What are the clinical presentations and treatment options for polymyositis, dermatomyositis, and inclusion body myositis?

Clinical Presentations of Inflammatory Myopathies: Polymyositis, Dermatomyositis, and Inclusion Body Myositis

The three major inflammatory myopathies (polymyositis, dermatomyositis, and inclusion body myositis) present with distinct clinical, laboratory, and histopathological features that allow for accurate diagnosis and guide appropriate treatment strategies. 1

Polymyositis (PM)

Clinical Presentation

• Symmetric proximal muscle weakness (hallmark feature)
• Insidious onset over weeks to months
• Difficulty rising from chairs, climbing stairs, and lifting objects
• Absence of skin manifestations
• Dysphagia and dysphonia in 30-40% of cases
• Extramuscular manifestations:
  • Interstitial lung disease (ILD)
  • Cardiac involvement (myocarditis, arrhythmias)
  • Raynaud's phenomenon

Laboratory Findings

• Elevated muscle enzymes (CK, LDH, AST, aldolase)
• Myositis-specific autoantibodies (anti-Jo-1, anti-SRP)
• EMG: Myopathic pattern with spontaneous fibrillations

Histopathology

• CD8+ cytotoxic T cells invading non-necrotic muscle fibers
• Endomysial inflammation

Dermatomyositis (DM)

Clinical Presentation

• Symmetric proximal muscle weakness (similar to PM)
• Distinctive cutaneous manifestations:
  • Heliotrope rash (pathognomonic purplish discoloration of eyelids)
  • Gottron's papules (erythematous, scaly papules over knuckles)
  • Gottron's sign (erythematous, macular rash over extensor surfaces)
  • V-sign (erythematous rash on anterior chest in V-distribution)
  • Shawl sign (erythematous rash over shoulders and upper back)
  • Periungual telangiectasias
  • "Mechanic's hands" (hyperkeratotic, fissured skin on lateral/palmar fingers)
• Dysphagia in up to 50% of cases
• Increased risk of malignancy (3-8 times higher than general population)
• Calcinosis cutis (especially in juvenile DM)
• Cutaneous vasculitis and ulcerations (in juvenile DM)

Laboratory Findings

• Elevated muscle enzymes (may be normal in amyopathic DM)
• Myositis-specific autoantibodies (anti-Mi-2, anti-TIF1-γ, anti-NXP-2)
• Type 1 interferon signature

Histopathology

• Perifascicular atrophy (hallmark feature)
• Perivascular inflammation with plasmacytoid dendritic cells
• Complement deposition on capillaries
• Reduced capillary density

Inclusion Body Myositis (IBM)

Clinical Presentation

• Distinctive pattern of weakness:
  • Asymmetric involvement
  • Selective early involvement of finger flexors and wrist flexors
  • Quadriceps weakness (knee buckling)
  • Ankle dorsiflexor weakness
• Slower progression than PM/DM (months to years)
• Older age of onset (typically >50 years)
• Male predominance
• Dysphagia in up to 60% of cases
• Associated peripheral neuropathy
• Refractory to immunosuppressive therapy

Laboratory Findings

• Modestly elevated or normal CK levels (typically <10x normal)
• Anti-cN1A (anti-NT5c1A) autoantibodies in 30-40% of cases

Histopathology

• Rimmed vacuoles
• Eosinophilic cytoplasmic inclusions
• Amyloid-β and phosphorylated tau protein deposits
• Endomysial inflammation with CD8+ T cells

Treatment Approaches

Polymyositis and Dermatomyositis

1. First-line therapy:

   • High-dose corticosteroids (prednisone 1-2 mg/kg/day) 1, 2, 3
   • Concurrent steroid-sparing agent (methotrexate 15-20 mg/week) 2

2. Second-line therapy (for refractory cases):

   • IVIG (1-2 g/kg divided over 1-2 days, monthly) 2
   • Mycophenolate mofetil
   • Azathioprine
   • Rituximab
   • Cyclosporine

3. For cutaneous manifestations:

   • Hydroxychloroquine (5 mg/kg/day) 2
   • Topical corticosteroids or tacrolimus 2
   • Sun protection

Inclusion Body Myositis

• Generally resistant to immunosuppressive therapy
• Focus on physical therapy and supportive care
• Experimental therapies in clinical trials

Important Clinical Considerations

Malignancy Screening

• Essential in newly diagnosed DM patients (especially those with anti-TIF1-γ antibodies)
• Common malignancies: ovarian, lung, pancreatic, stomach, colorectal 2

Cardiac Evaluation

• ECG and cardiac troponin measurement
• Echocardiography if symptoms or abnormal ECG
• Higher mortality in patients with myocarditis 2

Monitoring

• Regular assessment of muscle strength
• Tracking of muscle enzyme levels
• Evaluation of extramuscular manifestations
• Monitoring for treatment-related complications (osteoporosis, infections) 1

Pitfalls in Diagnosis

1. Misdiagnosing IBM as PM due to similar histopathological features early in disease
2. Failing to recognize amyopathic DM (skin manifestations without muscle involvement)
3. Overlooking drug-induced myopathies (statins, immune checkpoint inhibitors)
4. Confusing immune-mediated necrotizing myopathy with PM
5. Not considering muscular dystrophies with inflammatory features in the differential

Early recognition of the distinct clinical patterns of each inflammatory myopathy is crucial for appropriate treatment selection and improved outcomes.