Muscling in on myositis

Reproduced from Issue 118 of Arthritis Today

Dr Nicolo Pipitone, Dr Ernest Choy and Barbara Mason: running a clinical trial into myositis at Kings College Hospital, Dulwich

This rare but unpleasant disease is explained by Ernest Choy, Barbara Mason and Nicolo Pipitone.

Myositis is the name given to a group of diseases that results in inflammation of the muscles. When many muscles are involved, it is called “polymyositis” (from the Greek “poly”, which means many). Sometimes, a skin rash accompanies myositis, in which case it is called dermatomyositis.

The cause of myositis is unknown, but it is considered an autoimmune disease. In autoimmune diseases, the body's defence mechanism, the immune system, which normally wards off infections, turns against the body's own tissues. In the case of myositis, the immune system attacks the muscles.

Myositis is a relatively uncommon condition, and only about five new cases occur a year for every million people. Women are two to three times more likely to be affected than men. It can affect children as well as adults.

Symptoms

Muscles: The commonest symptom in patients with myositis is weakness in the upper arms, hips, and thighs. Because of the weakness in the upper arm, many patients find it to difficulty to comb and shampoo their hair, get dressed and reach for objects above their heads, while weakness in the thigh muscles makes climbing stairs and rising from a chair difficult.

Often muscle weakness starts slowly, although in children with dermatomyositis, symptoms may develop more rapidly. Occasionally, muscles of the gullet (the canal through which food and drink pass from the mouth to the stomach) are also affected, causing difficulty in swallowing. When the muscles of the throat are involved, the voice can become hoarse. In severe cases, muscles of the chest and heart could also be affected and patients can become short of breath. Although less common than weakness, more than half of the patients also experience muscle pain.

Skin: In dermatomyositis, a skin rash may appear before the development of muscle weakness or at the same time. Typically, a shadowy red rash affects the face, the exposed area of the upper chest, and upper back. Often a reddish-purplish swelling develops around the eyes (known as a heliotropic rash) and Gottron's papules (red scaly lesions) can appear over the knuckles or fingers.

Other organs: Myositis can make the patient feel generally unwell with excessive tiredness, fever, and weight loss. Joints feel achy in approximately one third of the patients. Whitish-bluish skin and discoloration of the hands (Raynaud's phenomenon) after exposure to the cold is another relatively common symptom. In the lungs, inflammation with scarring can occur, but rarely. Involvement of the heart can cause irregular heartbeat and breathlessness. Damage to the gut leading to bleeding is a rare complication that occurs mainly in children. Another rare complication more often seen in children is calcinosis (hard lumps of calcium under the skin or in the muscles).

Cancer: Very rarely, myositis especially dermatomyositis, may be triggered by cancer.

Diagnosis

The diagnosis of myositis is made often by a specialist based on the typical symptoms and signs. However, this requires confirmation by blood tests and a detailed examination of the muscles.

Blood tests: Many patients with myositis are mildly anaemic. In myositis, when muscles are damaged by inflammation, enzymes normally appear inside the muscle and leak into the blood. Therefore, increased levels of these enzymes are often found in the blood of patients with myositis. The most important of these enzymes is creatine phosphokinase.

The body normally produces substances called antibodies, which circulate in the blood and fight infections. Patients with autoimmune diseases such as myositis produce auto-antibodies, i.e. antibodies that react against the body's own tissues. A number of auto-antibodies are found in patients with myositis, the commonest being the anti-nuclear antibodies, present in 80% of patients. Another autoantibody, anti-Jo1, is found in approximately a quarter of patients who are more prone to develop inflammation and scarring of the lungs.

Electromyogram: Electromyogram measures the electrical activity of the muscles by means of special needles inserted directly into the muscles and sending a small electric current to stimulate the muscles. In myositis, because of damage and inflammation, the electrical activity of the muscles shows a number of abnormalities. However, these abnormalities can also be found in other muscle diseases. In addition, since myositis affects only some muscles, and since the involvement of a given muscle can be patchy, in 10% of patients the electromyogram can be normal.

Muscle biopsy: To make a definitive diagnosis of myositis, a sample of affected muscle has to be examined under the microscope. The sample is obtained by inserting a special needle into the affected muscle. The procedure is usually performed under local anaesthetic. Typically, in the muscles of myositis patients, white blood cells are abundant and the muscle fibres show signs of damage. However, inflammation in muscles in myositis does not affect the whole muscle but occurs in patches. If the biopsy misses the inflamed area, sometimes the muscle biopsy in myositis patient may be normal

Others investigations: Other investigations such as x-ray and MRI scan may be needed to determine if internal organs are affected.

Treatment

Corticosteroids (steroids): Corticosteroids are the standard treatment for myositis. They are usually given initially in high doses; for a few weeks. After myositis has improved, the dose is gradually reduced. The major drawback of corticosteroids is long-term side effects (including thinning of the bones) and, in some patients, they do not control the disease adequately.

Other treatments: Medicines that suppress the immune system (immunosuppressive agents) such as azathioprine, methotrexate and cyclosporin, are often given to patients who do not response adequately to corticosteroids. However, their use is based on experience in a small number of patients rather than on sound scientific evidence through clinical trials.

The SELAM trial

The Arthritis Research Campaign is currently funding the SELAM trial which aims to investigate the benefits of adding immunosuppressive agents, specifically methotrexate and/or cyclosporin, to the treatment of myositis patients currently taking corticosteroids. A few studies suggest that these two drugs may be effective in myositis, however this has never been proven scientifically by clinical trials.

The design of the trial will randomly assign patients who are currently taking corticosteroids to one of four study groups: to receive methotrexate and cyclosporin placebo (a dummy drug), methotrexate placebo and cyclosporin, both methotrexate and cyclosporin, or methotrexate placebo and cyclosporin placebo. This will allow the researchers to determine whether methotrexate, cyclosporin, or both together are effective treatments for myositis.

Recruitment of up to 100 patients started in January 2002. Patients are being enrolled from centres in London, Manchester, Liverpool, Birmingham and Newcastle and will receive trial medication for a period of 56 weeks.

• Dr Ernest Choy and his colleagues are running the £425,000 arc/BSR SELAM clinical trial into myositis at King's College, Dulwich. Arthritis Today will report on the trial's results in a future edition.

Other Articles in this Issue

• Life after anti-TNF
• Hip revision
• Focus on Keele Leading the field in primary care
• Pain – and how to manage it
• Spotlight on science