The Gastrointestinal Tract in Scleroderma

By Sidney Cohen, M.D., Temple University, Philadelphia, Pa. (originally published in "Scleroderma Foundation Newsline," Spring 1999)

It was a number of years ago at the University of Pennsylvania that I first became interested in scleroderma. I worked with Dr. Jimenez and other prominent rheumatologists at that institution, and it has really become a life-long interest. A gastroenterologist like myself, usually becomes involved after the diagnosis is made. We get involved in looking at the gastrointestinal tract (G.I.), preventing some of the complications, and treating the disorder as it affects the G.I. tract. There have been a number of advances that have been made in therapies which I would like to share with you.

A lot of what I have written will probably be controversial. We all eat and we all have a digestive tract. There have been a lot of anecdotal comments made about gastrointestinal function and about the therapy of this disorder.

The gut or the intestinal tract is involved in, perhaps, 80% to 100% of patients with the systemic form of scleroderma, as we will describe it. It involves all areas of the G.I. tract. The esophagus is the most common area, but it can involve the stomach, small bowel, colon, and the internal anal sphincter. The manifestations that a patient would feel, the complications, and the features of the illness would be dependent upon the most prominent site of involvement. The esophagus is the one area where most patients have problems and, fortunately, it has been the area where the most advancement has been made in therapy. Now we are able to prevent and treat many of the complications and features of this illness.

In the first stage of the illness, one loses the function of the sphincter that separates the stomach from the esophagus, allowing acid, bile, and food to regurgitate back into the esophagus, leading to the symptom of heartburn. Sometimes it leads to regurgitation of material into the mouth. This is perhaps the most common symptom.

This regurgitation leads to damage of the esophagus and breakdown of the tissue. It may lead to stricture formation, a condition called Barrett's Epithelium which will be described in detail below. It can also lead to bleeding and ulceration.

The lower two-thirds of the esophagus is made up of smooth muscle, which loses its function and becomes somewhat paralyzed allowing the acid and material to sit there for a long time worsening this complication. In the GI tract this is the most important symptom to prevent and is one that can be prevented.

The small bowel also becomes involved leading to dilation of the bowel, to bacterial overgrowth from the bacteria growing in the intestine, breaking down the food substances and causing a malabsorption or loss of material into the stool leading to weight loss and diarrhea. The bacteria also break down the lining of the small bowel damaging that site.

The large bowel may also be involved. One may get widemouthed diverticular (large pouches) in the colon, and the stomach may be involved later in the illness. In my experience treating patients with scleroderma, I see mainly esophageal involvement early on in the disease. I believe patients develop colonic involvement with the progression of the illness. Small bowel problems arise later and, lastly, gastric dysfunction may occur.

Esophageal Involvement

The symptoms may begin with heartburn, difficulty in swallowing as the esophagus becomes damaged, and large bowel disorder leading to severe constipation and obstipation. Then, with small bowel dysfunction, diarrhea, malabsorption, and possibly nausea, vomiting, and regurgitation with gastric involvement. Not every patient will develop this kind of involvement, fortunately, but these are the most serious complications that can occur.

It is important, in this illness, to know that barium itself often used in x-rays can cause complications. I rarely, in this condition, do barium studies anymore. We have seen many patients with barium impactions of the colon, especially if there is large bowel involvement. If barium is given for whatever reason, it must be flushed through the system promptly. In the past, we have seen serious complications in some people who had barium impactions in the colon requiring surgery for bowel obstruction. If barium is given, and occasionally it has to be given, it has to be flushed through with an agent like Colyte or some other laxative preparations. I warn you about this because we still see this problem arising from barium.

The disease goes through various stages. Early in the illness, many of the changes are related to neural dysfunction. This is important because you lose a lot of what we call the "reflex function" of the gut. Normally, when you eat there is something called gastro-colic response, which is the urge to move your bowels. Your stomach starts to work, your bowels start to chum and move things through, and a lot of these reflexes are lost early in the illness. But the gut, (the intestinal tract) can still respond to drugs that stimulate it directly. This is important clinically because some of the drugs like Propulsid®, or Cisapride®, or a drug called Reglan® or Urecholine® can act at various stages, especially the early stages of the illness. But later in the disorder, the muscle response is lost and the muscle becomes atrophic and fibrotic. Many times, I see patients who are past the responsive phase of the illness, given higher and higher doses of drugs which are not going to work. You cannot "drug" the organ into functioning if there is no tissue there to function. So, again, certain drugs like Propulsid®, a very safe and very effective drug, may work early in the illness but later in the illness lose its effectiveness. When we see patients without scleroderma who have bowel abnormalities, giving more drugs may be helpful. But in some scleroderma cases, it is just going to lead to drug toxicity and not be helpful. This is an important point to keep in mind.

In esophageal disease, the major clinical feature is heartburn and reflux. It is important that at the earliest stage of the illness this be treated effectively. The treatments of choice now are the proton pump inhibitors, Prilosec® or Prevacid®. I have a strong opinion regarding these drugs. I'm sure others may argue this, but it is very important to prevent esophageal complications and these drugs are safe and effective.

I see many patients with other esophageal conditions that are somewhat analogous to scleroderma with achalasia (inability of a muscle to relax) who have had various types of esophageal surgery. But when the esophagus is not functioning well, candidiasis, moniliasis, and fungal infection are not uncommon. But again, with Fluconazole and with other antifungals you can eradicate the problem. This is a very effective treatment and can be of great help in the correct patient population.

When the esophagus loses muscle tone and is dilated it can become about two to two-and-a-half times normal size. The lower part of the esophagus where there is usually a nice tight valve, is very patulous (standing open or spreading apart) allowing material to reflux up. Sometimes this causes large ulcerations of the esophagus. We now can prevent the ulcers and treat them effectively. You cannot prevent the widening of the gastroesophageal junction, but you can prevent the complications due to reflux.

In scleroderma, esophageal manometry is an essential diagnostic tool. It is not 100%, but virtually diagnostic. In the skeletal muscle in the upper portion of the esophagus, we can see a nice wave when the patient swallows. But, in the lower two-thirds, we can see loss of function. It shows as a very weak little wave, little blips, and then with time, even they disappear. When this happens, the esophagus loses the normal ability to push things down and to keep them down in the stomach. This is the evolution of the condition. These changes are typical of this condition, and are sometimes seen even before skin changes. Sometimes patients with Raynaud's phenomenon present with these esophageal changes only to develop the skin changes at a later point. As a gastroenterologist, I often see patients with reflux esophagitis who have a prominent history of Raynaud's. In some patients that I consider for surgical repair (fundoplication), I have found the early changes of systemic sclerosis, and in those patients, I would not do surgical intervention.

The esophagus goes through these changes, which I have described, where the function is very minimally impaired early, but impairment progresses as time goes on. And, then, in the very advanced 1 stages, the esophagus has no peristaltic function, the pressures are very weak, and the response to the agents (medicines) that stimulate the esophagus is lost. Again, an important point to remember ... drugs that may be useful initially may no longer be useful as the disease advances. Therefore, there is no reason to push patients to take more and more of these medications.

Loss of function of the lower part of the esophagus, I believe, is highly specific. It is very closely related to Raynaud's and, to repeat, the Raynaud's may precede esophageal involvement by many years. One patient I saw years ago had prominent Raynaud's and a prominent esophageal condition for over 20 years before developing the skin manifestations. So, Raynaud's is an important historical feature for all clinicians, not just rheumatologists.

Scleroderma can cause chronic, severe, progressive mucosal damage. About 40% of patients develop stricture or narrowing of the esophagus. With proton pump inhibitors, we can virtually abolish this. There was a time when we had to dilate the strictures weekly, and some patients daily. It was a very common practice to do so. With high-dose acid suppression (the elimination of acid secretion), the need for dilation has almost disappeared completely.

Barrett's Epithelium

However, what we do encounter is the problem of Barrett's esophagus. Barrett's esophagus is a complication in all patients with reflux, but especially complicated in this group of patients. It occurs in about 10% of all patients with prominent reflux symptoms, but almost 40% of patients because of inadequate early therapy. Barrett's tissue is what is called a metaplastic tissue. It is a change in the lining of the esophagus to a premalignant condition. It has to be monitored very aggressively.

A number of years ago, our institution published information on several patients with Barrett's tissue. Those patients had scleroderma and were doing well with their underlying illness but developed adenocarcinoma of the esophagus.

Barrett's is the precursor for adenocarcinoma. When followed closely, we can detect changes early before cancer presents itself. There are now ongoing studies with laser ablation of the Barren's tissue. You can remove the Barrett's tissue and the esophagus regenerates with normal tissue. It is not as easy as it sounds, but it can be done and it is another modality of therapy. However, the hope is that with proton pump inhibitor drugs you can prevent stricture formation or if a stricture forms, treat it with one dilation plus the proton pump inhibitor.

One can prevent the formation of Barrett's or, certainly, the progression of Barrett's tissue into the proximal or upper portions of the esophagus. Endoscopy with biopsy is needed to make this diagnosis. Some radiologists feel they can actually see Barrett's, but it is not really seen very well. I feel that those with Barrett's scleroderma need lifetime therapy using very high doses of H2 antagonists. Now, we've shifted over to omeprazole (Prilosec®) or the new drug Prevacid®, which gives almost total neutrality of the stomach acid for 24 hours.

With most patients my sense has been that prokinetics become less effective. Prokinetics are Propulsid®, Cisapride®, or Reglan®. I have avoided, and do not recommend fundoplication or surgery because the tissue in the esophagus itself does not work very well, and there is poor peristaltic function. Even physicians in other parts of the country where they were enthusiastic about fundoplication or creating an anti-reflux valve, have found they fail with time. My feeling is that this should not be a major consideration in scleroderma and I have avoided it. The cases I have seen performed elsewhere have not had good outcomes or shown to be a long-term improvement for patients.

In a recently done important maintenance study, it showed that patients who stayed on Prilosec® (omeprazole) can stay in remission. If they took nothing, they relapsed within 30 days. Almost 100% of patients who take Ranitidine® or Zantac® relapse. This study was not done on scleroderma patients but it holds true to an even greater extent in their condition.

One of the clinical findings that we have made as gastroenterologists, indicated that the maintenance therapy for scleroderma is the same as the initial therapy. In peptic ulcer disease, maintenance therapy was a lower dose of a drug, and we thought that we could use that same reasoning with esophagitis. It was not the case at all. The maintenance therapy is the same as the healing therapy. So, if you need omeprazole (Prilosec®) to heal the esophagus, which is usually the case, then you have to stay on it. This has been shown over and over again. One of the most difficult things to convince physicians of is that H2s just do not work. Some physicians and patients have the feeling that they can stop the Prilosec® (omeprazole) at some time, regardless of the number of papers that come out to the contrary. This lesson has been learned over and over again. If one has esophagitis and you heal the esophagitis, but then quit taking Prilosec® (omeprazole) it has been found that the patients relapse almost 100% of the time.

Scleroderma patients with esophagitis need to stay on a potent anti-secretory drug. This is the most important bit of advice that I can give to you in terms of this illness.

Small Bowel

In scleroderma, the small bowel becomes dilated and often very atonic (weak, lacking normal tone). The small bowel when dilated loses its propulsive function. Bacteria, which do not normally grow in the small bowel, now begin to grow. The bacteria break down and bind bowel salts. They break down the mucosa that absorbs the food, and you begin to lose fat and food into the stool. This condition is called malabsorption.

Sometimes, there is a markedly dilated small bowel resulting in a condition called intestinal pseudo-obstruction. If the patient is so unfortunate to develop this severity of illness, it is at this point that we move towards total parenteral nutrition using a "portacath" device (catheter usually in the shoulder). In "pseudo" (false) obstruction, the small bowel may require venting. "Venting" means to put a small jejunostomy or surgical tube into the jejunum (small intestine) to aspirate out the air which keeps the patient from becoming severely distended. We do this infrequently. However, it is not the norm to do total parenteral nutrition with a central line, and venting the small bowel. This would be done only in a very severe case of intestinal pseudo-obstruction in a patient with advanced scleroderma. It has been helpful, when done properly.

Another variance of scleroderma is dilated small bowel with spiculations (or sharp spires) causing a hide-bound appearance. It is due to fibrosis and atrophy in the small bowel usually in patients with severe malabsorption and weight loss. A number of years ago, a study was done looking at the motility in the gut. Normally when you eat, anything that stimulates the small bowel induces these high-amplitude (strong) contractions, which is the normal process that moves things through the bowel. In this condition, these contractions are lost to most of the stimuli. Whatever distends the bowel or normally stimulates it, no longer stimulates it. The bowel remains flaccid, atonic, and nonpropulsive. The gut does not work that well by gravity, so things just sit there and ferment, and bacteria begins to grow at that site.

This is something called "migrating motor complex." In the fasting stage you get motor complexes, and there has been some evidence that this can be induced by a drug called somatostatin. There have been some studies showing a drug called Sandostatin (somatostatin) can be used to stimulate small bowel function. It has been used on a number of patients. It must be injected daily, but in the right setting and in some patients, these powerful migrating complexes can be induced to go through the bowel, prevent the stasis, and the bacteria overgrowth and be most helpful. My personal experience has been it has not been as good as others have reported, but it has been helpful in a number of people with scleroderma and other forms of pseudo-obstruction. In the right person, the right setting, for the right amount of time, Sandostatin in the injectable form helps to create powerful contractions called the "house-keeper function" of the gut. It allows one to absorb food and to have normal passage through the bowel.

Diverticulitis

Let me remind you once again about the colon. The colon becomes very atonic and dilated, with very characteristic widemouthed diverticula. They rarely, if ever, cause what's called diverticulitis. We have all heard about people getting diverticulitis. The diverticula that are very common in Western society are about 1/4 or 1/8 the size of those seen in scleroderma and they get obstructed with stool, and break, resulting in diverticulitis.

Wide-mouthed diverticula rarely rupture, but one has to be aware and cautious when doing procedures, not to poke a scope into them. They do not have to be removed and nothing has to be done to them. The valve sometimes becomes atonic and many of these patients become severely constipated and obstipated. Again, with this condition one must be very careful in giving barium to make sure it is flushed through to prevent impaction.

Constipation also plays a role in scleroderma. When the normal individual eats, there is a tremendous increase in motility called the gastrocolic response. This is what causes many people to have the urge to move their bowels after they eat. In the person with scleroderma, as with many of the motor disorders of the gut, this gastrocolic response is lost and the urge to move the bowels is lost with it resulting in severe constipation. One has to try to counter this by taking laxatives, bulk feeding, and other gut stimulants.

Summary

So, again, scleroderma involves all aspects of the intestinal tract. In the esophagus, there may be sphincter incompetence, aperistalsis, stricture, Barrett's epithelium, and, occasionally, adenocarcinoma of the esophagus. The most effective treatment now is with proton pump inhibitors.

In the stomach there is diminished antral peristalsis or gastric pump action, and gastroparesis (i.e. a paralyzed stomach) which contributes to the bad reflux. This occurs very late in the illness and is more unusual. Small bowel involvement is seen all the time with diminished reflex contraction, diminished migrating motor complex, and bacterial overgrowth. Treatment is usually with antibiotics.

Sandostatin can be helpful in many of the patients to prevent severe malabsorption. Some patients, unfortunately, develop fecal incontinence with anal sphincter weakening. There are some electrical devices that have been used to stimulate the anal sphincter which have received mixed reviews. Sometimes they work, sometimes they don't. But, this again, is a rare problem. The common problems are severe reflux, malabsorption due to bacterial overgrowth, and severe constipation early in the illness leading to obstipation and sometimes fecal impaction. The good news is that most of these things such as esophageal problems and, bacterial overgrowth, can be treated and one can prevent severe constipation.

Total Parental Nutrition

One last area I would like to discuss is if and when one is a candidate for total parental nutrition (TPN). TPN is widely used. I believe that if a patient has severe small bowel, or gastroesophageal disease, TPN can be useful. However patients must realize if TPN is used, the disease may continue to progress, and may progress to areas that are not usually affected in the course of this illness. TPN is not an easy decision to be made particularly in a very advanced state of the disease. TPN should be used very sparingly in patients with pseudo-obstruction from scleroderma or other pseudo-obstruction syndromes. If a patient gets to the point of requiring TPN, I would combine this with a venting jejunostomy, so that the severe distention and atony (lack of muscletone) of the bowel can be relieved along with providing nutrition by vein.

Dr. Cohen is Chairman of the Department of Medicine at Temple University. He pioneered many of the studies that demonstrated the involvement of the gastrointestinal tract in scleroderma. This article is excerpted from a presentation by Dr. Cohen at a seminar sponsored by the Scleroderma Foundation of the Delaware Valley.