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08 February 2011

Crohn's disease

Crohn's disease is a chronic inflammation of the bowel. Crohn's disease affects both sexes equally and has a seasonal variation. The most common symptom is abdominal pain.

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Description

Crohn's disease is a chronic inflammation of the bowel that can affect any area from the mouth to the rectum. The other common inflammatory condition of the bowel is ulcerative colitis, which can be very difficult to distinguish from Crohn’s disease. As the name implies, ulcerative colitis only affects the colon.

Crohn's disease affects both sexes equally. The incidence in the Western world varies between two and six per 100 000 but seems to be on the rise. This might be because of better awareness of the diagnosis and better diagnostic facilities.

There is a trend for the frequency to increase with greater distance from the equator. The disease is much less common in Asia, Africa and South America. An interesting finding is a five-fold relative risk in patients of Jewish origin.

There seems to be a seasonal variation in the onset of Crohn's disease, peak times being autumn and early winter. This lends further credence to the hypothesis that there might be an infective trigger for presentation of this disease.

Cause

There is a long-held hypothesis that Crohn's disease is an auto-immune disease. This implies that the body's immune system, for reasons unknown, starts manufacturing antibodies that are self-directed, in this instance against the lining of the bowel. If this is indeed so, what could these triggers be?

Genetic factors

There is a clear familial link, the incidence of Crohn's being between 1 in 10 and 1 in 15 in a first-order family member. This is 50 times the population prevalence. This incidence is even higher in twins.

Environmental factors

Infection

Since Crohn's was recognised as a disease entity an infective cause has been suspected. However, this still cannot be proven. Longest runners in this race are the mycobacteria (tuberculosis-causing organisms), suspected even by Crohn himself.

Other organisms under investigation include the measles virus, Listeria, E. coli, a Helicobacter organism other than the one implied in peptic ulcers and even the normal intestinal flora turned hostile by a deregulated immune response.

Anti-inflammatory drugs

Longterm use of these drugs has been known to cause small bowel ulceration of a magnitude similar to that seen in Crohn's.

Smoking

Crohn's seems to be more common in smokers (the reverse is true of ulcerative colitis). The prognosis in smokers tends to be worse and relapses more frequent.

Sex steroids

The combined oral contraceptive pill has been associated with an increased risk of Crohn's.

Diet

Although a question frequently asked by Crohn's patients, and one postulated reason for the increase in prevalence during the past fifty years, there is remarkably little evidence on which to base a scientific reply. There is some consensus that carbohydrate consumption is higher in Crohn's patients.

Symptoms

The most common symptom is abdominal pain, often situated in the right lower abdomen. It can easily be confused with appendicitis. However, the pain pattern often can be very non-specific, occurring in any part of the abdomen and varying in intensity.

Abdominal bloating due to obstruction is a relatively late symptom. The stools might be normal, but very often diarrhoea is present. Rectal bleeding is much less common compared to ulcerative colitis. The course of the disease might be sub acute and relapsing over a long period of time, often wrongly diagnosed as an irritable bowel syndrome.

Extra-intestinal features of Crohn's are often valuable pointers towards the correct diagnosis. Peri-anal disease affects up to 15% of patients, including abscesses and fistulae around or near the anus. Inflammation of the eyes, skin rashes and arthritis can sometimes even precede the development of intestinal symptoms, and are interestingly enough more often associated with disease of the large bowel.

As Crohn's is a systemic disease patients tend to feel generally unwell and tired. Fever, weight loss and growth retardation in children are not uncommon.

Course

Bowel obstruction

This complication usually affects the small bowel. The most common site affected is the terminal part (ileum) just before the junction with the large bowel. Because of the inflammatory swelling of the bowel wall the lumen becomes so narrow that food cannot pass through, thus causing obstruction. This leads to abdominal cramping, bloating and vomiting.

Abscess formation

Inflammation can become so severe that the entire thickness of the bowel wall becomes involved. This leads to formation of abscesses which present as painful masses on abdominal examination.

Fistulae

Ulcers have the potential to tunnel through the surrounding tissue to affect nearby organs. In this way fistulae might develop between the small and large bowel, the bowel and skin, bowel and bladder, bowel and vagina, etc.

Nutritional complications

Extensive inflammation of the small bowel might lead to mal-absorption of various nutrients leading to deficiencies of proteins, iron, vitamins, etc. Blood loss contributes to the development of anaemia.

Diagnosis

Examination of the patient might be entirely normal. Tenderness or even a mass in the right lower abdomen should be pointers towards the diagnosis. Abscesses around the anus should arouse suspicion, and as mentioned above skin, eye and joint signs should be looked for.

Special investigations

Blood investigations might be normal. Anaemia or a raised sedimentation rate (a non-specific indicator of activity of disease) should not be ignored. Crohn’s of the colon can be detected by performing a colonoscopy, an investigation where a flexible fibre-optic instrument is passed via the rectum to the rest of the colon, visualising the colon and taking biopsies for histological examination of all suspicious areas.

The small bowel is investigated by performing a small bowel enema where a thin tube is passed through the nose, placed beyond the stomach and a special radio-opaque solution passed via the tube to fill the entire small bowel while X-ray pictures are taken. The swelling of the mucosal lining of the small bowel caused by Crohn's encroaches on the radio-opaque material causing the so-called "string sign", or can render a spiky appearance to the bowel wall caused by small abscesses.

Prognosis

It is impossible to predict the course of Crohn's disease. Some patients experience long periods of remission while in others the disease is aggressive with the development of complications. Once in remission it is important to stay on maintenance therapy, lead a healthy life-style and report any symptoms suggesting a relapse to your doctor. If a relapse is suspected, treatment should be vigorous to prevent complications and induce remission again.

Most patients with Crohn's are able to lead a fairly normal life, hold jobs and function successfully at home and in society. In fact, the richest man on this planet suffers from Crohn's disease and seems to be holding more than his own!

Treatment

Because there is no known cause for Crohn's there is no definite cure. The aim is to control symptoms and prevent complications by controlling the level of inflammation.

Drug therapy

Corticosteroids (cortisone) are by far the most effective drugs to treat active disease in an effort to induce a remission of symptoms. In a severely ill patient it might be necessary to admit the patient for intravenous feeding and cortisone in high doses.

Longterm treatment with cortisone are potentially hazardous because of unwanted side-effects.

More recently a much safer corticosteroid (budesonide, available in South Africa as Entocord) has been used to maintain remissions. Initial experience seems to indicate that remissions can be maintained for much longer periods without the dreaded cortisone complications.

5-ASA-drugs have been used since the early 1950's in an effort to control Crohn's. These drugs (Salazopyrin, Asacol and others) have anti-inflammatory properties, but it is not entirely clear how it reduces intestinal inflammation. They are of little use in the acute event but large studies suggest that they are of benefit in maintaining remissions. Unfortunately they also have unwanted side-effects, i.e. dyspeptic symptoms, suppression of sperm production and kidney damage in susceptible patients.

Immunosuppressants are used when there is no response to the above-mentioned drugs, or in an effort to decrease the dosage of corticosteroids. However, their usefulness are hampered by limited efficacy and potentially very dangerous side-effects due to the lowering of the patient's resistance to infection.

Antibiotics are used only to control secondary bacterial infection.

Surgery

Surgery is almost exclusively reserved for treatment of complications. Narrowed segments of the bowel (strictures) can be widened by an operation called stricturoplasty. At times it is necessary to remove the diseased portion, drain an abscess or operate on fistulae. Even though the bowel might appear normal after resection of the diseased portion, Crohn's often recurs in another part of the bowel.

In cases of severe, resistant Crohn's affecting only the large bowel, it sometimes is necessary to remove the entire colon (colectomy).

The distal end of the small bowel (ileum) is then brought out onto the skin through an orifice called a stoma and the faeces collected in a bag. It is also possible to join the ileum to the anus in a so-called "pouch procedure".

Diet

Nutritional intervention is crucial in malnourished patients, especially in children where growth retardation is a real danger. However, primary nutritional therapy has not been shown to have any major effect on the course of Crohn's. It is therefore difficult to give constructive advice that will be of general value.

Patients should be encouraged to have small, regular meals of high nutritional value and make their own explorations into dietary manipulation. For instance, reduction in the intake of dairy products is more likely to be beneficial than a rigid adherance to an unpalatable, enjoyment-spoiling diet.

Newer developments

There is on-going research into newer ways of treating Crohn's. The next decade will hopefully bring safer, more effective ways of controlling inflammation. For instance, a drug called anti-TNF (anti tumour necrosis factor) yield particularly encouraging results in the treatment of severe Crohn's resistant to other therapy.

TNF is a protein produced by the immune system that apparently plays an important role in the development of the inflammation of Crohn's disease Anti-TNF blocks the action of TNF, thus decreasing inflammation.

Reviewed by Prof Don du Toit (M.B.Ch.B) (D.Phil.) (Ph.D) (FCS) (FRCS)

 

 
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