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The topics that I’d 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, crons disease, chrohn's disease.
There is a spectrum of presentations in inflammatory bowel diseases. The major ones are ulcerative colitis and Crohn’s disease. There are minor ones, such as microscopic colitis. Ulcerative colitis is a mucosal disease and effects the colon only, whereas Crohn’s 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. Crohn’s 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 Crohn’s, with a prevalence of 100 or more for ulcerative colitis and 25 for Crohn’s. Interestingly, it’s 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 it’s terribly important for the understanding of these diseases, in fact I would say it’s the key to understanding what’s going on in your IBD patients. Ulcerative colitis, if you look at it macroscopically, it’s a continuous disease starting at the rectum. If it’s 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,
Crohn’s 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 Crohn’s 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 Crohn’s disease, is common. This is terminal ileitis. Here’s 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 Crohn’s 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 that’s 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. It’s an oral formulation. Olsalazine is used less now because of its side-effects. It’s 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 is
This is an illustration of the structure of sulfasalazine just to remind you that really the part that works is the aminosalicylate and the part that gives the side-effects is the sulfapyridine, and unfortunately you are stuck with the
This is an illustration of the effect of 5-ASA in active ulcerative colitis. Here you can see a nice dose response curve where the 4.8 grams a day causes improvement in 50% and remission in 25%, and so on down to placebo, where you have very low rates of improvement. It’s important to remember that this is a lot of pills for the patient to take, but it may well be worthwhile. Sulfasalazine is still very widely used because of its low cost and has major side-effects, including allergic reactions all the way through to the severity of Stevens-Johnson; hemolysis,
Systemic glucocorticoids are used in IBD. These include prednisone and prednisolone. All are IV. They induce remission in acute IBD, they reverse life-threatening colitis. They are not helpful for maintenance of remission and
If you want to move on to stronger immunosuppression, the most commonly used drug is mercaptopurine or azathioprine as precursor. Here you can see the effects of azathioprine in active Crohn’s disease, in achieving steroid typhi, inhaling fistulae and in overall clinical improvement as far superior to placebo.
Cytokine therapies are new are certainly not available on the market yet, but the most exciting development in the last few years in IBD, and this is the clinical application of all that knowledge we gained on cytokines in research on etanercept (Embrel)
Antibiotics, as I said, can be useful and the classic one used in IBD is metronidazole. The indications are mostly in Crohn’s disease, for perianal disease, mild to moderate colitis, ileocolitis and possibly ileitis. It does have toxicities, including nausea and orexia, diarrhea, furry tongue, monilial infections, puerperal neuropathy is the one I would point
Nutrition in IBD is very important. Obviously if something upsets your stomach, don’t eat it. It’s hard to convince patients of this sometimes. But it is also a therapy. Active IBD may lead to poor nutrition and poor nutrition really
Smoking is a very important issue in inflammatory bowel disease as more and more evidence comes to light. Smoking is bad for Crohn’s disease and seems to be somewhat protective against ulcerative colitis. Smokers with
The indications for surgery are very important. In ulcerative colitis this is a curative surgery but still it’s reserved for severe cases: exsanguinating hemorrhage, toxicity and perforation, suspected cancer - which goes along with high grade dysplasia, growth retardation, systemic complications and intractability are all important indications. Surgical options, as you probably know, include conventional ileostomy, continent ileostomy or Koch pouch and the ileo-anal anastomosis with reservoir, which can be very rewarding for patients to regain normal continence, provided you have a surgeon with extensive experience.
Postoperative recurrence is the rule in Crohn’s disease. You can see here this curve for recurrence rate is a percentage of patients and the years postoperatively so that over half or half your patients will have recurred by ten