Crohn's Ileitis Video (17.3 mb)

1. Crohn's Disease

Crohn's disease, or regional enteritis, is a chronic inflammatory disorder that can affect the small intestine and/or the large intestine. Inflammation, which may or may not be accompanied by noncaseating granulomas, extends through all layers of the gut wall to involve adjacent mesentery and lymph nodes. The inflammatory process is frequently discontinuous, with normal bowel separating portions of diseased bowel. This disease is characterized by an indolent variable course, by its diverse clinical manifestations, by its perianal and systemic complications, and by its tendency to recur after surgical resection.

The key pathological feature of Crohn's disease is an inflammatory process that extends through all layers of the bowel wall. Microscopic examination reveals (1) hyperplasia of perilymphatic histiocytes, (2) diffuse granulomatous infiltration, (3) discrete noncaseating granulomas in the submucosa and lamina propria, (4) edema and lymphatic dilation of all layers of the gut, and (5) monocytic infiltration within lymph nodules and Peyer's patches on the serosal surface of the bowel.

The mesentery in the vicinity of the diseased bowel is markedly thickened, fatty and edematous. Finger-like projections of thick mesentery characteristically extend over the serosal surface toward the antimesenteric border. The mucosal surface in the diseased segment has a characteristic "cobblestone" appearance, resulting from the combination of deep mucosal ulceration and nodular submucosal thickening. Ulcers are frequently elongated and tend to lie along the long axis of the bowel.

Since the serosa and mesentery are inflamed, a characteristic feature of Crohn's disease is the tendency for involved bowel loops to be firmly matted together by fibrotic bands. This adhesive process is often associated with the fistula formation characteristic of Crohn's disease. Fistulas begin as ulcerations and gradually burrow through the serosa into adjacent organs. Such fistulas communicate between the loops of small bowel themselves, as well as between loops of small bowel and colon, skin, perineum, bladder or vagina, or they may end blindly in indolent abscess cavities located within the peritoneal cavity, mesentery or retroperitoneal structures.

When the lesions of Crohn's disease are discontinuous, the intestine that lies adjacent to or between diseased segments (skip lesions) shows no gross or histological abnormalities.

Patients with Crohn's disease can be divided into those with small bowel disease alone (30%), those with both small and large bowel involvement (50%), and those with disease involving only the colon (20%) (Table 1). When Crohn's disease involves the small bowel, 80% of the time the terminal ileum is involved (Figure 1). In only 20% of cases are other areas of small bowel also affected. When the colon is involved in Crohn's disease (Crohn's colitis), all segments of the colon can be affected. Although absence of rectal disease is more characteristic of Crohn's disease than of ulcerative colitis, the rectum is involved in half those cases of Crohn's disease in which colonic disease exists.

Crohn's disease occurs throughout the world, with a prevalence of 10 to 100 cases per 10⁵ people (Table 2). The disorder occurs most frequently among people of European origin, is 3 to 8 times more common among Jews than among non-Jews, and is more common among whites than nonwhites. Although the disorder can begin at any age, its onset most often occurs between 15 and 30 years of age. There appears to be a familial aggregation of patients with Crohn's disease such that 20-30% of patients with Crohn's disease have a family history of inflammatory bowel disease.  

The etiological agent responsible for inflammatory bowel disease has not yet been determined. The abnormalities of T cells and/or macrophages and their interaction still remains the most feasible hypothesis (1-4). In synthesizing existing literature, one could propose the following sequence of pathological events leading to the development of inflammatory bowel disease. The gastrointestinal immune system becomes exposed to a mucosal antigen, perhaps even an antigen normally present within the lumen -i.e., a bacterial constituent of normal flora. However, on this occasion the antigen does not evoke the typical antigen-specific suppressor T-cell activity, mucosal unresponsiveness. Rather, because of an antigen-specific immunoregulatory defect, it evokes helper T-cell activity and sets in play an ongoing immune response. This immune response as an epiphenomenon leads eventually to the development of self-antigens and appearance of autoantibodies. Subsequently, in an attempt to down-regulate the antigen-specific response, antigen-nonspecific suppressor T cells appear. Initially, these antigen-nonspecific suppressor T cells may prevent disease progression; however, they are gradually depleted, leaving the unregulated antigen-specific helper T-cell activity to predominate. This unregulated antigen-specific immune response leads to the production of lymphokines, which stimulate migration of inflammatory and cytolytic cells to the region. Through this process the microscopic and gross morphological changes of inflammatory bowel disease are manifest.

The initiating antigen in the above process has yet to be identified. Mycobacteria have remained a contender as initiating antigen for a number of decades. However, recent studies have found no evidence for Crohn's disease-specific humoral or T-cell reactivity against a variety of mycobacterium species (5). Recent studies demonstrating an increase in intestinal permeability in healthy relatives of patients with Crohn's disease have proposed the hypothesis that Crohn's disease is caused by an epithelial permeability defect that allows exposure to an increased number of mucosal antigens (6). Whether the permeability abnormality is a genetic defect or of environmental origin remains to be determined.

The typical patient with Crohn's disease is a young adult whose illness begins with right lower quadrant pain, diarrhea and a low-grade fever. Examination reveals tenderness, guarding and a palpable mass in the right lower quadrant. If the illness has come on acutely and diarrhea is not prominent, these findings, along with an elevated white blood cell count, often lead to a clinical diagnosis of appendicitis with consequent laparotomy and discovery of the Crohn's disease.

More often, however, the clinical picture is insidious. The patient has recurrent episodes of mild diarrhea, abdominal pain, and fever lasting from days to weeks, and then has a spontaneous improvement in symptoms. If disease is confined to a small segment of intestine, this can go on for many years before a correct diagnosis is made.

The abdominal pain of Crohn's disease is localized to the right lower quadrant. When the colon is involved, crampy pain may occur in one or both lower abdominal quadrants. Fever, in the absence of complications, rarely exceeds 38ºC. Diarrhea tends to be moderate in severity, with five to six bowel movements per day when the disease is confined to the ileum. When the disease involves the colon, urgency, incontinence and rectal bleeding may also occur.

If the disease is not diagnosed, gradual deterioration will occur over a period of years; there will be shorter and shorter asymptomatic intervals, along with weight loss and increasing fatigue. A slow and persistent blood loss combined with poor food intake leads to anemia.

Malnutrition and malabsorption, with subsequent weight loss, are common at all stages of Crohn's disease. A variety of factors are responsible. Nevertheless, a voluntary decrease in food intake for fear of exacerbating abdominal symptoms is the primary cause of weight loss (Table 3).

Approximately 10-15% of individuals present without any of the above abdominal symptoms and are seen for the first time with perirectal disease, fever or one of the extraintestinal  manifestations (Table 4).

Whatever the presenting clinical features, only 20% of patients will remain completely asymptomatic during the next 10 years. The remainder will have recurrent attacks of abdominal pain, diarrhea, and low-grade fever. If the disease progresses to the state where surgery is required, recurrence is common, particularly at the site of anastomosis. Seventy-five percent of patients operated on for small bowel Crohn's disease have recurrences within 5 years and require another operation within 15 years. Additionally, the interval between operations appears to be shorter after the second or third operation than after the initial resection.

1.6.1 SMALL BOWEL OBSTRUCTION

Small bowel obstruction is the most common reason for surgery when Crohn's disease involves the small intestine. The obstruction results from inflammation and edema in an already strictured segment of bowel. The obstruction is often partial and is transient once the edema and inflammation are treated and allowed to resolve. Progression to complete obstruction is often slow and results from fibrotic stricturing. Complete obstruction may, however, occur suddenly when the small bowel becomes kinked off as a result of an adhesive inflammatory process.

Perianal and perirectal fistulas and fissures are particularly common in Crohn's disease and may be so severe as to overshadow other intestinal manifestations. Enteroenteric fistulas can develop between loops of bowel and may contribute to nutritional problems if they cause ingested nutrients to bypass areas of small bowel absorptive surface. Additionally, the presence of enteroenteric fistulas may lead to recirculation of intestinal contents and stasis, thus causing bacterial overgrowth within the lumen. Fistulas between loops of bowel and the urinary bladder ultimately lead to chronic urinary tract infections. Fistulas can also occur between bowel and cutaneous surfaces, bowel and the vagina, or bowel and other internal organs.

Free perforation is unusual in Crohn's disease. When free perforation does occur, it leads to frank peritonitis.

Insidious blood loss occurs with small bowel disease and often leads to an iron deficiency anemia. Frank bleeding of bright red rectal blood occurs with colonic disease and with perianal fistulas.

Malignant neoplasms occur both in the involved bowel and in the noninvolved bowel of patients with Crohn's disease three times more frequently than in the general population. Nevertheless, the frequency of malignancy is much lower than that observed in patients with ulcerative colitis.

Extraintestinal manifestations of Crohn's disease (Table 4) frequently develop alongside colonic involvement and perianal disease. Patients with one extraintestinal manifestation are at increased risk for developing a second.

Arthritis is the most common systemic manifestation and presents as migratory arthritis involving large joints, or as sacroiliitis or ankylosing spondylitis. Spondylitis or sacroiliitis may occur for many years prior to the manifestation of intestinal disease. There is no relationship between the course of spondylitis and sacroiliitis and the course of Crohn's disease. Migratory monoarthritis involves large joints and again runs a course independent of the intestinal disease.

Inflammation of the eye, skin and mucus membranes may also occur during the course of Crohn's disease. Iritis and episcleritis are frequent eye manifestations. Erythema nodosum and, less often, pyoderma gangrenosum are common skin conditions. Aphthous ulcerations of the buccal mucosa, tongue and lips are frequent, often refractory, problems.

Clinically important liver disease is not generally seen with Crohn's disease. Mild abnormalities in liver function studies may be observed in a few patients, and liver biopsy will often show a mild pericholangitis in these cases. Cholelithiasis occurs with a frequency of approximately 30% in patients with ileal disease and/or ileal resection. This high incidence is probably related to a bile salt deficiency that causes the production of a lithogenic bile conducive to cholesterol gallstone formation.

Nephrolithiasis occurs in 30% of patients with Crohn's disease. Oxalate stones and hyperoxaluria are common and are related to steatorrhea. Fat malabsorption increases the amount of dietary oxalate available for absorption in the colon.

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