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Every Day
January - April 2006 Issue
Understanding and Treating Scleroderma
Mary Ellen Csuka, MD
Medical College of Wisconsin Rheumatologist;
Director, Osteoporosis Program;
Named one of the “Best Doctors in America®” 2004 by Best Doctors, Inc.
Scleroderma, a rare rheumatologic disorder, is a complicated disease with myriad symptoms. Dr. Mary Ellen Csuka treats more scleroderma patients than any other doctor in the region. She talks here about the disease, its varied forms and promising treatments.
Q. What is scleroderma?
It is one of the connective tissue diseases, and it is also considered an autoimmune disease. The term scleroderma actually derives from the Greek term “sklero” which means hardening and “derma” which means skin. The classic initial description of the disease referred to the thickening and tightening of the skin, which initially was treated by dermatologists. However, we now know that the pathology is not confined to the skin, and often involves thickening of blood vessels, overproduction of collagen and fibrosis of various internal organs — the lungs, heart and intestinal tract — which results in various symptoms.
There are several presentations. The most benign form is called localized scleroderma, which is confined to the skin and subcutaneous tissues and occurs locally. It is called morphea if thickened skin presents as a patch or linear scleroderma if hard abnormal skin has the shape of a line. Localized scleroderma is not associated with internal organ involvement and therefore does not have any effect on life expectancy.
Then we have systemic sclerosis which is divided into two categories — limited and diffuse. Both these categories may have involvement of internal organs. The difference between limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis is determined by the extent of skin involvement. The diffuse cutaneous form of systemic sclerosis is defined by skin involvement above the elbows/knees and on the torso. The limited cutaneous form of systemic sclerosis is defined by skin thickening limited to below the elbows/knees and the face — what is called peripheral involvement only. In the past this form of systemic sclerosis was called CREST, which stands for calcinosis; Raynaud’s phenomenon; esophageal motility dysfunction; sclerodactyly; and telangiectasia. As features of CREST can be found in both subsets the term is no longer used to differentiate between the two subsets.
Q. What causes scleroderma?As with most autoimmune diseases, we do not have a specific cause. The current theory is that it is an abnormality of the immune system which causes inflammation, and results in overproduction of collagen and fibrous tissue. We suspect that there are some genetic factors that predispose people to developing scleroderma, but we do not know what exactly the specific trigger is.
Q. Whom does it affect?It generally affects women more than men by about 4 to 1 and it most commonly affects women in their 30s and 40s. It affects people across races. There are estimates of anywhere between 100,000 to 500,000 Americans who have scleroderma. About 5,000 new cases of systemic sclerosis diffuse cutaneous are diagnosed each year, which is generally the most serious form of scleroderma.
Q. Is there a typical case of scleroderma?With this disease, every patient has their own presentation. If there was a typical patient, it might be someone who has developed Raynaud’s phenomenon, and whose hands have become puffy. She might have decreased manual dexterity, and will not be able to make a fist. The skin has become thickened, she has reflux symptoms, and may be shortness of breath. If you know the disease you usually find other signs and symptoms that have been going on that just have not been on the patient’s radar screen. They’ll say, “Now that you mention it ...” when I ask about other problems. They think I am a soothsayer.
Q. Is scleroderma curable?Some of the signs and symptoms are treatable, and we have encouraging results from studies using immunosuppression therapy to treat the lung inflammation.
Still, most of the treatment at this point is directed toward symptom relief aimed at the specific organ system involved. We have not yet discovered the drug that alters the course of the disease as a whole. We have made progress in treating two serious complications: using angiotensin converting enzyme inhibitors — the ACE drugs — in the treatment of the renal hypertensive crisis; and managing of pulmonary hypertension with new agents available.
Q. What are the signs and symptoms? There are a wide variety of symptoms ranging from skin thickening and other skin symptoms to internal organ damage. Depending on the type of scleroderma they have, patients may also experience gastrointestinal symptoms, kidney, heart or lung problems and more.
In general, localized scleroderma does not affect internal organs. Most people with that form of the disease don’t develop any other signs or symptoms apart from those affecting the skin.
The first manifestation of scleroderma is often the hardening and thickening of the skin. Sometimes early on, there’s swelling, puffiness and the skin can appear very shiny. As the skin gets replaced with collagen underneath, it replaces the hair follicles, so patients will lose the hair on their skin. And they may see changes in skin color — areas where there is too much pigment and too little pigment. It can be very itchy. They also may get red dots, known as telangiectasia (the T in CREST), which are dilated blood vessels that can be found anywhere but are bothersome on the face.
Other symptoms include a particular facies that some patients get, where the mouth becomes pursed and the skin on the face becomes smooth and begins tightening. Patients will often first describe swelling of their extremities — they’ll often get edema, but as time progresses, the skin actually thickens and hardens.
Patients may also note calcinosis (the C in CREST), which are little bumps — deposits of calcium — under the skin. They’re very hard and occasionally they’ll drain, particularly if they’re over areas of pressure like the elbow. Patients will describe a chalk-like substance, the calcium, that’s coming out. This can be associated with localized inflammation, and if you have an open, draining ulcer, it can get infected as well.
Limited cutaneous patients will often have esophageal motility (the E in CREST). They’ll have reflux symptoms and will often describe the sensation that food is not passing through their esophagus. It will feel as though it’s stuck. That’s due to the fact that their lower esophagus muscle gets replaced with this fibrosis tissue and it doesn’t contract, so they have difficulty with food going down. The sphincter between the esophagus and the stomach doesn’t work well either, so they also get the acid reflux. If this doesn’t get treated and a lot of acid washes back, patients can end up with strictures.
If they have involvement of the entire GI tract, that can result in problems with malabsorption, diarrhea, constipation or the stomach not contracting properly. They can also have fecal incontinence because the lower sphincter is bad.
Ninety percent of patients with either the limited or diffuse forms will have Raynaud’s phenomenon, (the R in CREST), a condition where digital arteries go into spasm, usually in response to cold or sometimes emotional distress. Raynaud’s occurs in about 10 percent to 30 percent of the population, regardless of scleroderma, so it’s a relatively common symptom. The patient’s fingers will turn white, and when the spasm releases they may turn a bluish color. Then as the blood flow is returned to normal, they’ll turn red. Sometimes Raynaud’s is so severe and prolonged that it causes ischemia or loss of blood flow to the distal part of the digit. The patient may end up with finger ulcers, which are very painful and very debilitating.
The group that has diffuse cutaneous systemic sclerosis is the group with the higher morbidity and mortality overall. Patients who develop this form often get rapidly progressive skin thickening, so they have involvement of the upper arms in addition to the hands, torso and the thighs. Diffuse cutaneous patients, particularly if they have very rapid skin progression, are very much at risk for serious internal organ involvement, particularly the heart and lungs.
They’re also at risk for developing a complication known as hypertensive scleroderma renal crisis. This is a condition where they develop rapid onset of malignant hypertension which results in rapid decline of renal function. This used to be the most common cause of death in this condition. We’ve now developed some treatments, which seem to help at least 60 percent of the patients in this category, so there is some hope.
Another major concern with diffuse cutaneous patients is the development of interstitial lung disease, and that’s now the most common cause of death.
Overall, the organ system of most concern is the lungs. The disease causes fibrosis and patients will describe shortness of breath, the inability to take a strong deep breath, and a decreased ability to do usual activities. Those with limited cutaneous systemic sclerosis are the group that we’re most concerned about with respect to pulmonary artery hypertension, a serious lung complication.
With the heart, patients can get fibrosis in the heart, and this can sometimes affect the conducting system leading to irregular heart rates or arrhythmias. Pericardial effusion (fluid around the heart) is a rare complication, but it can result in heart failure because the muscle of the heart is replaced with fibrous tissue.
Patients may also have symptoms of arthritis, restricted range of motion of joints, and muscle weakness. They may also describe symptoms of Sjogren’s syndrome, which is dryness of the eyes and mouth.
Often, particularly in the diffuse cutaneous, the patients just don’t feel well, they’re systemically ill. They have weakness, they’re fatigued, their hands won’t close anymore because they’re swollen. Some of these symptoms you have to elicit because they’re only so many things a person can pay attention to at once.
You can imagine, with all those signs and symptoms, there may be a fair amount of psychological distress related to this diagnosis. I’m amazed — the majority of these patients are quite resilient.
Q. What are the treatment options?When I first see patients with scleroderma, everyone wants to know what to expect. One of the things I emphasize is that each person with scleroderma really is an individual case. If I have a patient with rheumatoid arthritis, I’m pretty good at being able to predict how it’s going to go. For somebody with lupus, you can usually outline what the problems are going to be. With scleroderma, I find it exceedingly difficult to tell the individual sitting in my room what’s going to happen. It’s really something we have to watch as it evolves. They can go to the Web sites, which have the worst case scenario, so I try to reassure them that I have a number of patients who really just do well.
When patients are diagnosed with systemic sclerosis, we educate them about hypertensive scleroderma renal crisis — the serious kidney complication — and recommend they monitor their blood pressure at home so they can let us know right away if there is an increase. There are treatments now that can help abort this complication. Back in the 70s, this was the most common cause of death.
With the use of angiotensin converting enzyme inhibitors (ACE drugs), we’re often able to treat the hypertension and preserve kidney function. Occasionally, patients will end up on dialysis but even if they do, a fair number of those patients will not be on long-term dialysis. Their kidney function will return, which is almost unheard of with most kidney problems.
Gastrointestinal complications — the acid reflux and difficulty swallowing — are usually treated with proton-pump inhibitors, elevating the head of the bed, not eating right before you go to bed, and changing the types of foods you eat.
If there is involvement of the small intestine, then we might have problems with malabsorption. And, when the small intestine doesn’t work properly, you get a condition called bacterial overgrowth. The bacteria grow in areas where it’s not moving, so occasionally patients will have to be on rotating antibiotics to control that symptom.
Then there’s one other complication of the lung called pulmonary artery hypertension. This can occur without any fibrosis. This manifestation is more frequently seen in the limited cutaneous systemic sclerosis.
The newest therapies being evaluated are looking at altering the course of pulmonary fibrosis — trying to stop the laying down of scar tissue in the lung to preserve lung function. Because we think of this as an autoimmune disease with inflammation, we’ve used a variety of immunosupression drugs. Cyclophosphamide has finally been the first drug that has demonstrated benefit in the placebo/control trial to result in at least stabilization of the lung signs and symptoms when compared to a placebo.
Q. When should you consult a physician?Anybody who has unexplained symptoms needs to see their physician, and there are tests to help sort things out. A lot of the Web sites say “It can be very difficult to treat this condition or to diagnose this condition.” By and large, scleroderma is not that hard to diagnose once you know what you’re looking for. It is true that probably within the first six months of several connective tissue diseases, such as lupus or scleroderma or dermatomyositis, it may not be clear which one you’re dealing with until they define themselves.
There are patients who have what we call overlap syndrome where they have features of lupus or features of dermatomyositis so there’s that nebulous group. For straightforward systemic sclerosis, it’s not that hard if you know what you’re looking for. It usually manifests itself pretty early in the diagnostic process.
Patients will come in for a variety of reasons, they’ll come in because their skin changes, they’ll come in because of esophageal symptoms, or nausea and vomiting and they can’t eat. They’ll come in because they have Raynaud’s and finger ulcers. A lot of people who have Raynaud’s will just put up with it, and it’s not until they have finger necrosis that they show up.
Patients should see their primary care physician first. If you’re short of breath, the first thing that comes to your mind is not going to be scleroderma. But if there’s any question of this particular condition, it really needs to be seen by a rheumatologist and my bias is that it be by someone comfortable with this condition because it is a relatively rare condition, even for rheumatologists.
You can imagine, with all those signs and symptoms, there may be a fair amount of psychological distress related to this diagnosis. I’m amazed — the majority of these patients are quite resilient.
Author: Mary Ellen Csuka, MD Source: Every Day Date: January - April 2006 Issue |
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