Inclusion body myositis
Encyclopedia
Inclusion body myositis (IBM) is an inflammatory
muscle
disease
, characterized by slowly progressive weakness and wasting of both distal and proximal muscles, most apparent in the muscles of the arm
s and legs
. There are two types: sporadic inclusion body myositis (sIBM) and hereditary inclusion body myopathy (hIBM).
In sporadic inclusion body myositis [MY-oh-sigh-tis] muscle, two processes, one autoimmune and the other degenerative, appear to occur in the muscle cells in parallel. The inflammation aspect is characterized by the cloning of T cells that appear to be driven by specific antigens to invade muscle fibers. The degeneration aspect is characterized by the appearance of holes in the muscle cell vacuole
s, deposits of abnormal proteins within the cells and in filamentous inclusions (hence the name inclusion body myositis).
sIBM is a rare yet increasingly prevalent disease, being the most common cause of inflammatory myopathy in the over 50s; the most recent research, done in Australia, indicates that the incidence of IBM varies and is different in different populations and different ethnic groups. The authors found that the current prevalence was 14.9 per million in the overall population, with a prevalence of 51.3 per million population in people over 50 years of age. As seen in these numbers, sIBM is an age-related disease – its incidence increases with age and symptoms usually begin after 50 years of age. It is the most common acquired muscle disorder seen in people over 50, although about 20% of cases display symptoms before the age of 50. Weakness comes on slowly (over months or years) and progresses steadily and usually leads to severe weakness and wasting of arm and leg muscles. It is slightly more common in men than women. Patients may become unable to perform daily living activities and most require assistive devices within 5 to 10 years of symptom onset. sIBM is not considered a fatal disorder – barring complications, all things being equal, sIBM will not kill (but the risk of serious injury due to falls is increased). One common and potentially fatal complication is dysphagia
. There is no effective treatment for the disease.
Eventually, sIBM results in general, progressive muscle weakness. The muscles in the thighs called the quadriceps and the muscles in the arms that control finger flexion—making a fist—are usually affected early on. Common early symptoms include frequent tripping and falling, weakness going up stairs and trouble manipulating the fingers—turning doorknobs, gripping keys, etc. Foot drop
in one or both feet has been a symptom of IBM and advanced stages of polymyositis
(PM).
During the course of the illness, the patient's mobility is progressively restricted as it becomes hard for him or her to bend down, reach for things, walk quickly and so on. 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.
When present, dysphagia
is a progressive condition in patients with inclusion body myositis and often leads to death from aspiration pneumonia. Dysphagia is present in from 40 to 85% of IBM cases.
Patients with sIBM usually eventually need to resort to a cane or a walker and in most cases, a wheelchair eventually becomes a necessity.
From a recent article: "The progressive course of s-IBM leads slowly to severe disability. Finger functions can become very impaired, such as for 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."
Currently, there are two major theories about how sIBM is caused:
1) Some researchers (e.g., Dalakas) advocate the theory that the inflammation-immune reaction, caused by an unknown trigger – likely an undiscovered virus or an autoimmune disorder, is the primary, proximal cause of sIBM and that the degeneration of muscle fibres and protein abnormalities are secondary features.
Despite the arguments "in favor of an adaptive immune response in s-IBM, a purely autoimmune hypothesis for s-IBM is untenable because of the disease's resistance to most immunotherapy."
2) Some researchers (e.g., Engel and Askanas) advocate the theory that sIBM is a degenerative disorder related to aging of the muscle fibres and that abnormal, potentially pathogenic protein accumulations in myofibers play a key causative role in s-IBM (apparently before the immune system comes into play). This theory emphasizes the abnormal intracellular accumulation of many proteins, protein aggregation and misfolding, proteosome inhibition, and endoplasmic reticulum
(ER) stress.
A recent review by Greenberg (2009) discusses the "limitations in the beta-amyloid-mediated theory of IBM myofiber injury,"
Dalakas (2006) said: "we can say that two processes, one autoimmune and the other degenerative, occur in the muscle cells in parallel."
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 antigens 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.
A self-sustaining T cell response would make sIBM a type of autoimmune disorder. One confusing aspect is that medications that lower the immune response do not improve sIBM symptoms, as would be expected in the case of an autoimmune disorder.
When studied carefully, it has not been impossible 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—about 15 or so—that have shown clear evidence of a virus called HTLV-1. This is a complex virus that can cause leukemia, but in most cases it lies dormant and people end up being lifelong carriers of the virus. It is too early to say that this is the particular virus directly involved in causing IBM. The Dalakas article 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.
As mentioned above, in the past, some researchers have suggested that it is the protein changes that are primary and that precede or trigger the abnormal immune response. From an article by Askanas and Engel: "Two hypotheses predominate regarding the key pathogenic mechanisms involved in s-IBM: an amyloid-beta-related degenerative process and an immune dysregulation. Ultimately, both may be considered important, and their possible interrelationship may be clarified. An intriguing feature is the accumulation within s-IBM muscle fibers of amyloid-beta (Ab), phosphorylated tau protein
, and at least 20 other proteins that are also accumulated in the brain of Alzheimer's disease
patients. In the s-IBM muscle fibers, there is evidence of misfolding of proteins, pathologic proteinaceous inclusions including aggresomes, abnormalities of the two protein-disposal systems involving the ubiquitin
proteasome
pathway and the lysosomes, mitochondrial dysfunctions, and oxidative stress
. The pronounced T-cell inflammation can be striking, and it is characterized by activated, antigen-driven, cytotoxic CD8
+ T-cells.
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.
There are also several very rare forms of hereditary inclusion body myopathy (myopathies) that are linked to specific genetic defects and that are passed on from generation to generation. Because these forms do not show inflammation, they are classified as myopathies and not myositis types. 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
.
A 2007 review that summarized current understanding of the contribution of genetic susceptibility factors to the development of sIBM concluded there is no indication that the genes responsible for the familial or hereditary conditions are involved in sIBM.
. 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. Other forms of muscular dystrophy (e.g. limb girdle) must be considered as well.
CK levels (at most ~10 times normal) are typical in sIBM but patients can also present with normal CK levels. Electromyography
(EMG) studies usually display abnormalities. Muscle biopsy may display several common findings including; inflammatory cells invading muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins. sIBM is a challenge to the pathologist and even with a biopsy, diagnosis can be ambiguous.
may supplement treatment to enhance quality of life.
(DM) and polymyositis
(PM) and all three illnesses were called idiopathic
(of unknown origin) myositis or inflammatory myopathies.
It appears that sIBM and polymyositis share some common features, especially the initial sequence of immune system activation, however, polmyositis 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.
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.
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
, characterized by slowly progressive weakness and wasting of both distal and proximal muscles, most apparent in the muscles of the arm
Arm
In human anatomy, the arm is the part of the upper limb between the shoulder and the elbow joints. In other animals, the term arm can also be used for analogous structures, such as one of the paired forelimbs of a four-legged animal or the arms of cephalopods...
s and legs
Human leg
The human leg is the entire lower extremity or limb of the human body, including the foot, thigh and even the hip or gluteal region; however, the precise definition in human anatomy refers only to the section of the lower limb extending from the knee to the ankle.Legs are used for standing,...
. There are two types: sporadic inclusion body myositis (sIBM) and hereditary inclusion body myopathy (hIBM).
In sporadic inclusion body myositis [MY-oh-sigh-tis] muscle, two processes, one autoimmune and the other degenerative, appear to occur in the muscle cells in parallel. The inflammation aspect is characterized by the cloning of T cells that appear to be driven by specific antigens to invade muscle fibers. The degeneration aspect is characterized by the appearance of holes in the muscle cell vacuole
Vacuole
A vacuole is a membrane-bound organelle which is present in all plant and fungal cells and some protist, animal and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic molecules including enzymes in solution, though in certain...
s, deposits of abnormal proteins within the cells and in filamentous inclusions (hence the name inclusion body myositis).
sIBM is a rare yet increasingly prevalent disease, being the most common cause of inflammatory myopathy in the over 50s; the most recent research, done in Australia, indicates that the incidence of IBM varies and is different in different populations and different ethnic groups. The authors found that the current prevalence was 14.9 per million in the overall population, with a prevalence of 51.3 per million population in people over 50 years of age. As seen in these numbers, sIBM is an age-related disease – its incidence increases with age and symptoms usually begin after 50 years of age. It is the most common acquired muscle disorder seen in people over 50, although about 20% of cases display symptoms before the age of 50. Weakness comes on slowly (over months or years) and progresses steadily and usually leads to severe weakness and wasting of arm and leg muscles. It is slightly more common in men than women. Patients may become unable to perform daily living activities and most require assistive devices within 5 to 10 years of symptom onset. sIBM is not considered a fatal disorder – barring complications, all things being equal, sIBM will not kill (but the risk of serious injury due to falls is increased). One common and potentially fatal complication is dysphagia
Dysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
. There is no effective treatment for the disease.
Classification
- The common type is sIBM (sporadic Inclusion Body Myositis): it strikes individuals apparently at random.
- 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.
- 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. See hereditary inclusion body myopathyHereditary inclusion body myopathyHereditary inclusion body myopathies are a heterogeneous group of genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults...
.
Signs and Symptoms
How sIBM affects individuals is quite variable as is the age of onset (which generally varies from the forties upwards). Because sIBM affects different people in different ways and at different rates, there is no "textbook case."Eventually, sIBM results in general, progressive muscle weakness. The muscles in the thighs called the quadriceps and the muscles in the arms that control finger flexion—making a fist—are usually affected early on. Common early symptoms include frequent tripping and falling, weakness going up stairs and trouble manipulating the fingers—turning doorknobs, gripping keys, etc. Foot drop
Foot drop
Foot drop is the dropping of the forefoot due to weakness, damage to the peroneal nerve or paralysis of the muscles in the anterior portion of the lower leg. It is usually a symptom of a greater problem, not a disease in itself. It is characterized by the inability or difficulty in moving the ankle...
in one or both feet has been a symptom of IBM and advanced stages of polymyositis
Polymyositis
Polymyositis is a type of chronic inflammation of the muscles related to dermatomyositis and inclusion body myositis.-Signs and symptoms:...
(PM).
During the course of the illness, the patient's mobility is progressively restricted as it becomes hard for him or her to bend down, reach for things, walk quickly and so on. 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.
When present, dysphagia
Dysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
is a progressive condition in patients with inclusion body myositis and often leads to death from aspiration pneumonia. Dysphagia is present in from 40 to 85% of IBM cases.
Patients with sIBM usually eventually need to resort to a cane or a walker and in most cases, a wheelchair eventually becomes a necessity.
From a recent article: "The progressive course of s-IBM leads slowly to severe disability. Finger functions can become very impaired, such as for 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
Dysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their 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."
Causes
The causes of sIBM are currently unknown, though it is likely that it results from the interaction of a number of factors, both genetic and environmental. The understanding of sIBM is slowly maturing and evolving.Currently, there are two major theories about how sIBM is caused:
1) Some researchers (e.g., Dalakas) advocate the theory that the inflammation-immune reaction, caused by an unknown trigger – likely an undiscovered virus or an autoimmune disorder, is the primary, proximal cause of sIBM and that the degeneration of muscle fibres and protein abnormalities are secondary features.
Despite the arguments "in favor of an adaptive immune response in s-IBM, a purely autoimmune hypothesis for s-IBM is untenable because of the disease's resistance to most immunotherapy."
2) Some researchers (e.g., Engel and Askanas) advocate the theory that sIBM is a degenerative disorder related to aging of the muscle fibres and that abnormal, potentially pathogenic protein accumulations in myofibers play a key causative role in s-IBM (apparently before the immune system comes into play). This theory emphasizes the abnormal intracellular accumulation of many proteins, protein aggregation and misfolding, proteosome inhibition, and endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
(ER) stress.
A recent review by Greenberg (2009) discusses the "limitations in the beta-amyloid-mediated theory of IBM myofiber injury,"
Dalakas (2006) said: "we can say that two processes, one autoimmune and the other degenerative, occur in the muscle cells in parallel."
Dalakas (2006) suggested that a chain of events causes IBM—some sort of virus, likely a retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
, triggers the cloning of T cells. These T cells appear to be driven by specific antigens 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
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
(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
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
(MHC) molecules that carry the antigen protein pieces, leading to more ER stress and more protein misfolding.
A self-sustaining T cell response would make sIBM a type of autoimmune disorder. One confusing aspect is that medications that lower the immune response do not improve sIBM symptoms, as would be expected in the case of an autoimmune disorder.
When studied carefully, it has not been impossible 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—about 15 or so—that have shown clear evidence of a virus called HTLV-1. This is a complex virus that can cause leukemia, but in most cases it lies dormant and people end up being lifelong carriers of the virus. It is too early to say that this is the particular virus directly involved in causing IBM. The Dalakas article 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.
As mentioned above, in the past, some researchers have suggested that it is the protein changes that are primary and that precede or trigger the abnormal immune response. From an article by Askanas and Engel: "Two hypotheses predominate regarding the key pathogenic mechanisms involved in s-IBM: an amyloid-beta-related degenerative process and an immune dysregulation. Ultimately, both may be considered important, and their possible interrelationship may be clarified. An intriguing feature is the accumulation within s-IBM muscle fibers of amyloid-beta (Ab), phosphorylated tau protein
Tau protein
Tau proteins are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes...
, and at least 20 other proteins that are also accumulated in the brain of Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
patients. In the s-IBM muscle fibers, there is evidence of misfolding of proteins, pathologic proteinaceous inclusions including aggresomes, abnormalities of the two protein-disposal systems involving the ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
proteasome
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...
pathway and the lysosomes, mitochondrial dysfunctions, and oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
. The pronounced T-cell inflammation can be striking, and it is characterized by activated, antigen-driven, cytotoxic CD8
CD8
CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...
+ T-cells.
- amyloidAmyloidAmyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various neurodegenerative diseases.-Definition:...
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.
- 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
Genetic Aspects of sIBM
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 - 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 antigenHuman leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
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.
There are also several very rare forms of hereditary inclusion body myopathy (myopathies) that are linked to specific genetic defects and that are passed on from generation to generation. Because these forms do not show inflammation, they are classified as myopathies and not myositis types. 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
Hereditary inclusion body myopathy
Hereditary inclusion body myopathies are a heterogeneous group of genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults...
.
A 2007 review that summarized current understanding of the contribution of genetic susceptibility factors to the development of sIBM concluded there is no indication that the genes responsible for the familial or hereditary conditions are involved in sIBM.
Differential Diagnosis
IBM is often initially misdiagnosed as polymyositisPolymyositis
Polymyositis is a type of chronic inflammation of the muscles related to dermatomyositis and inclusion body myositis.-Signs and symptoms:...
. 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. Other forms of muscular dystrophy (e.g. limb girdle) must be considered as well.
Diagnosis
Elevated creatine kinaseCreatine kinase
Creatine kinase , also known as creatine phosphokinase or phospho-creatine kinase , is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate...
CK levels (at most ~10 times normal) are typical in sIBM but patients can also present with normal CK levels. Electromyography
Electromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
(EMG) studies usually display abnormalities. Muscle biopsy may display several common findings including; inflammatory cells invading muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins. sIBM is a challenge to the pathologist and even with a biopsy, diagnosis can be ambiguous.
Treatment
There is no standard course of treatment to slow or stop the progression of the disease. sIBM patients do not reliably respond to the anti-inflammatory, immunosuppressant, or immunomodulatory drugs that have been tried. Management is symptomatic. Prevention of falls is an important consideration. Specialized exercise therapyExercise therapy for idiopathic inflammatory myopathies
Although they vary in particulars, polymyositis, dermatomyositis and inclusion body myositis are idiopathic inflammatory myopathies primarily characterized by chronic inflammation of human skeletal muscle tissue that ultimately causes the necrosis of muscle cells. This degeneration leads to...
may supplement treatment to enhance quality of life.
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 dermatomyositisDermatomyositis
Dermatomyositis is a connective-tissue disease related to polymyositis and Bramaticosis that is characterized by inflammation of the muscles and the skin.- Causes :...
(DM) and polymyositis
Polymyositis
Polymyositis is a type of chronic inflammation of the muscles related to dermatomyositis and inclusion body myositis.-Signs and symptoms:...
(PM) and all three illnesses were called idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
(of unknown origin) myositis or inflammatory myopathies.
It appears that sIBM and polymyositis share some common features, especially the initial sequence of immune system activation, however, polmyositis 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.
Dermatomyositis
Dermatomyositis
Dermatomyositis is a connective-tissue disease related to polymyositis and Bramaticosis that is characterized by inflammation of the muscles and the skin.- Causes :...
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.
External links
- Information and links to resources by Bill Tillier
- GeneReview/NIH/UW entry on Inclusion Body Myopathy 2
- Polymyositis and Dermatomyositis Discussion group http://www.icarecafe.com/?page_id=1107&group_id=8
- Information from The Myositis Association