What are the initial treatment recommendations for a patient diagnosed with myositis?

Initial Treatment for Myositis

Begin high-dose corticosteroids at 0.5-1 mg/kg/day (typically 60-80 mg prednisone daily) immediately upon diagnosis, and concurrently initiate a steroid-sparing immunosuppressive agent such as methotrexate, azathioprine, or mycophenolate mofetil to optimize outcomes and minimize steroid-related toxicity. 1, 2

Diagnostic Workup Before Treatment

Before initiating therapy, obtain the following essential tests:

• Muscle enzymes: CK, aldolase, AST, ALT, and LDH to quantify muscle inflammation 3
• Cardiac evaluation: Troponin, ECG, and echocardiogram (or cardiac MRI) to exclude myocardial involvement, which dramatically changes management 3, 2
• Inflammatory markers: ESR and CRP 3
• Autoantibody panel: Myositis-specific antibodies (anti-TIF1γ, anti-NXP2) and anti-AChR/antistriational antibodies to exclude myasthenia gravis overlap 3
• Urinalysis: To detect rhabdomyolysis 3
• Rheumatologic and neurologic examination: Focus on muscle strength testing and skin findings suggestive of dermatomyositis 3, 2

Treatment Algorithm by Disease Severity

Mild Disease (Grade 1)

Mild weakness with or without pain, not limiting daily activities:

• Continue with normal activities 3
• If CK/aldolase elevated with muscle weakness: Start prednisone 0.5 mg/kg/day 3
• Offer acetaminophen or NSAIDs for myalgia if no contraindications 3
• Hold statins temporarily 3

Moderate Disease (Grade 2)

Moderate weakness limiting instrumental activities of daily living:

• Initiate prednisone 0.5-1 mg/kg/day if CK ≥3× upper limit of normal 3
• Refer to rheumatology or neurology early 3
• NSAIDs as needed for pain 3
• Consider holding immune checkpoint inhibitors if applicable, resuming only when CK normalizes and prednisone <10 mg/day 3
• May require permanent discontinuation if extensive muscle involvement on EMG, MRI, or biopsy 3

Severe Disease (Grade 3-4)

Severe weakness limiting self-care activities, respiratory involvement, dysphagia, or rhabdomyolysis:

• Hospitalize immediately for severe compromise 3, 1
• Initiate prednisone 1 mg/kg/day orally OR methylprednisolone 1-2 mg/kg IV (or higher-dose bolus of 250-1000 mg for 1-5 consecutive days) 3, 1
• Urgent referral to rheumatology and/or neurology 3
• Consider plasmapheresis for acute or severe disease (but not immediately after IVIG, as it will remove immunoglobulin) 3, 4
• Consider IVIG therapy at 1-2 g/kg over 2 consecutive days, though onset of action is slower than plasmapheresis 3, 1, 4
• Add additional immunosuppressants if no improvement after 2 weeks: rituximab, TNFα antagonists, IL-6 antagonists, cyclophosphamide, or cyclosporine 3, 1

Corticosteroid Tapering Protocol

After achieving clinical response (typically 2-4 weeks):

• Taper by 10 mg every 2 weeks until reaching 30 mg/day 1
• Then taper by 5 mg every 2 weeks until reaching 20 mg/day 1
• Finally taper by 2.5 mg every 2 weeks 1

Steroid-Sparing Agents (Start Concurrently with Corticosteroids)

The following agents should be initiated at treatment onset, not delayed:

• Methotrexate (preferred first-line steroid-sparing agent) 3, 1, 2
• Azathioprine 3, 1, 2
• Mycophenolate mofetil 3, 1, 2

For patients not improving after 4-6 weeks on initial therapy, escalate to biologics or other immunosuppressants 3

Monitoring Treatment Response

• Muscle enzyme levels (CK, aldolase) and inflammatory markers (ESR, CRP) regularly 1, 2
• MRI with T1-weighted, T2-weighted, and fat suppression sequences to assess treatment response 1, 2
• Clinical muscle strength testing at each visit 3, 2

Critical Pitfalls to Avoid

• Never overlook cardiac involvement: Myocarditis is life-threatening and requires permanent discontinuation of immune checkpoint inhibitors if present 3, 2
• Screen for malignancy: Especially in adult dermatomyositis patients, as paraneoplastic myositis is common 1, 2
• Do not delay steroid-sparing agents: Starting them concurrently with corticosteroids reduces cumulative steroid exposure and improves outcomes 1, 2
• Avoid inadequate initial corticosteroid dosing: Underdosing leads to treatment failure and prolonged disease activity 1, 2
• Check IgA levels before IVIG: IgA-deficient patients can develop severe anaphylaxis with IVIG administration 4
• Do not give IVIG immediately before plasmapheresis: The immunoglobulin will be removed 3, 4

Special Considerations

Immune Checkpoint Inhibitor-Related Myositis

This context requires modified management:

• Grade 2: Hold checkpoint inhibitor temporarily; resume only if CK normalizes and prednisone <10 mg/day 3
• Grade 3-4: Hold checkpoint inhibitor; consider permanent discontinuation, especially if myocardial involvement 3
• Caution with rechallenge: While some patients tolerate reintroduction after symptom resolution and CK normalization, recurrence risk exists 3, 2, 5

Immune-Mediated Necrotizing Myopathy (IMNM)

• Requires similar treatment to dermatomyositis/polymyositis but may need more aggressive therapy due to potentially severe weakness 1
• Positive HMGCR antibodies support this diagnosis 4

Juvenile Dermatomyositis

• Start corticosteroids at 2 mg/kg/day up to maximum 60 mg/day 1
• Add subcutaneous methotrexate 15 mg/m² once weekly at treatment onset 1
• Taper corticosteroids after 2-4 weeks based on response 1