What are the cardinal signs and symptoms of polymyositis?

dermatomyositis?

overlap syndromes?

inclusion body myositis?

myositis associated with malignancy?

childhood dermatomyositis?

proximal muscle weakness (shoulder girdle - scapular winging, pelvic girdle - ), Neck flexors, Cricopharyngeal muscles, Upper esophageal musculature, Intercostal muscles

quadriceps atrophy (inclusion body myositis)

dermatomyositis: rashes:: heliotrope rash - around the eyelids, V rash on neck, Gottren's papules (acute scaling rash), subQ calcification (detectable on X-ray)

dermatomyositis in kids: eyelid heliotrope

Extramuscular manifestations

cardiac: CHF, arrhythmias

pulmonary: interstitial inflammation, fibrosis; diagnose with PFTs and

                 high resolution computed tomography (CT scan)
joints

How is the dx of polymyositis made?

dermatomyositis?

inclusion body myositis?

PM: 

results of muscle biopsy demonstrating degenerating and regenerating muscle fibers, inflammatory infiltrate consisting of mainly CD8 T-cells and macrophages, capillary obliteration, endothelial cell damage, increased connective tissue

focal and endomysial manifestation (location)

Inclusion body myositis:

cytotoxic T cell and macrophage laden inflammatory infiltrate; little or no musclefiber necrosis or degeneration  

Vacuoles within muscle fibers contain proteins including amyloid, apolipoprotein E and inducible form of nitric oxide synthetase; located around and within muscle fibers expressing MHC-Class I

DM:

inflammatory infiltrate mainly CD4 T cells and B cells (immune complex or antibody-mediated)

perivascular manifestation (location)

childhood form of DM: same

Early treatment for PM/DM?

immunosuppressants for PM/DM?

management protocol?

prednisone (IV if pharyngeal muscles are involved)

Methotrexate (IV or oral)

Azathioprine

Cyclophosphamide

IV Ig

Rituximab (biologic; anti-CD19 m Ab)

indications for immunosuppressives:

Life threatening active disease (eg. respiratory muscle paralysis) or chronic severe and progressive symptoms due to pulmonary disease

Steroid resistance

steroid dependence

intolerable steroid toxicity

What are laboratory abnormalities associated with PM/DM?

which auto-Ab is associated with poor response to tx?

Elevated:

CPK, aldolase, ALT, AST, LDH

non-specific: hematocrit, ESR

Serum autoantibodies:

anti-Jo-1 (anti-tRNA-synthetase)

- associated with PM or DM, relatively acute onset, fever, arthritis, Raynauds, interstitial lung disease

- moderate response to therapy

anti-Mi2 (anti-nuclear helicase)

- associated with DM and good response to therapy

anti-SRP (signal recognition peptide)

- associated with PM and rapid onset, severe weakness

- poor response to tx

Answer to 2nd question:

anti-SRP (associated with PM, rapid disease progression, and poor response to tx)

anti-PM-Scl - overlap syndrome with Scleroderma

anti-RNP: mixed connective tissue disease (mctd)

More on mctd:

clinical manifestations - raynaud's, tight skin, serositis, arthritis

serum autoantibodies - anti-ANA (speckled) and anti-RNP

What is the fatal complication of PM/DM?

Meaning if these pts die, what do they die of?

pulmonary complications: interstitial lung disease; respiratory lung muscle paralysis

(5-30% PM/DM)