Inclusion Body Myositis 101

General information

  • Most common muscle disease in patients older than 50 years. More common in white men, but can affect any group
  • Thought to be degenerative, rather than auto-immune. Associated with systemic autoimmune or connective-tissue diseases in up to 15 %

Clinical Manifestations

  • Difficulty with everyday tasks predominantly requiring the use of proximal muscles, such as getting up from a chair, climbing steps, stepping onto a curb, lifting objects, or combing their hair
  • Fine-motor movements that depend on the strength of distal muscles (especially foot extensors and finger flexors), such as buttoning a shirt, sewing, knitting, or writing, are affected fairly early in the course
  • The pharyngeal and neck-flexor muscles are often involved, causing dysphagia or fatigue and difficulty in holding up the head
  • May also progress slowly for years, and its clinical features may simulate those of limb-girdle muscular dystrophy.
  • Consider IBM in patients with polymyositis or dermatomyositis that is resistant to treatment.

Diagnostic Criteria

  • Muscle strength – myopathic muscle weakness with early involvement of the distal muscles
  • EMG – myopathic with mixed potentials
  • Muscle enzymes – normal or elevated
  • Muscle biopsy – definitive
  • Light microscopy —  endomysial inflammation, rimmed vacoules distributed around the edge, eosinophilic cytoplasmic inclusions
  • EM — granules contain membranous whorls. Filamentous inclusions in the cytoplasm or nucleus, prominent in the vicinity of the rimmed vacuoles, are pathognomonic

Treatment

  • Inclusion-body myositis is generally resistant to all therapies, and its rate of progression also appears to be unaffected by treatment.
  • Failed therapies — Steroids, MTX, Cyclophosphamide, Beta-interferon, TNF-a inhibitors, ATGAM, IVIg
  • Future possibilities
    • Alemtuzumab, a T-cell–depleting monoclonal antibody; reported slowed disease progression, improvement of strength in some patients, and reduction in endomysial inflammation
    • Follistatin, an antagonist of the myostatin pathway, has been shown to produce a dramatic increase in muscle mass in animals
    • Arimoclomol, a heat shock protein (HSP) coinducer may slow down the process of protein misfolding and aggregation