Inflammatory Myopathies: A Neurological Perspective on Myositis

Introduction

Dr. Shetty’s presentation to the Myositis Education and Support Program focused on inflammatory myopathies and their initial evaluation, testing, diagnosis, and treatment protocols.

Inflammatory Myopathies

Inflammatory myopathies are muscle diseases characterized by muscle weakness. The three major inflammatory myopathies are polymyositis, dermatomyositis, and inclusion body myositis. Each type has different findings:

• Patients with polymyositis (PM) and dermatomyositis (DM) typically experience weakness in muscles involved in lifting the arms above the head, getting up from a chair, or walking up stairs. In dermatomyositis, there is skin involvement characterized by a rash either on the eyelids, hands, or trunk of the body. Because dermatomyositis can sometimes be associated with malignancies, screening should always be conducted for this as well.
• Inclusion body myositis (IBM) can affect some of the same muscles as polymyositis and dermatomyositis but also often affects the hand muscles known as finger flexors and the quadriceps muscles. Other characteristics specific to IBM are that it usually affects people who are over 50 who do not respond well to medication.

One of the major effects of the inflammatory myopathies is difficulty in swallowing, known as dysphagia. If this occurs, it is important to bring this to the attention of your physician.

Muscle disease can also be associated with certain endocrinological problems, such as thyroid abnormalities.

Toxic myopathies refer to myopathies that are caused by medications such as steroids, chloroquine, colchicine, and statins.

Diagnosis

Each type of inflammatory myopathy (polymyositis, dermatomyositis, and inclusion body myositis) has specific findings upon examination, electromyographic testing, muscle enzyme level, and muscle biopsy.

People who have muscle disease generally present with the following upon examination:

• Complaints of muscle weakness, as evidenced by difficulty in climbing stairs
• Difficulty raising the arms above the head
• Difficulty opening jars.

Onset can be gradual and progressive; there may be varying degrees of muscle pain or cramps. When these complaints are present, a detailed neurological exam is indicated in order to find the source of the weakness and to determine which muscles are affected.

Blood Testing

Blood tests are also obtained to check muscle enzyme levels and to determine the presence of associated rheumatologic or connective tissue disorder markers that may be associated with myositis or muscle diseases. These tests, in conjunction with renal (kidney) and liver tests, are used to monitor inflammation and to rule out the possibility of medication toxicity.

The blood tests monitor levels of creatine kinase (CK, also known as creatine phosphokinase [CPK]). A rise in the CK level may be the first sign of a muscle disease flare and can occur prior to muscle weakness. It should be noted that CK levels are variable and are affected by race, gender, genetics, cholesterol-lowering drugs and activity level. All of these tests are conducted in order to determine the specific type of myopathy a person has.

Family History

Although family history can often be relevant, the absence of muscle disease in a family does not mean that the patient does not have muscle disease. History about family members is often incomplete. Many muscle diseases occur spontaneously or are not fully understood genetically.

Electromyography and Imaging

Further testing can include the use of electromyography (EMG) and imaging, such as MRI and ultrasound. These tests work in the following ways:

• Muscle MRI helps to assess tissue’s water content in patients with myositis or muscle disease.
• Comparison of different “fat suppressed sequences” helps to view the muscle and determine if muscle weakness is due to active inflammation or if there is atrophy of muscle or fatty replacement of muscle tissue.
• Nerve conduction studies and needle EMGs are conducted to determine abnormalities in specific nerves and muscles and if abnormal findings are consistent with myopathy.
• A muscle biopsy is obtained if there is sufficient evidence of myopathy. This may be used to diagnose a specific myopathy.

Treatment

The goal of treatment is to decrease muscle inflammation and to prevent further muscle loss or injury. Medical treatment is individualized, and there are no defined guidelines in the approach to treatment. However, randomized controlled clinical trials are evolving in order to better define this.

It is important to note that all treatment options, responses, and effects are personalized and that each individual will respond differently to a given plan. The physician will be able to assess your response to treatment based on your own report of the status of your disease, change in rash, and examination of muscle strength.

As Dr. Shetty emphasizes, “Most importantly, the treatment is based on a very close interchange between physician and patient who, together, assess the response to immunosuppressive therapy. This dialogue enables the doctor and patient to arrive at a treatment plan that is optimal for the patient.”

Factors that are taken into consideration for treatment are:

• Duration of the disease
• Clinical findings
• Response to prior therapy
• Potential contraindications to certain agents.

Corticosteroids and Immunosuppressive Agents

Medications that are commonly used in myositis include corticosteroids and other immunosuppressive agents such as Imuran (Azothioprine), Cellcept, Methotrexate, and Rituxan (still in trial stages). Although corticosteroids are often have a wide range of side effects, their effectiveness makes them an initial treatment approach. The dosing is individualized to the patient and weighed against potential side effects.

Caution is urged against the prolonged use of high doses of steroids. It should also be noted that steroids can cause a myopathy, which is often reversed when steroid dose is tapered.

Indications for use of immunosuppressives other than steroids include: progression of clinical symptoms, poor response to steroids, evidence of organ involvement, relapse when steroids are tapered, and undesirable effects from steroids (osteoporosis, cataracts, diabetes, hypertension acne, weight gain, and mood changes).

• Azothioprine (Imuran) can be effective and well tolerated but may take up to several months to work. Side effects include nausea, abdominal pain, bone marrow suppression, liver toxicity, increased risk of infection, and malignancy.
• Methotrexate can be administered in different ways and in various dosages and is sometimes effective in combination with other agents. Side effects include nausea, hair loss, liver toxicity, bone marrow suppression, and increased risk of infection.
• Cyclosporine is an immunosuppressive agent that can act faster than Imuran and is useful in the treatment of polymyositis and dermatomyositis. It can also be used in combination with methotrexate.

Intravenous Immunoglobulin (IVIG)

IVIG is administered intravenously and is derived from pools of serum from healthy individuals. IVIG provides antibodies and has an immunomodulatory effect, which can be used to treat dermatomyositis and polymyositis where other treatments have not proved effective.

Recent Research Developments

• The reasons for the therapeutic benefits of steroids in treating polymyositis and dermatomyositis is still unknown. The same is true for the other immunomodulating agents used in these two types of myositis.
• Ongoing clinical trials for patients with inflammatory myopathies are currently being conducted with FDA approved drugs that include TNF-alpha inhibitors (infliximab).
• Also being studied is the use of Rituximab (Rituxan) in treating polymyositis and dermatomyositis.
• Research on the interaction of genetics, pathology, and immune etiology (cause) of muscle diseases continues to evolve.
• Research is also being done toward the possibility of using other types of immune suppression, such as monoclonal antibodies and cytokine modulation.

Myositis Support Group at HSS

Learn more about the Myositis Education and Support Program, a free support and education group held monthly at Hospital for Special Surgery.

Posted: 8/19/2009

Summary by Suzan Fischbein, LCSW

Authors

Teena Shetty, MD
Associate Attending Neurologist, Hospital for Special Surgery
Associate Professor of Clinical Neurology, Weill Cornell Medical College

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