Inclusion body myositis

An inflammatory muscle disease characterized by slowly progressive weakness and wasting of both distal and proximal muscles, most apparent in the muscles of the arms and legs.

There are two types: sporadic inclusion body myositis (sIBM), which is more common, and hereditary inclusion body myopathy (hIBM).

In sporadic inclusion body myositis two processes, one autoimmune and the other degenerative, appear to occur in the muscle cells in parallel.

The inflammation aspect is characterized by 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 vacuoles, and deposits of abnormal proteins within the cells and in filamentous inclusions.

Weakness comes on over months or years and progresses steadily and usually leads to severe weakness and wasting of arm and leg muscles.

More common in men than women.

Patients may become unable to perform activities of daily living.

Most patients require assistive devices within 5 to 10 years of symptom onset.

sIBM is not considered a fatal disorder, 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.

Sporadic IBM is a rare yet increasingly prevalent disease.

Sporadic IBM is the most common cause of inflammatory myopathy in people over age 50.

Prevalence 14.9 per million in the overall population, with a prevalence of 51.3 per million population in people over 50 years of age.

Sporadic IBM is an age-related disease, increasing with age.

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.

Sporadic IBM is the common type and it strikes at random.

There is a type in multiple siblings in the same generation in several families, termed familial inflammatory IBM, but it is not passed on from generation to generation.

Several very rare forms linked to specific genetic defects and that are passed on from generation to generation, each inherited in different ways.

Sporadic IBM has a variable age of onset from the forties upwards.

Sporadic IBM results in general, progressive muscle weakness.

The muscles in the thighs and the muscles in the arms that control finger flexion are usually affected early on.

Common early symptoms include frequent tripping and falling, weakness going up stairs and trouble manipulating the fingers, including difficulty with tasks such as turning doorknobs or gripping keys.

Foot drop in one or both feet has been a symptom of IBM.

The patient’s mobility becomes progressively restricted.

Many patients have balance problems and fall easily.

Muscles cannot compensate for an off-balanced posture.

Pain has not been traditionally part of the process, but many patients report severe muscle pain, especially in the thighs.

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 cases.

Can result in diminished aerobic capacity.

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 course of s-IBM leads slowly to severe disability.

Finger functions can become very impaired.

Arising from a chair becomes difficult.

Walking becomes precarious, and falls are common sometimes resulting in major injury due to weakness of quadriceps and gluteus muscles depriving the patient of automatic posture maintenance.

A foot-drop can increase the likelihood of tripping.

Dysphasia is usually caused by upper esophageal constriction, and respiratory muscle weakness can sometimes occur.

The causes of sIBM are unknown.

Causes though likely to result from the interaction of both genetic and environmental processes.

Some 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.

An autoimmune hypothesis for s-IBM is unlikely because of the disease’s resistance to most immunotherapies.

Some suggest that sIBM is a degenerative disorder related to aging of the muscle fibers and that abnormal, potentially pathogenic protein accumulations in myofibers.

It is possible that two processes, one autoimmune and the other degenerative, occur in the muscle cells in parallel.

It has not been impossible to detect an ongoing viral infection in the muscles.

In the s-IBM muscle fibers, there is evidence of misfolding of proteins, proteinaceous inclusions, abnormalities of the ubiquitin proteasome pathway and the lysosomes, mitochondrial dysfunctions, and oxidative stress.

There is pronounced T-cell inflammation characterized by activated, antigen-driven, cytotoxic CD8+ T cells.

Protein TDP-43 is a very prominent and highly sensitive and specific feature of IBM, which is normally found within the nucleus but in IBM is found in the cytoplasm of the cell.

Not inherited and is not passed on to the children.

There are genetic features predispose a person to getting IBM.

Some 67% of IBM patients have a combination of human leukocyte antigen genes in a section of the 8.1 ancestral haplotype in the center of the MHC class II region.

It is not passed on from generation to generation, although the susceptibility region of genes may be.

There are, however, several very rare forms of hereditary inclusion body myopathy that are linked to specific genetic defects and that are passed on from generation to generation.

No indication that the genes responsible for the familial or hereditary conditions are involved in sIBM.

Often initially misdiagnosed as polymyositis,but 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.

Polymyositis has an onset of weeks or months.

Elevated creatine kinase CK levels are typical in sIBM, but can be normal.

Creatine kinase levels are at most 10 times normal.

A blood test for the Anti-cN1A (Mup44, NTc1A) is used to diagnosis IBM.

Muscle biopsy findings include: inflammatory cells invading muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins.

No standard course of treatment slows or stops progression of the disease.

sIBM patients do not reliably respond to the anti-inflammatory, immunosuppressant, or immunomodulatory drugs.

Management is symptomatic.

Fall prevention is a major consideration, as is physical therapy and mobility training.

sIBM and polymyositis share some features, especially 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, while IBM does not.

Dermatomyositis shares similar physical symptoms and histopathological traits as polymyositis, but exhibits a skin rash not seen in polymyositis or sIBM.

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