Inflammatory Myopathies

Inflammatory Myopathies: Overview - Muscle Under Siege

• Acquired, immune-mediated disorders causing chronic muscle inflammation and progressive weakness.
• Hallmarks: Symmetrical proximal muscle weakness, elevated creatine kinase (CK), characteristic electromyography (EMG) and muscle biopsy findings.
• Broad classification:
  • Dermatomyositis (DM): Characteristic skin rash.
  • Polymyositis (PM): Muscle inflammation without rash.
  • Inclusion Body Myositis (IBM): Affects distal muscles, older adults.
  • Immune-Mediated Necrotizing Myopathy (IMNM): Minimal inflammation, prominent necrosis.

⭐ Gottron's papules (on knuckles) and heliotrope rash (eyelids) are pathognomonic for Dermatomyositis.

Dermatomyositis (DM) - Rash & Rhabdo

• Autoimmune: progressive symmetrical proximal muscle weakness + pathognomonic skin rashes.
• Rash (Key Features):
  • Heliotrope rash (purplish edematous eyelids)
  • Gottron's papules (violaceous papules on knuckles, extensor surfaces)
  • Shawl sign (erythema: shoulders, upper back)
  • V-sign (erythema: anterior neck, chest)
• Muscle (Rhabdo Risk):
  • Symmetrical proximal weakness (difficulty rising, combing hair)
  • Myalgia, dysphagia
  • ↑↑CK (indicates muscle damage, rhabdomyolysis risk)
• Antibodies: Anti-Mi-2 (classic DM), Anti-Jo-1 (ILD, mechanic's hands), Anti-TIF1-γ (↑ malignancy risk).
• Biopsy: Perifascicular atrophy is hallmark.
• Associations: Malignancy (crucial to screen!), Interstitial Lung Disease (ILD).

⭐ Adult-onset DM carries a significant malignancy risk; Anti-TIF1-γ antibody strongly predicts this. Thorough screening is vital.

Polymyositis (PM) & IMNM - Pure Muscle Maelstrom

• Polymyositis (PM):
  • Symmetrical proximal muscle weakness (pelvic, shoulder girdle); insidious onset.
  • No skin rash (key differentiator from Dermatomyositis).
  • Pathology: Endomysial inflammation; CD8+ T-cell mediated muscle fiber injury.
  • Labs: ↑ CK, aldolase. EMG: myopathic changes.
  • Antibodies: Anti-Jo-1 (part of anti-synthetase syndrome), Anti-SRP.
• Immune-Mediated Necrotizing Myopathy (IMNM):
  • Acute/subacute severe proximal muscle weakness; often more severe than PM.
  • Markedly ↑ CK (often >50x ULN).
  • Pathology: Muscle fiber necrosis with minimal or no inflammatory infiltrate.
  • Antibodies: Anti-SRP, Anti-HMGCR (often statin-associated).

⭐ Anti-HMGCR antibodies are highly specific for statin-associated IMNM, which can persist even after statin discontinuation.

• General Treatment: Corticosteroids, immunosuppressants (e.g., methotrexate, azathioprine).

Inclusion Body Myositis (IBM) - Distinctly Different Decline

• Most common inflammatory myopathy in patients >50 years; male predominance.
• Onset: Insidious. Course: Progressive. Pattern: Asymmetric weakness.
• Hallmark: Weakness of finger flexors (esp. deep) & quadriceps.
• Dysphagia is frequent.
• Muscle Biopsy: Endomysial inflammation (CD8+ T cells), rimmed vacuoles, inclusions (TDP-43, p62, amyloid).
• CK: Normal or mildly elevated.
• Generally refractory to immunosuppressive therapy.

⭐ Profound, often asymmetric, weakness of quadriceps and finger flexors is highly suggestive, especially in elderly males.

Myopathies: Dx & Rx - Solve & Soothe

• Diagnosis (Dx):
  • Clinical: Symmetrical proximal muscle weakness, dysphagia. Skin signs in Dermatomyositis (DM).
  • Labs: ↑CK, ↑Aldolase. Specific autoantibodies (Anti-Jo-1, Anti-Mi-2, Anti-SRP).
  • EMG: Myopathic pattern (short duration, small amplitude units).
  • Muscle Biopsy: Gold standard; inflammation, necrosis. Perifascicular atrophy (DM).
• Treatment (Rx):
  • Corticosteroids: Prednisone (1-2 mg/kg/day) mainstay.
  • Immunosuppressants: Methotrexate (MTX), Azathioprine (AZA), Mycophenolate (MMF) as steroid-sparing.
  • IVIG: Severe/refractory disease, significant dysphagia.
  • Rehabilitation: Physiotherapy essential.

⭐ Anti-SRP myopathy often presents with acute, severe weakness, very high CK levels, and may respond poorly to initial steroid therapy.

High‑Yield Points - ⚡ Biggest Takeaways

• PM & DM: Hallmark is symmetric proximal muscle weakness.
• DM: Gottron's papules, heliotrope rash; associated with ↑ malignancy risk (especially ovarian, lung).
• Anti-Jo-1: Key antibody for antisynthetase syndrome (ILD, arthritis, mechanic's hands).
• IBM: Features asymmetric weakness, distal involvement (e.g., finger flexors), and rimmed vacuoles on biopsy.
• Muscle Biopsy: PM shows endomysial inflammation (CD8+ T-cells); DM shows perifascicular atrophy & perimysial inflammation (CD4+ T-cells).
• Labs: Elevated Creatine Kinase (CK) and abnormal EMG are characteristic findings.
• Treatment: Corticosteroids are the mainstay for PM/DM; IBM is often refractory to treatment.