NORD gratefully acknowledges Steven A. Greenberg, MD, Professor of Neurology, Harvard Medical School, for assistance in the preparation of this report.
Sporadic inclusion body myositis (sIBM) is an acquired progressive muscle disorder that becomes apparent during adulthood. The symptoms and progression of sIBM vary from one person to another. In most cases, sIBM is characterized by progressive weakness and degeneration (atrophy) of the muscles especially those of the arms and the legs. sIBM can progress to cause severe disability. sIBM is an autoimmune disease mediated by cytotoxic T cells, but the exact cause of the disorder is unknown. sIBM, like all autoimmune diseases, is a complex disorder and, most likely, multiple factors including genetic, immunological and environmental ones in combination all play a role in its development.
The distribution, severity and progression of muscle weakness vary from one person to another. In some patients, sIBM may affect one arm or leg more than the other. In most cases, the progression is very slow. The muscles of the anterior thighs (quadriceps) and wrist and finger flexors are usually affected more severely than other muscles. Many individuals with sIBM first present with a tendency to trip or fall or with difficulty with handgrip, or with difficulty swallowing.
Muscles in the wrists, fingers, and neck are commonly affected. Weakness in the hands may be the first noticeable symptoms in some people. Muscle weakness in the fingers can affect the grip making it difficult to perform functions such as gripping a golf club. Eventually, affected individuals may have difficulty manipulating objects with their hands such as turning a key, buttoning a shirt, or writing with a pen or pencil. In rare cases, muscle weakness in the neck can cause the head to drop.
Weakness of the muscles below the knees can cause the toes to catch when walking or the foot to drop increasing an affected individual’s tendency to fall. Affected individuals may also have trouble walking up stairs and or rising from a sitting position.
Difficulty swallowing (dysphagia) due to weakness of throat muscles may occur in individuals with sIBM. Dysphagia can potentially cause choking episodes. Facial muscle weakness occurs in some patients as well.
Muscle cramping, pain (myalgia) or tenderness do not usually occur, but has been reported. Although sIBM progresses slowly, it can eventually cause significant disability and many affected individuals eventually require an assistive device such as a cane, walker or wheelchair.
The cause of sIBM is unknown and complex. Researchers believe multiple immunological, genetic and environmental factors and factors related to aging all play a role in the development of the disorder. Researchers have identified two distinct processes – one autoimmune and one degenerative – that occur in individuals with sIBM. It appears likely that autoimmunity drives the disease and accounts for the minor “degenerative” pathological changes seen in sIBM skeletal muscle.
Numerous factors support that sIBM is an autoimmune disorder, especially the presence of certain inflammatory white blood cells in the muscle tissue of affected individuals. Autoimmune disorders occur when the body’s immune system mistakenly attacks healthy tissue. The inflammatory findings associated with sIBM led to it to be classified as an autoimmune inflammatory muscle disease along with other prominent inflammatory muscle diseases such as dermatomyositis and polymyositis. The identification of an autoantigen (NT5C1A) has confirmed IBM’s status as an autoimmune disease. However, sIBM, like a number of other autorimmune diseases, has not responded to some of the conventional therapies normally used to treat autoimmune disorders suggesting that distinct factors account for its refractory nature. In particular, cytotoxic T cells in sIBM muscle are highly differentiated and their phenotype overlaps with those of T cells in T-cell large granular lymphocytic leukemia, a similarly refractory disease.
In addition to the inflammatory process, researchers have emphasized that some muscle tissue of individuals with sIBM shows degenerative changes. Specifically, the muscle tissue of affected individuals sometimes contains sub-cellular compartments called vacuoles. These compartments have been reported to contain abnormal clumps of many different proteins. These clumps, often called “inclusion bodies”, give the disorder its name. This significant degenerative component has led some researchers to argue that sIBM is primarily a degenerative muscle disorder and not an inflammatory one. However, these changes are seen in other refractory autoimmune diseases (e.g., Sjogren syndrome and primary biliary cholangigits) and appear to be reflective of chronic exposure of tissues to highly T cell rich inflammatory environments.
It is unknown what triggers or underlies the inflammatory or degenerative changes that characterize sIBM, a feature shared by all other autoimmune diseases.
Some individuals with sIBM may have a genetic predisposition that makes them more susceptible to developing sIBM. A genetic predisposition means that a person may carry a gene for a disease but it may not be expressed unless something in the environment triggers the disease.
sIBM affects males slightly more often than females. Its prevalence is estimated to be between 10-112 people per 1,000,000 in the general population. It occurs with greater frequency in individuals more than 50 years of age. The prevalence is estimated to be 51-139 per 1,000,000 individuals in the general population over 50, making sIBM the most common acquired muscle disorder (myopathy) in that age group. Despite growing awareness of this disorder, many researchers believe it remains underdiagnosed.
Although sIBM does not occur with greater frequency in any specific ethnic or racial group, it apparently occurs less often in individuals of African descent.
The diagnosis of sIBM is made based upon a thorough clinical evaluation, a careful patient history, and a variety of specialized tests, such as a muscle biopsy. A muscle biopsy is a procedure in which a tiny amount of muscle tissue is surgically removed and studied under a microscope to detect characteristic changes that indicate sIBM. Additional tests that can be used to aid in a diagnosis include electromyography and blood tests that measure the amount of certain enzymes in muscle tissue. A blood test specifically for IBM was developed in 2013 and is now commercially available for diagnostic use.
During an electromyography, a needle electrode is inserted through the skin into an affected muscle. The electrode records the electrical activity of the muscle. This record shows how well a muscle responds to the nerves and can determine whether muscle weakness is caused by the muscle themselves or by the nerves that control the muscles. An electromyography can rule out nerve disorders such as motor neuron disease and peripheral neuropathy.
Blood tests may reveal elevated levels of the creatine kinase (CK), an enzyme that is often found in abnormally high levels when muscle is damaged. Elevated CK levels occur in some, but not all individuals affected with sIBM. The detection of elevated CK levels can confirm that muscle is damaged or inflamed, but cannot confirm a diagnosis of sIBM. It is typically used to exclude a diagnosis of sIBM.
There is no cure for sIBM and the disorder generally does not respond to conventional therapies for autoimmune disorders such as corticosteroids or drugs that suppress the immune system (immunosuppressive drugs). Some individuals have responded to these therapies for a short period of time or to a minor degree (i.e., there is not a full recovery of muscle strength). The specific types of immunosuppressive drugs that have been used to treat individuals with sIBM include azathioprine, methotrexate, cyclosporine, and cyclophosphamide.
Specific treatment options for affected individuals may include physical and occupational therapy to improve muscle strength and, when necessary, the use of various devices including braces, walkers or wheelchairs to assist with walking (ambulation).
Additional drugs have been studied as potential therapies for individuals with sIBM including the immunosuppressive drug, mycophenolate mofetil, and intravenous immunoglobulin, a concentrated preparation containing antibodies obtained from the fluid portion of the blood (plasma) of healthy individuals. Some individuals taking these medications have experienced short-lived improvement of symptoms but none of these medications have been scientifically demonstrated to have efficacy. More research is necessary to determine the long-term effectiveness and safety of these medications for the treatment of individuals with sIBM.
Very few investigational therapies are being studied for individuals with sIBM at the time of this writing. Bimagrumab, a monclonal antibody therapeutic against the activin type IIB receptor, has undergone an international registration trial and failed to show benefit for the primary outcome measure. Arimoclomol has also undergone phase 2 testing and failed to achieve proof of mechanism or demonstrate efficacy. Rapamycin is also undergoing investigator-initiated clinical trials.
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