What are the typical clinical presentations and treatments of myositis?

Myositis Clinical Presentation

Myositis presents primarily with symmetric proximal muscle weakness affecting the upper and lower extremities, with or without pain, and is distinguished from other conditions by elevated creatine kinase (CK) levels, abnormal electromyography (EMG), and characteristic muscle biopsy findings. 1, 2

Cardinal Clinical Features

Primary Symptom: Muscle Weakness

• Proximal muscle weakness is the hallmark, manifesting as difficulty standing from a seated position, lifting arms overhead, climbing stairs, and impaired mobility 1, 2
• Weakness predominantly affects limb-girdle muscles (shoulders and hips) with symmetric distribution in most subtypes 3, 4
• Pain may accompany weakness but is not universally present; true weakness distinguishes myositis from polymyalgia rheumatica-like syndromes where pain predominates without genuine weakness 1

Severity Grading by Functional Impact

• Grade 1 (Mild): Mild weakness with or without pain, not limiting daily activities 1
• Grade 2 (Moderate): Moderate weakness limiting instrumental activities of daily living (e.g., cooking, shopping) 1
• Grade 3-4 (Severe): Severe weakness limiting self-care activities (bathing, dressing, feeding), potentially requiring hospitalization 1

Life-Threatening Presentations Requiring Immediate Recognition

Myocarditis Association

Concurrent myocarditis carries 20% mortality risk and requires immediate recognition through troponin monitoring and ECG 2. Permanently discontinue immune checkpoint inhibitors if any myocardial involvement is detected 1.

Bulbar and Respiratory Involvement

• Dysphagia, dysarthria, dysphonia, or dyspnea indicate severe disease requiring urgent high-dose methylprednisolone (1-2 mg/kg IV) 1, 2
• These symptoms suggest involvement of bulbar muscles and potential respiratory compromise 1
• Consider plasmapheresis and IVIG therapy for severe compromise 1

Rhabdomyolysis

• Fulminant necrotizing course with markedly elevated CK (often >10,000 U/L) 1
• Monitor for acute kidney injury secondary to myoglobinuria 1

Subtype-Specific Presentations

Dermatomyositis

• Pathognomonic skin findings: heliotrope rash (violaceous periorbital edema), Gottron's papules (erythematous papules over knuckles), V-sign (erythema over anterior chest), shawl sign (erythema over shoulders/upper back) 2, 3
• Perifascicular atrophy on muscle biopsy 4
• Requires immediate malignancy screening in adults due to substantial cancer risk 2

Polymyositis

• Symmetric proximal weakness without skin manifestations 2, 3
• CD8+ T cell invasion of non-necrotic muscle fibers on biopsy 2, 4

Immune-Mediated Necrotizing Myopathy (IMNM)

• Severe myopathy with minimal inflammatory infiltrate on biopsy 2
• Often triggered by statins, viral infections, or malignancy 2
• Myofiber necrosis without prominent inflammation histologically 4
• Requires aggressive immunosuppression despite statin discontinuation 2

Inclusion Body Myositis (IBM)

• Atypical pattern: insidious onset with asymmetric weakness affecting distal muscles (wrist flexors, finger flexors) before proximal groups 2, 4
• Foot drop may be presenting feature (12% of atypical cases) 5
• Dysphagia as initial symptom in 50% of atypical presentations 5
• Rimmed vacuoles on muscle biopsy 4
• Refractory to immunosuppressive therapy, distinguishing it from other inflammatory myopathies 3, 4

Immune Checkpoint Inhibitor-Induced Myositis

• Median onset 4 weeks after ICI exposure 1
• More common with anti-PD-1/PD-L1 than anti-CTLA-4 agents 1, 2
• Concomitant myasthenia gravis or myocarditis confers ominous prognosis with high mortality 1, 2
• Positive anti-acetylcholine receptor and anti-striated muscle antibodies may be present with concurrent myasthenia gravis 1

Essential Diagnostic Workup

Laboratory Evaluation

• Creatine kinase (CK): Markedly elevated (often 3-10x upper limit of normal or higher) in true myositis; normal or mildly elevated in polymyalgia rheumatica-like syndrome 1, 2
• Inflammatory markers: ESR and CRP (elevated) 1
• Myositis-specific antibodies: anti-Jo-1, anti-SRP, anti-HMGCR, anti-Mi-2 1, 2
• AST, ALT, LDH (often elevated due to muscle breakdown) 1
• High-sensitivity troponin I (myocardium-specific) to rule out myocarditis; troponin T may be falsely elevated from skeletal muscle 1

Electrodiagnostic Studies

• EMG shows myopathic changes: short-duration, low-amplitude polyphasic motor unit potentials, early recruitment, spontaneous fibrillations 1
• Myotonic discharges may be present even without clinical myotonia 2

Imaging

• Muscle MRI identifies inflammation (edema on STIR sequences) and guides biopsy site 1, 2
• Fasciitis frequently reported on MRI in immune checkpoint inhibitor-induced myositis 1

Muscle Biopsy

• Essential to distinguish subtypes and confirm diagnosis 1, 2
• Specific patterns: perifascicular atrophy (DM), CD8+ T cell invasion (PM), myofiber necrosis without inflammation (IMNM), rimmed vacuoles (IBM) 2, 3, 4

Differential Diagnosis Considerations

Polymyalgia Rheumatica-Like Syndrome

• Marked pain and stiffness in proximal extremities WITHOUT true weakness 1
• Difficulty with active motion related to pain, not weakness 1
• CK levels normal or minimally elevated (key distinguishing feature) 1
• EMG and MRI show no evidence of myopathy or muscle inflammation 1
• Highly elevated inflammatory markers (ESR, CRP) 1

Statin-Associated Myopathy

• Typically presents with myalgia and mild CK elevation 2
• Resolves with statin discontinuation unless IMNM develops 2

Drug-Induced Myopathy

• Corticosteroids, alcohol, SGLT2 inhibitors can cause proximal weakness 2
• History of medication exposure is critical 2

Treatment Framework by Severity

Grade 1 (Mild Weakness)

• Continue immune checkpoint inhibitor if applicable 1
• If CK elevated with muscle weakness, initiate oral corticosteroids and treat as Grade 2 1
• Analgesia with acetaminophen or NSAIDs if no contraindications 1

Grade 2 (Moderate Weakness)

• Hold immune checkpoint inhibitor temporarily; may resume if CK normalizes and prednisone <10 mg/day 1
• Refer to rheumatologist or neurologist 1
• If CK elevated ≥3x upper limit of normal: initiate prednisone 0.5-1 mg/kg/day 1
• May require permanent discontinuation of ICI if objective findings present (elevated enzymes, abnormal EMG, abnormal muscle MRI or biopsy) 1

Grade 3-4 (Severe Weakness)

• Hold immune checkpoint inhibitor until Grade 1 or less while off immunosuppression 1
• Permanently discontinue if any myocardial involvement 1
• Consider hospitalization for severe weakness 1
• Initiate prednisone 1 mg/kg/day or equivalent 1, 2, 6
• For severe compromise (severely limited mobility, cardiac, respiratory, dysphagia): methylprednisolone 1-2 mg/kg IV or higher-dose bolus 1, 2
• Consider plasmapheresis and/or IVIG therapy 1, 2

Steroid-Refractory Disease (4-6 weeks without improvement)

• Add steroid-sparing immunosuppressant: methotrexate, azathioprine, or mycophenolate mofetil 1, 2, 7
• Consider rituximab (caution advised given long biologic duration) 1
• IL-6 inhibitors (tocilizumab) may be considered but contraindicated with colitis or GI metastases due to intestinal perforation risk 1
• TNF-α inhibitors if associated fasciitis present 1

Critical Monitoring Parameters

During Active Treatment

• Serial CK levels every 1-2 weeks initially 1
• Inflammatory markers (ESR, CRP) every 4-6 weeks 1
• Troponin monitoring if any cardiac symptoms develop 1
• Functional assessment of muscle strength at each visit 2

Long-Term Corticosteroid Complications

• Primary adverse outcomes: osteoporosis, compression fractures, avascular necrosis 2
• Bone density monitoring, calcium and vitamin D supplementation mandatory 2
• Add bisphosphonate if osteoporosis develops 2

Common Pitfalls to Avoid

• Do not confuse polymyalgia rheumatica-like syndrome (pain without weakness, normal CK) with true myositis 1
• Do not rechallenge with immune checkpoint inhibitors without rheumatology consultation; toxicity can return upon rechallenge 1
• Do not use troponin T alone to assess for myocarditis; it is expressed by skeletal muscle and may be falsely elevated 1
• Do not delay high-dose corticosteroids in severe cases while awaiting biopsy results 2
• Do not treat inclusion body myositis aggressively with immunosuppression; it is refractory and requires different management approach 2, 3, 4