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Sidney
Cohen, M.D., Temple University, Philadelphia, Pa. |
The Gastrointestinal Tract in Scleroderma
By Sidney Cohen, M.D., Temple University, Philadelphia, Pa.
(originally published in "Scleroderma Foundation Newsline,"
Spring 1999)
Editor's note: This is a long article. You can skip
directly to the subheads that interest you, by clicking on
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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. |
