Progress in Scleroderma during the past 20 years
Professor Carol Black CBE
At the 20th Anniversary of The Scleroderma Society, 5th October, 2002
Part 1
Considerable progress has been made although at times it does seem like climbing Mount Everest. I first became involved in scleroderma as a houseman in 1970. My first patient was a woman of 26 who had kidney disease and there was nothing we could do for her. Things have definitely changed, for example kidney disease is something we see much more rarely than 30 years ago and we are much better at taking care of it.
Scleroderma is a little like a cube: multidimensional, multifaceted and very difficult to solve. It’s not just a question of finding the cause because there are a large number of factors that interact to give someone scleroderma. I think you will all agree that 20 years ago there was ignorance and considerable apathy also in the medical profession. It’s always difficult for a doctor to look after things without much to offer. You feel a great sense of failure when you really feel helpless to effect the outcome, it all seemed too complex so people rather ignored it and there was definitely a sense of hopelessness for patients. There were no societies, no helplines and people were really out there on there own trying to cope with a dreadful disease. Scleroderma was in fact an orphan disease, which in medical terms means a rare disease, only so many people per community or country suffer. Therefore on the whole researchers weren’t interested in it and pharmaceutical companies find it difficult to support because they do have to earn a living and you don’t earn a great deal from looking after patients who come under the orphan disease category. It is very difficult but I’ve always believed that if you go on putting little on little then very often something big will happen and I think this is what has happened over the last 20 years. People have been adding little to little and there have been changes that I’m now going to show you.
Classification
This may not seem such a tremendous leap forward but we didn’t have a classification of scleroderma 20 years ago. We just had the word Scleroderma; you may say what does that matter? Why do we need to subdivide people? It actually matters a great deal because we know that Primary Raynaud’s patients are never going to develop scleroderma. However Autoimmune Raynaud’s patients have proteins of antibodies circulating in the blood and have a much greater risk of developing scleroderma, SLE (Lupus) or another connective tissue disease. These patients need to be identified so that they can be followed up regularly to monitor any changes.
There are now 4 divisions within scleroderma, the newest being Limited scleroderma, these patients have Raynaud’s and antibodies in the blood specific to scleroderma, (this is not a term used by everybody in the world) but it’s a very mild subset of the disease. The late Professor LeRoy and Professor Medsger described this antinuclear antibody. Doctors are now aware that this patient is now within the family of scleroderma and must receive very regular follow up and tests for organ function.
Then there is the Localised forms of scleroderma and there are several of these and they are mainly skin diseases although it can affect the underlying muscle and in children of course the underlying bone and severe wasting of the muscle. This is what I think is the recent advance in classification this new subset, there has now been described an overlap between skin manifestations of Localised scleroderma and systemic sclerosis but I’ve never had a patient in whom localised scleroderma has become internal scleroderma. We have tended to see a few patients in which the localised lesions look more like the much more diffuse lesions of systemic sclerosis.
We have a much better appreciation and so does the medical community of the danger of Limited Cutaneous Scleroderma. The patients who have very mild changes in their hands and face, quite a lot of telangiectasia, these patients were often ignored because everyone thought the symptoms were very mild and it would "Just go away" but we know now that 15% of these patients will get pulmonary hypertension. For those patients with Pulmonary Hypertension I don’t need to tell you that it is a really important diagnosis to make and to make it as early as possible.
Circulating proteins in the blood, the anti nuclear antibodies which all patients with scleroderma will have measured, are very useful to us because they tell us which type of organ is most at risk, so there have been important advances in 20 years that have improved our management. I previously mentioned that renal disease is decreasing in its severity and part of that is because when you have a blood test we always look for anti polymerase antibodies, if you have it we put you on drugs to try and protect your kidneys. Quite a rare antibody is anti pm-scl and indicates to us the patients who might have inflammation in their muscles.
We can now draw an imaginary map of what happens to a patient with scleroderma with the 2 main subsets. Diffuse scleroderma, the skin score is quite high early on in the disease travelling pretty fast during first 1-2 years and then tends to plateau and soften whereas the organ involvement is rising quite severely too but can tend to go on and take over from the skin score. Whereas with the Limited form skin is less of a problem but pulmonary hypertension can start to take off and is something that we really must watch for, as is quite bad gut disease.
Assessment
The most important thing is to be able to assess each patient’s subset and to look for things proactively in order to try and stop them developing. Certainly none of this was available 20 years ago, indeed I would say in many units not even 10 years ago. I know this doesn’t seem like rocket science but it is so important to us when we are trying to assess the value of different drugs in scleroderma that we have improvements in the way we assess the disease. As you know it’s a very difficult disease to assess accurately, when we do, what you will all have probably experienced if you come to the Royal Free, a skin score, this is when we sort of pinch your skin to see just how tight and just how much give there is in it. It is very useful to us, now in trial there are other methods of skin assessment. We don’t use them every time you come to clinic but they are being investigated in the context of clinical trials.
We are now trying very hard in our patient clinic to try and get an indication of quality of life, because its not just about how long we are all going to live but what sort of quality of life we have while we are alive. We are trying very hard to introduce these indices into our patient clinic so that we can then look back and take these indices and compare them with skin score and the drugs patients have been on.
We have got much better organ-based assessments by looking at the markers in the blood. We can look to see if they correlate with the severity and whether they correlate with organ involvement. They are all things that will tell us more about where any individual patient is with their disease, we also have a severity score that has now been validated and there is a lot of work both in America and in Europe on activity in the disease. This is all ongoing work that is making it better for us to be able to assess exactly where an individual patient is at with the disease.
This is the first part of the serialisation of Professor Carol Black’s talk at the Scleroderma Society’s 20th AGM on the 5th October 2002 at The John Lister Post Graduate Centre, Wexham Park, Reading UK. It has been transcribed (with edits) from a recording taken at that time. The next part on Research will be in the Spring 2003 issue of Scleroderma News.