Inclusion Body Myositis
Inclusion body myositis
Inclusion body myositis (IBM) is an inflammatory muscle disease characterized by progressive muscle weakness and wasting. The common feature of IBM is the abnormal finding of inclusion bodies, or granular material, in muscle fibers. The onset generally occurs gradually over months or years, and persons often experience falling and tripping as the first symptoms. Inclusion body myositis affects both proximal (closest to the center of the body) and distal (farthest from the center of the body) muscles.
Sporadic inclusion body myositis is the most common muscle disease in people aged 50 years and older with an unknown cause. The disease was named in 1971, when scientists noted a case of myositis (muscle inflammation) that showed granular material in muscle fibers called inclusion bodies. The inclusion bodies are now recognized to contain abnormal deposits of amyloid proteins, similar to those found in the brain of patients with Alzheimer's disease. The deposits may represent a protein product left within the muscle fibers as they degenerate.
The onset of IBM is insidious, with symptoms often having been present for more than five years before diagnosis. The course of the disease is progressive over months or years, leading to severe disability. IBM may appear identical to another inflammatory myositis called polymyositis , although differences are clear in more than half of cases.
Weakness and impairment of muscle function are the hallmarks of IBM, and weakness distribution is variable, with both proximal (closest to the center of the body) and distal (farthest from the center of the body) muscles affected. Diminished deep-tendon reflexes and wasting (atrophy) of the involved musculature occur. Thus, loss of finger dexterity and grip strength may be present, while falling and tripping appear as the first signs. Patients often suffer from fatigue and reduced tolerance to exertion, and consequently become out of breath easily.
There are no data currently available for the incidence of IBM internationally, although it has been reported in Europe and Asia. IBM is thought to account for approximately 15–20% of all cases of inflammatory myositis in the United States. Mortality rate (rate of deaths) is difficult to assess, as most people with IBM are older and may die of other coexisting medical problems. There is no race prevalence, but it is uncommon among African Americans. The male/female ratio is 3:1 and most affected individuals are 50 years or older. Nevertheless, IBM does not seem to affect life expectancy.
Causes and symptoms
The causes of IBM remain unknown and it is thought to be a multifactorial disease. Aging factors may play an important role as pathogenic (disease-causing) components. Research has been made to establish whether IBM might be influenced by environmental factors. Thus, inflammation may be a secondary component occurring in response to foreign proteins called antigens, such as viral proteins or altered muscle proteins, and perhaps induces an autoimmune response (a reaction of the organism against itself).
A possibility that excessive accumulation of certain proteins within muscle fibers can induce inflammation is supported by the findings in transgenic mice studies in which mice were modified to express these human proteins. The results have shown that when synthesizing large amounts of the protein in the muscles, mice developed an age-related motor deficit with muscle inflammation. Also, aging muscle fiber was shown to promote accumulation of abnormal proteins, suggesting an aging-based degenerative process. It has been shown that muscle can secrete this protein and thus, it might cause inflammation by stimulating the immune system to react against the affected muscle. The stimulus for excessive amyloid production is unknown, and whether this precedes inflammation, or vice-versa, remains to be determined.
Genetic causes of IBM have also been proposed, and studies focused on human leukocyte antigen genes that encode for proteins that influence immune response. They were found related to the development of IBM, but their role is not clear.
As an acquired process, weakness or impairment of muscle function in the area(s) affected is the primary symptom of IBM. The distribution of weakness is variable, but most muscles are affected, including those in the neck, hip, quadriceps, back, shoulder, wrist, and finger. Many people with IBM notice shrinking, or atrophy, in the arms and thighs as the muscles become weaker. As thighs are affected by atrophy, sudden falls may occur.
Lower leg weakness can cause difficulty lifting up the foot, which can lead to tripping. Difficult swallowing, or dysphagia, is a common problem in up to 40% of persons with IBM, and choking may become a problem when ingesting some types of food or liquids. Weakness of facial muscles is sometimes seen. Fatigue and reduced tolerance to exertion are common, and cardiac disease is also present in those with IBM, although its relation to IBM has not been demonstrated. The disease itself does not cause pain ; however, weakened muscles can predispose to injuries affecting bones, joints and soft tissues. Elderly patients normally die of other clinical problems rather than of IBM, and most suffer some degree of disability as disease progresses.
The IBM diagnosis is carried out according to clinical features and laboratory studies. The illness lasts longer than six months and the age of onset is greater than 30 years old. People with IBM have considerable quadriceps and wrist and finger flexor weakness. Blood tests show high levels of creatine kinase, a muscle enzyme released by damaged muscle. Electromyography (EMG) can be used to detect the electrical impulses of muscle contraction, which exhibit a different pattern in IBM patients. Although useful, EMG cannot be taken as a definite diagnosis.
As IBM muscles are damaged, muscle biopsy is the definitive test. In a muscle biopsy, a small sample of the muscle is taken under local anesthesia. Laboratory analysis can identify the inclusion bodies within muscle fibers and the invasion of the damaged tissue by immune cells featuring the inflammation with muscle destruction. This appearance will allow the pathologist and clinician to confirm the diagnosis of IBM. None of the other clinical or laboratory features are mandatory if muscle biopsy features are diagnostic. Muscle biopsy is also important for the exclusion of other neuromuscular diseases.
It has been suggested that magnetic resonance imaging (MRI) may be useful detecting active myositis and recognizing selective patterns of muscle involvement in IBM. MRI is also helpful in selecting an appropriate biopsy site. The results of such studies are also useful to guide therapeutic decisions when a biopsy is not possible or the biopsy findings are inconclusive.
Because of the imprecise nature of muscle weakness in IBM, a diagnosis is sometimes delayed for years after the onset of weakness. In some patients, the initial biopsy may not disclose the diagnosis, and a second biopsy may be necessary.
A neurologist or rheumatologist is the primary consultant for IBM treatment, along with allied health care areas including but not limited to physical therapists and otolaryngologists (ear, larynx, and upper respiratory tract specialists).
Currently, no treatment has been shown to be effective against the different forms of IBM. Some moderate success has been obtained with the drug therapy combination of corticosteroids and methotrexate or human intravenous immunoglobulins. New therapeutic protocols are currently being tested. Physical therapy, occupational therapy, and ergotherapy (treatment of disease by muscular exercise ) are commonly prescribed.
Recovery and rehabilitation
In most cases of IBM, there is continued deterioration in spite of the treatment reduction of muscle inflammation and immune cells invasion of muscle tissue. Because of the slow progression, any treatment trial should last for at least six months (possibly 12–18 months) to evaluate benefits. Physical therapy and occupational therapy may help patients as disability increases.
No treatment has shown to be effective against IBM; however, new therapies are currently being tested. The National Institute of Neurological Disorders and Stroke (NINDS) is sponsoring a study entitled "Immune Abnormalities in Sporadic Inclusion Body Myositis." This is an investigative study intended to better define the pathogenesis of IBM. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is recruiting patients to a study, "Study and Treatment of Inflammatory Muscle Diseases," which intends to obtain useful material for immunological studies and to sponsor standard therapies for patients. It is likely that in the future more therapeutic trials of drugs in IBM will be organized.
IBM generally worsens progressively and slowly. Some observations of stabilizations and remissions, spontaneous or under treatment, have been reported but are usually only temporary.
Exercise is generally helpful by getting the most out of diseased muscles. Falls and injuries, however, can cause substantial disability. Patients, therefore, have the difficult task of undertaking regular exercise within their capability, but avoiding injury through accident. Because weakened muscles cannot carry an excessive load, keeping to an ideal weight is helpful. A well-balanced diet is also helpful. Patients with severe inflammation of the muscles may need extra protein to balance their loss.
Askanas, Valerie, Georges Serratrice, and W. Engel. Inclusion Body Myositis and Myopathies. New York: Cambridge University Press, 1998.
Parker, James N., and Philip M. Parker. The Official Patient's Sourcebook on Inclusion Body Myositis. San Diego: Icon Group International, 2002.
Mastaglia, F. L., M. J. Garllep, B. A. Phillips, and P. J. Zilko. "Inflammatory Myopathies: Clinical, Diagnostic and Therapeutic Aspects." Muscle & Nerve (April 2003): 407–425.
"Inclusion Body Myositis." The Myositis Association. March 4, 2004 (April 27, 2004). <http://myositis.org>.
"NINDS Inclusion Body Myositis Information Page." National Institute of Neurological Disorders and Stroke. March 4, 2004 (April 27, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/inclusion_doc.htm>.
Myositis Association of America. 755 Cantrell Ave., Suite C, Harrisonburg, VA 22801. (540) 433-7686; Fax: (540) 432-0206. [email protected] <http://www.myositis.org>.
Marcos do Carmo Oyama
Iuri Drumond Louro, MD, PhD