What is the initial treatment for myositis?

Initial Treatment for Myositis

Start high-dose oral prednisone at 1 mg/kg/day immediately for patients with confirmed myositis, and strongly consider adding a steroid-sparing agent like methotrexate from the outset to better control disease activity and reduce corticosteroid-related toxicity. 1, 2

Severity-Based Treatment Algorithm

Grade 1 (Mild Weakness)

• Continue monitoring if CK is normal and provide symptomatic relief with acetaminophen or NSAIDs 1
• If CK is elevated AND muscle weakness is present, initiate prednisone 0.5 mg/kg/day despite mild symptoms 1
• Hold statins if the patient is taking them 1

Grade 2 (Moderate Weakness Limiting Daily Activities)

• Initiate prednisone 0.5-1 mg/kg/day if CK is elevated ≥3× upper limit of normal 1
• Refer urgently to rheumatology or neurology for co-management 1
• Permanently discontinue immune checkpoint inhibitors if this is immune-related myositis with objective findings (elevated enzymes, abnormal EMG, abnormal MRI, or biopsy) 1
• Consider hospitalization if weakness is progressing 1

Grade 3-4 (Severe Weakness Limiting Self-Care)

• Hospitalize immediately and initiate prednisone 1 mg/kg/day orally, or methylprednisolone 1-2 mg/kg IV for severe compromise 1, 3
• Permanently discontinue immune checkpoint inhibitors and do not rechallenge 1
• Add IVIG therapy (1-2 g/kg divided over 2 days) for patients not responding adequately to corticosteroids within 2-4 weeks 1, 4
• Consider plasmapheresis for refractory cases or life-threatening presentations, as it has faster onset than IVIG 1, 3

Critical Cardiac Evaluation (Mandatory for All Grades)

Obtain troponin I (more specific than troponin T in skeletal muscle disease) and ECG immediately for every patient with suspected myositis, as myocarditis occurs in up to 20% of cases and dramatically increases mortality 1, 3

• If troponin is elevated, ECG is abnormal, or any cardiac symptoms exist (dyspnea, palpitations, chest pain, syncope), obtain urgent cardiac MRI 1
• Permanently discontinue immune checkpoint inhibitors if any myocardial involvement is detected 1
• Escalate to high-dose IV methylprednisolone (1-2 mg/kg or higher) immediately for myocarditis 1
• Consider abatacept or alemtuzumab as rescue therapy for glucocorticoid-refractory myocarditis 1

Essential Baseline Laboratory Workup

Before initiating treatment, obtain:

• CK, aldolase, AST, ALT, LDH (all can be elevated in myositis) 1, 3
• ESR and CRP (inflammatory markers) 1
• Troponin I and ECG (cardiac screening) 1
• Urinalysis for myoglobinuria (screen for rhabdomyolysis) 1, 3
• Myositis-specific autoantibodies (anti-Jo1, anti-SRP, anti-HMGCR, anti-TIF1γ, anti-NXP2) 1
• Anti-acetylcholine receptor and antistriational antibodies (screen for myasthenia gravis, which coexists in 12.5% of cases) 1

Corticosteroid Management Principles

Three critical principles predict favorable outcomes: 5

1. Administer adequate initial loading dose (1 mg/kg/day for moderate-severe disease) 1, 5
2. Continue the initial dose until CK normalizes, not just improves—achieving low-normal CK predicts prolonged remission 5
3. Taper slowly only after CK normalization; tapering while CK is elevated frequently causes relapse 5

Do not taper prednisone below 10 mg/day until at least 4-6 weeks of stable, normal CK levels 1, 5

Steroid-Sparing Agents (Add Early)

Combine corticosteroids with another immunosuppressive agent early to better control disease and reduce steroid toxicity 2, 6

First-line steroid-sparing agent:

• Methotrexate (therapeutic effect observed within 8 weeks) 6

If inadequate response after 4-6 weeks or inability to taper steroids:

• Add mycophenolate mofetil, azathioprine, or continue methotrexate 1, 6
• Consider IVIG for refractory dermatomyositis (only therapy with positive double-blind placebo-controlled trial) 4, 7

For severe refractory disease:

• Rituximab shows evidence of benefit, particularly in patients with certain myositis-specific autoantibodies 2, 6
• Avoid TNF-α antagonists—they exacerbate interstitial lung disease and myositis and increase infection risk 6

Common Pitfalls to Avoid

Do not assume all CK elevations require corticosteroids—exercise-induced muscle damage can produce CK >10,000 U/L without requiring treatment; muscle weakness, not just pain, indicates true myositis 1, 3

Do not taper steroids based on clinical improvement alone—a CK rise within the normal range signals impending relapse; wait for low-normal CK before tapering 5

Do not miss myocarditis—normal cardiac enzymes cannot always rule it out; maintain high suspicion with any dyspnea, bulbar symptoms, or severe weakness 1

Do not administer IVIG immediately before plasmapheresis—it will be removed 4

Do not miss coexisting myasthenia gravis—present in 12.5% of myositis cases; check for bulbar symptoms (dysphagia, dysarthria, dysphonia) and obtain anti-AChR antibodies 1

Check IgA levels before administering IVIG—IgA-deficient patients can have severe anaphylactic reactions 4

Monitoring During Treatment

• CK levels weekly until normalized, then monthly during taper 1, 5
• Muscle strength assessment at each visit 1
• ESR and CRP to track inflammatory response 1
• Cardiac monitoring if any baseline abnormalities 1