Inflammatory myopathy

Definition

Inflammatory myopathy is a term that defines a group of muscle diseases involving inflammation and degeneration of skeletal muscle tissues. They are thought to be autoimmune disorders. In inflammatory myopathies, inflammatory cells surround, invade, and destroy normal muscle fibers as though they were defective or foreign to the body. This eventually results in discernible muscle weakness. This muscle weakness is usually symmetrical and develops slowly over weeks to months or even years.

When using the term inflammatory myopathy, one is actually considering three separate disease entities, namely dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM). Although all of these diseases result in muscle weakness, each is unique in its development and treatment.

Description

Inflammatory myopathies include a diverse group of disorders ranging from localized varieties confined to a single muscle or group of muscles, to diffuse forms in which there is widespread involvement of the skeletal muscles.

Inclusion body myositis (IBM) mainly affects individuals over the age of 50. The onset is truly insidious with symptoms often having been present for more than five years before diagnosis. Clinically and histologically, IBM may appear identical to another inflammatory myositis called polymyositis, although differences are clear in more than half the patients.

Weakness in (IBM) may be localized in the extremities, or asymmetric, and it may be accompanied by diminished deep-tendon reflexes. Disease progression is usually slow and steady in some, while it seems to plateau in others, leaving them with fixed weakness and atrophy (muscle wasting) of the involved musculature. In the muscle tissue, a characteristic change in IBM is the presence of intracellular rimmed vacuoles (pockets). The muscle fibers with pockets are now recognized to contain abnormal deposits of amyloid proteins.

Polymyositis usually occurs after the second decade of life and is a subacute myopathy (one that occurs over time) that evolves over weeks or months, and presents with weakness of the arm and leg muscles. PM mimics many other myopathies. It should be viewed as a syndrome of diverse causes that occurs separately or in association with other autoimmune disorders. In PM, muscle fibers are found to be in varying stages of necrosis (tissue death) and regeneration.

Dermatomyositis (DM) is identified by a characteristic skin rash accompanying or, more commonly, preceding muscle weakness. DM affects children and adults and presents a varying degree of muscle weakness that develops slowly, over weeks to months.

Demographics

In the United States and Canada, IBM accounts for approximately 15–28% of all cases of inflammatory myopathies. IBM most frequently affects men with a male to female ratio of 3:1. No race predilection for IBM is known, but it is uncommon among African-Americans and has been reported in Europe and Asia. Assessing demographic data is difficult due to the fact that IBM patients often exhibit other medical problems.

Polymyositis (PM) is most common among black people and is most prevalent in women, with a male to female ratio of 1:2. In the United States, its incidence is one per 100,000 persons per year. Dermatomyositis (DM) affects mainly white people and is more prevalent in women, with a male to female ratio of 1:2. In the United States, the estimated incidence is 5.5 cases of DM per one million people.

Causes and symptoms

Inclusion body myositis (IBM) is thought to be a sporadic disease, meaning one that is not hereditary. The cause of IBM remains unknown, but is thought to be a form of autoimmune disease, where the immune system responds in a harmful manner to the rest of the body. Very rarely, IBM can be present within families, and it is not known whether this form is inherited or if family members have another susceptibility to whatever causes the sporadic form of the disease.

The trigger mechanism for all inflammatory myopathies remains unknown. Some scientists maintain that a viral illness causes an injury that activates a flawed immune response. Other scientists, noting that cancer sometimes occurs along side some types of inflammatory myopathy, are investigating the relationship between the two diseases. A genetic predisposition may exist for DM, and abnormal activities of certain white blood cells may be involved in the cause of both the skin and the muscle disease.

Weakness of muscle function in the area affected is usually the first symptom of inflammatory myopathy. The distribution of weakness is variable, and involvement of the knee extensor muscle and the wrist and finger flexor muscles are common. Fatigue is common, along with reduced tolerance to exertion, difficulty swallowing (dysphagia), and some forms of heart disease.

In polymyositis (PM), weakness and muscle pain on both sides of the body at rest or with use are the first signs of the disease. The weakness becomes chronic, lasting for weeks or months. If swallowing muscles are involved, dysphagia may occur. Joint pain and difficulty kneeling, climbing, or descending stairs, raising arms, and arising from a sitting or lying position are also noticeable.

People often present with skin disease as one of the initial manifestations of DM. A characteristic rash preceding or accompanying muscle weakness, or a confluent, purple-red rash with swelling in surrounding tissues appears. Other rashes seen with DM include swelling at the nail beds and a scaly purple eruption over the knuckles. Muscle involvement varies from mild to severe. The muscle wall of the heart or lung tissues may also become inflamed as a consequence of DM. Some cancers have been associated with DM, a finding much more common in adults over 60 years old.

Diagnosis

A muscle biopsy provides a definitive diagnosis for inflammatory myopathies. Muscle biopsy is also important for the exclusion of other neuromuscular diseases. Blood levels of creatine kinase, an enzyme present in the brain and skeletal and cardiac muscles, are usually elevated in persons with muscle damage, and are useful in the diagnosis of inflammatory myopathies.

According to The Myositis Association, the main clinical features for diagnosis of inclusion body myositis (IBM) are:

• Duration of illness greater than six months
• Age of onset greater than 30 years old
• Muscle weakness that affects the arms and legs
• At least one of the following: weakness when flexing the fingers, differing degrees of weakness when flexing and extending the wrist, and weakness in the quadriceps muscle of the thigh.

In polymyositis (PM), the presence of inflammation in muscle tissue is hallmark of the disease. The diagnosis of PM is made when a person has continued elevated levels of serum creatine kinase and characteristic findings on muscle biopsy. Polymyositis is difficult to diagnose due to its ability to mimic other chronic diseases.

People with dermatomyositis (DM) often have characteristic rashes that accompany chronic weakness, making the tentative diagnosis easier for the physician and patient. Skin lesions can include red, raised areas on the surface of the joints of the arms and legs, face, or upper body.

Treatment team

A neurologist or rheumatologist is the primary consultant for both IBM and PM, with allied health care areas including but not limited to physical therapists and otolaryngology.

Treatment

Currently, no treatment has been shown to be effective against the different forms of IBM. Some moderate success has been obtained with the combination of corticosteroids and methotrexate or human intravenous immunoglobulins (IVIg). New therapeutic protocols are currently being tested.

In PM, however, high-dose corticosteroid therapy constitutes the first-line of treatment, and leads to improvement in more than 70% of persons with PM. Different therapeutic alternatives can be attempted with immunosuppressants, notably azathioprine, methotrexate and intravenous immunoglobulins (IVIg). The same approach is useful for DM.

Recovery and rehabilitation

In most cases of inflammatory myopathies, there is continued deterioration, in spite of any reduction of muscle inflammation that treatments may provide. Because of the slow progression, any medication regimes often continue for at least six months (possibly 12-18 months) to gain the most benefit. Physical therapy and occupational therapy help with walking, limb range of motion and positioning if the person's disability increases.

About 30% of persons with PM achieve complete recovery, with the majority of patients having a persistent deficit in movement and strength.

Clinical trials

The National Institute of Neurological Disorders and Stroke (NINDS) has sponsored 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 examining whether the drug infliximab (Remicade) is safe for treatment of DM and PM. Information about all current clinical trials can be found at the U.S government website for clinical trials: http://www.clinicaltrials.org.

Prognosis

IBM generally worsens progressively and slowly. Sometimes the condition stabilizes spontaneously or while the person is under treatment, but periods are usually transient and the inflammation reoccurs.

Before the era of corticosteroids, PM and DM were particularly severe diseases with spontaneous survival rates of less than 40%. Currently, in the absence of an underlying disease such as cancer, PM and DM in adults have a relatively favorable prognosis, with a five-year survival rate of around 90%. For children, the vascular damage of DM can be responsible for severe complications, such as perforations or hemorrhages.

Special concerns

Exercise is generally helpful to retain movement, and helps to get the most out of diseased muscles. Falls and injuries, however, can cause substantial disability for a person with an inflammatory myopathy. It is important, therefore, to maintain regular exercise within a safe capacity and avoid injury. Because weakened muscles cannot carry an excess load, keeping to an ideal weight is also helpful. A well-balanced diet is important and people with severe inflammation of the muscles may need extra protein.

Resources

BOOKS

Kilpatrick, James R., compiler. Coping with a Myositis Disease. Birmingham, AL: AKPE, 2000.

PERIODICALS

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.

OTHER

"NINDS Inclusion Body Myositis Information Page." National Institute of Neurological Disorders and Stroke. (February 11, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/inclusion_doc.htm>.

ORGANIZATIONS

Muscular Dystrophy Association. 3300 E. Sunrise Drive, Tucson, AZ 85718,. (800) 572-1717. mda@mdausa.org. <http://www.mdausa.org/index.html>.

Myositis Association of America. 755 Cantrell Ave., Suite C, Harrisonburg, VA 22801. (540) 433-7686; Fax: (540) 432-0206. maa@myositis.org. <http://www.myositis.org>.

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