The Biology of Crohn's Disease
Crohns Disease
The image above shows the three main sites of intestinal involvement in Crohn's Disease. These are: Ileum, Ileocolic and Colon.

Crohn's Disease is a chronic, episodic, inflamation of the intestinal system that's characterized by an inflammation that affects the entire wall of the region of the bowel involved. Crohn's disease is also known as regional enteritis and is a trype of inflammatory bowel disease (IBD).

The symptoms of Crohn's can be many and varied and depend on the region of the gastrointestinal tract and can affect anywhere from the mouth to the anus, though the colon tends to be the main site of inflammation.

The main symptoms of Crohn's disease are all associated with bowel problems and include abdominal pain, cramps, diarrhoea and weight loss. As an inflammatory disease Crohn's disease can also present compllications such as rashes, arthritis and eye inflammations which are all associated with an up-regulated immune system.

The disease itself was named after Burrill Bernard Crohn and American gastroenterologist who, in 1932 first described a series of patients with inflammation of the terminal ileum (the part of the ileum next to the colon).

Causes

The precise cause of Crohn's disease is unknown, though the disorder has all the characteristics of an autoimmune disorder. Indeed, the condition occurs when the immune system attacks and contributes to the damage of the gastrointestinal tract by causing severe inflammation. Resent research, however, has revealed that there is a genitic component to the disease with mutations in the CARD15 gene being strongly associated with the disease. In addition scientists have now linked over eight genes that are associated with the disease showing that genetics paly a role though environmental factors have also been linked to the development of the disease.

Diets high in sweet, fatty or refined foods may play a role. A retrospective Japanese study found that those diagnosed with Crohn's disease had higher intakes of sugar, fat, fish and shellfish than controls prior to diagnosis. Crohn's disease sufferers also tend to have lower intakes of fructose and fruit, water, potassium, magnesium and vitamin C prior to their diagnosis.

It has also been hypothesized that the bacterium Mycobacterium avium subsp. paratuberculosis is involved mostly as it causes a very similar disorder, Johne's Disease in cattle.

Diagnosis

Diagnosis of Crohn's disease is notoriously challenging and often requires multiple tests to ensure an accurate diagnosis. On occsion, even when all the tests are applied Crohn's disease may not manifest itself. The various tests that can be employed are summarized below:

Endoscopy

A colonoscopy is by far the most reliable form of diagnosis as the procedure allows for direct visualization of the colon and the terminal ileum (by far the most common site for the disease). During the procedure a gastroentorologist may also perform biopsies by removing small samples of diseased tissues for subsequent laboratory analyses. During this procedure the finding of a patchy distribution of disease, with involvement of the colon or ileum but not the rectum, is suggestive of Crohn's disease.

Radiological Tests

As a colonoscopy can only examine the Colon and the terminal ileum a radiological procedure is sometimes used to examine the remainder of the small intestine. The usual method is a barium follow-through x-ray where barium sulphate is ingested and fluoroscopic images of the bowel are taken over time.

CT and MRI scans may also be employed as these are useful in looking for intra-abdominal complications of Crohn's disease such as abscesses, small bowel obstruction, or fistulae.

Blood Tests

Blood tests are sometimes employed to examine for anaemia and vitamin B12 deficinency as B12 is absorbed in the ileum. Blood tests can also examine for up-regulation of the immune system which is associated with Crohn's disease.

Comparison with Ulcerative Colitis

The disease whose symptoms are closest to Crohn's disease is ulcerative colitis, as both ar inflammatory diseases of the bowel and both can affect the colon in a similar fashion. As a result, in any diagnosis it is important to distinguish between these two diseases as their progressions and eventual treatments are very different.

Treatment

Just as the cause of Crohn's disease is mysterious there is no know cure and most treatments are aimed at alleviating the disease during its active phases. Treatment of Crohn's disease involves first treating the acute disease to attain remission and then focusses on maintaining remission.

As Crohn's disease is an autoimmune disorder the first stage of attaining remission is the use of anti-inflammatory drugs to stabilize the condition. The main class of drugs used tend to be aminosalicylate anti-inflammatory drugs and 5-ASA compounds have been shown to be useful in the treatment of mild-to-moderate Crohn's disease. In addition corticosteroid anti-inflammatory drugs may also be used to alleviate moderate so severe flare-ups of the disease. However, the side-effects of these drugs can be severe and they tend to be used sparingly.

If there are severe complications such as fistulae, small bowel obstruction, colon cancer, small intestine cancer and fibrostenotic strictures or if the disease resists treatment with drugs then the removal of the affected section of intestine and the rejoining of the healthy sections may be surgically performed.

Once initial remission is achieved the next stage of treatment is to maintain remission. For many continued treatment with aminosalicylates is sufficient but for a number of patients more aggressive immunnosuppressive drugs must be used. Mercaptopuring immunossuppressants (Azathioprine and 6-mercaptopurine (6-MP)) are the most used immunosuppressants for this purpose. Another drug that can be used is Infiximab, a mouse–human chimaeric antibody that targets tumour necrosis factor, a cytokine in the inflammatory response. This drug is administered intravenously.

Though changes in diet are sometimes recommended for Crohn's disease there is no real evidence that diet causes or cures Crohn's disease. Though people sensitive to certain foodstuffs may find benefits from removing those foods from the diet and a food diary can be useful in finding these foodstuffs by comparing symptoms with dietary intake. There is also some evidence that fish oil may reduce the chance of relapse in less severe cases.

Prognosis

It should be noted that Crohn's disease is a chronic conditoin that cannot be cured. The best that can be hoped for is the maintenance of remission. It should also be noted that Crohn's disease is associated with an increased risk of small bowel and colorectal carcinoma. Howeever, with appropriate treatment and stabilizatoin most sufferers achieve a healthy lifestyle and mortality for the disease is extremely low.