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Systemic sclerosis (ssc) is a multisystem disease characterized by autoimmune phenomenna, vascular abnormalities, and fibrosis

The gastro-intestinal tract in systemic sclerosis
Professor László Czirják
Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary
Systemic sclerosis (SSc) is a disease abnormality affecting the vessels and the connective
tissue. Besides the skin, joints, muscles, several internal organs can also be involved in
SSc including the gastrointestinal tract (GI). The internal organ symptoms are complex
(different organs can be damaged at the same time to different extent), and
heterogeneous (the involvement does not follow the same pattern in a particular
patient). Patients with SSc may develop abnormalities of the digestive system from the
mouth to the anal canal. The GI complications usually originate from decreased
gastrointestinal movements. The increased stiffness and weakness of the muscle in the
GI tract leads to decreased movement of food (“dysmotility”). Dysmotility is a term
used to describe diseases of the muscles of the gastrointestinal tract (esophagus,
stomach, small and large intestines). In patients with SSc, the esophagus-stomach-
intestinal movements become „lazy”. The disturbed movements (with other words,
diminished peristalsis) is caused by the injury of nerves of the GI system, and also by
the weakness and damage of smooth muscles that are responsible of the movements all
along the GI system, therefore the muscles in the GI tract are not able to work
properly. GI involvement is present in more than 80% of the patients, and both subsets
(diffuse and limited SSc) are equally affected.

GI involvement consists of a variety of complaints including heartburn, difficulty in
swallowing, nausea-vomiting, bloating, constipation, diarrhea, and abdominal pain. The
symptoms can profoundly influence the quality of life. Furthermore, some symptoms
can be even life threatening.

The gastrointestinal tract starts with the oral cavity. Decrease in oral aperture caused
by the skin involvement around the mouth may cause difficulties in eating. Saliva
production is often decreased ending up with dry mouth and throat. A sensation of food
sticking in the throat may also occur. Dental decay problems are also often present,
therefore effective tooth cleaning is very important in patients with SSc. Because of the
decreased ability to mouth opening, it is difficult to keep oral hygiene.

Esophagus is the tube for food travelling between the mouth and the stomach. The
esophagus is a commonly involved organ in SSc. Swallowing difficulties are often
present in SSc. Symptoms include chest pressure, and a burning feeling after eating.
These particular symptoms are caused by the slow movement of food through the
esophagus. Furthermore, the narrowing of the lower part of the esophagus can also
occur. The lower esophageal sphincter (valve) is a gate which opens to permit food to
enter the stomach and then closes to prevent food from coming back up. In patients
with SSc, this particular gate between the esophagus and stomach may not close
perfectly, and the acid from the stomach can backwash into the esophagus causing a
burning pain (“heartburn”). The gastro- esophageal reflux disease /GERD/) in SSc
therefore means that the acidic content of the stomach regularly gets backward to the
esophagus because of the insufficient closing between the stomach and esophagus. A
frequent acid backwash causes inflammation and scarring of the lower portion of the
esophagus, ending with a narrowing (“stricture”) of the tube. This particular chronic

inflammation and scarring further worsens the swallowing problems. Without therapy,
some patients may develop a serious esophagus narrowing. In this case, the patient may
even need to have the esophagus dilated periodically to improve swallowing.

Acid production of the stomach can be reduced, and the gastro-esophageal reflux
disease can be improved by avoiding the consumption of alcohol, fatty or spicy foods,
chocolate, tobacco and caffeine. An upright position after meals, eating small and
frequent meals is useful. It is also advised to avoid eating for several hours before
bedtime. These particular lifestyle measures prevent or at least decrease acid backwash
into the esophagus. Elevating the head of the bed six to eight inches is also helpful. The
treatment is to reduce the acid production of the stomach by using proton pump
inhibitor or H2 blocker agents. High doses and long term treatment are often required.
Motility-increasing agents might also be occasionally used.

In summary, the overall advices for patients with esophageal involvement are as follows:
Lifestyle maneuvers

-Avoid eating 2-3 hrs before bedtime
-Stop smoking
-Elevate the head of the bed
-Minimize reflux producing foods (alcohol, caffeine, citrus juices)
-Try to avoid certain drugs (NSAIDS, anticholinergics, tricyclic antidepressants)
-Avoid pill induced esophagitis (NSAIDs, bisphosphonates,
doxycycline/tetracycline, potassium chloride, ascorbic acid, quinidine, ferrous
-„Take you pills at least one hour before bedtime with a full glass of water.”

-Proton pump inhibitors, (±H2 blockers, or alone); Often higher doses are
necessary than usual, usually for lifetime (!)
-Avoid abrupt withdrawal of proton pump inhibitors.

Complaint of gastric (stomach) manifestations includes early satiety, bloating,
dyspepsia, nausea, and vomiting. This is caused by abnormal gastric motility and the
final outcome is a delayed gastric emptying.

Similar symptoms may be present in patients with small bowel involvement, and
furthermore abdominal pain, diarrhea, and weight loss can also occur. Movements of
the bowel become „lazy”; the weak bowel muscles do not work efficiently in pushing
food through the bowel. Due to the low small bowel intestinal movements, bacteria
ascend backward from the large bowel to the originally sterile small bowel. Small
intestinal bacterial overgrowth is often present in SSc. These bacteria appearing in the
small bowel cause chronic bowel inflammation, diarrhea, and abnormal absorption of
the food substances. This condition called „malabsorption” leads to weight loss. Patients
may also experience a bloating and abdominal pain. Intestinal pseudo-obstruction (false
blockage in the bowels) is a severe condition also caused by severely decreased bowel
movements. Symptoms include cramps, stomach pain, nausea, vomiting, bloating, fewer
bowel movements than usual, and loose stools. This is a severe condition that needs
immediate medical intervention.

In case of diarrhea or malabsorption, there is a need to use antibiotics. Supplementary
vitamins, calcium and iron may also be necessary. The amount of fatty foods in the diet

should be reduced, and the amount of carbohydrates increased. In severe cases,
professional help by a dietician may also be required. If the malabsorption is very
severe, a long term total parenteral nutrition may also be necessary. This is an effective
long-term therapy for intestinal failure. Bone mineral density testing is mandatory
because bone loss (osteoporosis) is often a consequence of a poor nutrition and

Large bowel involvement is also a frequent gastrointestinal complication. Constipation
and diarrhoea are everyday problems for many SSc patients, symptomatic treatment
may be effective. Patients with SSc often develop anorectal disease. Fecal incontinence
is a frequent manifestation of disease. This may be aggravated when patients have

In summary, the overall advices for patients with bowel involvement are as follows:
Lifestyle measures

-Small, frequent meals are important
-Increase fluid intake. Liquids should be emphasized over solid foods
-Avoid excessive high fiber food intake
-Low in fat (fat delays gastric emptying)
-Avoid difficult-to-chew foods (vegetables, fiber)
-Encourage moderate physical exercise
-Diarrhea: lactose should be avoided, substitution of dietary fat with medium-
chain triglycerides

-Monthly rotating antibiotics
-Prokinetics before meal
-Treatment of malabsorption

-Symptomatic treatment of constipation:
-Bulk laxatives (methylcellulose, polycarbophyl; PEG, sorbitol, avoid mineral
Stimulant laxatives (senna, cascara sagrada, aloe, etc.); other symptomatic drugs
Other gastrointestinal manifestations
The most important vessel-related GI disease is the „watermelon stomach” (with other
name: gastric antral vascular ectasia /GAVE/). This is a condition caused by
abnormally formed vessels in the stomach. The lining of the stomach bleeds, causing it
to look like the characteristic stripes of a watermelon when viewed by endoscopy.
Watermelon stomach may cause chronic bleeding and as a consequence severe anemia.
It is usually treated with endoscopic laser surgery.

Primary biliary cirrhosis is a chronic progressive liver disease characterized by
destruction of ducts and finally causing liver cirrhosis. It can be associated with the
limited form of systemic sclerosis.

EULAR has recently published the recommendations for the treatment of SSc. The GI
system related recommendations are as follows:
-Despite the lack of specific randomized control trials, experts believe that proton pump
inhibitors should be used for prevention of SSc-related gastro esophageal reflux,
esophageal ulcers and strictures.
-Despite the lack of specific randomized control trials, experts believe that prokinetic
drugs should be used for the management of SSc-related symptomatic motility
disturbances (dysphagia, GERD, early satiety, bloating, pseudoobstruction, etc.).
-Despite the lack of specific randomized control trials experts believe that, when
malabsorption is due to bacterial overgrowth, rotating antibiotics may be useful in SSc

The approach to these GI-related manifestations, we should carefully evaluate the
clinical features of a particular patient. History taking is suitable to call the attention to
most of the motility disorders, since esophageal dysmotility, gastroparesis, intestinal
bacterial overgrowth, colonic dysmotility or anorectal involvement present typical
symptoms. Functional studies (barium swallowing, esophagus manometry, gastric
emptying studies, culture of intestinal fluid, H2 breath test, fat excretion test, colonic
transit studies, and anorectal functional tests) are the usual investigations that provide
a deeper insight into the GI involvement. Esophago-gastro-bulboscopy, colonoscopy or
capsule endoscopy are also used to detect the extent of GI problems in patients with

In the future, there is also a need to further increase the knowledge of the scleroderma
patients about their GI involvement. To achieve this particular goal, a crucial issue that
patient’s organizations devoted to this particular topic should spread information about
the disease in all over the world. Another important aspect of the patient’s contribution
to improvement of their care is the active participation in the development of different
health measurement instrument and scales.



Veterinary Microbiology 95 (2003) 75–89Interleukin 6, serum amyloid A and haptoglobinexperimentally infected with Actinobacillus C. Hultén , E. Johansson , C. Fossum , P. Wallgren a Department of Clinical Chemistry, P.O. Box 7038, Uppsala, Sweden b Division of Immunology, Department of Veterinary Microbiology, BMC, c Department of Large Animal Clinical Sciences, Faculty of Veter

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