of the intestinal epithelium and its covering mucous layer are also recognized as being important components in IBD pathogenesis.
and in extracellular matrix (ECM) degradation via secretion of IL-21, which induces matrix metalloproteinases (MMPs), has been highlighted (37). TH17 cells are induced in response to IL-23 production by macrophages and dendritic cells.
TABLE 11.1 IMPORTANT CYTOKINES IN INFLAMMATORY BOWEL DISEASE
cytoplasmic antibody (atypical p-ANCA) and antimicrobial antibodies such as anti-Saccharomyces cerevisiae (ASCA) antibody, among others, have a demonstrated role in distinguishing IBD from non-IBD; UC from CD; disease onset, duration, location, and behavior in CD; and disease progression, severity, and pouchitis in UC (43,44).
A second minor peak in incidence occurs in patients aged 50 to 70 years.
TABLE 11.2 CLINICAL FEATURES OF CROHN DISEASE RELATED TO SITE OF BOWEL INVOLVEMENT
TABLE 11.3 DISEASES CLINICALLY MIMICKING CROHN DISEASE
TABLE 11.4 CROHN DISEASE: ASSOCIATIONS
TABLE 11.5 GASTROINTESTINAL FORMS OF CROHN DISEASE
as multiple, minute, white nodules resembling peritoneal seeding by carcinoma or the serosal tubercles characteristic of tuberculosis. They are usually distributed along the serosal lymphatics and may be seen on the surface of the adjacent mesentery and peritoneum. These may represent an early stage of the disease. Initially, the intestinal wall remains pliable, even though it may appear slightly thickened (Figs. 11.7 and 11.8). With disease progression, the bowel becomes increasingly fibrotic and rigid (Fig. 11.8). Eventually, strictures may develop, usually in the area of the distal ileum at the area of the ileocecal valve (Fig. 11.6). Large inflammatory pseudotumors may form at this site, simulating a carcinoma. Granulomas within the lymph nodes may be grossly visible as tiny gray-white specks (Fig. 11.9).
of discrete ulcers in areas of otherwise normal mucosa may precede the development of more flagrant changes of CD by weeks or years.
FIG. 11.10 Endoscopic view of aphthous ulcers. Aphthous ulcers appear as erythematous “pimplelike” mucosal lesions. The aphthous ulcers are outlined by the arrows.
The nature of the obstructive symptoms depends on the part of the bowel that is affected. The most severe stenosis usually affects the ileocecal valve. Multiple strictures may be present (Fig. 11.16). The strictures result from transmural inflammation, fibrosis, scarring, and fibromuscular proliferation. Rectal strictures are not unique to CD because they also complicate other disorders (Table 11.6).
and may contain inspissated feces. In addition to the presence of bulky, lobulated polyps, one may also see narrow, tall, filiform polyps.
FIG. 11.15 Crohn disease complicated by ischemic colitis. The ischemic area is in the upper right-hand portion of the mucosa and is covered by a fibrinous pseudomembranous exudate.
TABLE 11.6 RECTAL STRICTURES: ETIOLOGY
FIG. 11.17 Mucosal polyposis. Irregularly sized cobblestone-like structures are present. They represent residual islands of mucosa. The clefts between them represent linear ulcers.
TABLE 11.7 RESECTION FEATURES THAT SUGGEST A DIAGNOSIS OF CROHN DISEASE
lial neutrophils are also present (Fig. 11.24). Further extension of an erosion leads to an ulcer (Fig. 11.25).
FIG. 11.21 Crohn disease. Portion of colonic mucosa showing marked glandular distortion with relative preservation of the mucinous content within the glands.
A thin stream of mucus, neutrophils, and inflammatory debris exudes from the ulcer mouth and empties into the bowel lumen (Figs. 11.24 and 11.25). The ulcers progressively enlarge, forming a continuum with the deeper ulcers normally seen in CD. Larger ulcers may eventually become lined by a reparative single layer of atrophic cuboidal epithelial cells. There is an associated loss of villi and reduction in the number of crypts in previously ulcerated areas. Edges of an ulcer are likely locations for findings pyloric gland metaplasia, especially in the small bowel (Fig. 11.27).
branch and penetrate deeply into the underlying bowel wall, producing adhesions, fistulae, abscesses, and peri-intestinal inflammatory pseudotumors (Fig. 11.29). Fistulae contain acute inflammatory cells and a granulation tissue lining with conspicuous pale, plump histiocytic cells. Giant cells may also be present. Occasionally, reparative intestinal epithelium may be seen lining a fissure or fistula tract.
FIG. 11.25 Crohn disease. Further extension of the aphthous ulcer. There is more extensive inflammation and wider area of ulceration extending from the aphthous ulcer than one sees in Figure 11.24.
in a single section. They extend down to, but usually not through, the muscularis mucosae and have a number of terminal branches that are given off at right angles to the neck, so that they are usually seen in cross section. The glands are lined by clear or pale-staining columnar cells containing indistinct neutral mucin granules. The nuclei appear oval or round and are located near the base of the cell. The glandular structures have a looser architectural pattern than either pyloric or Brunner glands (92).
neutrophils may infiltrate along the dilated vessels. In more advanced stages of the disease, fibrous tissue replaces the edema.
FIG. 11.31 Paneth cell metaplasia. Numerous Paneth cells with eosinophilic cytoplasmic granules are present in these rectal crypts.
FIG. 11.32 Lymphangiectasia in Crohn disease. This section from the ileum of a patient with Crohn disease shows prominent dilation of the lymphatics in the submucosa and basal mucosa.
such as lymph nodes sampled from a resection specimen. Although the presence of granulomas represents a useful diagnostic feature for CD, they can be seen in various other conditions (see Table 11.8).
FIG. 11.36 Crohn disease. Inflammation extends through the full thickness of the bowel wall. Prominent lymphoid aggregates are present within the submucosa and muscularis propria.
ileum to a maximum number in the rectum (97). The granulomas also occur in various other tissues and organs, including the lymph nodes, pancreas, mesentery, peritoneum, liver, lung, kidney, and, occasionally, bones, joints, and skeletal muscle. The presence of granulomas does not indicate disease activity, nor does it affect the postoperative recurrence rate. Granulomas are more often found in pediatric CD biopsies and, although documented on biopsy, can be absent in 36% of adult resections and 50% of pediatric resections (98).
FIG. 11.38 Microgranuloma in a colonic biopsy from a patient with Crohn disease. Note the presence of a compact histiocytic granuloma in the basal portion of the mucosa. The glands surrounding the lesion lack neutrophilic inflammation.
FIG. 11.39 Early mucin granuloma in a mucosal biopsy from a patient with ulcerative colitis. This specimen shows evidence of basal plasmacytosis, which is most evident in (B). A: One sees several crypt abscesses. The right one has ruptured and herniated with extension into the surrounding lamina propria. Histiocytic cells collect at the area of herniation. B: A crypt that has ruptured and is associated with two giant cells intermingling with apoptotic cell fragments and with extravasating inflammatory cells. These lesions have a completely different appearance than the microgranulomas associated with Crohn disease. Compare this photograph with Figure 11.38.
TABLE 11.8 DIFFERENTIAL DIAGNOSIS OF GRANULOMAS IN THE INTESTINE
with or without Langerhans giant cells, often with a surrounding cuff of lymphocytes (Fig. 11.37). Nodal granulomas also contain centrally located T lymphocytes and dendritic cells. Older lesions may show varying degrees of hyalinization and fibrosis. The granulomas may be numerous or very difficult to find. Granulomas that have definite foci of necrosis or suppuration, or are restricted to the edges of ruptured crypts, are not specific for CD.
FIG. 11.42 Granuloma in Crohn disease. This granuloma is arising in association with a dilated submucosal lymphatic. Granulomas in Crohn disease are commonly located adjacent to lymphatics.
FIG. 11.44 Vasculitis in Crohn disease. Not all cases of vasculitis are as dramatic as those illustrated in Figure 11.40. This patient with CD had only minimal vascular inflammation. Such changes might be seen in a patient with severe ulcerative colitis, so that these features may show histologic overlap.
FIG. 11.45 Neural hyperplasia in Crohn disease. Submucosal nerves are prominent in this ulcerated area from a resection specimen.
FIG. 11.51 Inflammatory pseudopolyps. A: The inflammatory pseudopolyps present in this photograph differ from those shown in Figure 11.50, in that they represent residual islands of mucosa and submucosa. They contain a prominent submucosal core. The surrounding tissues are ulcerated down to the level of the muscularis propria. B: Higher magnification of the pedunculated lesion indicated by the arrow in (A). One can see the central fibrovascular submucosal core with a covering of granulation tissue and extravasated red cells. C: Higher magnification of the lesion.
FIG. 11.52 Filiform polyp in Crohn disease. This long filiform polyp was one of dozens present in the colon. They are characterized by long submucosal extensions covered by regenerative mucosa.
and histiocytes in variable numbers. This focal inflammation affects both the neck region and deep aspects of the gastric glands and is more commonly seen in the antrum than in the body of the stomach. In addition, granulomas may be seen in 9% to 16% of patients (102,103) (Fig. 11.55).
FIG. 11.56 Esophageal Crohn disease. Figures (A) and (B) are from the esophagus of the child whose stomach is depicted in Figure 11.55. A: The esophageal squamous mucosa shows nonspecific inflammation and regenerative changes. B: Although no granulomas were present in this biopsy, a multinucleated giant cell is present in the submucosa. C: Increased intraepithelial lymphocytes, with or without a few eosinophils and neutrophils can be seen in esophageal biopsies, especially in children.
lesions remain in up to one third of patients and are associated with more severe CD phenotype in pediatric patients (110,111).
include steroid-related osteonecrosis often affecting the hip or knee, as well as secondary viral or bacterial infections. An increased risk of melanoma has also been reported in IBD patients while taking immunomodulators (116).
TABLE 11.9 COMPLICATIONS OF CROHN DISEASE
peristalsis and hypoproteinemia augments the bowel wall edema. The mortality associated with toxic megacolon has decreased, likely due to early recognition and optimized medical and surgical management. Other complications include massive hemorrhage and pulmonary embolism.
TABLE 11.10 FACTORS ASSOCIATED WITH RELAPSE OR EXACERBATION OF ULCERATIVE COLITIS SYMPTOMS