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Crohn's Disease

Crohn's disease is a recurrent segmental inflammatory disorder that may affect the any location in the gastrointestinal tract from the mouth to the anus.  Crohn's disease is of unknown etiology. Fifty percent of patients have involvement of both the small intestine and colon, whereas one third have disease limited to their small intestine and the remaining 20% have inflammation.

EPIDEMIOLOGY

CD occurs among all age groups but have a peak incidence in the second and third decades. CD incidence has risen over the past 20 years; CD has an incidence and prevalence rates.

Inflammatory bowel disease (IBD) included Crohn's disease.

CLINICAL MANIFESTATIONS

The symptoms and signs of CD also are determined by the site and extent of inflammation. Gastroduodenal CD mimics peptic ulcer disease, with nausea, vomiting, and epigastric pain. Patients with

COMPLICATIONS

INTESTINAL COMPLICATIONS

Rectal bleeding is a common manifestation of both UC and CD. In UC the superficial inflammation induces capillary hemorrhage, manifested as bright red coating of stool or

Toxic megacolon, once thought to occur only with UC, also occurs in CD and infectious colitis. Toxic megacolon develops in seriously ill individuals when transmural inflammation extends into the muscular layer.

CANCER

Cancer of the colon is a long-term complication of UC. Its development depends on two factors: the extent of mucosal involvement (pancolitis greater than left-sided colitis) and the duration of

EXTRAINTESTINAL COMPLICATIONS

The extraintestinal manifestations of IBD can be divided into complications of gastrointestinal inflammation or diseases associated with IBD. The latter occur most often with "colitis" but can occur in either UC or CD when the colon is inflamed.

Nutritional and metabolic abnormalities occur with chronic disease, inadequate intake of calories, maldigestion, and malabsorption. Blood and protein loss contribute to iron deficiency anemia and hypoalbuminemia. Deficiencies of calcium, magnesium, or zinc are most often noted with small intestinal CD.

Diarrhea is aggravated by malabsorption of fat or bile salts due to ileal disease or resection. Diarrhea due to fat malabsorption is diagnosed by increased fecal fat (greater than 5 grams per day) and treated with a low-fat diet.

Skin and mucous membrane changes are common in IBD. Oral aphthae occur in CD, and fissuring of the lips or mouth may be due to zinc deficiency or Candida infection. Inflammatory skin disorders associated with IBD, pyoderma gangrenosum and erythema nodosum, tend to correlate with the disease activity in the colon.

Ocular complications of IBD share many inflammatory components with the

DIAGNOSIS

There are no pathognomonic clinical, endoscopic, or histologic features of the idiopathic IBD's. The physician must therefore consider the entire clinical picture and the evolution of the illness. It is particularly important to exclude other disorders that may mimic the broad range of IBD symptoms and findings. First it is important to establish the presence of intestinal inflammation. A cardinal feature is the exudation of inflammatory cells into the lumen, manifested by fecal leukocytes or red blood cells on stool examination. Symptoms of rectal bleeding, tenesmus associated with the passage of pus, nocturnal pain and diarrhea, fever, night sweats, weight loss.

ENDOSCOPY

Patients presenting with colitic symptoms of rectal bleeding, cramping, tenesmus, mucopus, or watery diarrhea in conjunction with fecal leukocytes warrant a colonic examination. A proctoscopic examination or flexible sigmoidoscopy reveals the presence and pattern of distal colonic inflammation.

RADIOGRAPHY

Radiographic examination should begin with a supine and upright view of the abdomen. Associated findings of nephrolithiasis, cholelithiasis, or arthritis of the spine or sacroiliac joints may be identified. Intestinal dilatation or air-fluid levels suggesting obstruction preclude aggressive barium studies until the patient's clinical condition is stabilized. In colitis, a plain view of the abdomen often demonstrates a tubular, ahaustral segment of colon in the presence of distal UC with fecal matter proximal to diseased mucosa. Intestinal edema, ulceration, or thumb-printing may give a gross estimate of disease activity.

DRUG THERAPY

Aminosalicylates

Sulfasalazine

Introduced into clinical medicine in the early 1940s, sulfasalazine (Azulfidine)* has since become a mainstay in the therapy for inflammatory bowel disease. Controlled trials have shown its efficacy for active Crohn's disease involving the colon, and although the studies have not uniformly demonstrated the drug's benefit in isolated ileitis, there appears to be a subset of patients with Crohn's ileitis who benefit from its use.

Topical 5-Aminosalicylic Acid Agents

Controlled trials confirmed the hypothesis that 5-ASA might be the active moiety in sulfasalazine. Moreover, 80 to 90% of patients intolerant of or allergic to sulfasalazine tolerate the 5-ASA derivative. Although not well studied in controlled trials in Crohn's disease, the enema and suppository forms of 5-ASA, known generically as mesalamine (Rowasa).

Oral 5-Aminosalicylic Acid Agents

For the patient with small bowel Crohn's disease or with colonic disease above the rectosigmoid, oral 5-ASA agents can be considered an alternative to sulfasalazine. Available oral forms include mesalamine (Pentasa)* encapsulated in ethylcellulose microspheres, mesalamine (Asacol)* coated with an acrylic resin that dissolves at pH greater than 6, and olsalazine (Dipentum) that links 5-ASA.

Antibiotics

Metronidazole (Flagyl)* is the best studied of the antimicrobial agents and has been shown in controlled trials to be effective in active Crohn's colitis and ileocolitis but not in isolated ileitis. A largely uncontrolled experience suggests utility in perianal disease as well. Although there are no trials investigating its use.

Corticosteroids

For patients not responding to or intolerant of the preceding measures, and for those presenting with severe manifestations of disease activity, corticosteroids need to be considered. Hydrocortisone enemas (Cortenema) can be used in patients with active proctosigmoiditis; foam preparations (Cortifoam) are available.

For patients with mild to moderate symptoms and with colonic disease proximal to the rectosigmoid, and for those with small bowel involvement, prednisone 40 to 60 mg per day is initiated and continued at the initial dose for 10 days to 2 weeks. If a desired response is obtained, the dosage should be tapered by 5 mg every 7 to 10 days. Once remission is achieved, there is no benefit of continued steroid therapy as prophylaxis against relapse.

More rapidly metabolized forms of steroids have emerged as efficacious in short-term trials with considerably fewer side effects than standard preparations. Budesonide enemas have proved to be as effective as hydrocortisone and 5-ASA enemas in ulcerative proctosigmoiditis but have not been formally studied in distal Crohn's colitis. A slow-release oral preparation of budesonide has been shown to be more effective.

Immunomodulators

6-Mercaptopurine (Purinethol) and azathioprine (Imuran)* have emerged as important agents in the management of Crohn's disease patients dependent on steroids and refractory to other agents and with nonhealing fistulas. In more seriously ill patients, their use adjunctively with steroids as initial therapy should be considered. The drugs can be used interchangeably and should be started at 50 mg per day.

Nonspecific Antidiarrheal Drugs and Cholestyramine

For patients with mild chronic symptoms, agents such as loperamide (Imodium), diphenoxylate with atropine (Lomotil), codeine, and deodorized tincture of opium may be of use.

Cholestyramine (Questran) can be of major benefit in the patient with nonstenosing ileitis or in one who has had an ileal resection. In such patients, watery diarrhea due to bile acid malabsorption can usually be controlled with 1 scoop or packet (4 grams) in a glass of juice taken once or twice daily.

NUTRITIONAL SUPPORT

General Dietary Instructions and Nutritional Supplements

Food is the best source of nutrition, and the emphasis for most patients should be on normalization of the diet and adequate caloric intake. Patients with intestinal strictures and partial obstruction may benefit from a

Enteral and Parenteral Diets

Although there is some debate about their actual utility, both enteral diets and total parenteral nutrition have been shown to be useful as primary therapy in inducing remissions in certain patients with Crohn's disease.