Editing Inclusion body myositis

{{short description|Inflammatory muscle disease in older adults}}
{{Infobox medical condition (new)
| name            = Inclusion body myositis
| synonyms        =sIBM
| image           =
| caption         =
| pronounce       =
| field           = [[Rheumatology]], [[Neurology]], [[Neuromuscular medicine]]
| symptoms        = Weakness
| complications   =
| onset           = Typically after age 45<ref name="Weihl2019Review" />
| duration        =
| types           =
| causes          =
| risks           =
| diagnosis       =
| differential    = [[deconditioning]], hereditary muscle diseases<ref name="Weihl2019Review" />
| prevention      =
| treatment       =
| medication      =
| prognosis       =
| frequency       = 5-71/1,000,000<ref name="Weihl2019Review">{{cite journal |last1=Weihl |first1=CC |title=Sporadic Inclusion Body Myositis and Other Rimmed Vacuolar Myopathies. |journal=Continuum (Minneapolis, Minn.) |date=December 2019 |volume=25 |issue=6 |pages=1586–1598 |doi=10.1212/CON.0000000000000790 |pmid=31794461|s2cid=208531761 }}</ref>
| deaths          =
}}

'''Inclusion body myositis''' ('''IBM''') ({{IPAc-en|m|aI|ou|'|s|aI|t|I|s}}) (sometimes called '''sporadic inclusion body myositis''', '''sIBM''') is the most common [[Inflammatory myopathy|inflammatory muscle disease]] in older adults.<ref>{{cite journal|last1=Ahmed|first1=Mhoriam|last2=Machado|first2=Pedro M|last3=Miller|first3=Adrian|last4=Spicer|first4=Charlotte|last5=Herbelin|first5=Laura|last6=et|first6=al|title=Targeting protein homeostasis in sporadic inclusion body myositis|journal=Science Translational Medicine|date=March 23, 2016|volume=8|issue=331|pages=331ra41|doi=10.1126/scitranslmed.aad4583|pmid=27009270|pmc=5043094}}</ref> The disease is characterized by slowly progressive weakness and wasting of both proximal muscles (located on or close to the [[torso]]) and distal muscles (close to hands or feet), most apparent in the [[finger]] [[flexor]]s and [[knee]] [[extensor]]s.<ref>{{cite journal|last1=Jackson|first1=CE|last2=Barohn|first2=RJ|last3=Gronseth|first3=G|last4=Pandya|first4=S|last5=Herbelin|first5=L|last6=and|first6=The Muscle Study Group|title=Inclusion body myositis functional rating scale: a reliable and valid measure of disease severity|journal=Muscle and Nerve|date=April 2008|volume=37|issue=4|pages=473–476|doi=10.1002/mus.20958|pmid=18236463|s2cid=22284747}}</ref> IBM is often confused with an entirely different class of diseases, called [[Hereditary inclusion body myopathy|hereditary inclusion body myopathies]] (hIBM).<ref>[http://ibmmyositis.com/ IBMmyositis.com]</ref><ref>[https://cureibm.org/ cureibm.org]</ref> The "M" in hIBM is an abbreviation for "myopathy" while the "M" in IBM is for "myositis".<ref name="Greenberg2019Review">{{cite journal |last1=Greenberg |first1=SA |title=Inclusion body myositis: clinical features and pathogenesis. |journal=Nature Reviews. Rheumatology |date=May 2019 |volume=15 |issue=5 |pages=257–272 |doi=10.1038/s41584-019-0186-x |pmid=30837708|s2cid=71146208 }}</ref> In IBM, two processes appear to occur in the muscles in parallel, one autoimmune and the other degenerative. Inflammation is evident from the invasion of muscle fibers by [[Lymphocyte|immune cells]]. Degeneration is characterized by the appearance of [[vacuole|holes]], deposits of [[Amyloid|abnormal proteins]], and filamentous inclusions in the muscle fibers.<ref>{{cite journal|last1=Machado|first1=P|last2=Dimachkie|first2=MM|last3=Bahron|first3=RJ|title=Sporadic Inclusion Body Myositis: new insights and potential therapy|journal=Current Opinion in Neurology|date=October 2014|volume=27|issue=5|pages=591–598|doi=10.1097/WCO.0000000000000129|pmid=25159931|pmc=4248565}}</ref> sIBM is a rare disease, with a prevalence ranging from 1 to 71 individuals per million.<ref>{{cite journal|last1=Machado|first1=P|last2=Brady|first2=S|last3=Hanna|first3=MG|title=Update in inclusion body myosities|journal=Current Opinion in Rheumatology|date=2013|volume=25|issue=763–771|pages=763–771|doi=10.1097/01.bor.0000434671.77891.9a|pmid=24067381|pmc=4196838}}</ref><ref>{{cite web | url=http://rarediseases.org/rare-diseases/sporadic-inclusion-body-myositis/ | title=Sporadic Inclusion Body Myositis}}</ref>

Weakness comes on slowly (over months to years) in an asymmetric manner and progresses steadily, leading to severe weakness and wasting of arm and leg muscles. IBM is more common in men than women.<ref>{{cite web | url=http://patient.info/doctor/inclusion-body-myositis | title=Inclusion Body Myositis. IBM information; Age Related illness| date=20 June 2016}}</ref> Patients may become unable to perform [[activities of daily living]] and most require assistive devices within 5 to 10 years of symptom onset.<ref>{{cite web | url=http://www.ibmfoundation.org/index.php/understanding-ibm | title=Understanding IBM}}</ref> sIBM does not significantly affect [[life expectancy]],<ref name="Weihl2019Review" /> although death related to [[malnutrition]] and [[respiration (physiology)|respiratory]] failure can occur.<ref>{{cite journal|last1=Cox|first1=FM|last2=Titulaer|first2=MJ|last3=Sont|first3=JK|last4=Wintzen|first4=AR|last5=et|first5=al|title=A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities|journal=Brain|date=November 1, 2011|volume=134|issue=11|pages=3167–3175|doi=10.1093/brain/awr217|pmid=21908393|doi-access=free}}</ref> The risk of serious injury due to falls is increased.<ref name="Weihl2019Review" /> There is no effective treatment for the disease as of 2019.<ref name="Weihl2019Review" />

==Classification and terminology==
'''IBM''' stands for "inclusion body ''myositis:'' not "inclusion body ''myopathy.''"<ref name="Greenberg2019Review" /> The 'inclusion body' refers to a histological finding of rimmed vacuoles in muscle tissue.<ref name="Greenberg2019Review" /> However, IBM does not refer to the collection of diseases that feature these inclusion bodies. It refers to a specific disease entity.<ref name="Greenberg2019Review" />

Multiple genetic diseases that feature inclusion bodies have been grouped into "''hereditary'' inclusion body ''myopathies'' (hIBM)."<ref name="Greenberg2019Review" /> ''Myopathy'' is used because inflammation is not a prominent finding. There is inconsistency in what individual disease entities fall under the category of hIBM.<ref name="Greenberg2019Review" /> The term "''sporadic'' inclusion body ''myositis''" (sIBM) was introduced as a way to refer to IBM to avoid confusion with hIBM.<ref name="Greenberg2019Review" /> However, one author discourages use of sIBM, as it implies that IBM and hIBM differ only in inheritance; they actually have unrelated mechanisms and manifestations of disease.<ref name="Greenberg2019Review" />

==Signs and symptoms==
[[File:Affected quadriceps (rectus femoris) in IBM.png|thumb|right|Affected quadriceps (rectus femoris) in IBM]]

sIBM causes progressive muscle weakness.<ref name="Weihl2019Review" /> How sIBM affects individuals is variable, including the age of onset (which generally varies from the forties upwards) and rate of progression. Because of this variability, there is no "textbook case".<ref>{{Cite journal |last1=Evangelista |first1=Teresinha |last2=Weihl |first2=Conrad C. |last3=Kimonis |first3=Virginia |last4=Lochmüller |first4=Hanns |last5=Clemen |first5=Christoph |last6=Deshaies |first6=Ray |last7=Evangelista |first7=Teresinha |last8=Eymard |first8=Bruno |last9=Greensmith |first9=Linda |last10=Hilton-Jones |first10=David |last11=Kimonis |first11=Virginia |last12=Kley |first12=Rudy |last13=Lochmüller |first13=Hanns |last14=Meyer |first14=Hemmo |last15=Mozaffar |first15=Tahseen |date=August 2016 |title=215th ENMC International Workshop VCP-related multi-system proteinopathy (IBMPFD) 13–15 November 2015, Heemskerk, The Netherlands |journal=Neuromuscular Disorders |language=en |volume=26 |issue=8 |pages=535–547 |doi=10.1016/j.nmd.2016.05.017 |pmid=27312024 |pmc=5967615 |issn=0960-8966}}</ref>

Common early symptoms include frequent tripping and falling and difficulty going up stairs. [[Foot drop]] in one or both feet can occur.<ref>{{Cite web|title=Inclusion Body Myositis|url=https://understandingmyositis.org/myositis/inclusion-body-myositis/|access-date=2021-06-12|website=www.google.com}}</ref> Part of the cause for this dysfunction is the early involvement of the [[quadriceps]] muscles.<ref name="Weihl2019Review" /> Weakness of the [[tibialis anterior muscle]] is responsible for foot drop. Another common early symptom is trouble manipulating the fingers, such as difficulty with tasks such as turning doorknobs or gripping keys. Weakness of finger flexion and ankle dorsiflexion occurs early.<ref name="Weihl2019Review" /> sIBM also preferentially affects the [[List of flexors of the human body#Upper limb|wrist flexors]], [[biceps]], and [[triceps]].<ref name="Weihl2019Review" />

During the course of the illness, the patient's mobility is progressively restricted as it becomes difficult to bend down, reach for things, and walk quickly. Many patients say they have balance problems and fall easily, as the muscles cannot compensate for an off-balanced posture. Because sIBM makes the leg muscles weak and unstable, patients are very vulnerable to serious injury from tripping or falling down. Although pain has not been traditionally part of the "textbook" description, many patients report severe muscle pain, especially in the thighs.{{citation needed|date=February 2021}}

[[File:Inclusion body myositis arms.png|thumb|left|Affected arms and fingers in IBM]]

Progressive difficulty swallowing ([[dysphagia]]) is present in 40 to 85% of IBM cases and often leads to death from [[aspiration pneumonia]].<ref name="pmid18936555">{{cite journal |vauthors=Oh TH, Brumfield KA, Hoskin TL, Kasperbauer JL, Basford JR |title=Dysphagia in inclusion body myositis: clinical features, management, and clinical outcome |journal=Am J Phys Med Rehabil |volume=87 |issue=11 |pages=883–9 |year=2008 |pmid=18936555 |doi=10.1097/PHM.0b013e31818a50e2 |s2cid=11878442 }}</ref>

IBM can also result in diminished capacity for aerobic exercise. This decline is most likely a consequence of the sedentary lifestyle leading to disuse [[muscle atrophy]] that is often associated with the symptoms of IBM (i.e. progressive muscle weakness, decreased mobility, and increased level of fatigue). Therefore, one focus of treatment should be the improvement of aerobic capacity.<ref>{{cite journal  |vauthors=Johnson LG, Collier KE, Edwards DJ, et al |title=Improvement in aerobic capacity after an exercise program in sporadic inclusion body myositis |journal=J Clin Neuromuscul Dis |volume=10 |issue=4 |pages=178–84 |date=June 2009 |pmid=19494728 |doi=10.1097/CND.0b013e3181a23c86 |s2cid=14686189 }}</ref>

Patients with sIBM usually eventually need to resort to a cane or a walker and in most cases, a wheelchair eventually becomes a necessity.

"The progressive course of s-IBM leads slowly to severe disability. Finger functions can become very impaired, such as manipulating pens, keys, buttons, and zippers, pulling handles, and firmly grasping handshakes. Arising from a chair becomes difficult. Walking becomes more precarious. Sudden falls, sometimes resulting in major injury to the skull or other bones, can occur, even from walking on minimally irregular ground or from other minor imbalances outside or in the home, due to weakness of quadriceps and gluteus muscles depriving the patient of automatic posture maintenance. A foot-drop can increase the likelihood of tripping. [[Dysphagia]] can occur, usually caused by upper esophageal constriction that often can be symptomatically improved, for several months to years, by bougie dilation per a GI or ENT physician. Respiratory muscle weakness can sometimes eventuate."<ref name="pmid16432144">{{cite journal |vauthors=Askanas V, Engel WK |title=Inclusion-body myositis: a myodegenerative conformational disorder associated with Abeta, protein misfolding, and proteasome inhibition |journal=Neurology |volume=66 |issue=2 Suppl 1 | pages = S39–S48 |year=2006 |pmid=16432144 |doi=10.1212/01.wnl.0000192128.13875.1e|s2cid=24365234 }}</ref>

==Causes==
The cause of IBM is unknown. IBM likely results from the interaction of a number of genetic and environmental factors.<ref name="General Information About IBM">{{cite web|title=Inclusion Body Myositis (IBM)|url=http://ibmmyositis.com/aboutibm1old.htm|access-date=7 May 2017|archive-date=16 October 2018|archive-url=https://web.archive.org/web/20181016125546/http://ibmmyositis.com/aboutibm1old.htm|url-status=dead}}</ref>

There are two major theories about how sIBM is caused. One hypothesis suggests that the inflammation-immune reaction, caused by an unknown trigger&nbsp;– likely an undiscovered virus or an autoimmune disorder – is the primary cause of sIBM and that the degeneration of muscle fibers and protein abnormalities are secondary features.<ref name="pmid16932602">{{cite journal |author=Dalakas MC |title=Sporadic inclusion body myositis--diagnosis, pathogenesis and therapeutic strategies |journal=Nat Clin Pract Neurol |volume=2 |issue=8 |pages=437–447 |year=2006 |pmid=16932602 |doi=10.1038/ncpneuro0261|s2cid=7462545 |url=https://zenodo.org/record/1233387 }}</ref> Despite the arguments "in favor of an adaptive immune response in sIBM, a purely autoimmune hypothesis for sIBM is untenable because of the disease's resistance to most immunotherapy."<ref>{{EMedicine|article|1172746|Inclusion Body Myositis}}</ref>

The second school of thought advocates the theory that sIBM is a degenerative disorder related to aging of the muscle fibers and that abnormal, potentially pathogenic protein accumulations in myofibrils play a key causative role in sIBM (apparently before the immune system comes into play). This hypothesis emphasizes the abnormal intracellular accumulation of many proteins, protein aggregation and misfolding, [[proteosome]] inhibition, and [[endoplasmic reticulum]] (ER) stress.<ref name="pmid16432144"/>

One review discusses the "limitations in the beta-amyloid-mediated theory of IBM myofiber injury."<ref name="pmid19080758">{{cite journal |author=Greenberg SA. |title=Inclusion body myositis: review of recent literature |journal=Curr Neurol Neurosci Rep |volume=9 |issue=1 |pages=83–89 |year=2009 |pmid=19080758 |doi=10.1007/s11910-009-0013-x |s2cid=16391053 }}</ref>

Dalakas (2006) suggested that a chain of events causes IBM – some sort of virus, likely a [[retrovirus]], triggers the cloning of [[T cells]]. These T cells appear to be driven by specific [[antigen]]s to invade muscle fibers. In people with sIBM, the muscle cells display "flags" telling the immune system that they are infected or damaged (the muscles ubiquitously express MHC class I antigens) and this immune process leads to the death of muscle cells. The chronic stimulation of these antigens also causes stress inside the muscle cell in the [[endoplasmic reticulum]] (ER) and this ER stress may be enough to cause a self-sustaining T cell response (even after a virus has dissipated). In addition, this ER stress may cause the misfolding of protein. The ER is in charge of processing and folding molecules carrying antigens. In IBM, muscle fibers are overloaded with these [[major histocompatibility complex]] (MHC) molecules that carry the antigen protein pieces, leading to more ER stress and more protein misfolding.<ref name="pmid16932602"/>

A self-sustaining T cell response would make sIBM a type of autoimmune disorder. When studied carefully, it has not been possible to detect an ongoing viral infection in the muscles. One theory is that a chronic viral infection might be the initial triggering factor setting IBM in motion. There have been a handful of IBM cases – approximately 15 – that have shown clear evidence of a virus called [[HTLV-1]]. The HTLV-1 virus can cause [[leukemia]], but in most cases lies dormant and most people end up being lifelong carriers of the virus. One review says that the best evidence points towards a connection with some type of retrovirus and that a retroviral infection combined with immune recognition of the retrovirus is enough to trigger the inflammation process.<ref name="pmid16932602"/>
* [[amyloid]] protein
* The hypothesis that [[beta amyloid]] protein is key to IBM has been supported in a mouse model using an Aβ vaccine that was found to be effective against inclusion body myositis in mouse models. Although this vaccine is likely, not safe for human use, it still shows that attacking Aβ has efficacy in mice against IBM.<ref>{{cite journal |title=Immunization with amyloid-β attenuates inclusion body myositis-like myopathology and motor impairment in a transgenic mouse model |vauthors=Kitazawa M, Vasilevko V, Cribbs DH, LaFerla FM |journal=The Journal of Neuroscience |date=13 May 2009 |volume=29 |issue=19 |pages=6132–41 |quote=Inclusion body myositis...features include T-cell mediated inflammatory infiltrates and aberrant accumulations of proteins, including amyloid-β (Aβ), tau, ubiquitinated proteins, apolipoprotein E, and β-synuclein in skeletal muscle. ... active immunization markedly reduces intracellular Aβ deposits and attenuates the motor impairment compared with untreated mice...Aβ oligomers contribute to the myopathy process as they were significantly reduced in the affected skeletal muscle from immunized mice. In addition, the anti-Aβ antibodies produced in the immunized mice blocked the toxicity of the Aβ oligomers in vitro, providing a possible key mechanism for functional recovery. |doi=10.1523/JNEUROSCI.1150-09.2009 |pmid=19439591 |pmc=3049190}}</ref>
* Following up on earlier leads, the Greenberg group report finding that the protein TDP-43 is a very prominent and highly sensitive and specific feature of IBM. This protein is normally found within the nucleus but in IBM is found in the cytoplasm of the cell. This important advance should help develop a new screening technique for IBM and may provide clues in terms of a therapeutic approach<ref>{{cite journal |title=Sarcoplasmic redistribution of nuclear TDP-43 in inclusion body myositis |author=Salajegheh, M, Pinkus, JL, Taylor, JP, Amato, AA, Nazareno, R, Baloh, RH, Greenberg, SA. |journal=Muscle Nerve |year=2009 |volume=40 |issue=1 |pages=19–31 |doi=10.1002/mus.21386 |pmid=19533646 |pmc=2700211}}</ref>

===Genetics===
sIBM is not inherited and is not passed on to the children of IBM patients. There are genetic features that do not directly cause IBM but that appear to predispose a person to getting IBM&nbsp;– having this particular combination of genes increases one's susceptibility to getting IBM. Some 67% of IBM patients have a particular combination of [[human leukocyte antigen]] genes in a section of the 8.1 ancestral haplotype in the center of the MHC class II region. sIBM is not passed on from generation to generation, although the susceptibility region of genes may be.<ref name="pmid16932602"/>

There are also several rare forms of hereditary inclusion body myopathy that are linked to specific genetic defects and that are passed on from generation to generation. Since these forms do not show features of muscle inflammation, they are classified as myopathies rather than forms of myositis. Because they do not display inflammation as a primary symptom, they may in fact be similar, but different diseases to sporadic inclusion body myositis. There are several different types, each inherited in different ways. See [[hereditary inclusion body myopathy]].<ref>{{Cite web |title=Inclusion body myopathy 2: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/condition/inclusion-body-myopathy-2/ |access-date=2022-11-18 |website=medlineplus.gov |language=en}}</ref>

A 2007 review concluded there is no indication that the genes responsible for the familial or hereditary conditions are involved in sIBM.<ref name="pmid17366591">{{cite journal |vauthors=Needham M, Mastaglia FL, Garlepp MJ |title=Genetics of inclusion-body myositis |journal=Muscle Nerve |volume=35 |issue=5 |pages=549–561 |year=2007 |pmid=17366591 |doi=10.1002/mus.20766|s2cid=23665612 }}</ref>

==Diagnosis==
[[File:Inclusion body myositis histology.jpg|thumb|right|Inclusion body myositis histology]]

Elevated [[creatine kinase]] (CK) levels in the blood (at most ~10 times normal) are typical in sIBM but affected individuals can also present with normal CK levels. [[Electromyography]] (EMG) studies display variable abnormalities such as increased insertional activity,<ref>{{Cite journal |last1=Moghadam-Kia |first1=Siamak |last2=Oddis |first2=Chester V. |last3=Aggarwal |first3=Rohit |date=2016 |title=Approach to asymptomatic creatine kinase elevation |journal=Cleveland Clinic Journal of Medicine |language=en |volume=83 |issue=1 |pages=37–42 |doi=10.3949/ccjm.83a.14120 |pmid=26760521 |pmc=4871266 |issn=0891-1150}}</ref> increased spontaneous activity (fibrillation potentials and sharp waves),<ref name="Weihl2019Review" /> and large/broad or short/narrow motor unit potentials.<ref name="Weihl2019Review" /> On EMG, recruitment patterns can be reduced or increased. Findings can vary even within the same muscle of an affected individual.<ref name="Weihl2019Review" /> Muscle biopsy may display several common findings including inflammatory cells invading muscle cells, vacuolar degeneration, and [[inclusion bodies]] of aggregations of multiple proteins.<ref name="NORD">{{cite web |title=Sporadic Inclusion Body Myositis |url=https://rarediseases.org/rare-diseases/sporadic-inclusion-body-myositis/ |website=NORD (National Organization for Rare Disorders)}}</ref> sIBM is a challenge to the pathologist and even with a biopsy, diagnosis can be ambiguous.<ref>{{Cite web |title=muscle biopsy revealed: Topics by Science.gov |url=https://www.science.gov/topicpages/m/muscle+biopsy+revealed.html |access-date=2022-10-28 |website=www.science.gov}}</ref>

A diagnosis of inclusion body myositis was historically dependent on muscle biopsy results. Antibodies to cytoplasmic 5'-nucleotidase (cN1A; [[NT5C1A]]) have been strongly associated with the condition.<ref name="Weihl2019Review" /> However, other inflammatory conditions, such as lupus, can have a positive anti-NT5C1A.<ref name="Weihl2019Review" /> As of 2019, it remains to be established whether a positive anti-NT5C1A antibody test can make muscle biopsy unneeded.<ref name="Weihl2019Review" />
[[File:Inclusion body myositis MRI.jpg|thumb|left|Inclusion body myositis MRI]]

Muscle imaging can help establish the pattern of muscle involvement and selection of a biopsy site.<ref name="Weihl2019Review" />

===Differential diagnosis===
IBM is often initially misdiagnosed as [[polymyositis]]. A course of [[prednisone]] is typically completed with no improvement and eventually, sIBM is confirmed. sIBM weakness comes on over months or years and progresses steadily, whereas polymyositis has an onset of weeks or months. [[Muscular dystrophy]] (e.g., [[limb girdle muscular dystrophy]]) must be considered as well.{{citation needed|date=February 2021}} sIBM can be mistaken for physical deconditioning.<ref name="Weihl2019Review" />

Hereditary myopathies can mimic sIBM, both in signs and symptoms and in the appearance of muscle biopsies. A small percentage of those initially diagnosed with sIBM are later found to have pathogenic mutations in the genes ''[[Valosin-containing protein|VCP]]'' and ''[[SQSTM1]]'', which are known to cause hIBM.<ref name="Weihl2019Review" />

IBM has a distinctive pattern of muscle involvement that distinguishes it among inflammatory myopathies.<ref name="Greenberg2019Review" /> Characteristic of IBM is weakness of finger flexion, knee extension, and ankle dorsiflexion.<ref name="Greenberg2019Review" /> Other inflammatory myopathies cause a proximal muscle weakness pattern, such as weakness of hip flexion, abduction, and extension, as well as shoulder abduction.<ref name="Greenberg2019Review" /> IBM and other inflammatory myopathies both cause bicep/tricep weakness.<ref name="Greenberg2019Review" />

===Classification===
* The common type is sIBM; it strikes individuals apparently at random.<ref>{{cite journal |vauthors=Karpati G, O'Ferrall EK | date = Jan 2009 | title = Sporadic inclusion body myositis: Pathogenic considerations| journal = Ann Neurol | volume = 65 | issue = 1| pages = 7–11 | doi=10.1002/ana.21622| pmid = 19194875 | s2cid = 41203262 }}</ref>
* There is a type that has been observed in multiple siblings in the same generation in several families, termed ''familial inflammatory sIBM'', but it is not passed on from generation to generation.<ref name="pmid16932602" />
* There are also several very rare forms of ''hereditary inclusion body myopathy'' (hIBM) that are linked to specific genetic defects and that are passed on from generation to generation, each inherited in different ways.<ref>{{cite journal |author1=Broccolini A. |author2=Mirabella M. | year = 2014 | title = Hereditary inclusion-body myopathies | journal = Biochim. Biophys. Acta | volume = 1852| issue = 4| pages = 644–650| doi = 10.1016/j.bbadis.2014.08.007 | pmid=25149037| doi-access = free }}</ref>

==Management==
There is no standard course of treatment to slow or stop the progression of the disease as of 2019.<ref name="Weihl2019Review" /> sIBM patients do not reliably respond to [[anti-inflammatory]], [[immunosuppressant]], or [[immunomodulatory | immunomodulatory medications]].<ref>{{Cite journal |last1=Suzuki |first1=Naoki |last2=Mori-Yoshimura |first2=Madoka |last3=Yamashita |first3=Satoshi |last4=Nakano |first4=Satoshi |last5=Murata |first5=Ken-ya |last6=Inamori |first6=Yukie |last7=Matsui |first7=Naoko |last8=Kimura |first8=En |last9=Kusaka |first9=Hirofumi |last10=Kondo |first10=Tomoyoshi |last11=Higuchi |first11=Itsuro |last12=Kaji |first12=Ryuji |last13=Tateyama |first13=Maki |last14=Izumi |first14=Rumiko |last15=Ono |first15=Hiroya |date=2016-11-08 |title=Multicenter questionnaire survey for sporadic inclusion body myositis in Japan |journal=Orphanet Journal of Rare Diseases |language=en |volume=11 |issue=1 |page=146 |doi=10.1186/s13023-016-0524-x |pmid=27821140 |pmc=5100251 |issn=1750-1172 |doi-access=free }}</ref> Most of disease management is [[Symptomatic treatment|supportive care]].<ref name="Weihl2019Review" /> Prevention of falls is an important consideration.<ref name="Weihl2019Review" /> There is no consensus on [[Exercise therapy for idiopathic inflammatory myopathies|exercise guidelines]]; however, physical therapy is recommended to teach the patient a home exercise program, to teach how to compensate during mobility-gait training with an assistive device, transfers and bed mobility.<ref>{{Cite web|date=March 17, 2019|title=Inclusion Body Myositis Information Page|url=https://www.ninds.nih.gov/Disorders/All-Disorders/Inclusion-Body-Myositis-Information-Page|access-date=June 25, 2021|website=National Institute of Neurological Disorders and Stroke}}</ref> An exercise regimen preferentially minimizes a patient's risk of injury and corresponds to the patient's goals.<ref name="Weihl2019Review" /><ref>{{Cite journal |last1=Naddaf |first1=Elie |last2=Barohn |first2=Richard J. |last3=Dimachkie |first3=Mazen M. |date=August 22, 2018 |title=Inclusion Body Myositis: Update on Pathogenesis and Treatment |journal=Neurotherapeutics |volume=15 |issue=4 |pages=995–1005 |doi=10.1007/s13311-018-0658-8 |issn=1933-7213 |pmc=6277289 |pmid=30136253}}</ref>

==Other related disorders==
When sIBM was originally described, the major feature noted was muscle inflammation. Two other disorders were also known to display muscle inflammation, and sIBM was classified along with them. They are [[dermatomyositis]] (DM) and [[polymyositis]] (PM) and all three illnesses were called [[idiopathic]] (of unknown origin) myositis or inflammatory myopathies.<ref>{{cite web |url=https://www.lecturio.com/concepts/dermatomyositis-dm/| title=Dermatomyositis (DM)
|website=The Lecturio Medical Concept Library |access-date= 11 July 2021}}</ref>

It appears that sIBM and polymyositis share some features, especially the initial sequence of immune system activation, however, polymyositis comes on over weeks or months, does not display the subsequent muscle degeneration and protein abnormalities as seen in IBM, and as well, polymyositis tends to respond well to treatments, IBM does not. IBM is often confused with (misdiagnosed as) polymyositis. Polymyositis that does not respond to treatment is likely IBM.<ref>[http://www.myositis.org/your-myositis-community/live-discussions/406-when-myositis-doesnt-respond-to-treatment When myositis doesn't respond to treatment] Retrieved 20 April 2015.</ref>

[[Dermatomyositis]] shares a number of similar physical symptoms and histopathological traits as polymyositis, but exhibits a skin rash not seen in polymyositis or sIBM. It may have different root causes unrelated to either polymyositis or sIBM.<ref>{{Cite journal |last1=Malik |first1=Asma |last2=Hayat |first2=Ghazala |last3=Kalia |first3=Junaid S. |last4=Guzman |first4=Miguel A. |date=2016-05-20 |title=Idiopathic Inflammatory Myopathies: Clinical Approach and Management |journal=Frontiers in Neurology |language=en |volume=7 |page=64 |doi=10.3389/fneur.2016.00064 |pmid=27242652 |pmc=4873503 |issn=1664-2295|doi-access=free }}</ref>

Mutations in [[valosin-containing protein]] (VCP) cause [[multisystem proteinopathy]] (MSP), which can present (among others) as a rare form of inclusion body myopathy.<ref>{{cite journal |vauthors=Harrison AF, Shorter J |title=RNA-binding proteins with prion-like domains in health and disease |journal=Biochem. J. |volume=474 |issue=8 |pages=1417–1438 |date=April 2017 |pmid=28389532 |pmc=5639257 |doi=10.1042/BCJ20160499 }}</ref>

==Epidemiology==
Prevalence of disease in a rigorous [[meta-analysis]] in 2017 was 46 patients per million.<ref name="Greenberg2019Review" /> The earliest published prevalence was in 2000 and put at 5 per million.<ref name="Greenberg2019Review" /> A 2017 study in Ireland reported 112 per million.<ref name="Greenberg2019Review" /> It is not believed that the disease prevalence is increasing with time, but rather diagnostics and reporting are improving.<ref name="Greenberg2019Review" />

Estimates of the mean age of onset range from 61 to 68 years old.<ref name="Greenberg2019Review" />

==Society and culture==
In the biographical drama film [[Father Stu]], the protagonist, a boxer-turned-Catholic priest, has sIBM.<ref name="Fleming2022FrStu">{{cite news |last1=Fleming |first1=Kristen |title='Father Stu': How a motorcycle accident turned this former boxer into a priest |url=https://nypost.com/2022/04/13/father-stu-motorcycle-accident-turned-ex-boxer-into-priest/ |access-date=27 April 2022 |work=New York Post |date=13 April 2022 |archive-url=https://web.archive.org/web/20220422233802/https://nypost.com/2022/04/13/father-stu-motorcycle-accident-turned-ex-boxer-into-priest/ |archive-date=22 April 2022}}</ref><ref name="Rapold2022FrStu">{{cite news |last1=Rapold |first1=Nicolas |title='Father Stu' Review: Screwball Salvation |url=https://www.nytimes.com/2022/04/13/movies/father-stu-review.html |access-date=27 April 2022 |work=The New York Times |date=13 April 2022 |archive-url=https://web.archive.org/web/20220416085407/https://www.nytimes.com/2022/04/13/movies/father-stu-review.html |archive-date=16 April 2022}}</ref>

Musician [[Peter Frampton]] was diagnosed with the disease in 2019.

Sportscaster and former [[Major League Baseball]] pitcher [[Mike Krukow]] has been diagnosed with the disease.<ref>{{cite web |title=Ex-Giants All-Star, current broadcaster reveals muscle disease |url=https://www.foxsports.com/stories/mlb/ex-giants-all-star-current-broadcaster-reveals-muscle-disease |website=Fox Sports |access-date=14 May 2025}}</ref>

== See also ==
* [[Inflammatory myopathies]]

==References==
{{Reflist}}

== External links ==
* [https://www.ncbi.nlm.nih.gov/books/NBK1262/ GeneReview/NIH/UW entry on Inclusion Body Myopathy 2]
{{Medical resources
|  DiseasesDB     = 30691
|  ICD11          = {{ICD11|FB30}}
|  ICD10          = {{ICD10|M60.8}}
|  ICD9           = {{ICD9|359.71}}
|  ICDO           =
|  OMIM           = 147421
|  MedlinePlus    =
|  eMedicineSubj  = neuro
|  eMedicineTopic = 422
|  MeshID         = D018979
|  Orphanet        = 611
|  GeneReviewsNBK  = NBK1262
|  GeneReviewsName = Inclusion Body Myopathy 2
}}

{{Systemic connective tissue disorders}}
{{Myopathy}}

{{DEFAULTSORT:Inclusion Body Myositis}}
[[Category:Systemic connective tissue disorders]]
[[Category:Muscular disorders]]
[[Category:Inflammations]]