Diagnostic Considerations

Patients with Crohn disease frequently present with abdominal pain, nonbloody diarrhea, weight loss, fever, and, sometimes, obstructive symptoms such as nausea, early satiety, and vomiting. World Health Organization diagnostic criteria for Crohn disease include the following^[57]:

Discontinuous or segmental lesions as well as a cobblestone appearance or longitudinal ulcer noted on radiologic studies, endoscopy, and resected specimens
Transmural inflammation, as evidenced by clinical evaluation, radiologic studies, biopsy findings, and resected specimens
Noncaseating granulomas, as revealed on biopsy findings and resected specimens
Fissures and fistulas, as evidenced by clinical evaluation, radiologic studies, and resected specimens
Perianal disorders on clinical evaluation

A variety of intestinal manifestations and extraintestinal manifestations (EIMs) also may be observed in conjunction with either Crohn disease or ulcerative colitis. Features differentiating the two forms of inflammatory bowel disease (IBD) are summarized in Table 1, below.

Table 1. Characteristics Differentiating Crohn Disease and Ulcerative Colitis (Open Table in a new window)

Characteristic
	Crohn Disease	Ulcerative Colitis
Distribution	Entire gastrointestinal tract	Colon only, though gastritis is recognized
Distribution	Skip lesions	Continuous involvement proximally from rectum
Pathology	Full thickness	Mucosa only
Pathology	Granulomas (15-30% in biopsy specimens; 40-60% in surgically resected bowel)	No granulomas
Radiology	Entire gastrointestinal tract	Colon only
	Skip lesions	Continuous involvement proximally from rectum
	Fistulae, abscesses, fibrotic strictures	Mucosal disease only
Cancer risk	Increased	Estimated to be 3% at 10 years, 8% at 30 years, and 18% at 30 years after diagnosis^[47]; risk is higher in patients with primary sclerosing cholangitis and long-standing colitis (> 8-10 y); may be lower in subsequent studies (see Intestinal Manifestations).
Presentation
	Crohn Disease	Ulcerative Colitis
Bleeding	Occasional	Very common
Obstruction	Common	Uncommon
Fistulae	Common	None
Weight loss	Common	Uncommon
Perianal disease	Common	Rare

Other diagnostic considerations

Despite extensive workup, 15% of patients with isolated colitis have an undetermined type of IBD that shows features of both Crohn disease and ulcerative colitis. The distinction is often difficult to make, especially if the patient meets all diagnostic criteria for ulcerative colitis but is a smoker or has rectal sparing—features that suggest the possibility of Crohn disease or IBD of undetermined type.

In addition, there is a subpopulation of patients with Crohn colitis who will not develop small bowel disease in their lifetime. This group represents approximately 20% of the colitis patients.

Tuberculosis is also in the differential diagnosis of Crohn disease. Simple clinical findings (eg, fever, rectal bleeding, diarrhea, symptomatic duration) appear to be most accurate for differentiating Crohn disease from intestinal tuberculosis.^[57]Anti–Saccharomyces cerevisiae antibodies (ASCA) do not help in differentiating small bowel tuberculosis from small bowel Crohn disease, but if both ASCA and interferon-gamma release assays are available and the ASCA result is positive, while the interferon gamma release assay result is negative, the specificity for Crohn disease is high, particularly in Asian populations.^[57]Endoscopy in combination with radiologic and laboratory findings are also useful for differentiating between Crohn disease and intestinal tuberculosis.

In addition to excluding ulcerative colitis and intestinal tuberculosis, guidelines from the World Gastroenterology Organization recommend ruling out the following in the differential diagnoses of Crohn disease^{[58, 57]}:

Behςet disease
Celiac disease
Irritable bowel syndrome (IBS) (if inflammatory changes are present, it is not IBS)
Nonsteroidal anti-inflammatory drug (NSAID) enteropathy

Differential Diagnoses

Workup

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Media Gallery

Crohn disease. The colonoscopy image reveals a large ulcer and inflammation of the descending colon in a 12-year-old boy with Crohn disease.
Crohn disease. This laparoscopic view depicts creeping fat along the mesentery of the terminal ileum.
Crohn disease. On this laparoscopic photograph, the mesentery of the terminal ileum is being coagulated with a sealing device (LigaSure). Note that the ligation of the mesentery proceeds near the border of the ileum rather than at the base of the mesentery.
Crohn disease. This postoperative photograph depicts incisions used for laparoscopic ileocolectomy in a 14-year-old male adolescent with obstruction of the terminal ileum. Note the 2-cm incision in the right lower abdomen, through which the specimen was extracted and extracorporeal anastomosis performed. A 12-mm umbilical incision is nicely hidden in the depths of the umbilicus. A 5-mm incision is visible in the left lower abdomen, and another is in the left suprapubic region just above the top of the pants.
Crohn disease. Colonic granuloma in a patient with Crohn disease is shown (hematoxylin-eosin staining). Image courtesy of Dr E. Ruchelli.
Crohn disease. Aphthous ulcers. A double-contrast barium enema examination in a patient with Crohn colitis demonstrates numerous aphthous ulcers.
Crohn disease. This double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right colon in a patient with Crohn colitis.
Crohn disease. Cobblestoning in Crohn disease. This is a spot view of the terminal ileum from a small bowel follow-through study. It demonstrates linear longitudinal and transverse ulcerations that create a cobblestone appearance. Also, note the relatively greater involvement of the mesenteric side of the terminal ileum and the displacement of the involved loop away from the normal small bowel secondary to mesenteric inflammation and fibrofatty proliferation.
Crohn disease. Crohn disease of terminal ileum. The small bowel follow-through study demonstrates the string sign in the terminal ileum. Also, note the pseudodiverticula of the antimesenteric wall of the terminal ileum, secondary to greater distensibility of this less-involved wall segment.
Crohn disease. This spot view of the terminal ileum from a small bowel follow-through study in a patient with Crohn disease demonstrates the string sign, consistent with narrowing and stricturing. Also, note a sinus tract originating from the medial wall of the terminal ileum and the involvement of the medial wall of the cecum.
Crohn disease. Enterocolic fistula in a patient with Crohn disease. The double-contrast barium enema study demonstrates multiple fistulous tracts between the terminal ileum and the right colon adjacent to the ileocecal valve (so-called double-tracking of the ileocecal valve).
Crohn disease. Active small bowel inflammation in a patient with Crohn disease. This computed tomography scan demonstrates small bowel wall thickening, mesenteric inflammatory stranding, and mesenteric adenopathy.
Crohn disease. This computed tomography scan from a patient with terminal ileal Crohn disease shows an enteroenteral fistula (arrow) between loops of diseased small intestine.
Crohn disease. A teenaged patient with Crohn disease underwent contrast-enhanced, upper gastrointestinal computed tomography scanning with small-bowel follow-through. Several loops of small bowel are in the pelvis. Note the loop of distal bowel with thickened wall (solid arrow), which is contrasted with a less-involved loop of bowel in which the intestinal wall is not thickened at all (dotted arrow).
Crohn disease. This computed tomography scan depicts Crohn disease in the fundus of the stomach.
Crohn disease. This magnetic resonance image demonstrates an inflamed terminal ileum in 10-year-old girl with Crohn disease.
Crohn disease. The histologic image shows granuloma in the mucosa of a patient with Crohn disease.

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Table 1. Characteristics Differentiating Crohn Disease and Ulcerative Colitis

Characteristic
	Crohn Disease	Ulcerative Colitis
Distribution	Entire gastrointestinal tract	Colon only, though gastritis is recognized
Distribution	Skip lesions	Continuous involvement proximally from rectum
Pathology	Full thickness	Mucosa only
Pathology	Granulomas (15-30% in biopsy specimens; 40-60% in surgically resected bowel)	No granulomas
Radiology	Entire gastrointestinal tract	Colon only
	Skip lesions	Continuous involvement proximally from rectum
	Fistulae, abscesses, fibrotic strictures	Mucosal disease only
Cancer risk	Increased	Estimated to be 3% at 10 years, 8% at 30 years, and 18% at 30 years after diagnosis^[47]; risk is higher in patients with primary sclerosing cholangitis and long-standing colitis (> 8-10 y); may be lower in subsequent studies (see Intestinal Manifestations).
Presentation
	Crohn Disease	Ulcerative Colitis
Bleeding	Occasional	Very common
Obstruction	Common	Uncommon
Fistulae	Common	None
Weight loss	Common	Uncommon
Perianal disease	Common	Rare

Table 2. ASCRS Indications for Surgical Management of Crohn Disease

Operative Indication	Factors for Considering Surgery
Failed medical therapy	Presence of disease-related symptoms not responsive to medical management; condition demonstrates an inadequate response When first- and second-line therapies do not induce remission safely in severe disease Before escalating medical therapy in severe or steroid-dependent disease with limited extent (eg, disease with stricturing behavior, patients who have contraindications or risk factors for further medical therapy)
Perforation	Presence of symptoms or signs of free perforation Immediate resection of perforated segment (has a relatively high mortality) After small bowel resection or perforation, other procedures can be performed, as needed (eg, end stoma, diverted or nondiverted anastomosis)
	When large anteroparietal, interloop, intramesenteric, or retroperitoneal abscesses cannot be or are unsuccessfully managed with antibiotics and percutaneous drainage Perform surgical drainage in such cases, with or without resection
	Persistent enteric fistulae and symptoms or signs of localized or systemic sepsis despite appropriate medical management Persistent sepsis warrants excision of the diseased bowel, whether or not an abscess is present For target or “innocent bystander” organs, diseased bowel is typically resected, noninflamed bowel primarily closed, and other internal organs primarily closed or allowed to heal by secondary intention Note: Operative intervention may be avoided for asymptomatic internal fistulae
Obstruction	Presence of symptomatic strictures in regions not amenable or responsive to medical therapy
Obstruction	Presence of asymptomatic colonic strictures that cannot be adequately surveyed by biopsy or cytology brushing
Inflammation	Presence of acute colitis and symptoms or signs of impending or actual perforation (eg, transverse colon distention > 6 cm on abdominal x-ray or persistent gaseous colonic distention indicate toxic megacolon, pneumatosis coli, evolving local peritonitis, multiple organ failure) Presence of severe or fulminant colitis
Inflammation	Worsening acute colitis or failure to significantly improve despite 48-96 hours of appropriate medical therapy
Hemorrhage	Presence of massive hemorrhaging of any origin that (1) cannot be or fails to be managed with interventional or endoscopic techniques and (2) occurs in hemodynamically unstable patients Mesenteric angiography with embolization may be attempted when adequate endoscopic visualization is not possible or when the bleeding source cannot be identified; if this technique is not successful or the patient is hemodynamically unstable, laparotomy with or without intraoperative endoscopy and resection of the responsible bowel segment may be required
Neoplasia	Presence of chronic Crohn disease of the ileocolon or colon (endoscopic surveillance) Presence of adenomatous-appearing polyps (excision)
	Presence of carcinoma, DALM, high-grade dysplasia, multifocal colonic or rectal low-grade dysplasia (resection)
	Presence of chronic Crohn disease of the terminal ileum, ileocolon, or upper GI region
Growth retardation and EIMs	Presence of significant growth retardation in prepubertal patients despite appropriate medical therapy
Growth retardation and EIMs	Presence of symptomatic dermatologic, oral, ophthalmologic, or joint disorders refractory to medical therapy (resection of diseased intestine)
ASCRS = American Society of Colon and Rectal Surgeons; DALM = dysplasia-associated lesion or mass; EIM = extraintestinal manifestation; GI = gastrointestinal. Source: Strong SA, Koltun WA, Hyman NH, Buie WD, for the Standards Practice Task Force of The American Society of Colon and Rectal Surgeons. Practice parameters for the surgical management of Crohn’s disease. Dis Colon Rectum. 2007;50(11):1735-46.^[7]

Table 3. ASCRS Recommendations for Site-Specific Operative Management of Crohn Disease

Site	Surgical Intervention
Terminal ileum, ileocolon, upper GI tract	Resection of the affected bowel for jejunal, proximal ileal, terminal ileal, or ileocolic disease in the absence of existing or impending short bowel syndrome Ileocolostomy or proximal loop ileostomy in cases where there is concern about damage to nondiseased bowel, superior mesenteric vessels, retroperitoneal structures Drainage of any septic foci with later definitive resection (after several months’ delay)
	Strictureplasty for nonphlegmonous jejunal, ileal, or ileocolic strictures in the absence of existing or impending short bowel syndrome Strictureplasty when multiple jejunal or proximal/terminal ileum strictures are present
	Bypass or strictureplasty for symptomatic gastric or duodenal disease
	Endoscopic dilatation of symptomatic, accessible strictures of the intestinal tract Note: Surgical services should be available in case of perforation
Colon	Subtotal or total colectomy with end ileostomy for colonic disease requiring emergency or urgent surgery (via laparoscopic or open approach)
	Segmental or total colectomy with or without primary anastomosis for colonic disease requiring elective surgery
	Total proctocolectomy or proctectomy with stoma creation for rectal disease requiring surgery
ASCRS = American Society of Colon and Rectal Surgeons; GI = gastrointestinal. Source: Strong SA, Koltun WA, Hyman NH, Buie WD, for the Standards Practice Task Force of The American Society of Colon and Rectal Surgeons. Practice parameters for the surgical management of Crohn’s disease. Dis Colon Rectum. 2007;50(11):1735-46.^[7]

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Author

Leyla J Ghazi, MD Assistant Professor, Department of Medicine, Associate Program Director, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine

Leyla J Ghazi, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, Crohn's and Colitis Foundation of America

Disclosure: Nothing to disclose.

Specialty Editor Board

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Chief Editor

Praveen K Roy, MD, MSc Clinical Assistant Professor of Medicine, University of New Mexico School of Medicine

Praveen K Roy, MD, MSc is a member of the following medical societies: Alaska State Medical Association, American Gastroenterological Association

Disclosure: Nothing to disclose.

Acknowledgements

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy