TREATMENT AND RESEARCH IN SCLERODERMA:

The Scene in 2006

Dr Shouvik Dass - Scleroderma Research Fellow

Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital, Leeds

In recent years, the approach of doctors and other professionals who deal with people with Scleroderma has changed. This is because of more understanding of the path the illness can take and increased awareness of the treatment options. Part of this has been down to the development of some new therapies for Scleroderma, although there is much more to treatment than just drug treatment.

The first thing to point out in an article like this is that no two patients with scleroderma are the same. It is also important to bear in mind that the more severe forms of the disease are considerably rarer than milder forms. Three events seem to occur in Scleroderma - a problem with the immune system, as suggested by the finding of autoantibodies in blood tests; a problem then with the circulation – which is why Raynaud's is almost always seen in Scleroderma; and then the illness almost seems to spill over from the circulation into the skin and other organs, leading to fibrosis, which is hardening and scarring. This fibrosis can take place on both the inside and outside. That is why we see skin involvement as well as similar problems in the lungs, kidneys, gastric system, etc.

The modern approach to Scleroderma treatment falls into three main areas:

•  Treat the symptoms

•  Prevent the complications

•  Treat the complications

A good team approach is necessary – not just rheumatologists who usually are the main doctors involved but also other medical specialists such as dermatologists, chest specialists, etc. Just as important as doctors are other professionals such as Specialist Nurses, Podiatrists, Physiotherapists and Occupational Therapists.

Treating the symptoms:

This involves practical measures as well as some prescription medications. Firstly, in dealing with the symptoms of Raynaud's syndrome, gloves and hand warmers are helpful. It has been suggested that repeated attacks of Raynaud's may provoke worsening of Scleroderma, so staying warm is important. Other tablets which can improve the circulation include drugs often used to control blood pressure (they help to open the blood vessels) such as amlodipine or nifedipine. There is a range of these, so if someone gets side effects with one - headaches are the commonest – another drug can be tried. Heartburn and acid reflux are another common symptom and there are effective tablets for this.

Preventing the Complications:

One of the biggest advances in recent times has been the awareness of the complications of scleroderma and the fact that they can be detected early. This has become more important as new treatments become available. Clearly, treatment will be more effective if given before a patient suffers damage from an untreated complication.

The most potentially seriously affected organs in Scleroderma can be the lungs and kidneys. There are a number of tests which can be done to see if these complications are developing. Some of these are very simple –regular blood pressure checks and urine tests for the kidneys – and others take a little more effort such as pulmonary function (breathing) tests and echocardiograms (scans of the heart). These are useful in picking up the early stages of Scleroderma in the lungs and the circulation between the lungs and heart. In most centres such tests are usually done once a year.

Treating the complications:

If complications are found as a result of testing, early treatment is best.

Finger or foot ulcers are quite common, especially in severe Raynaud's because the skin's healing powers are lessened by poor circulation. Often ulcers can be infected and treatment with a combination of antibiotics and a drug called iloprost is needed. Iloprost is a copy of a natural body substance called prostaglandin, which is very powerful at opening up the circulation. So far it is only available as a drip, so people sometimes need to be admitted to hospital for a few days to have this treatment. A trial is currently being carried out to study a tablet form.

Another new drug called bosentan is also being studied for ulcers, including prevention of ulcers developing, although it is not yet licensed.

Treatment of lung disease usually involves dampening down the immune system, which in Scleroderma attacks the body itself (an autoimmune disease). Drugs that do this to the immune system include cyclophosphamide and azathioprine. Cyclophosphamide, in particular, has recently been shown to be effective in treating lung inflammation. It does have some side effects, however: some patients feel sick after the cyclophosphamide drip and as it damps down the immune system, people may be more prone to infection. It carries a risk of causing infertility so is not always suitable for younger people. Much current research work is aimed at finding other treatments for lung disease in Scleroderma.

Pulmonary hypertension is a complication affecting the pulmonary artery, which carries blood from the heart to the lungs. Pressure in the artery may rise, either on its own or because of lung disease. People may become more breathless. Standard blood pressure tablets and Warfarin (which prevents blood clots) are often the first choices in treatment, but recently newer drugs have become available. These include iloprost – but this is given continuously through a permanent line inserted into a big blood vessel; the drug is carried in a syringe which is kept in a bag clipped to a belt, so patients can walk around with it etc. – and the new drug bosentan. Sildenafil (also known as Viagra) is also being used for this – since it also opens up the blood flow.

New Directions in Scleroderma :

For the first time, several new drugs are being tested in Scleroderma. Trials usually need lots of patients to show that a drug is safe and that it works and so Scleroderma doctors have been sharing information both nationally and internationally. Patients now have the opportunity to try out new treatments in a safe and controlled way. Not all of these drugs may be helpful but at least people are getting the chance to try some different treatments.

One of the new treatments being tested is a stem cell transplant. This involves giving large doses of chemotherapy type drugs to wipe out the body's immune system, which is abnormal in Scleroderma. Stem cells are immature cells in the body which can develop into a new immune system and in this transplant a patient's own stem cells are removed (by a method like donating blood) before the chemotherapy and then given back afterwards to build a new immune system. No stem cells from an embryo are needed – the patient gives his or her own. Clearly, this is a procedure that carries some risk and hazard, so is being tested in people who have severe Scleroderma. A trial across Europe is being done at the moment, comparing it to standard dose cyclophosphamide.

For doctors and other professionals now is an exciting and fulfilling time to be involved with Scleroderma. Our understanding of the disease is advancing; and in a practical sense we now know that early detection of problems and treatment is very important. Hopefully in the next few years, we may have more treatments for the problems we see. Those of us who treat Scleroderma patients and carry out research are always very grateful to those patients who are able to take part in trials and studies. Our aim is to improve life for all Scleroderma patients.