DSI Newsletter: Polymyositis/Dermatomyositis

DSI Newsletters, Issue 61:
Polymyositis/Dermatomyositis

What are Polymyositis and Dermatomyositis?
Polymyositis (PM) is a chronic disease that causes inflammation and weakness of the muscles. PM is a muscular disease featuring inflammation of the muscle fibers. The cause of the disease is not known (idiopathic). It begins when white blood cells, the immune cells of inflammation, spontaneously invade muscles. The muscles affected are mostly those closest to the trunk or torso. This results in weakness which can be severe. It is a chronic illness with periods of increased symptoms, called flares or relapses, and decreased symptoms, known as remissions.
Polymyositis is slightly more common in females. It affects all age groups, although its onset is most common in middle childhood and in the twenties. Polymyositis occurs throughout the world. Polymyositis can be associated with skin rash and is then referred to as "dermatomyositis." It also can affect other areas of the body and is, therefore, a systemic illness. Occasionally, it is associated with cancer, or with other diseases of connective tissue (Other CTD/Connective Tissue Disorders include: systemic lupus erythematosus, scleroderma and rheumatoid arthritis).
Dermatomyositis (DM) is a related disease in which a skin rash occurs along with the muscle problems of polymyositis. In about half of the people who have PM or DM, the heart muscle is affected. These diseases are rare.
How do they occur?
To date, no cause of polymyositis has been isolated by scientific researchers. PM or DM probably occurs when the body's immune system attacks its own tissues. It is not known why this happens. An underlying cancer may also be related to the disease. PM or DM occurs twice as often in women as men. They occur most often between ages 50 and 70, or in children 5 to 15 years old.
There are indicators of heredity (genetic) susceptibility that can be found in some patients. There is indirect evidence of infection by a virus that has yet to be identified in a form of polymyositis that is particularly resistant to treatment, called inclusion body myositis/IBM. This form of polymyositis is diagnosed by the pathologist, a physician specialist who interprets the microscope findings of muscle tissue. The muscle tissue in this form of polymyositis displays clear areas within the muscle cells (called vacuoles) when viewed under the magnification of a microscope.
What are the symptoms?
Polymyositis can begin suddenly or slowly. Symptoms may include:

weakness, especially in the hips, thighs, upper arms, and shoulders
muscle and joint pain
weight loss
fatigue
fever
tremors of the hands
shortness of breath, even at rest
problems swallowing.

If you have dermatomyositis, you also have a violet or deep reddish-purple rash.
Weakness of muscles is the most common symptom of polymyositis. The muscles involved usually are those that are closest to the trunk of the body. The onset can be gradual or rapid. This results in varying degrees of loss of muscle power and atrophy. The loss of strength can be noticed as difficulty getting up from chairs, climbing stairs or lifting above the shoulders. Trouble with swallowing and weakness lifting the head from the pillow can occur. Occasionally, the muscles ache and are tender to the touch (25% of patients).
Patients can also feel fatigue, a general feeling of discomfort and have weight loss and/or low-grade fever.
With skin involvement (dermatomyositis), the eyes can be surrounded by a violet discoloration with swelling. There can be scaly reddish discoloration over the knuckles, elbows and knees (Gottron's sign). There can also be reddish rash on the face, neck and upper chest. Hard lumps of calcium deposits can develop in the fatty layer of the skin, most commonly in childhood dermatomyositis.
Heart and lung involvement can lead to irregular heart rhythm, heart failure, and shortness of breath.
Because polymyositis can present in combination with other illnesses (see related articles on systemic lupus erythematosus, scleroderma and rheumatoid arthritis), it can also have overlap features with them; the Overlap syndrome. Both polymyositis and dermatomyositis can sometimes be associated with cancers, including lymphoma, breast cancer, lung cancer, ovarian cancer, and colon cancer. The cancer risk is reported to be much greater with dermatomyositis than polymyositis.
How do they affect the heart?
The inflammation weakens the heart muscle. The heart can't squeeze as well, and congestive heart failure may develop. Congestive heart failure is the buildup of fluid in body tissues that can happen when the heart is not working well. The disease also may cause heart rhythm irregularities and very fast heart rates. Inflammation of the pericardial sac, which surrounds the heart, may cause some fluid buildup inside the sac.
How are they diagnosed?
Your health care provider will ask about your medical history and your symptoms. Your provider will examine you. The inflammation causes a breakdown of muscle cells, so you may have a blood test to look for abnormal amounts of broken cells. Other types of tests might include:

biopsy of the involved area (the removal of a small sample of muscle after an anesthetic) to check for inflammation
an electromyogram, or EMG, a test that looks at muscle strength and function.

How does the doctor identify polymyositis?
When a patient first sees the doctor, the recent symptoms especially concerning weakness will be discussed. The condition of many other body areas might be reviewed, for example, the skin, heart, lungs and joints. An examination will further focus on these and other systems. Various measures of strength might be noted.
Blood testing usually reveals abnormally high levels of muscle enzymes, CPK or creatinine phosphokinase, aldolase, SGOT/AST, SGPT/ALT, and LDH. These enzymes are released into the blood by muscle that is being damaged by inflammation. They can also be used as measures of the activity of the inflammation. Other routine blood and urine tests can also look for internal organ abnormalities. Chest X-rays, mammograms, PAP smears and other screening tests might be considered.
An electromyograph (EMG) and nerve conduction velocity are electrical tests of muscle and nerves that can show abnormal findings typical of polymyositis as well as exclude other nerve-muscle diseases.
Imaging of the muscles using radiology tests, such as magnetic resonance imaging (MRI scanning) can show areas of inflammation of muscle. This can sometimes be helpful to determine muscle biopsy sites.
A muscle biopsy is used to confirm the presence of muscle inflammation typical only of polymyositis. This is a surgical procedure whereby muscle tissue is removed for analysis by a pathologist, a specialist in examining tissue under a microscope. Muscles often used for biopsy include the quadriceps muscle of the front of the thigh, the biceps muscle of the arm and the deltoid muscle of the shoulder.
How are they treated?
There is no known cure for PM/DM. If diagnosed with polymyositis, treatments might include:

ongoing physical therapy to prevent further weakness
supportive care for other symptoms such as shortness of breath or pain
prednisone or other anti-inflammatory drugs. These drugs work better for some people than for others. If further treatment is needed, powerful drugs that interfere with the body's normal immune system may be used. These are the same drugs used to control the rejection problem in heart and kidney transplants and must be used very carefully.

You may need to see a rheumatologist, a specialist in diseases of the connective tissue.
Call your health care provider right away if you have shortness of breath and trouble swallowing.
How is polymyositis treated?
Initially, polymyositis is treated with high doses of corticosteroids. These are medications related to cortisone and can be given by mouth or intravenously. They are given because they can have a powerful effect to decrease the inflammation in the muscles. They usually are required for years and their continued use will be based on what the doctor finds related to symptoms, examination and muscle enzyme blood test.
Corticosteroids have many predictable and unpredictable side effects. In high doses they commonly cause increase in appetite and weight, puffiness of the face and easy bruising. They can also cause sweats, facial hair growth, upset stomach, sensitive emotions, leg swelling, acne, cataracts, osteoporosis, high blood pressure, worsening of diabetes and increased risk of infection. A rare complication of cortisone medications is severe bone damage (avascular necrosis) which can destroy large joints, such as the hips and shoulders. Further, abruptly stopping corticosteroids can cause flares of the disease and result in other side effects including nausea, vomiting and decreased blood pressure.
Corticosteroids do not always adequately improve polymyositis. In these patients, immunosuppressive medications are considered. These medications can be effective by suppressing the immune response that attracts the white blood cells of inflammation to the muscles. Many types are now commonly used and others are still experimental. Methotrexate can be taken by mouth (Rheumatrex, Trexall) or by injection into the body. Azathioprine (Imuran) is an oral drug. Both can cause liver and bone marrow side effects and require regular blood monitoring. Cyclophosphamide (Cytoxan), chlorambucil (Leukeran) and cyclosporine (Sandimmune) have been used for serious complications of severe disease, such as scarring of the lungs (pulmonary fibrosis). These also can have severe side effects which must be considered with each patient individually. Treatment with intravenous infusion of immunoglobulins (IVIG) has been shown to be effective in severe cases of polymyositis.
Patients with calcium deposits (calcinosis) from dermatomyositis can sometimes benefit by taking diltiazem (Cardizem) to shrink the size of the calcium deposits. This effect, however, occurs slowly — frequently over years, and is not always effective. The complication of calcium deposits in muscles and soft tissues occurs more frequently in children than adults. Physical therapy is an important part of the treatment of polymyositis. When to begin, and the continued degree of exercise and range of motion of extremities is customized for each patient.
Patients can ultimately do well, especially with early medical treatment of disease and disease flares. The disease frequently becomes inactive, and rehabilitation of atrophied muscle becomes a long-term project. Monitoring for signs of cancer, heart, and lung disease are essential.
As mentioned above, the form of polymyositis called inclusion body myositis is often more resistant to treatment than the usual form of disease. As scientists better define the specific causes of the different forms of polymyositis, treatment will be more accurately aimed at cure of this disease.
How long will effects last?
It is difficult to predict the course of this disease. Once diagnosed you might:

have a severe episode at the time of diagnosis, and then do well
have ongoing flare-ups of the disease, but little progression
have it affect your breathing muscles or heart. If you have these complications, you will need to work even more closely with your health care provider to manage your disease.

What are antinuclear antibodies/ANA?
Normally, we have antibodies in our blood that are used to repel invaders into our body, such as virus and bacteria microbes. Antinuclear antibodies (ANAs) are unusual antibodies, detectable in the blood, that have the capability of binding to certain structures within the nucleus of the cells. The nucleus is the innermost core within the body's cells and contains the DNA, the genetic material. ANAs are found in patients whose immune system may be predisposed to cause inflammation against their own body tissues. Antibodies that are directed against one's own tissues are referred to as auto-antibodies. The propensity for the immune system to work against its own body is referred to as autoimmunity. ANAs indicate the possible presence of autoimmunity and provide, therefore, an indication for doctors to consider the possibility of autoimmune illness.
Polymyositis At A Glance

Polymyositis and dermatomyositis (PM/DM) are chronic inflammatory diseases of muscle.
Muscle weakness is the most common symptom of PM/DM.
The cause of PM/DM is unknown.
Diagnosis of PM/DM involves physical examination of muscle strength, blood tests for muscle enzymes, electrical tests of muscle and nerves, and confirmed by muscle biopsy.
Treatment of PM/DM involves high doses of cortisone-related medications, immune suppression, and physical therapy.

Polymyositis
Related Medications
Prednisolone is a synthetic adrenal corticosteroid. Corticosteroids are natural substances produced by the adrenal glands located adjacent to the kidneys. Corticosteroids have potent anti-inflammatory properties, and are used in a wide variety of inflammatory conditions such as arthritis, colitis, asthma, bronchitis, certain skin rashes, and allergic or inflammatory conditions of the nose and eyes. There are numerous preparations of corticosteroids including oral tablets, capsules, liquids, topical creams and gels, inhalers and eye drops, and injectable and intravenous solutions. Prednisolone that is prescribed in oral tablet and liquid forms is addressed in this article.

GENERIC NAME: azathioprine
BRAND NAME: Imuran
DRUG CLASS: Azathioprine is classified as an immunosuppressant medication. Azathioprine is used to suppress the immune system in patients who have had kidney transplants. Although its exact mechanism of action in rheumatoid arthritis is not known, its effect in suppressing the immune system appears to decrease the activity of this illness.

GENERIC NAME: cyclophosphamide
BRAND NAME: Cytoxan
DRUG CLASS AND MECHANISM: Cyclophosphamide is a drug that is used primarily for treating several types of cancer. In order to work, cyclophosphamide first is converted by the liver into two chemicals, acrolein and phosphoramide. Acrolein and phosphoramide are the active compounds, and they slow the growth of cancer cells by interfering with the actions of deoxyribonucleic acid (DNA) within the cancerous cells. It is, therefore, referred to as a cytotoxic drug. Unfortunately, normal cells also are affected, and this results in serious side effects. Cytoxan also suppresses the immune system and is also referred to as immunosuppressive.

Sincerely:
Joseph Saponaro, MD, DABIM, FACP, CPI, CCI, CCTI, CCRC, CCRP
PI (Principal Investigator), DSI (Drug Study Institute)
Board Certified Internist, JPMC (Jupiter Preventive Medicine Center)
DABIM (Diplomat American Board of Internal Medicine)
FACP (Fellow American College of Physicians)
CPI (Certified Physician Investigator) by the AAPP/APPI
(American Academy of Pharmaceutical Physicians/ Academy of Pharmaceutical Physicians and Investigators)
CCTI (Certified Clinical Trial Investigator) by the ACRP (Association of Clinical Research Professionals)
CCI (Certified Clinical Investigator) by the DIA (Drug Information Association)
CCRC (Certified Clinical Research Coordinator) by the ACRP (Association of Clinical Research Professionals)
CCRP (Certified Clinical Research Professional) by SoCRA (Society of Clinical Research Associates)
IRB Member, Jupiter Medical Center
Ethics Committee Member, Jupiter Medical Center
Member, ARENA (Applied Research Ethics National Association)
Member, PRIM&R (Public Responsibility in Medicine and Research)
Member: The American College of Preventive Medicine
Member, SIMPD (Society for Innovative Medical Practice Design)
Member, ACPM (American College Preventive Medicine)
Founder, CertifiedResearchers.com
Expert Medical Witness, ExpertMD

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