Small intestine & ampulla

Inflammatory disorders

Crohn's disease

Editorial Board Member: Aaron R. Huber, D.O.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
Alaaeddin Alrohaibani, M.D.
Mary Wong, M.D., M.B.A.

Last author update: 6 January 2022
Last staff update: 8 December 2023

Copyright: 2003-2024,, Inc.

PubMed Search: Crohn's disease

Alaaeddin Alrohaibani, M.D.
Mary Wong, M.D., M.B.A.
Page views in 2023: 19,121
Page views in 2024 to date: 6,699
Cite this page: Alrohaibani A, Makhoul E, Wong M. Crohn's disease. website. Accessed April 14th, 2024.
Definition / general
  • Idiopathic chronic inflammatory condition that may involve any part of the upper and lower gastrointestinal tract
  • Tends to involve the distal ileum and proximal large intestine
Essential features
  • Diagnostic criterion: segmental disease, transmural inflammation, noncaseating granulomas, deep fissuring ulcers, ileal involvement
  • Distal ileum is the most commonly involved part of the small intestine
  • Risk of colorectal carcinoma increases with duration and extent of disease
  • Inflammatory bowel disease (IBD), Crohn's disease (CD), Crohn's
ICD coding
  • ICD-10: K50 - Crohn's disease of the small intestine
  • May occur anywhere in the GI tract, from oral cavity to perianal area
  • Terminal ileum is the most commonly affected site (80%), with 33% having ileitis alone
  • 50% of patients have ileocolitis (involvement of both terminal ileum and colon)
  • About 20% of patients have limited colon disease, of which only half will have rectal sparing
  • 33% of patients have perianal disease
  • 5 - 15% can have oral gastroduodenal involvement, with significantly fewer patients developing esophageal and proximal small intestinal involvement
  • Reference: UpToDate: Clinical Manifestations, Diagnosis, and Prognosis of Crohn Disease in Adults [Accessed 22 October 2021]
  • Unclear, as overall pathogenesis remains poorly understood
  • Inappropriate immune response has been implicated, with vast literature delineating the role of both host and microbial factors in its pathogenesis (Nat Rev Immunol 2008;8:458)
  • Dysregulation in epithelial barriers, immune cells and secreted mediators have been shown to play a role (J Clin Invest 1983;72:142, Gut 2013;62:1734, Gastroenterology 2009;136:1261)
  • Microbiota may induce inflammatory bowel disease if a concurrent underlying genetic defect is present (Nature 2012;491:119)
  • More than 200 loci have been identified, many of which are shared among both Crohn's disease and ulcerative colitis (UC), indicating the overlap between these 2 entities; these loci lead to modulation of protein expression, rather than amino acid change, which supports that each locus confers an increased risk of developing Crohn's disease (Nature 2012;491:119, Inflamm Bowel Dis 2015;21:1166)
Clinical features
  • Abdominal pain, diarrhea (bloody or nonbloody), fatigue and weight loss are classic symptoms (Am J Gastroenterol 2000;95:3458, Clin Gastroenterol Hepatol 2006;4:614, Am J Gastroenterol 2018;113:481)
  • Patients with distal terminal ileal involvement can present with right lower quadrant abdominal pain
  • Distal ileum is the most commonly involved site
  • Given the transmural inflammation nature in Crohn's disease, some advanced conditions can present with bowel obstruction due to fibrotic stricture formation
  • Extraintestinal manifestations and associations include (Inflamm Bowel Dis 2011;17:471, J Crohns Colitis 2016;10:239, J Crohns Colitis 2019;13:541):
    • Joint and bones: arthropathies and osteoporosis
    • Eye: iritis, uveitis and episcleritis
    • Skin: erythema nodosum, pyoderma gangerosum, Sweet syndrome
    • Liver: primary sclerosing cholangitis, cholelithiasis
    • Kidney: nephrolithiasis
    • Lung: asthma, bronchiectasis, chronic bronchitis, interstitial lung disease, bronchiolitis obliterans with organizing pneumonia, sarcoidosis, necrobiotic lung nodules and pulmonary infiltrates
  • Multimodality approach with clinicopathologic correlation and exclusion of other differential diagnoses
  • Colonoscopy with ileoscopy, esophagogastroduodenoscopy (EGD) and endoscopic ultrasound are helpful in evaluating Crohn's disease as well as differentiating Crohn's disease from ulcerative colitis (Aliment Pharmacol Ther 2014;39:823)
  • Endoscopy also plays a pivotal role in evaluating the severity of the disease and surveillance of neoplasms
  • Characteristic endoscopic findings of Crohn's disease include (Med Clin North Am 1990;74:51, Gastrointest Endosc 1977;23:150, Gastrointest Endosc 1984;30:167):
    • Aphthous ulcers
    • Linear and serpiginous ulcers (giving a cobblestone appearance)
    • Skip lesions
    • Fistulas and strictures
    • Isolated terminal ileum involvement, uninvolved rectum
  • May be normal
  • High white blood cells, anemia, elevated C reactive protein, electrolyte abnormalities, vitamin D deficiency and vitamin B12 deficiency may be found
  • Elevated fecal calprotectin or lactoferrin (stool inflammatory markers), which can be used as a screening tool and determine the need for endoscopy (BMJ 2010;341:c3369)
Radiology description
Prognostic factors
  • Disease course and severity may vary but is usually chronic and intermittent
  • 50% of patients experience intestinal complications (strictures, fistula and abscess) 20 years after diagnosis (Intest Res 2015;13:19)
  • Involvement of terminal ileum, ileocolonic and upper GI have higher risk of developing complications (Gastroenterology 2010;139:1147)
  • Smoking, age < 40 years, perianal or rectal involvement and steroid requiring conditions are risk factors for disease progression (Gastroenterology 2006;130:650, Gut 2012;61:1140)
  • Carcinoma may develop in longstanding disease with cumulative risk of 2.9% at 10 years, 5.6% at 20 years and 8.3% at 30 years after Crohn's disease diagnosis (World J Gastroenterol 2014;20:9872)
    • 2 most important risk factors: duration and extent of disease
Case reports
Clinical images

Images hosted on other servers:

Longitudinal ulcers,
cobblestone appearance
and aphthous ulcers

Lymphoid follicles with red ring sign

Gross description
Gross images

Contributed by Elias Makhoul, D.O.

Small intestine with ulcer

Creeping fat



Images hosted on other servers:
Terminal ileum: mucosal (inflammatory) pseudopolyps

Terminal ileum: mucosal (inflammatory) pseudopolyps

Terminal ileum: cobblestone change

Thickened bowel wall and fat wrapping

Microscopic (histologic) description
  • Features of activity: active inflammation with cryptitis, crypt abscess and ulceration
  • Features of chronicity: pyloric gland metaplasia, architectural distortion, crypt loss, crypt atrophy, basal lymphoplasmacytosis, fibrosis and stromal hypertrophy
  • Skip lesions (portions of normal appearing small intestine with scattered areas of disease)
  • Transmural lymphoid aggregates (beading or rosary pattern)
  • Noncaseating granulomas (not related to crypt injury)
  • Deep fissuring ulcers
  • Aphthous ulcers (small ulcers occurring over lymphoid aggregates)
  • Obliterative muscularization of submucosa (Arch Pathol Lab Med 2001;125:1331)
  • Dysplasia (low or high grade) and carcinoma may be present in patients with longstanding disease
  • Note: Some features of Crohn’s disease may also be seen in fulminant, untreated ulcerative colitis, such as aphthous ulcers, deep ulceration with transmural inflammation and superficial fissuring ulcers
  • References: Circulation 1965;32:332, Histopathology 2012;60:1034, Virchows Arch 2014;464:511, Virchows Arch 2018;472:81, Mod Pathol 2015;28:S30
Microscopic (histologic) images

Contributed by Mary Wong, M.D., M.B.A.

Transmural inflammation with granulomas

Noncaseating granulomas

Pyloric metaplasia

Ulceration with overlying stricture

Virtual slides

Images hosted on other servers:

Gastritis with granulomatous inflammation

Molecular / cytogenetics description
Sample pathology report
  • Terminal ileum and cecum, ileocecectomy:
    • Segment of terminal ileum with features consistent with history of Crohn's disease, including:
      • Moderately to markedly active chronic ileitis with patchy ulcerations
      • Fibromuscular stricture with decreased luminal circumference
      • Scattered noncaseating granulomas
    • No dysplasia identified
    • Immunostain for CMV is negative
Differential diagnosis
  • Ulcerative colitis:
    • Small bowel typically not involved except in case of backwash ileitis
    • Absence of granulomas and segmental disease (these features are more specific for CD)
    • Typically superficial inflammation with lack of transmural lymphoid aggregates
      • Deep or serosal based lymphoid aggregates may be seen adjacent to ulceration in both UC and CD
    • Absence of deep fissuring ulceration
      • Superficial fissures may be seen in fulminant disease
  • Infectious enteritis:
    • May show overlapping features of inflammatory bowel disease
    • Correlation with microbiologic studies is necessary for exclusion
  • Drug associated enteritis (e.g. NSAIDs):
    • Patchy active inflammation
    • Tends to lack significant features of chronicity
  • Behçet disease:
    • Form of vasculitis
    • Recurrent aphthous stomatitis and genital ulcers may be present
  • Ischemia:
    • Withering crypts and hyalinization of lamina propria
  • References: Ann Gastroenterol 2011;24:271, Curr Gastroenterol Rep 2010;12:249
Board review style question #1

A 30 year old woman presents with abdominal pain and bloody diarrhea. The patient is refractory to medical management and a resection of the small intestine is performed. What diagnosis is most consistent with the histological findings?

  1. Backwash ileitis
  2. Crohn’s disease
  3. Drug associated enteritis
  4. Infections enteritis
Board review style answer #1
B. Crohn's disease

Comment Here

Reference: Crohn's disease
Board review style question #2
In fulminant disease, sometimes it is difficult to differentiate between Crohn's disease and ulcerative colitis. Which one of the following features can be seen in both fulminant, untreated Crohn's disease and ulcerative colitis?

  1. Deep fissuring ulceration
  2. Deep or serosal based lymphoid aggregates adjacent to ulceration
  3. Granulomas
  4. Segmental disease
Board review style answer #2
B. Deep or serosal based lymphoid aggregates adjacent to ulceration

Comment Here

Reference: Crohn's disease
Back to top
Image 01 Image 02