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Scleroderma

Scleroderma is caused by a vascular lesion that leads to ischemia, fibrosis and activation of connective tissue disease with a lot of collagen deposition. In the skin you see a kind of taut skin and eventually that can become what we call "hidebound" skin where you can’t even pick up the skin from the soft tissue scleroderma. Just bound down like it’s dried out and contracted. It is a rare disease with a prevalence of about 200 per million in the United States.

Systemic sclerosis is the group of patients who have scleroderma of the skin and then other organ involvement. Systemic sclerosis with diffuse sclerodermas, what we normally call scleroderma or progressive systemic sclerosis, as some people call it. In the outline it is sometimes abbreviated PSS. Systemic sclerosis with limited sclerodermas, or CREST - which I’ll go over that - that’s a specific form that is generally milder. You can have CNS scleroderma. Actually, one of my parents good friends died of this. He had no skin manifestations but associated internal organ involvement.

Scleroderma-like syndromes; some of these are occupationally related, which is interesting because it makes us think that maybe it is a toxin in the environment. Someone mentioned earlier this week about tryptophan causing eosinophilic myalgia syndrome, which is a scleroderma-like syndrome. Also polyvinyl chloride silica, not silicone, silica.

There is an association with silicone prostheses, whether they are breast implants or whatever, with any connective tissue disease. And this has been fairly well documented by some extensive epidemiological studies of breast implants.

Another interesting thing is bone marrow transplant. Sometimes they get scleroderma-like illness that makes us think there is an immunologic mechanism to this. Scleroderma-associated syndromes. And interesting thing is PKU, phenyl ketonuria.

Again, the etiology isn’t known, but it is interesting that some of these occupational exposures do seem to cause it. It is not a genetic disease. It doesn’t run in families so it’s thought that some sort of occupational exposure or environmental exposure is what triggers it. We also have the story of - I forget what kind of oil it was - in Spain, the toxic oil syndrome where the patients used this oil in cooking.

There are three phases of scleroderma. Whatever the inciting incident is, you get vascular lesions, probably mainly in the endothelium. There are substances produced from T-cells that appear to be toxic to endothelial cells. Exactly what role this plays in the disease isn’t known, but this leads to myointimal cell proliferation, which then causes microvascular change. These cells are rather specific for scleroderma on biopsy.

The hallmark is this hidebound skin that you can see. It’s a little hard to see in a mild case on photography. Sometimes patients will complain that their hands feel a little puffy in the morning, and occasionally it will be mistaken for synovitis. I have seen a couple of patients where I diagnosed scleroderma and the original rheumatologist diagnosed rheumatoid arthritis.

Besides the skin, a number of organs can be involved. The skin is almost always involved. Raynaud’s phenomenon usually occurs at the onset or sometimes before. It can be present for years before. Often it will accelerate in severity when the patient develops scleroderma.

If you have a typical Raynaud’s phenomenon, very severe with digital ulceration involving the thumb or involving the toes, then you might consider - and again, this is based on each patient individually - consider an angiogram, and I think now that the MRA technology is such that you might then do a pretty decent medium to large vessel angiogram, which is rather noninvasive. To look at small vessels it’s going to be necessary to do the old-fashioned angiogram. So if you have a patient that does not fit the normal pattern of Raynaud’s.

The GI involvement: actually, in many patients, it’s mildly clinical or subclinical. But this is a picture of a barium swallow. Obviously you need to have the radiologist look at it while it’s actually going on. What happens is they have very hypo-motile esophageal muscles and often a lot of reflux, which is what I think this slide is showing. And that can lead to esophagitis, stricture, a lot of pain and can be important symptomatically.

Esophageal problems can be found in patients with rheumatoid arthritis, lupus, and other connective tissue diseases, so it’s not specific for scleroderma but it’s more common and usually more severe. If you were to do barium swallows in all connective tissue disease patients you’d find that the abnormal ones pop up pretty frequently.

Pulmonary involvement: as I mentioned, now this is the most severe involvement, the most common cause of death in these patients. One thing to remember is that the x-ray is very insensitive. Obviously I can’t show a picture of pulmonary, of a DLCO. I don’t even know what it looks like.

The treatment, unfortunately, is not going to come out well. If there is any evidence that this is an inflammatory vasculitis, then you might consider using steroids or immunosuppressive drugs. Otherwise you are going to have to try some kind of vasodilator to bring down the pulmonary pressure. I do not think primary pulmonary hypertension patients are candidates for lung or heart/lung transplants. Scleroderma patients are basically not candidates for any transplant. They just don’t do it. I guess with the shortage of organs they feel like these patients don’t do well. I don’t think there is any data to show that they don’t do well, but I think they are just not willing to risk using the organs on these patients.

The next case is a 46-year-old white female presents to your office with a 10-year history of Raynaud’s phenomenon with two color changes. That’s how I write it in my chart. Raynaud’s phenomenon with two color changes. I don’t pick out the colors. It’s just to remind me that this patient probably has definite Raynaud’s, I mean, it sounds very very clear, whereas no color change or one color change isn’t as strong a comment in my treatment.

The most likely diagnosis for this patient is CREST. This is very clearly CREST. There is some overlap with primary biliary cirrhosis, which is usually found in this same type of patient, middle-aged, white female but she has no itching. The serology that is most likely to be positive.