.

Inclusion Body Myositis.

(IBM).

Site presented by Bill Tillier.


■ 1. Introduction.  

■ 2. More for new patients.    

■ 3. Treatment.  

■ 4. Management.  

■ 5. Causes.

■ 6. Research.  

■ 7. Coping with IBM.  

■ 8. Complications.  

■ 9. Relevant webpages.  

■ 10. Various aspects of IBM.

■  Website Miscellaneous:

Search the site.


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■ 1. Introduction:

▣ 1.1 Inclusion Body Myositis (IBM). This web page focuses on Inclusion Body Myositis (IBM). In the past it has been commonly known as sporadic inclusion body myositis (sIBM). This disease occurs spontaneously — it just strikes "out of the blue" and is not inherited: it is acquired during one's life. There is usually no one in the family who has the disease other than the patient and it is not passed on to subsequent generations.

⧈ This page is a good starting point for a person interested in IBM and contains information suitable to take to a family physician.

⧈ The site provides two levels of information:

      Basic introductions aimed at the IBM patient, his or her family, and caregivers;

    ⚀  Selected research on IBM intended for physicians.

▣ 1.2 Key information for new patients: Basic. If you have been diagnosed with inclusion body myositis here is what you need to know to begin with.

⧈ This is a serious and challenging disease.

⧈ It is a disease that strikes and weakens the muscles. Not all muscles are impacted, for example, the heart is not affected. It does not affect the nerves.

⧈  As more and more muscle cells are affected, the muscle becomes weaker and weaker, and more and more function is lost.

⧈ Different muscles groups are affected at different rates.

⧈ The disease starts in different people at different ages.

⧈ The disease affects different people in different ways, and at different rates, so, you cannot really compare yourself with others.

⧈ In most cases, the muscles of the arms and legs are affected first and weakness in the hands and tripping are common first symptoms.

⧈ The disease can lead to severe disability and often, eventually, necessitates use of a wheelchair.

⧈ Depending on how you are affected, you will face various challenges:

 If the disease affects your arms, you will have problems picking up objects and using your fingers.

 If the disease affects your legs, you will have trouble with falling.

 If the disease affects your throat, you may have trouble swallowing.

 If the disease affects the muscles of breathing, you will have problems getting enough air, especially at night.

⧈ Over the past 40 years doctors have struggled to describe the disease accurately.

⧈ Doctors argue over what type of disease it is, today, many agree that it is an autoimmune disease, however, other doctors disagree.

⧈ Doctors have not discovered what causes the disease.

⧈ Doctors have not developed any treatments that have been proven to slow down or stop the disease.

⧈ Many people suggest different diets or supplements but, there is no research that shows that any of these are helpful.

⧈ The most effective thing you can do is watch for, and manage, complications and prevent injuries due to falls.

⧈ A common serious complication is weakness in swallowing (dysphagia) that can cause choking or aspiration (taking food into the lungs) causing pneumonia (sometimes a cause of death). Swallowing involvement is a critical factor that should be investigated as soon as an IBM diagnosis is made.

⧈ Another serious complication is respiratory impairment caused by weakness of the diaphragm. Respiratory involvement is a critical factor that should be investigated as soon as an IBM diagnosis is made. Respiratory dysfunction can be identified, treated and monitored. The most common causes of death in IBM patients are complications due to respiratory failure and aspiration pneumonia (associated with both weak respiration and dysphagia — weakness in swallowing). Therefore, ongoing monitoring and awareness of these issues is highly recommended to both the patient and his or her physicians.

⧈ IBM does not appear to be directly genetic (it is not passed on to children) however, genetics may be involved in creating a predisposition to developing the disease.

⧈ The disease strikes people later in life, usually developing after age 40.

⧈ Over time, the disease will progress and get worse and worse.

⧈ Although people may feel the disease goes up and down, research has shown that it does not and that it slowly marches on.

⧈ Generally speaking, this disease is not fatal but may involve complications that can be fatal, for example, problems involving swallowing and falling.

⧈ As patients get older, they need more and more help to accomplish the day-to-day functions of life like getting up in the morning, showering, going to the bathroom, eating, etc.

⧈ Because the disease comes on very slowly it may take years to really notice that you are ill and seek help.

⧈ The diagnosis of this disease is very hard and many patients describe going to many doctors and having it take years to get a diagnosis (takes up to 5 years on average).

⧈ Inclusion body myositis is often mistaken by doctors for a different disease called polymyositis.

⧈ Examination of muscle tissues under the microscope reveals that the muscle cells have been invaded by T cells, a type of white blood cell involved in the immune response against viruses and other pathogens.

⧈ Recent research on the involvement of the immune system strongly suggests that IBM is an autoimmune disorder. However, drugs used to treat other autoimmune disorders are ineffective against IBM.

Figure 1.1

The common early presentation of weakness is shown in red (below, left).

pattern late

Weakness may develop in the diaphragm and the esophagus (illustrated in orange, above, right).

Figure 1.2

Greenberg2019fig3

A recent illustration is helpful (Greenberg, 2019).

hbutt

▣ 1.3 Hot button issues: the following questions appear over and over and therefore it may be helpful to address them here. These answers are based on the most recent research available.

⧈ Stem cell therapy: patients often inquire about the status of stem cell therapy. Use of stem cell therapy holds great promise but, at this stage, has not yet been developed to the point where it can reliably help patients. Some patients resort to going to countries where the use of stem cell therapy is not regulated by the government. It should be noted that this approach exposes patients to unknown risks. For more information see: Website.

⧈ There must be a medication! Many patients try various medications, usually some sort of steroids. Many patients report being on prednisone and suffering side effects and not being able to get off the drug. Some patients report benefits from these drugs. Research has shown that these medications generally do not help in IBM and, in some cases, may actually speed up progression and may lead to higher mortality. Today, in 2021, no medication is recommended for IBM patients. In some patients who have severe problems swallowing, as a last resort, some of these medications will be used to see if any improvement can be gained.

⧈ Falls. One of the early and consistent issues with IBM is unexpected falling. Muscle weakness in the legs causes instability in the knee. IBM patients experience two major types of falls: first, the knee may suddenly collapse causing the person to fall straight down. These falls are sudden and unexpected and you do not have time to grab onto anything. The second type of fall occurs when the person loses balance and the muscles in the legs cannot compensate, and the person slowly falls over. Fall prevention is extremely important as falls often lead to broken bones and head injuries. It may be helpful to use a knee brace or a cane or a walker. Many patients put off using such assistance until they have had many falls. As well, generally, two other factors come into play. An effective thing to do is to create an exercise program under the guidance of a therapist. As well, people with IBM tend to move less and therefore it is critical to manage your weight to ease pressure on existing muscles.

⧈ Psychological acceptance. IBM is a chronic and progressive illness that eventually may severely impair one’s normal activities. It is often difficult for people to come to grips that they have a disease like this. It is normal for people to initially be in denial and have anxiety about what the future will bring. Having to give up the normal activities of life involves a difficult, ongoing adjustment calling for flexibility and adaptation. Some patients have reported experiencing this loss as a feeling of grief similar to that experienced when you lose a loved one. Again, losing functions and having to adapt is a slow and ongoing process that you have to deal with over time. Generally, it is extremely helpful to have communication with other IBM patients who can give advice and context to the new patient. As well, is often helpful to have some sort of counselling in order to better come to grips with the diagnosis of IBM.

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■ 2. More for new patients:

▣ 2.1 Several videos from the Johns Hopkins Myositis Center.

▣ 2.2 Information pages.

▣ 2.3 Diagnosis. If you have arrived here I am assuming that you have received a diagnosis of IBM. It is well known that diagnosing muscle conditions is challenging and especially IBM, because it is quite rare, and because the symptoms it presents are often quite varied. More information on the diagnosis of IBM can be found here: Johns Hopkins Medicine

▣ 2.4 Blood tests in IBM. (Creatine kinase and Anti-cytosolic 5'-nucleotidase).

▣ 2.5 Comorbidties of IBM.

▣ 2.6 Jerry King's youtube IBM channel. (This is not my website).

▣ 2.7 Webpage credibility.

▣ 2.8 Seven warning signs of bogus science. (This is not my website).

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■ 3. Treatment:

▣ 3.1 Summary: Based upon research, no treatment is recognized as effective for IBM (as of 2021). Based upon their experience and opinions, doctors may try medications with IBM patients however, this is a clinical judgment where any possible benefits must be weighed against potential side effects.

▣ 3.2 Snedden, A. M., Lilleker, J. B., & Chinoy, H. (2021). In pursuit of an effective treatment: The past, present and future of clinical trials in inclusion body myositis. Current Treatment Options in Rheumatology. https://doi.org/10.1007/s40674-020-00169-4

⧈ Purpose of review No clinical trial in sporadic inclusion body myositis (IBM) thus far has shown a clear and sustained therapeutic effect. We review previous trial methodology, explore why results have not translated into clinical practice, and suggest improvements for future IBM trials.

⧈ Recent findings Early trials primarily assessed immunosuppressive medications, with no significant clinical responses observed. Many of these studies had methodological issues, including small participant numbers, nonspecific diagnostic criteria, short treatment and/ or assessment periods and insensitive outcome measures. Most recent IBM trials have instead focused on nonimmunosuppressive therapies, but there is mounting evidence supporting a primary autoimmune aetiology, including the discovery of immunosuppression-resistant clones of cytotoxic T cells and anti-CN-1A autoantibodies which could potentially be used to stratify patients into different cohorts. The latest trials have had mixed results. For example, bimagrumab, a myostatin blocker, did not affect the 6-min timed walk distance, whereas sirolimus, a promotor of autophagy, did. Larger studies are planned to evaluate the efficacy of sirolimus and arimoclomol.

⧈ Summary Thus far, no treatment for IBM has demonstrated a definite therapeutic effect, and effective treatment options in clinical practice are lacking. Trial design and ineffective therapies are likely to have contributed to these failures. Identification of potential therapeutic targets should be followed by future studies using a stratified approach and sensitive and relevant outcome measures.

▣ 3.3 The best approach is to manage the complications that may arise from the disease. Evaluation of swallowing and respiration are critical, ongoing issues. Prevention of falls is an important consideration.

▣ 3.4 "Standard of care for most patients with IBM involves strictly nonpharmacological management, including emotional support, physical therapy, education on fall precautions and exercise." From: Greenberg, 2019.

▣ 3.5 "Currently, no evidence is available to support any specific treatment in clinical practice. To date, there are no effective or approved treatment options for inclusion body myositis" From: (Hanna et al., 2019).

▣ 3.6 Also see: Needham, M., & Mastaglia, F. L. (2016). Sporadic inclusion body myositis: A review of recent clinical advances and current approaches to diagnosis and treatment. Clinical Neurophysiology, 127(3), 1764-1773. https://doi.org/10.1016/j.clinph.2015.12.011

▣ 3.7 Exercise in inclusion body myositis.

⧈ Also see 9.2.

▣  3.8 A cautionary note: There is a strong tendency for both doctors and patients to "want to do something" — anything — to try to slow down or reverse the symptoms of a major debilitating and chronic illness like IBM. For patients, it can be very frightening and frustrating to simply "do nothing." Caution must be used when no significant benefits of treatment can be demonstrated and when treatments all have significant potential side effects.

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■ 4. Management:

▣ 4.1 When faced with a progressive disabling disease that has no effective and reliable treatment options, day to day management becomes critically important to avoid complications. Management involves two critical components; awareness and prevention. We need to be aware of the possible consequences of inclusion body myositis and be able to proactively prevent complications. Simple and consistent practices can prevent many of the complications that can threaten one's life.

▣ 4.2 Because this illness is dynamic (it keeps changing over time) and progressive, your symptoms will likely change dramatically over time. People are always having to deal with new issues and new weaknesses and it's important to monitor these changes carefully and try to keep adapting as changes keep occurring. In this disease, coping has to be ongoing and keep up with the changes in the symptoms as they are experienced. (See Coping.)

▣ 4.3 As muscles in the legs are often affected, this creates a major vulnerability to tripping and falling. Prevention of falls is critical.

▣ 4.4 A common complication is weakness in swallowing and one must be vigilant to prevent choking (See Complications: Dysphagia).

▣ 4.5 Individuals with IBM whose mobility is restricted need to be aware of complications related to this, including:

⧈ 4.5.1 The development of swelling (edema), especially around the ankles.

⧈ 4.5.2 Limited mobility means limited exercise, often reflected in weight gain.

⧈ 4.5.3 Limited mobility creates the risk of skin problems including skin breakdown and ulceration from sitting in one place for long periods.

▣ 4.6 Potential impacts on respiration (diaphragm weakness) are less common but serious. Awareness of respiratory shallowness, especially while sleeping, is important, leading to proper assessment and management. (See Complications: Respiration).

▣ 4.7 We must prevent iatrogenic complications. This means complications introduced by efforts to treat the illness. In this case, the most common is the harm caused by prednisone. This medication has often been prescribed although it has not demonstrated any positive effect and many people needlessly suffer its complications.

▣ 4.8 Diet: Generally speaking I have not seen any suggestion that a particular diet will actually help inclusion body myositis. I believe if you get an overall balanced and healthy dietary intake, you should be okay. One thing I would emphasize is that with IBM, the less you move, the less energy you need and therefore the less food you should eat. If you are in a wheelchair you must eat a reduced amount of food to avoid gaining weight.

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■ 5. Causes:

Note: there is no consensus within the research community concerning the basic causes of inclusion body myositis.

▣ 5.1 After nearly 50 years of research, the basic causes of IBM remain unknown. It appears that multiple factors work together to cause IBM (a multifactorial disorder). It is also very complicated to determine if an effect causes the disease or, if the effect is caused by the disease.

▣ 5.2 Three basic theories have been proposed over the years. (presented in the order of likelihood based on contemporary research)

⧈ 5.2.1 That the immune system is somehow involved in damaging the muscle cells, then causing protein abnormalities.

 IBM appears to be an autoimmune disease. In these diseases, in response to some unknown cause, the immune system begins to produce antibodies that attack the body's own tissues. Normally, the immune system is triggered by some foreign invader (like a virus) and this causes the production of antibodies designed to attack and kill the invader. In autoimmune diseases, immune defences attack normal body tissues. Common examples are rheumatoid arthritis, lupus, Type 1 diabetes, and Sjögren's syndrome. Treatment for autoimmune diseases generally focuses on reducing immune system activity.

 For some reason, the medications that normally reduce the activity of the immune system have not improved the symptoms of IBM.

 IBM is sometimes also associated with cases of Sjögren's syndrome.

 The families of patients with IBM also often have various other autoimmune disorders (for example, Crohn's disease, rheumatoid arthritis, autoimmune hepatitis, lupus, etc.).

⧈ 5.2.2 That protein abnormalities damage the muscle cells, then causing immune system abnormalities. This is often referred to as the degenerative aspect, or theory, of IBM.

⧈ 5.2.3 An older theory was that a virus is the cause, however, no virus has ever been clearly linked to causing IBM.

▣ 5.3 It could also be possible that autoimmune factors and protein degeneration are both involved in the causes of IBM.

▣ 5.4 Over the years, abnormalities associated with part of the cell called the mitochondrion have been implicated and recent research has emphasized this aspect (see De Paepe, 2019).

▣ 5.5 Until the basic causes are discovered, a specific treatment will remain elusive.

Figure 5.1

Greenberg63

From: Greenberg, S. A. (2016). Inclusion Body Myositis. CONTINUUM: Lifelong Learning in Neurology, 22(21), 1871-1888.
https://doi.org/10.1212/01.CON.0000511071.58338.1e

Figure 5.2

Britson

From: Britson, K. A., Yang, S. Y., & Lloyd, T. E. (2018). New Developments in the Genetics of Inclusion Body Myositis.
Current Rheumatology Reports, 20(5), 26.

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■ 6. Research:

▣ 6.1 Current IBM Research.

▣ 6.2 There are two main approaches to research; 1) general research into muscles (and muscle diseases) and 2) research specifically focused on IBM.

⧈ 6.2.1 General Muscle Research:

 Muscles are very complex systems and research into their basic structures and functions continues.

 The causes of some muscle diseases (like IBM) are unknown and in turn, few specific treatments are available. Until more specific treatments are developed, researchers are looking into trying to develop general approaches to enhance muscle function.

 If researchers could boost muscle function it might be possible to offset the effects of the different muscle diseases. Even a small increase in function could be very important to the patient having one of these illness.

 In normal muscle, there is a mechanism to stop muscle growth. Without this inhibitory system, muscle growth could go unchecked. Researchers are trying to take advantage of this inhibitory system. If this system could be short-circuited then more muscle growth would occur. The basic goal is to have the body produce more muscle than normal. The underlying muscle disease will not be treated but with more muscle being produced, the overall impact of the disease may be reduced. As mentioned, even small gains might be very important for the affected patient.

 An example of a general approach to increase muscle growth is a drug called Bimagrumab. This drug has been used to try to produce more muscle in various conditions. A new report says its safe to use but did not appear to work in IBM: See: (Hanna et al., 2019).

⧈ 6.2.2 IBM Research:

 Research specifically focused on IBM attempts to understand what causes the disease and how it operates. The basic cause of IBM is not currently understood and this is a major focus of IBM research.

 Most research on the treatment of IBM has looked at using existing medications and examining their impact on IBM. Generally speaking, no medication has shown significant improvements in IBM patients (see above).

 2017: "For the past two decades, the field of IBM research has been split with some researchers suggesting that IBM pathogenesis begins with inflammation leading to myodegeneration and others favouring a primary degenerative myopathy stimulating autoimmunity. Now with emerging therapies aimed at targeting muscle degeneration and other therapies focused on immune modulation, it is essential to understand the connection between these two pathologies. A siloed approach that ignores one or the other will not advance future therapeutics. Instead, additive therapies or dual acting therapies that focus on both aspects of disease pathogenesis will likely need to be employed."
From: http://doi.org/10.1111/nan.12384

 Generally, today, IBM is viewed as both a degenerative and an autoimmune disease.

 Summary: IBM is a very complex and challenging disease to research. Much has been learned about the disease, but frustratingly, more remains unknown. The understanding of IBM and its causes is a very slowly evolving phenomenon.

▣ 6.3 Other IBM Research:

⧈ 6.3.1 Past research.

⧈ 6.3.2 Highlighted Research  

▣ 6.4 IBM as an autoimmune disease: Simplified.

⧈ 6.4.1 Autoinflammation and autoimmunity:

▣ 6.5 Functional assessment of IBM.

▣ 6.6 Statins and IBM.

7. Coping.    

8. Complications.    

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■ 9. Relevant Webpages:

▣ 9.1 A key resource: Myositis Support and Understanding (MSU)

▣ 9.2 Exercise in Place: Myositis Support and Understanding (MSU)

▣ 9.3 Other Relevant Webpages:

⧈ 9.3.1 Web sites for IBM Information:

 Cure IBM is dedicated to inclusion body myositis awareness, education, and research. Cure IBM Website.

 National Organization for Rare Disorders (NORD)
https://rarediseases.org/rare-diseases/sporadic-inclusion-body-myositis/

 IBM overview: http://www.patient.co.uk/doctor/inclusion-body-myositis

 Muscular Dystrophy UK IBM overview:
IBM Alert Card: http://www.musculardystrophyuk.org/news/news/new-inclusion-body-myositis-alert-card-launched/
See it here: Alert Card

 National Institute of Neurological Disorders and Stroke (NINDS) site on IBM:. https://www.ninds.nih.gov/Disorders/All-Disorders/Inclusion-Body-Myositis-Information-Page

 Washington University School of Medicine in St. Louis, MO, has announced the opening of an IBM Specialty Clinic devoted to inclusion body myositis. IBM Specialty Clinic at Washington University, St. Louis.

 Wikipedia entry: https://en.wikipedia.org/w/index.php?title=Inclusion_body_myositis&oldid=1011707161

 IBM Facebook pages:

        □ IBM Facebook Page #1 (open):

        □ IBM Facebook Page #2 (membership):

 Clinical Trials for IBM:

        □ You can find information on the latest clinical trials on IBM by going to this website and entering inclusion body myositis on the search line: NIH Clinical Trials: http://clinicaltrials.gov/

 Yale IBM Registry: Yale IBM Registry.

 Donate to Fund IBM Research: Donation Suggestions of Cure IBM.

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■ 10. Various aspects of IBM:

▣  10.1 Brief History of IBM: A few highlights.

▣  10.2 How common is IBM?

▣  10.3 Classification of IBM:

▣  10.4 Genetics of IBM:

▣  10.5 Miscellaneous IBM:

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↩ 10. Various

▣ 10.2 How common is IBM?

⧈ 10.2.1 Terminology: First, it is important to understand some terminology. This Information is from the New York State Department of health.

 10.2.1.1 What is incidence? Incidence is a measure of disease that allows us to determine a person's probability of being diagnosed with a disease during a given period of time. Therefore, incidence is the number of newly diagnosed cases of a disease. An incidence rate is the number of new cases of a disease divided by the number of persons at risk for the disease. If, over the course of one year, five women are diagnosed with breast cancer, out of a total female study population of 200 (who do not have breast cancer at the beginning of the study period), then we would say the incidence of breast cancer in this population was 0.025. (or 2,500 per 100,000 women-years of study)

 10.2.1.2 What is prevalence? Prevalence is a measure of disease that allows us to determine a person's likelihood of having a disease. Therefore, the number of prevalent cases is the total number of cases of disease existing in a population. A prevalence rate is the total number of cases of a disease existing in a population divided by the total population. So, if a measurement of cancer is taken in a population of 40,000 people and 1,200 were recently diagnosed with cancer and 3,500 are living with cancer, then the prevalence of cancer is 0.118. (or 11,750 per 100,000 persons)

 10.2.1.3 What is morbidity? Morbidity is another term for illness. A person can have several co-morbidities simultaneously. So, morbidities can range from Alzheimer's disease to cancer to traumatic brain injury. Morbidities are NOT deaths. Prevalence is a measure often used to determine the level of morbidity in a population.

 10.2.1.4 What is mortality? Mortality is another term for death. A mortality rate is the number of deaths due to a disease divided by the total population. If there are 25 lung cancer deaths in one year in a population of 30,000, then the mortality rate for that population is 83 per 100,000.

⧈ 10.2.2 Prevalence of IBM:

 10.2.2.1 The prevalence of IBM is very difficult to establish for several reasons:

    -There is no system of collection of statistics for rare diseases. When your doctor diagnoses you, this information generally is not shared in any database.

    -This is a very difficult disease to diagnose and it is clear that many cases are misdiagnosed.

    -Because the illness is related to aging, many patients assume that mild symptoms are simply signs of getting older and do not seek medical diagnosis.

 10.2.2.2 Men get IBM slightly more often than females, about on average 1.6 times (so for every 16 men there would be 10 women with IBM).

 10.2.2.3 Numbers reflecting the prevalence of IBM are probably underestimates because of the high rate of misdiagnosis. In a good study published in 2017, the overall prevalence of IBM was 46 patients per million.

    -From: Greenberg, S. A. (2019). Inclusion body myositis: Clinical features and pathogenesis. Nature Reviews Rheumatology 2019, 1. https://doi.org/10.1038/s41584-019-0186-x

 10.2.2.4 IBM should be considered in patients with appropriate symptoms who are older than 30 years.

 10.2.2.5 Symptom onset before age 60 occurs in 18 % to 20 % of patients.

 10.2.2.6 In an Olmsted County population study the estimated incidence of IBM, adjusted for sex and age to the 2000 US Census population, was 7.9 cases per million inhabitants with a prevalence of 70 cases per million inhabitants.

 10.2.2.7 IBM is rare in African Americans and in non-Caucasians.

    -From: Dimachkie, M. M., & Barohn, R. J. (2010.2). Inclusion body myositis. Current Neurology and Neuroscience Reports, 10.2(1), 321. https://doi.org/10.1007/s11910-012-0321-4

 10.2.2.8 Using the highest published prevalence rate, it is estimated that 23,000 people are affected in the United States and 72,000 people are affected in the United States, European Union, Canada, Australia, and Japan combined.

 10.2.2.9 Evidence for a truly increasing prevalence of the disease in Japan has been suggested by muscle pathology-based diagnosis of archived materials, with an estimated prevalence of 1.3 per million in 1991 and 9.8 per million in 2003.(2) The last US-based published estimate of 71 per million was based on 2008 data; it is likely that current true US prevalence is higher.

    -From: Greenberg, S. A. (2016). Inclusion Body Myositis. CONTINUUM: Lifelong Learning in Neurology, 22(21), 1871-1888. https://doi.org/10.1212/01.CON.0000511071.58338.1e

gprev

⧈ 10.2.3 Age:

 10.2.3.1 As seen below, IBM is an age-related disease. It's onset is usually well into adulthood.

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gage

From: Greenberg, S. A. (2016). Inclusion Body Myositis.
CONTINUUM: Lifelong Learning in Neurology, 22(21), 1871-1888.
https://doi.org/10.1212/01.CON.0000511071.58338.1e

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↩ 10. Various

▣ 10.3 Classification of IBM:

⧈ 10.3.1 The past and current classification: Inclusion body myositis is a type of muscle disease, usually listed under the umbrella of muscular dystrophy diseases. IBM has traditionally been classified along with polymyositis (PM) and dermatomyositis (DM), but the features of IBM are clearly distinct from these other types.

⧈ 10.3.2 The classification of muscle diseases has been evolving over time as more and more research discoveries are made. Different diseases are being recognized and categories adjusted. Muscle diseases have been classified mainly based on their clinical presentation. Today, the recognition of antibodies associated with different muscle diseases has impacted classification.

Figure 10.3.2.1

overall

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 Figure 10.3.2.1 is based upon:
Simon, J. P., Marie, I., Jouen, F., Boyer, O., & Martinet, J. (2016).
Autoimmune Myopathies: Where Do We Stand?
Frontiers in Immunology, 7(JUN), 1-7. https://doi.org/10.3389/fimmu.2016.00234

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Figure 10.3.2.2

inmclass

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Figure 10.3.2.2 is based on: Mariampillai, K., Granger, B., Amelin, D., Guiguet, M., Hachulla, E., Maurier, F., … Benveniste, O. (2018).
Development of a new classification system for idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific autoantibodies.
JAMA Neurology, 75(12), 1528.
JAMA Neurol. 2018;75(12):1528-1537. doi:10.1001/jamaneurol.2018.2598

 Notes on Figure 10.3.2.2

        □ ^ trigger: statin use

        □ * trigger: malignancy

        □ ** anti-NT5c1A— anti-cN1A: Found in approximately 50 to 60% of IBM patients.

        □ According to Greenberg (2019), Anti-cN1A antibodies are highly specific to IBM and are seen in 90-95% of patients with IBM compared with 5-10% of patients with polymyositis, dermatomyositis or non-immune neuromuscular diseases. However, these antibodies have only moderate diagnostic sensitivity, ranging from 37% to 76%. Varying sensitivities may be related to the different methods of testing that have been used. In other words, these antibodies are very specific to IBM — if you have them, you probably have IBM but, they are not that sensitive to IBM — only about 50 to 60% of IBM patients will have these antibodies.

        □ Anti-NT5C1A autoantibodies were detected in 71 (61%) of 117 patients with IBM, 2 (5%) of 42 patients with PM, 2 (5%) of 42 healthy volunteers, 24 (15%) of 159 patients with DM, 10 (23%) of 44 patients with Sjögren's syndrome, and 13 (14%) of 96 patients with systemic lupus erythematosus" (Lloyd et al., 2016).

        □  Anti-cN-1A autoantibodies are demonstrated in one third of the patients with sIBM and in less than 5% with other IIMs or neuromuscular diseases. A recent study demonstrated that positive anti-cN-1A sIBM patients are included in a more severe sIBM subtype and represent a homogeneous group as exhibiting higher mortality risk, less proximal upper limb weakness (not typical of sIBMs) and a cytochrome oxidase deficiency in muscular fibers, when compared to negative patients" (Palterer et al., 2018).

        □ Update: Paul et al. (2020). Anti-cN1A antibodies do not correlate with specific clinical, EMG or pathological findings in sporadic inclusion body myositis. Muscle & Nerve, mus.27157. https://doi.org/10.1002/mus.27157 Results: Anti-cN1A antibodies were present in 47/92 (51%) patients with sIBM. Comparison of seropositive and seronegative cohorts yielded no significant difference in clinical features, including facial weakness, oropharyngeal and respiratory involvement, or disease severity. The antibody titer did not correlate with the clinical phenotype, CK value or presence of myotonic discharges on EMG. Anti-cN1A antibody positive patients appeared to have more frequent autoaggressive inflammation on muscle biopsy but not as an isolated myopathological feature.

        □ Update: Ikenaga et al (2020). Myositis associated anti-NT5C1A autoantibody in clinical practice. MedRxiv, 2020.03.25.20043760. https://doi.org/10.1101/2020.03.25.20043760

              — Anti-NT5C1A was found in 182/287 patients with IBM (63%)

              — Conclusions: This is the largest description of patients tested by a clinical diagnostic lab for anti-NT5C1A. We confirm the sensitivity and specificity of anti-NT5C1A for IBM and identified clinicopathologic features in IBM which correlate with anti-NT5C1A status. Notably, anti-NT5C1A testing increased both the diagnostic sensitivity and specificity of IBM when combined with patient age, gender and creatine kinase (CK) level. We propose that future IBM diagnostic criteria include anti-NT5C1A testing.

        □ For information on myositis-associated autoantibodies see: https://understandingmyositis.org/myositis-antibody-testing/

 10.3.2.3 Summary: Antibodies are protective proteins produced by the immune system in response to the presence of a foreign substance, called an antigen. Antibodies recognize and latch onto antigens in order to remove them from the body. In the case of an autoimmune disease autoantibodies mistakenly recognize a person’s own tissues and attack them as if they were invaders. Researchers have discovered various autoantibodies directed against various tissues in the body, including skeletal muscle. These discoveries have led to the classification of myositis as an autoimmune disease. Some autoantibodies are only found in specific muscle disorders—myositis-specific [auto] antibodies (MSAs). Other [auto] antibodies may be linked to more than one disorder. When one of these disorders includes a muscle disorder it is called a myositis-associated antibody (MAA). It is a major challenge for researchers to decide if newly discovered autoantibodies belong to either the MSAs or MAAs group. In some cases, the detection of an autoantibody may help with making the diagnosis of a particular condition, in some cases, they are correlated to the way a disease progresses.

 References:

        □ Allenbach, Y., Benveniste, O., Goebel, H.H., & Stenzel, W. (2017). Integrated classification of inflammatory myopathies. Neuropathology and Applied Neurobiology, 43(1), 62-81. https://doi.org/10.1111/nan.12380

        □ Greenberg, S. A. (2019). Inclusion body myositis: Clinical features and pathogenesis. Nature Reviews Rheumatology 2019, 1. https://doi.org/10.1038/s41584-019-0186-x

        □ Lloyd, T. E., Christopher-Stine, L., Pinal-Fernandez, I., Tiniakou, E., Petri, M., Baer, A., … Mammen, A. L. (2016). Cytosolic 5'-Nucleotidase 1A as a target of circulating autoantibodies in autoimmune diseases. Arthritis Care & Research, 68(1), 66-71. https://doi.org/10.1002/acr.22600

        □ Montagnese, F., Babacic, H., Eichhorn, P., & Schoser, B. (2019). Evaluating the diagnostic utility of new line immunoassays for myositis antibodies in clinical practice: A retrospective study. Journal of Neurology, 266(6), 1358-1366. https://doi.org/10.1007/s00415-019-09266-4

        □ Palterer, B., Vitiello, G., Carraresi, A., Giudizi, M. G., Cammelli, D., & Parronchi, P. (2018). Bench to bedside review of myositis autoantibodies. Clinical and Molecular Allergy, 16(1), 5. https://doi.org/10.1186/s12948-018-0084-9

        □ Santos, L. R., & Isenberg, D. (2019). Myositis. In Neuroimmune Diseases (pp. 787-808). Cham: Springer. https://doi.org/10.1007/978-3-030-19515-1_27

⧈ 10.3.3 Myositis versus myopathy.

 10.3.3.1 IBM is an abbreviation for 'inclusion body myositis' not 'inclusion body myopathy' (Greenberg, 2019, Milone, 2017). The abbreviation IBM refers clearly and only to the single disease IBM, not to the hereditary inclusion body myopathies ("hIBMs"). On this page, IBM will only refer to inclusion body myositis and I will not specify sporadic.

 10.3.3.2 The hereditary, myopathy type is clearly distinct from the myositis forms.

 10.3.3.3 It would be less confusing if, in the future, researchers and doctors used IBM to specify inclusion body myositis, dropped the terms "sporadic" and "hIBM" and used the the names of each specific form of hereditary myopathy discovered, e.g. GNE mutation myopathy, DES mutation myopathy, VCP mutation myopathy, MYHC2A mutation myopathy, and others yet to be discovered (?).

ibmchart

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Figure 10.3.3.4

 Notes on Figure 10.3.3.4

        □ * GNE The most common form of HIBM was originally described in Middle Eastern patients and is tied to mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE, MIM# 603824) gene, hence the name GNE myopathy (MIM# 605820). Was called Nonaka myopathy. At one time was called Inclusion Body Myopathy 2.

        □ # VCP The other common form is Hereditary inclusion-body myopathy associated with Paget's disease of bone (PDB) and frontotemporal dementia (IBMPFD1, MIM# 167320). There are also two other forms. This is a rare multisystem degenerative autosomal dominant disorder due to mutations of the valosin-containing protein gene (VCP, also see: MIM# 601023).

        □ + MYHC2A This form of autosomal dominant HIBM was first described in a large multigeneration family from Sweden (MIM# 605637). At one time was called Inclusion Body Myopathy 3.

 10.3.3.5. See: Broccolini, A., & Mirabella, M. (2015). Hereditary inclusion-body myopathies. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1852(4), 644-650. https://www.sciencedirect.com/science/article/pii/S0925443914002609?via%3Dihub

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↩ 10. Various

▣ 10.4 Genetics of IBM:

⧈ 10.4.1 Genetic predisposition.

 10.4.1.1 Due to their genetic make-up, some individuals within the population appear to be more at risk of developing inclusion body myositis than others. The two major forms of myositis, IBM and fIBM, are not directly genetic and are not passed on to subsequent generations. It appears that these forms are related to a region of genes that increase the likelihood or chance of developing various autoimmune disorders. This is called a genetic predisposition.

 10.4.1.2 It is clear that many factors contribute to the development of inclusion body myositis and genetic predisposition appears to be one risk factor.

⧈ 10.4.2 Familial IBM (fIBM)

 10.4.2.1 Familial IBM refers to rare cases where (typical) IBM is seen in two or more patients within a single generation of siblings in a family (it is not passed on to subsequent generations).

 10.4.2.2 The symptoms and features of fIBM are very similar to those seen in IBM. The familial occurrence of such a rare disorder likely highlights the importance of genetic predisposition in the causation of IBM.

⧈ 10.4.3 Hereditary inclusion body myopathy (hIBM)

 10.4.3.1 Hereditary inclusion body myopathy refers to a group of ultra-rare inherited disorders; passed on from parents to children. Note that these diseases are called myopathy (myopathies) and their characteristics are different from inclusion body myositis, but at this point, these various myopathies are still lumped together with inclusion body myositis.

 10.4.3.2 "The hIBM diseases lack the two main characteristic features of IBM: its distinctive pattern of muscle weakness and the presence of muscle histological immune cell infiltration" (Greenberg, 2019).

 10.4.3.3 Greenberg (2019) points out that it is a mistake to think IBM and hIBM reflect the same pathophysiological process that can either occur sporadically or be inherited: "IBM", is an entirely different disease than the group of diseases known as hereditary inclusion body myopathies, often abbreviated as "hIBM."

 10.4.3.4 The different forms of hereditary inclusion body myopathy are caused by mutations in different genes that can be passed from generation to generation.

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↩ 10. Various

▣ 10.5 Miscellaneous IBM:

⧈ 10.5.1 Selections from Outlook (TMA).

⧈ 10.5.2 IBM in Images.

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▣ Website Miscellaneous:

▣ How to Use PDF files:

⧈ Note: some of the PDF files on this site are large and take considerable time to open. PDF files are like a photocopy of an article. To use them you need to install a PDF reader (many computers already have one installed). If you click on a PDF file and you have a reader, it will open automatically. If you need to install a reader, it is easy. You can get a free reader download at: http://get.adobe.com/reader/

▣ Mission Statement:

⧈ There are many excellent web sites that present information on various neuromuscular disorders. When I looked at the web, I was struck by how scattered the information was, and the fact that much of the information is very technical. Therefore, the primary intention of this site is to help integrate different sources and to provide background to help the reader cope with complex medical jargon and methods. I am not trying to be comprehensive and I do not want to be redundant and present information that is already covered elsewhere.

▣ Disclaimer:

⧈ I am not a medical Doctor and this information is not intended to be read as medical advice nor is it a substitute for medical advice. Please consult your Physician if you have medical concerns. I have done my best to offer a layman's interpretation of this material. Any opinions offered are personal and do not reflect those of my employer. Thanks.

▣ Contact: For comments or improvements, please contact Bill at bill.tillier@gmail.com

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▣ Page Created: April 06, 2001.

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