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Crohn's Disease

The topics that Iíd like to cover include the definitions, the etiology and the epidemiology of inflammatory bowel disease. The pathology, the complications, the presentation, and therapy and crohn's disease.

There is a spectrum of presentations in inflammatory bowel diseases. The major ones are ulcerative colitis and Crohnís disease. There are minor ones, such as microscopic colitis. Ulcerative colitis is a mucosal disease and effects the colon only, whereas Crohnís disease is a transmural disease, with inflammation through all the layers of the bowel, associated with ileitis, ileocolitis, and colitis.

The etiology of inflammatory bowel disease really is unknown, but there are several lines of evidence involving disordered immune regulation, stimulation of the bowel by intestinal luminal antigens, particularly bacterial, altered permeability of the intestinal epithelium and the generation of soluble mediators of inflammation. This area has been the greatest area of expansion in our knowledge of recent times. The cytokines are deeply involved in the pathogenesis of inflammatory bowel disease and our knowledge of cytokines has exploded in the last few years. There are several pairs of cytokines, pro-inflammatory and anti-inflammatory pairs. So IO-1 is the pro-inflammatory cytokine of the two. IO-1 receptor antagonist is anti-inflammatory and so you can match them across here with TNF IL8 and TGF beta. Our knowledge of these has been expanded greatly by the use of transgenic mice, where these genes have either been enhanced or knocked out, to determine what the effect is of an imbalance within these

Inflammatory bowel disease seems to be a western disease. Highest incidence areas cover North America, Europe, Australia and South Africa. These are fairly common diseases. Crohnís disease is less common than ulcerative colitis. The ratio is about 3:10 to 8:10. Incidences of 5:8 per 100,000 population per year for UC, 5:6 for Crohnís, with a prevalence of 100 or more for ulcerative colitis and 25 for Crohnís. Interestingly, itís a disease of 

Heredity in inflammatory bowel disease is a great concern for patients and their families and indeed there is a 10% to 25% occurrence of inflammatory bowel disease in relatives of those affected. Interesting study from Bayliss in

Pathology is something we all waded through in medical school but itís terribly important for the understanding of these diseases, in fact I would say itís the key to understanding whatís going on in your IBD patients. Ulcerative colitis, if you look at it macroscopically, itís a continuous disease starting at the rectum. If itís mild you might only

Pseudopolyps are a non-malignant phenomenon. They are an inflammatory phenomenon. You can see here in cross-section. They do look like regular polyps seen in other patients. Severe ulcerative colitis, shown here,

Crohnís disease is very different, as I said. It can occur anywhere from the mouth to the anus. But the commonest sites of involvement particularly are the ileocolonic region with almost half of patients having involvement here. A third will have small bowel alone and about a fifth will have colonic disease alone. Perineal complications are typical of Crohnís disease and characteristic and occur in about a third of patients. Here we can see a perianal fistulae and

Obstruction, because of the transmural nature of Crohnís disease, is common. This is terminal ileitis. Hereís the cecum and the appendix. You can see intense narrowing here with dilatation in between due to inflammation and possibly fibrosis in the bowel wall. This is fistula formation. This is aortoenteric fistula in Crohnís disease where a

There are complications of inflammatory bowel disease related to chronic inflammation, and the systemic complications are glomerulonephritis and amyloidosis related to the elevated inflammatory proteins and immune complexes. This is relatively uncommon now that we have better treatments. Local complications are still common. Anal disease particularly with chronic anusitis, fissures, fistulae, abscess and strictures, and in the bowel, stricturing, sinuses and fistulae. And also inflammatory tissue associated with the bowel. This is an illustration of perineal

We move on now to the treatment of inflammatory bowel disease, and clearly the major categories are: medical, surgical, supportive - such as nutritional and stoma - and social and psychological support, which is very important. The only curative therapy is surgical and thatís only for ulcerative colitis. If you look at medical therapy, we certainly

If you look at the 5- ASA drugs, sulfasalazine is the mainstay that has been with us for many years, and the cheapest. Itís an oral formulation. Olsalazine is used less now because of its side-effects. Itís also an oral formulation. Mesalamine is really the drug of choice now for remission reduction for mild and moderate disease and it comes in oral and enema form, and para-aminosalicylic acid.