Abbreviations
CD
Crohn’s disease
GI
gastrointestinal
IBD
inflammatory bowel disease
ICV
ileocecal valve
ITB
intestinal tuberculosis
PIP
postinflammatory polyps
PSC
primary sclerosing cholangitis
UC
ulcerative colitis
Introduction
Crohn’s disease (CD) can affect any part of the gastrointestinal (GI) tract, from the mouth to the anus, and can also penetrate the GI tract at various depths. To address this variability, several classifications have been developed to categorize CD. The Montreal classification, an evolution from the earlier Vienna classification , divides CD based on the age of onset, disease location, and disease phenotype ( Table 4.1 ). More recently the classifications have been expanded to incorporate age groups, disease locations, and etiopathogenetic factors ( Table 4.2 ).
Table 4.1
The Montreal classification of Crohn’s disease .
| Age at diagnosis (A) | ||
| A1 16 years or younger | ||
| A2 17–40 years | ||
| A3 over 40 years | ||
| Location (L) | Upper GI modifier (L4) | |
| L1 terminal ileum | L1+L4 | Terminal ileum+upper GI |
| L2 colon | L2+L4 | Colon+upper GI |
| L3 ileocolon | L3+L4 | Ileocolon+upper GI |
| L4 upper GI | – | – |
| Behavior (B) | Perianal disease modifier (p) | |
| B1 nonstricturing, nonpenetrating | B1p | Nonstricturing, nonpenetrating+perianal |
| B2 stricturing | B2p | Stricturing+perianal |
| B3 penetrating | B3p | Penetrating+perianal |
A , Age; B , behavior; GI , gastrointestinal; L , location.
Table 4.2
Proposed classification of inflammatory bowel diseases.
| Criteria | Class | Description | Examples | |
|---|---|---|---|---|
| Disease location, extent, and depth±granulomas | Ulcerative colitis | Classic UC | ||
| Crohn’s disease | Classic CD | |||
| Indeterminate colitis | ||||
| Age of onset | Very early onset | Age 0 | IL-10/ILR mutations | |
| Early onset | Age 0–10 years | |||
| Age 10–17 years | ||||
| Regular onset | Age 17–40 years | |||
| Late onset | Age>50 years | |||
| Phenotype | Inflammatory | Inflammatory CD; classic UC | ||
| Stricturing | Stricturing CD; UC with stricture | |||
| Penetrating | Fistulizing CD | |||
| Locations | Oral | |||
| Upper GI | ||||
| Jejunum | ||||
| Ileum | ||||
| Colon | ||||
| Rectum | ||||
| Perianal | ||||
| Extraintestinal | Metastatic CD of the skin, lung, and liver | |||
| Concurrent or immune-mediated disorders | IBD | Isolated UC or CD of the gut | ||
| IBD-V | IBD + | IBD+classic extraintestinal manifestations | UC with concurrent PSC | |
| IBD ++ | IBD+autoimmune and/or autoinflammatory disorders±classic extraintestinal manifestations | IBD with concurrent microscopic colitis, celiac disease, hidradenitis suppurativa | ||
| IBD ± | Diseases sharing clinical features and possible etiopathogenetic pathways with classic IBD±classic extraintestinal manifestations of IBD, autoimmune disorders, or autoinflammatory disorders | Lymphocytic colitis, collagenous colitis; Behcet disease, cryptogenic multifocal ulcerous stenosing enteritis, ulcerative jejunitis | ||
| Etiology of IBD | Primary or idiopathic | Monogenic | IL-10, IL-10Ra, IL-10Rb mutations | |
| Very-early-onset IBD | ||||
| Polygenic | Classic UC; classic CD | |||
| Secondary | Identifiable pathogens | Mycobacterial paratuberculosis | ||
| Medication-induced | Mycophenolate-associated colitis; ipilimumab-associated colitis | |||
| Organ transplantation-induced | Postsolid organ transplant IBD-like conditions, cord colitis syndrome | |||
| Surgery induced | Pouchitis, Crohn’s disease-like conditions of the pouch, postcolectomy enteritis, bariatric surgery-associated IBD | |||
| Genetic etiology | Monogenic | IL-10/IL-R mutations, familial Mediterranean fever | ||
| Polygenic | Classic CD and classic UC | |||
| Disease spread process | Intrinsic (inside-out) | Starting from the lymphatic system or mesentery, spreading to gut mucosa | Subset of obese CD patients; subset of sclerosing mesenteritis or lymphangitis | |
| Extrinsic (outside-in) | External trigger (e.g., bacteria) leading to mucosal inflammation | Fulminant UC: from mucosal disease to transmural inflammation | ||
CD , Crohn’s disease; IBD , inflammatory bowel disease; IBD-V , IBD-variant; PSC , primary sclerosing cholangitis; UC , ulcerative colitis.
This chapter is focused on the inflammatory phenotype of CD. Fibrostenotic (Chapter 5), fistulizing (Chapter 6), and perianal (Chapter 7) phenotypes are discussed in separate chapters.
Esophagogastroduodenoscopy and ileocolonoscopy play a key role in the diagnosis, differential diagnosis, disease monitoring, and assessment of the treatment response of CD, and surveillance ( Table 4.2 ).
Common endoscopic features of Crohn’s disease
Endoscopic features of CD range from erosions to deep ulcers to stricture or fistula. The range of endoscopic presentation is illustrated in Fig. 4.1 . These endoscopic features can be the initial presentations, and sequential events at different stages of disease before, during, or after medical therapy. For example, the healing of deep ulcers can result in endoscopic appearance of postinflammatory polyps, mucosal scars, or mucosal ridges or bridges. Progression of severe ulcers can lead to stricture and fistula ( Fig. 4.1 ).
Patterns and evolution of small bowel inflammation in Crohn’s disease.
Healthy small bowel and large bowel are characterized by intact villi and normal pit pattern, respectively ( Fig. 4.2 ). Subtle mucosal changes can be illustrated with image-enhanced endoscopy, such as magnified endoscopy, virtual chromoendoscopy (e.g., narrow-band imaging [NBI]), and dye-based chromoendoscopy. The mildest forms of inflammatory CD are shortened villi ( Fig. 4.3 ) and erythema ( Figs. 4.4 and 4.5 ). Overlying exudates on the mucosal surface should be washed off ( Fig. 4.5 A). Loss of vascular pattern may also be an early sign of mucosal inflammation or mucosal healing ( Fig. 4.6 ). Granular mucosa without ulcers is also a sign of mild inflammation ( Fig. 4.7 A–C). Granularity with ulcers ( Fig. 4.7 D) indicates a more severe form than granularity alone. The enlarged form of granular mucosa is nodular mucosa ( Fig. 4.8 A–C). Mucosal nodularity with ulcers in between gives rise to characteristic “cobblestoning” mucosa ( Fig. 4.8 D). Some patients with CD may present with mucosal edema in the small bowel or large bowel with surrounding inflamed or ulcerated mucosa ( Fig. 4.9 ). This mucosal edema pattern is different from hypoalbuminemia or angioedema-associated bowel wall edema.
Mucosa and villi in normal terminal ileum. (A–D) Slightly varied length of the villi with lymphoid aggregates on white light, magnified white light, narrow-band imaging, and magnified narrow-band imaging.
Flattened villi can be an early sign of mucosal inflammation in Crohn’s disease. (A and B) The fattened villi may not be obvious on white light endoscopy, even with magnification (B). (C and D) The flattened villi are highlighted with narrow-band imaging with (D) or without magnification.
Mucosal erythema in two patients with Crohn’s disease. (A and B) Erythema of the colon on white light (green circle) can be highlighted with narrow-band imaging. (C and D) Erythema in the proximal rectum. The erythematous mucosa is characterized by a prominent pit pattern on magnified narrow-band imaging.
Exudates and erythema in a patient with Crohn’s colitis. (A and B) Washing off exudates reviewed mucosa. (C and D) Erythematous mucosa featured a coarse pit pattern on narrow-band imaging with or without magnification.
Normal and abnormal vascular patterns in the small and large bowel. (A) Normal vascular pattern in the terminal ileum. However, most normal individuals may have not clear, transparent vascular patterns. (B) Loss of vascular pattern in a patient with quiescent Crohn’s ileitis. (C) Normal vascular pattern in the colon. (D) Blurred vascular pattern and mucosal scar in a patient with quiescent Crohn’s ileitis.
Mucosal granularity in Crohn’s disease. (A and B) Granular mucosa of the terminal ileum on white-light and magnified narrow-band imaging in a patient with Crohn’s disease. (C and D) Granular mucosal with small ulcers of the terminal ileum on white light and narrow-band imaging in a separate patient with Crohn’s disease.
Nodularity and “cobblestoning” of the small bowel mucosa in Crohn’s disease. (A and B) Nodular mucosa of the terminal ileum without ulcers in two patients. (C) Nodular mucosa at the ileocolonic anastomosis. (D) Nodular mucosa with ulcers in between made the appearance of “cobblestones.”
Edema or congestion of the mucosa in a patient with Crohn’s colitis. (A–D) Severe edema of the colon mucosal with linear ulcers in between on white-light, narrow-band, and magnified imaging.
Erosions and ulcers represent the range of epithelial, mucosal, or submucosal depletion. Erosions are featured with depletion of the epithelia with a size<5 mm and absence of scars after healing ( Fig. 4.10 ). Ulcers, on the contrary, are characterized but surface defect>5 mm, to the level of the muscularis mucosae or deeper. The ulcers can be small or large, regular- or irregular-shaped, clean-based, with or without a raised border ( Figs. 4.11–4.13 ). The progression of inflammation and ulcers can lead to the development of intramural fibrosis, neural hyperplasia, muscular hypertrophy, and the formation of stricture and fistula ( Fig. 4.1 ).
Erosions in Crohn’s disease. (A and B) Erosions of the terminal ileum were highlighted with magnified narrow-band imaging. (C and D) Erosions in the terminal ileum in a separate patient.
Regular-shaped ulcers in Crohn’s disease. (A–D) A small, clean-based ulcer with a slightly raised edge in the terminal ileum, highlighted by magnified and narrow-band imaging.
Irregular-shaped ulcers in Crohn’s disease. (A and B) Irregular-shaped, friable, superficial ulcers at the ascending colon in a patient with Crohn’s disease. (C and D) Irregular-shaped, clean-based ulcer with regenerative islands in a colon fold from a patient with Crohn’s colitis.
Irregular-shaped ulcers in a patient with Crohn’s ileitis. (A–C) The ulcers in the terminal ileum. (D) Magnification of one of the ulcers on narrow-band imaging.
The healing process of mucosal inflammation or ulceration results in PIPs, mucosal scars ( Fig. 4.13 ), and mucosal ridges or bridges ( Figs. 4.14 and 4.15 ).
Postinflammatory polyps (PIP) and mucosal bridges/ridges. (A and B) PIPs of the colon in two patients with quiescent Crohn’s ileocolitis. (C) PIPs and mucosal scars in the colon in a patient with quiescent Crohn’s colitis. (D) Extensive mucosal bridges and ridges in a patient with quiescent Crohn’s ileocolitis.
Taenia coli and mucosal ridges and mucosal bridges. (A) The taenia coli in a healthy individual. (B and C). Linear mucosal scars in two patients with quiescent Crohn’s colitis, mimicking taenia coli. (D) Mucosal bridge in a patient with Crohn’s ileocolitis who had ileocolonic resection and ileocolonic anastomosis.
