What is the diagnosis and treatment for myositis?

Diagnosis and Treatment of Myositis

Diagnostic Approach

Myositis diagnosis requires a systematic evaluation combining clinical assessment, laboratory testing, imaging, and often tissue confirmation, with particular attention to life-threatening complications including myocarditis and myasthenia gravis. 1

Clinical Presentation

The hallmark symptoms include:

• Proximal muscle weakness affecting limb-girdle, axial, and potentially bulbar muscles (dysphagia, dysarthria, dysphonia) 1
• Myalgia with or without weakness 1
• Oculomotor symptoms including ptosis and diplopia, suggesting possible concurrent myasthenia gravis 1
• Dropped head syndrome in some cases 1
• Life-threatening manifestations requiring immediate attention: dyspnea, palpitations, chest pain, or syncope indicating possible myocarditis 1

Essential Laboratory Workup

Creatine kinase (CK) elevation is present in the majority of myositis patients and is the key distinguishing feature from myalgia alone (where CK remains normal). 1

Complete diagnostic panel includes:

• CK, AST, ALT, LDH 1
• Myositis-associated autoantibodies (though often negative; positive findings may include ANA, anti-PM/Scl, anti-Jo1, anti-SRP, anti-TIF1 gamma) 1
• Paraneoplastic antibodies 1
• Anti-acetylcholine receptor (anti-AChR) antibodies if myasthenia gravis suspected 1

Cardiac Evaluation (Mandatory)

Cardiac assessment must be systematic for every patient with suspected myositis due to the high mortality risk from concurrent myocarditis (approximately 20% mortality in checkpoint inhibitor-related myositis versus <10% in idiopathic forms). 1

Required cardiac workup:

• Cardiac troponin (troponin I preferred over troponin T, as troponin T is expressed in skeletal muscle and can be falsely elevated) 1
• Electrocardiography 1
• Cardiac MRI if clinical syndrome, elevated troponin, or ECG abnormalities present 1

Important caveat: Normal cardiac enzymes cannot completely rule out myocarditis. 1

Imaging and Electrodiagnostic Studies

• MRI demonstrates muscle edema, fasciitis (frequently reported), and guides biopsy site selection 1
• Electromyography (EMG) shows spontaneous activity, myogenic recruitment pattern, and muscle fibrillations 1
• Muscle biopsy (on individual basis) confirms inflammatory and necrotic changes with variable degrees of muscle damage 1

Differential Considerations

• Rule out dermatomyositis if skin involvement present 1
• Distinguish from polymyalgia rheumatica-like syndrome (pain without true weakness, normal CK) 1
• Exclude myasthenia gravis as concurrent or alternative diagnosis 1

Treatment Algorithm

Grade 2 (Moderate) Symptoms

Corticosteroids at 0.5-1 mg/kg/day prednisone represent first-line therapy for grade 2 myositis. 1

• Discontinue immune checkpoint inhibitors for grade 2 symptoms 1
• Improvement typically noted within days after ICI discontinuation 1
• Over 80% achieve favorable clinical outcome within several months 1

Severe Symptoms (Bulbar, Respiratory, or Cardiac Involvement)

High-dose corticosteroids (pulses then 1-2 mg/kg/day) plus additional immunomodulatory therapy are mandatory for life-threatening presentations. 1

Additional treatment options (required in ~40% of patients):

• Intravenous immunoglobulin (IVIG) 1
• Plasma exchange or selective separation 1
• Immediate ICI withdrawal is necessary 1

The median corticosteroid dosage used is 70 mg/day, with 10% receiving IV methylprednisolone pulses. 1

Refractory or Corticosteroid-Dependent Cases

For steroid-refractory myositis, IL-6 receptor inhibitors should be considered, with TNF-α inhibitors added if fasciitis is present. 1

Second-line immunosuppressive options include:

• Methotrexate 1
• Mycophenolate mofetil 1
• Abatacept (reported successful resolution of severe glucocorticoid-refractory myocarditis) 1
• Alemtuzumab (T-cell directed therapy for refractory myocarditis) 1

Referral to rheumatologist is recommended for corticosteroid-dependent or refractory cases. 1

Critical Management Pitfalls

• Do not rely on normal cardiac enzymes alone to exclude myocarditis 1
• Do not confuse elevated troponin T with myocardial involvement in the setting of skeletal muscle inflammation 1
• Do not delay treatment in patients with bulbar symptoms, dyspnea, or suspected myocarditis—these require immediate high-dose immunosuppression 1
• Recognize early presentation in checkpoint inhibitor-related cases (median 4 weeks exposure, often within first month) 1
• Screen for concurrent myasthenia gravis (present in 12.5% of reported cases) which portends worse prognosis 1

Prognosis Considerations

Checkpoint inhibitor-related myositis carries approximately 20% mortality risk, primarily due to myocarditis, compared to <10% in idiopathic inflammatory myositis. 1 Patients with concomitant myocarditis and/or myasthenia gravis have particularly ominous prognosis with high mortality rates. 1