• Extreme caution with restarting causative therapy (e.g., immune checkpoint inhibitors) 1
• Do not restart until CK normalized and clinical manifestations resolved 1
• Cases of toxicity returning upon rechallenge have been reported 1

Differential diagnosis:

• With elevated transaminases, consider immune-mediated hepatitis as alternative diagnosis 1
• Check for temporal arteritis symptoms (headache, visual disturbances, jaw claudication) - urgent ophthalmology referral needed as permanent visual loss can occur within days 1

Special Populations

TIF1-gamma positive dermatomyositis:

• Associated with increased malignancy risk in adults - thorough cancer screening mandatory 3
• May be more resistant to conventional immunosuppression - treat both myositis and underlying malignancy 3

Post-viral myositis:

• Most cases are self-limited but require same severity-based approach 4
• Monitor closely for progression to severe disease requiring aggressive treatment 4

Adjunctive Management

• Implement physical therapy early to prevent joint contractures and muscle atrophy 2
• Individualized supervised exercise combined with pharmacological treatment is evidence-based 5
• Monitor for systemic complications: pulmonary, gastrointestinal, and joint involvement 6
• Screen for comorbidities: cancer risk, cardiovascular disease, thromboembolism risk, fracture risk 6