CHAPTER 30
Crohn’s disease : clinical manifestations and management

Gil Y. Melmed^1,2, Christina Ha^1,2, and Dermot P.B. McGovern^1,2

¹ F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars‐Sinai Medical Center, Los Angeles, CA, USA

² David Geffen School of Medicine at UCLA, Los Angeles, CA, USA,

Introduction

Crohn’s disease is characterized by relapsing and remitting chronic intestinal inflammation in a genetically susceptible host. It is closely related to ulcerative colitis, but is distinguished by key features including anatomical disease location and clinical expression. The clinical manifestations of Crohn’s disease are varied, as inflammation may involve any part of the digestive tract, may include noncontiguous segments of inflammation (i.e., “skip lesions”) with intervening normal segments of bowel, and can lead to fibrostenosing and perforating complications from transmural inflammation. Most commonly, Crohn’s disease affects the terminal ileum and colon, but can involve any portion of the gastrointestinal (GI) tract from the mouth to the anus. The terms “involvement” or “disease” refer to the presence of inflammation that can be visualized radiographically, endoscopically, and histologically.

Endoscopy

Colonoscopic findings of Crohn’s disease include various manifestations of inflammation, including erythema, erosions, ulceration, and stricturing. Ulcers are characterized morphologically as aphthous, linear, serpiginous or stellate (Figures 30.1 and 30.2).

Several instruments have been developed for clinical trials to score Crohn’s endoscopic disease activity. The most commonly used indices include the Crohn’s Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score (SES), which correlate highly with one another and score the presence, size, and extent of ulceration and inflammation in the ileum and individual colonic segments (Table 30.1). In addition to inflammation, colonoscopy can also identify healing of the mucosa, which can look normal or can display areas of scarring suggestive of prior inflammation (Figure 30.3). Polypoid lesions in patients with Crohn’s disease should be biopsied to assess for dysplasia, although benign inflammatory polyps of no malignant potential are commonly seen in areas of active or prior inflammation (Figure 30.4). A stricture is an area of narrowing, or stenosis, that may be due to fibrosis, inflammation/edema, or both (Figure 30.5).

Capsule endoscopy can identify small bowel Crohn’s disease with a high degree of accuracy. Capsule endoscopy is highly sensitive for the detection of small intestine mucosal lesions that could be missed on barium studies or even cross‐sectional enterography studies, and can be useful for disease diagnosis, particularly when conventional endoscopy and colonoscopy are not diagnostic in the appropriate clinical setting (Figures 30.6 and 30.7).

Histology

At the time of endoscopic evaluation, biopsies for histopathological evaluation can be helpful to establish the diagnosis, discriminate between Crohn’s and ulcerative colitis, exclude certain infections such as cytomegalovirus (Figure 30.8), and assess for dysplasia or malignancy. Noncaseating granulomata are considered pathognomonic for Crohn’s disease in this setting, although they are only seen in about 15% of patients with Crohn’s disease (Figure 30.9). Typically, a full assessment of the extent and severity of inflammation requires a combination of colonoscopic and histological findings together with small bowel imaging, which can assess for Crohn’s inflammation and stricturing more proximal than the reach of the colonoscope. Furthermore, there can be disparities between endoscopic and histological findings, due to the focal/patchy nature of the disease both endoscopically and histologically.

Radiographic aspects of Crohn’s disease

Cross‐sectional imaging modalities (computed tomography and magnetic resonance imaging [MRI]) with enterography protocols have largely replaced small bowel follow‐through (SBFT) for the routine evaluation of known and suspected Crohn’s disease. These modalities are first‐line imaging techniques that can rapidly and accurately identify areas of mucosal inflammation, fibrostenotic and penetrating complications, and many extraintestinal manifestations of Crohn’s disease. Furthermore, they may be used to detect changes in inflammation and response to treatment. Barium SBFT is occasionally useful in some situations, including the evaluation of complex fistula tracts and for the evaluation of obstruction (Figure 30.10). Small bowel ultrasound is an efficient, accurate, and noninvasive modality for the evaluation of small bowel Crohn’s disease when performed by experienced operators.

Photo depicts colonoscopic ulceration in Crohn’s disease. — **Figure 30.1** Colonoscopic ulceration in Crohn’s disease. This is a long, deep, linear ulcer characteristic of severe endoscopic inflammation.

Table 30.1 Simple Endoscopic Score for Crohn’s disease (SES‐CD). The total SES‐CD score is the sum of the variables for the five bowel segments (ileum, right colon, transverse colon, left colon, and rectum). This scoring index is commonly used to assess inflammation in clinical trials.

Source: Data from Sipponen T., Nuutinen H., Turunen U., Farkkila M. Endoscopic evaluation of Crohn’s disease activity: comparison of the CDEIS and the SES‐CD. Inflamm Bowel Dis 2010;16:2131.

	0	1	2	3
Presence and size of ulcers	None	Aphthous ulcers (less than 0.5 cm)	Large ulcers (0.5–2 cm)	Very large ulcers (>2 cm)
% ulcerated surface	None	<10%	10–30%	>30%
Affected surface	None	<50%	50–75%	>75%
Presence of narrowing	None	Single, traversable	Multiple, traversable	Cannot be traversed

Enterography studies (CTE and MRE) are distinguished from routine cross‐sectional techniques in that they involve adequate distension of the small bowel to identify and characterize mucosal inflammation. Intravenous contrast is also administered during these studies, in order to identify areas of mucosal hyperenhancement suggestive of active inflammation. Typical findings of active inflammation using enterography protocols include the “comb sign,” which refers to engorgement of the vasa recta, and the “target sign,” which refers to the trilaminar enhancement of the layers of the bowel wall, including enhancing mucosa (bright), submucosal edema (dark), and enhancing serosa (bright) (Figures 30.11 and 30.12).

Both CTE and MRE can identify small bowel inflammation with a high degree of accuracy. CTE offers rapid image acquisition and is generally less expensive than MRE. Because of the speed in which images are acquired, motion artifact is minimized. In contrast, MRE offers high‐quality images without exposure to ionizing radiation, and is more sensitive to identifying soft tissue abnormalities including fistulas and perianal complications. Furthermore, MRE protocols acquire multiple images of the same location at different time points that may allow for clarification of areas of questionable distension or enhancement.

Extraintestinal manifestations and complications

Extraintestinal manifestations of Crohn’s disease can include eye inflammation (iritis, uveitis, episcleritis), joint involvement (axial or peripheral arthritis, sacroileitis), skin manifestations (pyoderma gangrenosum, erythema nodosum, and others), and biliary involvement (primary sclerosing cholangitis). These extraintestinal manifestations may be present in up to 25% of patients, may sometimes be part of the presenting constellation of symptoms, and may even precede bowel inflammation and the diagnosis of Crohn’s or ulcerative colitis by months or even years.