Information on the following diseases can be found in the Related Disorders section of this report:

• Dermatomyositis
• Idiopathic Polymyositis
• Distal Myopathy
• Mixed Connective Tissue Disease
• Oculopharyngeal Muscular Dystrophy

Inclusion body myositis is characterized by a distinct, progressive muscle weakness of the proximal and distal muscles of the arms and legs. The muscle weakness may affect the biceps, triceps, quadriceps, iliopsoas, tibialis anterior, finger flexors, and the wrist flexor. It is thought to be an inflammatory disease of the skeletal muscles. Although IBM is not usually associated with skin rash, malignancy, or collagen vascular disease, exceptions to each of these rules has been found in certain patients.

Most often, the earliest noticeable symptoms of IBM are tripping and falling, as well as dropping materials from the hands. The muscles affecting swallowing may also be affected, although this is less common.

Clinically, IBM differs from dermatomyositis and polymyositis because it lacks the features of a collagen vascular disease, which include symptoms of fever, headache, joint and muscle pain, and weakness. It has a relatively benign and protracted course lasting at least six months.

In polymyositis and Inclusion Body Myositis there is evidence of macrophages (scavenger cells) surrounding, invading, and destroying living (non-necrotic) muscle fibers.
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Inclusion body myositis seems to be a distinct type of inflammatory muscle disease. In most cases, its cause is unknown. A viral or possibly a neurogenic cause (related to or starting in the nervous system) has been suggested, but both theories remain simply theories at this time. In some cases, a family history of IBM has been observed. In such cases, Inclusion Body Myositis appears to be inherited as an autosomal dominant genetic trait. The inherited form of the disorder (sometimes called i-IBM) is even less common and usually presents earlier than does the sporadic form (sometimes called s-IBM). Other authorities consider the disorder known as inclusion body myopathy to be distinct from inclusion body myositis. The issue remains unresolved.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
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Inclusion Body Myositis occurs primarily in individuals greater than the age of 30 with the average age of onset being 53. However, young adults in their teens have been affected. It seems to affect mostly males.

Symptoms of the following disorders can be similar to those of Inclusion Body Myositis. Comparisons may be useful for a differential diagnosis:

Dermatomyositis is a systemic connective tissue disorder characterized by inflammatory and degenerative changes in the muscles, subcutaneous tissues and skin. Symptoms may come and go, but the main symptom is muscle weakness, most often in the hip and shoulder, usually accompanied by a rash. There is often underlying cancer in 50% of adult cases. This disorder may possibly be an autoimmune disease. (Autoimmune disorders are caused when the body's natural defenses (antibodies, lymphocytes, etc.), against invading organisms suddenly begin to attack healthy tissue.) (For more information on this disorder, choose "Dermatomyositis" as your search term in the Rare Disease Database.)

Idiopathic Polymyositis is a systemic connective tissue disorder characterized by inflammatory and degenerative changes in the muscles leading to weakness and some degree of muscle atrophy. The areas primarily affected are the hip, shoulder, and chest. (For more information on this disorder, choose "Polymyositis" as your search term in the Rare Disease Database.)

Distal Myopathy affects predominantly the small muscles of the extremities. Onset is usually after age 40, with weakness and wasting of small muscles of the hands. Autosomal dominant inheritance is thought to be a cause.

Mixed Connective Tissue Disease (MCTD) is a rheumatic disease characterized by overlapping features similar to those of systemic lupus erythematous (SLE), scleroderma and polymyositis. The cause is unknown, but it is suggested that the immune system may be involved. MCTD appears to be more common than polymyositis and less common than scleroderma. Symptoms of MCTD may include Raynaud's phenomena (cold and numbness of fingers), arthritis, swollen hands, inflammatory proximal muscle weakness, dysfunction of the esophagus, and lung disease. MCTD is often used to describe what may be an overlapping group of connective tissue diseases that cannot be diagnosed in more specific terms. (For more information on this disorder, choose "MCTD" as your search term in the Rare Disease Database.)

Oculopharyngeal Muscular Dystrophy usually occurs in adulthood. Extraocular muscles are involved initially and the muscles used for swallowing tend to become affected. The typical facial appearance, especially drooping of the eyelids, resembles that found in myasthenia gravis. The inheritance pattern often follows an autosomal dominant pattern. However, occasional sporadic cases and cases with autosomal recessive inheritance have occurred.

The diagnosis of Inclusion Body Myositits may be confirmed by a thorough clinical evaluation, a careful patient history, and a variety of specialized tests, such as a muscle biopsy. However, even if the muscle biopsy does not show the classic histologic findings, but the muscle weakness and degeneration (atrophy) are present, the diagnosis of IBM should still be considered. In some cases, more than one muscle biopsy may be required for confirmation of the diagnosis of IBM.

Inclusion Body Myositis does not readily yield to treatment with steroids or other immunosuppressive drugs. This helps distinguish IBM from Dermatomyositis and Polymyositis. Researchers are trying to understand the cause of IBM in order to develop more effective therapies. Other treatment is symptomatic and supportive.

A new unit of the National Institute of Environmental Health Sciences, called the Environmental Autoimmunity Group (EAG), has been established in Bethesda, MD, at the NIH to conduct pioneering research in understanding the genetic and environmental risk factors that may result in autoimmune disease.

The EAG is currently enrolling families in which an adult or child meets criteria for rheumatoid arthritis/juvenile rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, or myositis and in which a twin or sibling of the same gender, who is within 47 months of age, does not have any one of these four illnesses or another autoimmune disease. Subjects may enroll at the NIH Clinical Center in Bethesda or in their local doctors’ offices. Patients remain under the care of their personal physicians while participating in the study. There is no charge for study-related evaluations and medical tests at the NIH.

For information about the NIH Twin-Sibs Study, call 1-800-411-1222.

Other studies sponsored by two different institutes of the NIH are recruiting patients with IBM. These are:

1. Studies of Immune Dysregulation in Patients with Sporadic Inclusion Body Myositis (s-IBM).

This clinical trial is being sponsored by the National Institute of Neurological Disorders and Stroke and expects to recruit about 20 patients.

This trial offers no new therapy but is expected to contribute substantially to better understanding of the disorder. Fundamental to this trial is the hypothesis that s-IBM is an autoimmune disease. The goal of the study is to find and identify one or more autoantigens that lead to the degeneration of the patient’s muscles.

For further information, contact:
Patient Recruitment and Liaison Office
National Institute of Neurological Disorders and Stroke (NINDS)
9000 Rockville Pike
Bethesda, MD 20892

Tel: 1-800-411-1222
e-mail: prpl@mail.cc.nih.gov

Study ID Numbers: 020121; 02-N-0121

2. Studies on the Natural History and Pathogenesis of Polymyositis, Dermatomyositis, and Related Disorders.

This clinical trial is being sponsored by the National Institutes of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the NIH.

This study of inflammatory muscle diseases – the idiopathic inflammatory myopathies, including dermatomyositis, polymyositis, myositis and inclusion body myositis – is intended to help to further understand what causes these disorders and to promote the recognition of their signs and symptoms.

Participants can expect to be part of genetic studies, muscle biopsy studies, electromyographic (measuring the electrical activity of muscles, and studies of muscle strength, including the muscles involved in swallowing. A sample of the participant’s white blood cells will be collected for study, and magnetic resonance imaging (MRI) studies will be undertaken on some participants comparing the results of MRI investigations with the results of muscle biopsies.

NIAMS expects that almost 10,000 persons will participate in this trial.

For further information, contact:
Patient Recruitment and Liaison Office
National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS)
9000 Rockville Pike
Bethesda, MD 20892

Tel: 1-800-411-1222
e-mail: prpl@mail.cc.nih.gov

Study ID Numbers: 910196; 91-AR-0196

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Entry Number; 147421: Last Edit Date; 1/24/2003.

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Entry Number; 600737: Last Edit Date; 1/24/2003.

TEXTBOOKS
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REVIEW ARTICLES
Yazici Y, Kagen LJ. Clinical presentation of the idiopathic inflammatory myopathies. Rheum Dis Clin North Am. 2002;28:823-32.

Dalakas MC. Understanding the immunopathogenesis of inclusion-body myositis: present and future prospects. Rev Neurol (Paris). 2002;158:948-58.

Askanas V, Engel WK. Inclusion-body myositis and myopathies: different etiologies, possibly similar pathogenetic mechanisms. Curr Opin Neurol. 2002;15:525-31.

Kissel JT. Misunderstandings, misperceptions, and mistakes in the management of the inflammatory myopathies. Semin Neurol. 2002;22:41-51.

Dalakas MC. The molecular and cellular pathology of inflammatory muscle diseases. Curr Opin Pharmacol. 2001;1:300-06.

JOURNAL ARTICLES
Mastaglia FL, Zilko PJ. Inflammatory myopathies: how to treat the difficult cases. J Clin Neurosci. 2003;10:99-101.

Tawil R, Griggs RC. Inclusion body myositis. Curr Opin Rheumatol. 2002;14:653-57.

Hengstman GJ, Brouwer R, Egberts WT, et al. Clinical and serological characteristics of 125 Dutch myositis patients. Myositis specific antibodies aid in the differential diagnosis of the idiopathic inflammatory myopathies. J Neurol. 2002;249:69-75.

Rutkove SB, Parker RA, Nardin RA. A pilot randomized trial of oxandrolone in inclusion body myositis. Neurology. 2002;58:1081-87.

Sultan SM, Ioannou Y, Moss K, et al. Outcome in patients with idiopathic inflammatory myositis: morbidity and mortality. Rheumatology (Oxford). 2002;41:22-26.

Dabby R, Lange DJ, Trojaborg W, et al. Inclusion body myositis mimicking motor neuron disease. Arch Neurol. 2001;58:1253-56.

Rose MR, McDermott MP, Thornton CA, et al. A prospective natural history study of inclusion body myositis: implications for clinical trials. Neurology. 2001;57:548-50.

FROM THE INTERNET
NINDS inclusion Body Myositis Information Page. Reviewed 11-08-2001:4pp.
http://accessible.ninds.nih.gov/health_and_medical/disorders/inclusion_doc.htm

Diagnostic Criteria for Inclusion Body Myositis. Reprinted from Griggs RC, Askanas V, DiMauro S, et al. Ann Neurol. 1995;38:705-13.
http://132.230.36.11/neuromirror/ibmdx.html

Barkhaus PE, Periquet MI. Inclusion Body Myositis. eMedicine. Last Updated: November 15, 2002:16pp.
www.emedicine.com/neuro/topic422.htm

Hill M, Hammans S. Inclusion Body Myositis. Muscular Dystrophy Campaign. 4pp.
www.muscular-dystrophy.org/information/KeyFacts/ibm.html