What is myositis?

Myositis: Definition, Types, and Clinical Presentation

Myositis is an inflammatory condition affecting skeletal muscles that can be severe and potentially fatal, characterized primarily by muscle weakness rather than pain, and often involving proximal extremities. 1

Types of Myositis

• Idiopathic Inflammatory Myopathies (IIMs) - A group of systemic disorders with chronic muscle inflammation leading to weakness, often affecting multiple organ systems including skin, joints, lungs, gastrointestinal tract, and heart 1, 2

• Infectious Myositis - Caused by bacteria, fungi, viruses, or parasites, presenting with localized or diffuse muscle inflammation 3, 4

• Drug-Induced Myositis - Can be triggered by medications such as statins or immune checkpoint inhibitors (ICPis) 1, 5

• Immune-Mediated Necrotizing Myopathy (IMNM) - A severe form with minimal inflammatory infiltrate on biopsy 1

Clinical Presentation

Primary Symptoms

• Muscle weakness - Predominantly in proximal extremities (shoulders, hips), causing difficulty standing up, lifting arms, and moving around 1
• Functional limitations - Problems with activities of daily living 1
• Myalgia - Muscle pain occurs primarily in severe cases 1, 3

Associated Features

• Elevated muscle enzymes - Particularly creatine kinase (CK), which is often markedly elevated 1
• Systemic symptoms - May include fever and weight loss 1
• Extramuscular manifestations - Can involve skin (in dermatomyositis), joints, lungs, heart, and gastrointestinal tract 1, 2

Specific Subtypes

Dermatomyositis

• Characterized by distinctive skin manifestations including:
  • Erythematous, photosensitive rash with poikiloderma
  • Gottron papules
  • Periorbital edema
  • Heliotrope rash
  • Periungual telangiectasias 1

Polymyositis

• Symmetric proximal muscle weakness
• Distinct immunohistopathologic features with CD8+ cytotoxic T cells invading non-necrotic muscle fibers 1

Inclusion Body Myositis

• Features suggesting degenerative neuromuscular disease
• Muscle fiber vacuolization
• Abnormal accumulation of amyloid-β and phosphorylated tau proteins 1

ICPi-Associated Myositis

• Rare but potentially fatal complication of immune checkpoint inhibitor therapy
• More common with PD-1/PD-L1 inhibitors than with CTLA-4 agents
• Can present as reactivation of pre-existing myositis or as de novo condition
• May have fulminant necrotizing course with rhabdomyolysis
• Can involve the myocardium, requiring urgent treatment
• Particularly dangerous when occurring with myocarditis and/or myasthenia gravis (high mortality) 1

Diagnostic Approach

Laboratory Tests

• Muscle enzymes - CK, transaminases (AST, ALT), LDH, and aldolase 1
• Inflammatory markers - ESR and CRP 1
• Cardiac evaluation - Troponin to assess myocardial involvement 1
• Autoantibody testing - Myositis-specific autoantibodies may define subgroups and predict outcomes 1

Imaging

• MRI - Shows increased intensity and edema in affected muscles; useful for identifying biopsy sites and monitoring treatment response 1, 5
• EMG - May show muscle fibrillations indicative of myopathy 1

Muscle Biopsy

• Confirms diagnosis in uncertain cases
• Particularly important when overlap with neurologic syndromes is suspected 1

Treatment Approach

General Principles

• Corticosteroids - Cornerstone of initial treatment; high-dose administration (bolus in severe cases) 1
• Immunosuppressants - May be needed in addition to corticosteroids 1
• Plasmapheresis - Consider in cases with poor response to corticosteroids or life-threatening situations 1
• IVIG - May be indicated in severe cases 1

Treatment Based on Severity

• Mild (Grade 1) - Continue immunotherapy if applicable; consider oral corticosteroids if CK is elevated with muscle weakness 1
• Moderate (Grade 2) - Temporary hold on immunotherapy; NSAIDs as needed; referral to specialist; prednisone 0.5-1 mg/kg if CK is elevated 1
• Severe (Grade 3-4) - Hold immunotherapy; hospitalization for severe weakness; high-dose corticosteroids (1-2 mg/kg); consider plasmapheresis and IVIG 1

Prognosis and Complications

• Cardiac involvement - Can lead to fatal complications if myocardium is affected 1
• Respiratory compromise - May occur with involvement of respiratory muscles 1
• Rhabdomyolysis - Severe muscle breakdown can lead to kidney damage 1
• Co-occurrence with other conditions - Particularly concerning when myositis occurs with myasthenia gravis or myocarditis 1

Important Considerations

• Early recognition is critical to prevent irreversible damage and potentially fatal complications 1
• Differential diagnosis should include polymyalgia rheumatica, fibromyalgia, drug-induced myopathy, and muscle dystrophies 1
• Myositis-specific autoantibodies can help identify subsets with predominant extramuscular symptoms 2
• Integrated analysis of clinical, laboratory, imaging, and pathology data is often necessary for definitive diagnosis 5