frequently have concomitant food intolerances, the role of dietary habits remains debatable.21 Rather

than a causative effect, it is felt that the microbiome in the human GI tract is heavily influenced by

dietary intake, leading to a local environment ripe to foster susceptibility to Crohn disease.

DIAGNOSIS

As is well documented, Crohn disease falls under the umbrella of inflammatory bowel disease along

with ulcerative colitis. In both conditions, there is no specific test at present to permit a definitive

diagnosis; rather a combination of history and physical examination, laboratory, radiographic and

endoscopic findings is utilized. This, in part, contributes to ∼5% to 15% of patients with ulcerative

colitis that will eventually be diagnosed with Crohn disease or patients who carry a diagnosis of

indeterminate colitis.22,23 Once diagnosed, Crohn patients are often categorized in several different

manners, the most common of which involves either the site of disease or the patient’s phenotypical

manifestations (i.e., fibrostenotic, fistulizing, inflammatory). By location, the ileum (∼60%) has the

highest rate of disease incidence (Fig. 50-1). Localized inflammation in the ileocecal region occurs in

∼45% of patients, whereas ∼25% to 33% will have colonic involvement, 25% will have more proximal

small bowel disease, and <10% will have upper GI or perianal disease. In general, patients with

concomitant perianal disease tend to have a more severe clinical course,24 and perianal disease in the

setting of Crohn’s may precede abdominal manifestations in up to 45%.25

When stratifying by disease pattern or phenotype, patients may have fibrostenotic (i.e., stricturing),

fistulizing (i.e., penetrating), or inflammatory (i.e., phlegmonous) characteristics. Due to the

heterogeneous nature of the disease, these manifestations may occur independently, concomitantly, or

may even vary along the longitudinal course of the disease. Fibrostenotic patterns may occur in any

location, though most commonly occur in the terminal ileal region, where patients present with

obstructive-type symptoms such as nausea, vomiting, and decreased oral intake. Due to the recurrent

chronic nature that results in progressive thickening of the bowel wall, medical management is typically

unsuccessful and surgical intervention is required. Inflammatory disease may present with a wide range

of symptoms such as abdominal pain, fever, and an abdominal mass and/or weight loss. Bowel

movements may either be diarrhea or follow an obstructive pattern due to luminal narrowing or

extrinsic compression from the phlegmon. Finally, penetrating or fistulizing disease also has a variable

presentation. Patients may be completely asymptomatic, as in the case of many entero-enteral fistulas,

present with anorectal abscesses and/or fistulas, or more commonly complain of symptoms mirroring

involvement of the secondarily involved organ–recurrent urinary tract infections or pneumaturia,

vaginal discharge, diarrhea, cutaneous feculent drainage, and/or hip/back pain from psoas involvement.

While medical management continues to be a major component of each of the latter two patterns,

surgery is often required for resolution of symptoms.

Figure 50-1. Terminal ileum with forceps pointing to intraloop chronic abscess cavity.

Clinical Evaluation

Small Bowel

The distribution of disease will in large part dictate the clinical presentation. The terminal ileum (along

with the cecum) is the most commonly affected site, in addition to isolated more proximal small bowel

disease. Patients with disease in this location will classically present with abdominal pain, fever,

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fatigue, nausea, and vomiting. The weight loss seen is a byproduct of both decreased oral intake as well

as the malabsorptive process associated with Crohn’s. When the disease is in the terminal ileum and

ileocecal region, patients may present with a slow onset of right lower quadrant pain following meals,

an abdominal mass, and (when the psoas is involved) pain with hip extension. Obstructive symptoms

may also occur in patients with either fibrostenotic or acute inflammation (Fig. 50-2). Diarrhea tends to

be nonbloody, though heme-positive stools may occur, and rarely gross blood is a manifestation from a

small bowel source.

Colonic

Colonic involvement may occur in isolation in approximately one in four patients, though it is most

often seen concomitantly in those with perianal (left-sided) or terminal ileal (cecal and ascending colon)

disease.26 Within the colon the distribution is somewhat variable, with approximately one-third of

patients having total colonic involvement, 40% showing segmental disease, and left-sided only in up to

30%.27 Regardless of the exact location within the large intestine, patients with colonic involvement

may experience abdominal pain, and in some cases, malnutrition. Diarrhea is often of smaller volume

and may be from several sources – malabsorptive (e.g., salt/water and bile acid malabsorption),

infectious (e.g., CMV super-infection), or as a result from an entero-colonic fistula.28,29 Unlike ulcerative

colitis, rectal bleeding is not routine, and bowel movements are often nonbloody, except in those with

moderate-to-severe Crohn colitis. In addition, similar to disease in the small bowel, patients can

experience hip pain from fistulas, cramping and obstructive symptoms. Patients with chronic disease

may also demonstrate pseudopolyps on endoscopic examination (Fig. 50-3).

Anorectal

Bissel30 was the first to describe the anorectal component of Crohn, almost two years after the original

description of the disease. Despite advances in the understanding of many features of Crohn disease,

perianal complaints have been recognized as one of its most challenging aspects. Isolated perianal

disease is the presenting symptom in ∼5% to 15% of Crohn patients; though over the course of their

lifetime, it is seen in 25% to 80%. The perianal area in Crohn patients has classically been felt to be a

“window” into the abdomen, and perianal involvement is clearly more common in those with

concomitant rectal or colonic disease.31,32 In addition, active disease in the perineum is felt to act as a

harbinger of an overall more virulent course.33 The traditional anorectal complaints witnessed in nonCrohn patients are similar to those with the disease, including “standard” hemorrhoids, fissures,

abscesses and fistulae. However, Crohn patients may also manifest edematous (elephant ear) skin tags

(Fig. 50-4), blue discoloration of the anus, and abscesses and fistulas that are often recurrent, multiple,

and located well away from the anal verge. While fissures due to hypertonicity may be identified, more

often Crohn fissures present as deep-seated, burrowing fissures – more like ulcers – and may be

multiple, off the midline, extending in the muscle and associated with large skin tags. Finally, patients

with long-standing Crohn’s may develop anal stenosis or an anal stricture at the verge secondary to

repeated bouts of chronic inflammation.

Figure 50-2. Endoscopic view of a terminal ileum stricture and active Crohn disease.

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Figure 50-3. Endoscopic view of colonic pseudopolyps.

Figure 50-4. Anorectal Crohn disease. Large “elephant ear” skin tag.

Clinical evidence of perianal Crohn, as manifested by many of these features, is often deemed a

hallmark of disease diagnosis, although occasionally a biopsy may be necessary. Due to local sepsis and

perianal tenderness, patients may need to undergo an examination under anesthesia to fully identify the

extent of the disease. Patients presenting with perianal findings consistent with Crohn disease should

undergo a full alimentary tract evaluation, as previously stated, with endoscopic and radiologic

evaluation. In addition, a thorough physical examination to identify any extraintestinal manifestations

should be performed.

Upper Gastrointestinal Disease

Upper GI Crohn encompasses disease from the mouth through the jejunum. The incidence of upper tract

involvement varies widely, with most studies reporting overall rates of <5%. In patients with ileocolic

disease, concomitant upper GI manifestations occur in 0.5% to 13%, yet up to 40% of patients will

demonstrate early subclinical evidence of Crohn disease on radiologic and endoscopic evaluation.34

Importantly, when patients have upper GI Crohn disease, they almost uniformly have concomitant

disease of lower tract and should be evaluated to determine the extent of involvement. Upper tract

disease is hallmarked by both obstructive symptoms and fistulas.35 Patients typically present with

abdominal pain, cramping, nausea, vomiting, or intolerance of oral intake leading to weight loss. While

fistulas may be virtually to any site, the majority involving the proximal tract are gastrocolic or

ileogastric in nature. Patients may be asymptomatic or present with diarrhea from high-output and

colonic involvement. Crohn disease of the esophagus is exceedingly rare, involving <0.5% of patients.

Most patients will have inflammation or ulcers, though strictures and fistula have also been reported. As

with other upper tract Crohn disease, extra-esophageal disease is nearly always present.36

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Extra-Intestinal Disease

Similar to ulcerative colitis, patients with Crohn disease may have manifestations from the disease

process that extend outside of the GI tract (Table 50-1). Extra-intestinal disease (EID) has been reported

in ∼6% to 47% of patients with inflammatory bowel disease, and has an increased concordance among

siblings and first-degree relatives – suggesting a genetic component that has been linked to the major

histocompatibility complex (MHC) on chromosome 6.37,38 EID occurs secondary to the systemic

inflammatory process associated with the underlying disease and affect a wide range of organ systems.

While the GI tract may be the primary source, the dysfunction in immune regulation incites a pathologic

response that may occur in nearly every location in the body simultaneous with, preceding, or following

GI manifestations.39 Overall, rheumatologic/joint problems (e.g., peripheral or sacroiliac arthritis,

arthralgias) are the most common, occurring in up to one-third of patients. Other more frequent sites of

involvement include the skin (Fig. 50-5), eyes, and hepatobiliary system; while the renal, pulmonary,

nervous, and coagulation systems are typically involved to a lesser extent. It is important to distinguish

between manifestations that parallel bowel disease activity (episcleritis, peripheral arthritis, and

erythema nodosum) from those that do not (ankylosing spondylitis, pyoderma gangrenosum, and

primary sclerosing cholangitis). Surgical intervention directed at the bowel may occasionally be

required for recalcitrant EID that may appropriately go into remission following bowel resection.40

Table 50-1 Classification of Extra-intestinal Manifestations of Crohn Disease

Figure 50-5. Peristomal pyoderma gangrenosum. (Courtesy of W. Brian Sweeney, MD.)

Radiology

Fluoroscopic Imaging

Radiologic work-up for Crohn patients is an invaluable part of the diagnostic evaluation. In addition to

providing information on the acute process (i.e., abscess, phlegmon, fistula, stricture), diagnostic

imaging is used to determine the extent of disease. Historically, contrast studies such as a barium enema

have helped diagnose Crohn disease by identifying longitudinal and transverse linear ulcerations that

create cobblestone and nodular patterns, skip lesions, fistulas, and strictures.41 A small bowel followthrough has also been a long-standing modality utilized to evaluate for strictures, active disease

(highlighted by ulceration, mucosal granularity, and loss of villous morphology), and fistulas (Fig. 50-

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6).

Computed Tomography

In many centers, computed tomography (CT) has now largely replaced the barium enema and small

bowel follow-through, with the added ability to identify the extent of the disease and involvement of

surrounding structures, manifested by segmental bowel thickening (Fig. 50-7), mesenteric fat stranding,

and intra-abdominal fluid.42 Additionally, CT is useful to identify secondarily involved organs or

provide information that may be pertinent to preoperative planning, such as bladder or vaginal air

indicating presence of a fistula, an adjacent psoas abscess in ileocecal disease, or ureteral obstruction

that may require stenting. CT and magnetic resonance (MR) enterography provide improved detail of

the mucosal surface and are especially useful in depicting fistulas and strictures, along with the added

benefit of lower levels of radiation exposure. The latter is especially relevant considering the generally

younger patient population, body habitus, and potential need for life-long repeat imaging associated

with Crohn’s.

Figure 50-6. Small bowel follow-through demonstrating a tight stricture with proximal dilation.

Figure 50-7. Coronal cut of a CT demonstrating a jejunal stricture.

Magnetic Resonance Imaging

MR enterography in particular has been shown to be over 85% accurate in predicting stenosis (Fig. 50-

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8), abscess and fistula in preoperative planning, as well as changing the surgical strategy/approach in

up to 10% of Crohn patients.43 Furthermore, its sensitivity (85% to 90%), specificity (100%), and

negative predictive value (77%) have made it ideal for detecting recurrent disease after surgery.44,45

MRI has also particularly been useful in the evaluation of complex perianal fistulas seen in Crohn

patients, identifying secondary “hidden” tracts and occult abscesses that lend to higher failure rates if

not addressed.46 More recently, diffusion-weighted imaging and magnetization transfer imaging

sequences have allowed bowel resolution previously not achievable to help identify disease, depict

disease activity, and target interventions.47

PET Scan

Another modality typically not associated with inflammatory bowel disease, 18F-FDG positron emission

tomography (PET) has been used for Crohn disease largely in academic and research centers to date.48

While cost seems to be somewhat prohibitive, this emerging indication has the potential to (a)

determine disease activity in a noninvasive manner, (b) provide information regarding subclinical

disease, (c) deliver a qualitative measure of response to treatment, and (d) indicate disease activity that

would otherwise be unobtainable by traditional methods.

Video Capsule Endoscopy

Finally, video capsule endoscopy uses wireless technology to capture continuous images of the upper GI

tract mucosa. As up to 30% of patients will have disease limited to the small bowel, capsule endoscopy

plays a unique role to determine disease presence and activity that are outside the reach of endoscopy

and the limitations of traditional small bowel imaging. While the diagnostic yield may not be as high, it

has been shown to be comparable to ileocolonoscopy and better than small bowel follow-through for

the detection of small bowel inflammation.49 Furthermore, negative predictive values range from 96%

to 100%, essentially ruling out the diagnosis of Crohn’s when the results are normal.50 Of note, it is

imperative to exclude the presence of moderate–severe strictures prior to its use, as their presence can

result in bowel obstruction from the capsule becoming lodged at the point of stenosis (Fig. 50-9).

Figure 50-8. MR enterography demonstrating a small bowel stricture.

Figure 50-9. Video capsule endoscopy “pill” lodged in a Crohn stricture causing a bowel obstruction. (Courtesy of Justin A.

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