Katie DePlatchett, M.D. AM Report May 26, 2010 Inflammatory Myopathies

Infammatory Myopathies Polymyositis Dermatomyositis Inclusion body myositis Overlap myositis – related to connective tissue disorder Cancer-associated myositis myositis with clinical paraneoplastic features and without an overlap autoantibody

Polymyositis Symmetric proximal muscle weakness Elevated serum muscle enzymes* CK, CK-MB, AST, ALT, LD, Aldolase Myopathic changes on EMG Muscle biopsy cellular infiltrate is predominantly within the fascicle with inflammatory cells invading individual muscle fibers cell–mediated, increased numbers of cytotoxic CD8+ T cells, which appear to recognize an antigen on the muscle fiber surface

Polymyositis - histopathology

Dermatomyositis Symmetric proximal muscle weakness Elevated serum muscle enzymes Myopathic changes on EMG Muscle biopsy humorally–mediated disorder (CD4 cells), cellular infiltrate, located principally in perifascicular regions, focused around blood vessels Rash

Dermatomyositis - histology

Dermatomyositis – skin findings Gottron’s sign Heliotrope rash Shaw sign & V sign Mechanic’s hands Psoriasiform changes in scalp

What about auto-antibodies??? ANA present in up to 80% of myositis-specific autoantibodies: anti-Jo-1, highly specific, associated w/ ILD anti-SRP antibodies antibodies to Mi-2, (a nuclear helicase) Not diagnostic but affects prognosis

Inclusion body myositis insidious onset more prominent distal muscle weakness & atrophy (wrists, fingers, anterior tibial) Asymmetric muscle involvement On average, serum muscle enzyme levels are lower in IBM than in PM presence of typical inclusion bodies on muscle biopsy

Overlap Myositis Myopathy associated with the other connective tissue diseases scleroderma, systemic lupus erythematosus, mixed connective tissue disease varies from clinically insignificant to typically severe PM or DM in which myopathy dominates the clinical picture anti-Ro, anti-La, anti-Sm, or anti- ribonucleoprotein (RNP) antibodies.

Differential Diagnosis Drug induced: statins, colchicine, hydroxychloroquine, steroids, etoh, cocaine HIV ALS Myasthenia gravis Muscular dystrophies Inherited metabolic myopathies Amyloid & Sarcoid myopathies

Work-up Serology: CK, CK-MB, AST, ALT, adolase, ANA, anti-Jo1, anti-SRP, anti-Sm, anti-Ro Utox, HIV Muscle biopsy +/- EMGs Age appropriate cancer screening for those with dermatomyositis

Treatment Steroids, PT/rehab Minimal data of long-term follow-up of pts PM: 50% were refractory to steroids DM, 87% responded to steroids but 92% flared when therapy was tapered. Overlap myositis: 89 to 100% responded to steroids, depended on specific antibodies. Methotrexate or Azathioprine

Prognosis Determinants of prognosis: the specific type of myositis disease severity delay in diagnosis Certain autoantibody profile PM: least likely to respond to steroids Overlap myositis: most likely to respond to steroids.