What is inclusion body myopathy (inclusion body muscular dystrophy)?

Inclusion Body Myositis: A Progressive Inflammatory and Degenerative Muscle Disease

Inclusion body myositis (IBM) is the most common acquired inflammatory myopathy in adults over age 50, characterized by distinctive asymmetric weakness of the quadriceps and finger/wrist flexors, with muscle biopsy showing rimmed vacuoles, endomysial inflammation, and characteristic protein deposits. 1, 2

Clinical Presentation

IBM presents with a highly recognizable pattern that distinguishes it from other myopathies:

• Weakness pattern: Early and often asymmetric involvement of quadriceps muscles and forearm flexors (wrist and finger flexors) 1
• Age of onset: Typically occurs after age 50 years, with male predominance (3:1 ratio) 3
• Progression: Insidious onset with slow, progressive weakness affecting both proximal and distal muscles 3, 2
• Associated features:
  • Dysphagia is prominent and can lead to feeding tube placement or recurrent aspiration pneumonia 3
  • Foot drop may occur 2
  • Muscle atrophy, particularly of forearm flexors, finger flexors, and quadriceps 3

Diagnostic Features

The diagnosis relies heavily on clinical examination, as biopsy findings may be absent in some cases 1:

Muscle biopsy findings (when present):

• Rimmed vacuoles (bluish on H&E staining, reddish on modified Gomori-Trichrome) 4
• Endomysial mononuclear inflammatory infiltrate 3, 1
• Small groups of atrophic fibers 1
• Eosinophilic cytoplasmic inclusions 1
• Congophilic deposits 3

Laboratory findings:

• Creatine kinase levels may be only minimally elevated (unlike other inflammatory myopathies) 3

Classification criteria: IBM receives a score of 3.1 points for rimmed vacuoles in the 2017 EULAR/ACR classification system 4

Pathophysiology

The pathogenesis remains incompletely understood, with both inflammatory and degenerative features 1, 5:

• May represent either an autoimmune inflammatory myopathy or a primary degenerative myopathy with secondary inflammation 1
• One prevailing theory involves overproduction of beta-amyloid precursor protein in muscle fibers, though this remains controversial 1
• Recent research has identified TDP-43 deposition and mis-splicing as important disease mechanisms 5
• Type 2 muscle fiber selective vulnerability has been demonstrated 5

Distinction from Hereditary Forms

Hereditary inclusion body myopathies (HIBMs) are separate entities with different features 6, 7:

• Autosomal recessive or dominant inheritance 6
• Most commonly due to GNE gene mutations affecting sialic acid biosynthesis 6, 7
• Present in early adulthood (not after age 50) 7
• Typically spare the quadriceps (opposite of sporadic IBM) 7
• Show rimmed vacuoles without inflammation on biopsy 7

Treatment and Prognosis

IBM is generally refractory to immunosuppressive therapy, distinguishing it from other inflammatory myopathies 1, 8:

• No proven effective pharmacotherapy currently exists 2, 9
• Immunomodulatory agents used for dermatomyositis and polymyositis are typically ineffective 1, 10
• Exercise remains the primary therapeutic modality 8
• Physical therapy and assistive devices are essential early in the disease course 3

Functional assessment: The Inclusion Body Myositis Functional Rating Scale evaluates 10 specific tasks including swallowing, handwriting, handling utensils, fine motor tasks, dressing, standing, walking, hygiene, turning in bed, and moving from sitting to standing 3

Emerging therapies under investigation include agents targeting autophagy, myostatin inhibition, and T-cell dysregulation, though recent trials (including sirolimus) have not shown satisfactory results 9, 5, 8

The disease leads to progressive disability, with dysphagia representing a major contributor to morbidity and mortality 9, 8. Early referral to physiatry for assistive devices and management of dysphagia is critical for maintaining quality of life 3.