Muscle
Inflammatory muscle
Inclusion body myositis

Author: Meggen A. Walsh, M.D. (see Authors page)
Editor: Jesse Kresak, M.D.

Revised: 4 February 2016, last major update February 2016

Copyright: (c) 2016, PathologyOutlines.com, Inc.

PubMed Search: Inclusion body myositis [title] muscle
Cite this page: Inclusion body myositis. PathologyOutlines.com website. http://pathologyoutlines.com/topic/muscleinclusionbody.html. Accessed April 28th, 2017.
Definition / general
  • An inflammatory myopathy of predominantly skeletal muscle usually seen in ages 50+
  • The main histologic finding is rimmed vacuoles with accumulation of specific proteins of autophagy
Essential features
  • Myopathic muscle with increased internal nuclei and myofiber size variation
  • Inflammatory response is primarily centered around myofibers and is not perivascular
  • "Rimmed vacuoles" are seen with Gomori trichrome stain and protein inclusions of autophagy with special stains
Terminology
Epidemiology
  • In North America, constitutes 16 - 28% of inflammatory myopathies
  • Male to female ratio is 3:1
  • Most occur in older individuals, although congenital and childhood forms have been described (reference)
  • The average age is between 40s - 70s in men and slightly older in females
Sites
  • Generally affects the proximal leg and distal arm musculature; however, any skeletal muscle can be involved
  • Dysphagia can also occur
Clinical features
  • This is a progressive muscle weakness with an insidious onset
  • Patients may have other autoimmune disorders
  • Generally, it affects proximal leg and distal arm musculature and patients can have asymmetry of their weakness
  • The non-dominant side may be affected to a greater extent than the dominant side
  • The most common complaint is quadriceps weakness
  • Finger flexor and ankle dorsiflexion weakness can be noted clinically
  • Dysphagia is a common symptom (J Neurol 2005;252:1448)
  • Generally, patients do not report myalgias (muscle pain or cramps)
Diagnosis
  • Muscle biopsy
  • Serum creatine kinase (CK) can be normal or elevated
  • Typically, patients do not have autoantibodies
Treatment
  • Physical therapy and occupational therapy (exercise program) may be of some assistance (J Rehabil Med 2003;34:31)
  • Recalcitrant to steroid therapy and will progress despite high dose steroids, in contrast to polymyositis, which generally responds to steroid therapy
Laboratory
  • CK, aldolase and AST levels can be elevated (all are non-specific markers of muscle damage)
Radiology description
  • Has a limited role for diagnosis
Prognostic factors
  • Refractory to steroids or immunotherapy
  • Generally, weakness slowly progresses, although complete wheelchair dependence occurs in only 3% (J Neurol 2005;252:1448)
Case reports
Microscopic (histologic) description
  • Variation in myofiber sizes with small angulated myofibers, either individually or in groups
  • Hypertrophied myofibers can also be seen
  • An increase in internal nuclei (normal muscle can have up to 3% of myofibers having internal nuclei) can be seen
  • There can be a brisk inflammatory response including CD8+ lymphocytes, which may invade non-necrotic myofibers
  • Occasional myofibers undergoing phagocytosis by CD68+ macrophages can be identified
  • Regenerating, basophilic myofibers can be seen
  • The Gomori Trichrome stain shows "rimmed vacuoles", although the extent of myofibers having classic rimmed vacuoles varies (Dubowitz: Muscle Biopsy: A Practical Approach, 2013, 4th Edition)
  • The vacuoles disrupt the myofiber architecture and can lack NADH-TR staining (Dubowitz: Muscle Biopsy: A Practical Approach, 2013, 4th Edition)
Microscopic (histologic) images

Images hosted on PathOut server courtesy of Meggen Walsh, M.D.

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Myopathic features

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Ubiquitin

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CD3

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Gomori trichrome

Cytology description
  • Cytology is of limited to no benefit - muscle needle biopsy may not provide a large enough sample to obtain myofibers with rimmed vacuoles
Positive stains
  • Gomori trichrome shows rimmed vacuoles and can show ragged red fibers in areas
  • Congo Red (amyloid) positive "apple-green" birefringence positive inclusions (Arch Neurol 1991;48:1229)
  • Ubiquitin and LC3B highlight the inclusions
  • Ubiquitin, B-amyloid, B-amyloid precursor protein (APP), α-synuclein, tau, TDP43, and LC3B can be seen in the inclusion bodies
  • CD8+ T lymphocytes highlight the inflammatory response and infiltrate non-necrotic myofibers
Negative stains
  • Rarely, cytochrome oxidase / COX negative fibers are seen
Electron microscopy description
Molecular / cytogenetics description
Differential diagnosis
  • Amyotrophic lateral sclerosis: progressive muscle weakness despite therapy, with predominantly, neurogenic changes on muscle biopsy and minimal to no inflammation
  • Dermatomyositis: an inflammatory myositis, but inflammation is generally perivascular with CD4+ T cells and perifascicular myofiber atrophy
  • Polymyositis: in the differential if rimmed vacuoles are not present in inflammatory myositis, because immunostudies for ubiquitin or LC3 show coarse granular staining which suggests inflammatory myositis