What is the appropriate workup and treatment for a patient with suspected myositis?

Myositis Workup and Treatment

Begin with a focused clinical assessment emphasizing muscle weakness pattern (proximal and symmetric), skin examination for dermatomyositis findings, and immediate cardiac evaluation with troponin and ECG, followed by comprehensive muscle enzyme testing including CK, aldolase, AST, ALT, and LDH. 1, 2

Initial Clinical Assessment

Muscle Strength Evaluation:

• Document symmetric proximal muscle weakness affecting shoulders and hips that limits instrumental activities of daily living (dressing, climbing stairs) 1, 3
• Muscle weakness is the hallmark finding—not pain—which distinguishes myositis from other rheumatologic conditions 1, 2, 3
• Perform objective strength testing in all muscle groups with complete neurologic examination 2, 3

Skin Examination:

• Look specifically for heliotrope rash (violaceous discoloration of eyelids), Gottron's papules (raised violaceous papules over knuckles), V-sign (erythema on anterior chest), shawl sign (erythema over shoulders/upper back), and cutaneous ulcers 4, 3
• These findings indicate dermatomyositis, which has distinct treatment implications 4, 3

Critical Systems Assessment:

• Evaluate for dysphagia and respiratory muscle weakness, as these indicate severe disease with higher mortality 4, 3
• Assess for cardiac symptoms (chest pain, dyspnea, palpitations) as myocardial involvement is a medical emergency 1, 4, 3

Essential Laboratory Testing

Immediate Cardiac Evaluation:

• Obtain troponin and ECG immediately in all suspected myositis cases, as cardiac involvement dramatically alters management and carries high mortality 1, 2, 4, 3
• Add echocardiogram if any clinical suspicion of myocardial involvement 1, 4

Muscle Enzyme Panel:

• Order CK, aldolase, AST, ALT, and LDH—all can be elevated in myositis 1, 2, 4, 3
• CK ≥3× upper limit of normal indicates significant disease requiring treatment 2, 3
• Aldolase, LDH, AST, and ALT can be elevated even when CK is normal, particularly in dermatomyositis 4

Inflammatory Markers:

• Measure ESR and CRP for diagnosis and monitoring 1, 2, 4, 3

Secondary Causes Investigation:

• Review medications (statins, fibrates, colchicine, hydroxychloroquine) 2
• Consider holding statins to eliminate confounding drug-induced myopathy 3

Advanced Diagnostic Testing

When to Pursue Advanced Testing:

• Order autoimmune myositis antibody panel for grade 2 or higher severity 1, 3
• Consider paraneoplastic autoantibody testing, as myositis can be paraneoplastic 1, 4

MRI of Proximal Limbs:

• MRI is the imaging modality of choice, showing active inflammation, pattern of involvement, and guiding biopsy location 2, 4, 3, 5
• Can reveal inflammatory changes even when muscle enzymes are normal 4
• Order for grade 2 or higher cases, or when diagnosis uncertain 1, 2

Electromyography (EMG):

• Shows myopathic changes (fibrillations) when diagnosis uncertain or neurologic overlap suspected (myasthenia gravis) 1, 2, 4, 3
• Particularly important when considering overlap syndromes 1

Muscle Biopsy:

• Consider when diagnosis remains uncertain after initial workup 1, 2, 4, 3
• Can show inflammatory myopathy even with normal CK 4
• Essential for excluding muscular dystrophies and inclusion body myositis, which are treatment-resistant 6

Treatment Algorithm by Severity

Grade 1 (Mild Weakness, Normal Activities):

• Offer prednisone 0.5 mg/kg/day orally if CK/aldolase elevated with muscle weakness 2, 3, 7
• Complete examination and laboratory workup as above 1
• Monitor CK, ESR, CRP weekly initially 2

Grade 2 (Moderate Weakness, Limits Instrumental ADLs):

• Hold immune checkpoint inhibitors if applicable 1
• Initiate prednisone 0.5-1 mg/kg/day orally 1, 3, 7
• If CK ≥3× upper limit of normal, initiate prednisone 0.5-1 mg/kg 1, 2
• Order autoimmune myositis panel, EMG, MRI of affected proximal limbs 1, 2
• Early referral to rheumatologist or neurologist 1, 2, 3
• May resume immune checkpoint inhibitors only when symptoms controlled, CK normal, and prednisone <10 mg/day 1
• Permanently discontinue immune checkpoint inhibitors if any evidence of myocardial involvement 1, 3

Grade 3-4 (Severe Weakness, Limits Self-Care or Life-Threatening):

• Hold immune checkpoint inhibitors and permanently discontinue if any myocardial involvement 1, 3
• Consider hospitalization for severe weakness limiting mobility, respiratory function, or causing dysphagia 1, 2
• Initiate prednisone 1 mg/kg/day orally, or methylprednisolone 1-2 mg/kg IV for severe cases 1, 3, 7
• Urgent referral to rheumatologist and/or neurologist 1, 2
• Ensure hydration with urine output >0.5 mL/kg/hour to prevent myoglobin-induced acute kidney injury 2

Escalation for Treatment Failure

If no improvement after 2-4 weeks or worsening:

• Add synthetic DMARD: methotrexate or leflunomide 1, 2
• Consider biologic DMARD: TNF-α or IL-6 receptor inhibitors 1
• Do not use IL-6 inhibitors in patients with colitis due to intestinal perforation risk 1
• Test for hepatitis B, C, and latent/active TB before starting DMARD therapy 1

Monitoring Strategy

Serial Laboratory Monitoring:

• Recheck CK, ESR, CRP weekly initially 1, 2, 4, 3
• Perform serial muscle strength assessments 4, 3
• Do not restart immune checkpoint inhibitors until CK normalizes and clinical manifestations resolve 3

Critical Pitfalls to Avoid

Myocardial Involvement:

• This is a medical emergency with high mortality requiring immediate recognition 1, 4, 3
• Always check troponin in all suspected myositis cases 1, 2, 4

Myositis-Myasthenia Gravis Overlap:

• Has ominous prognosis with high mortality 3
• Test for anti-acetylcholine receptor antibodies when neurologic overlap suspected 1, 3

Treatment-Resistant Cases:

• Consider inclusion body myositis (most common acquired muscle disease >50 years, largely refractory to immunosuppression) or muscular dystrophies 8, 6
• Muscle biopsy essential before committing to long-term immunosuppression 6

Normal CK Does Not Exclude Myositis:

• Aldolase, LDH, AST, ALT can be elevated when CK is normal, particularly in dermatomyositis 4
• MRI and EMG can show changes despite normal enzymes 4