Crohn Disease

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A chronic, relapsing inflammatory GI tract disorder, most commonly involving the terminal ileum (80%)

  • Hallmark features of Crohn disease (CD)
    • Transmural inflammation resulting in fibrotic, strictures, fistulae, fissures, or abscesses
    • Noncaseating granulomas (30%)
    • Skip lesions: segmental disease distribution interspersed with normal mucosa; can also be continuous, mimicking ulcerative colitis (UC)
    • Diverse presentations: ileitis (1/3), ileocolitis (1/3); isolated colitis (1/3)
  • Early disease
    • Ulcerations: focal lesions with surrounding edema, resembling aphthous ulcers
    • Perianal disease (pain, anal fissures, perirectal abscess) may precede intestinal disease.
    • May present as wasting illness or anorexia
  • Developed disease
    • Mucosal cobblestoning; luminal stenosis; creeping fat; fissures between mucosal folds result in strictures or fistulae.


  • 8 to 15 cases per 100,000 North American adults; incidence rising in North America and Western Europe
  • Bimodal age distribution: Predominant age is 15 to 25 years, with a second smaller peak at 50 to 70 years.
  • Women slightly more affected than men; increased incidence in northern climates
  • Increased risk in whites versus nonwhites: 2- to 5-fold
  • Increased risk in Ashkenazi Jews: 3- to 5-fold

U.S. adults: 100 to 200 cases per 100,000

Etiology and Pathophysiology

  • General: Clinical manifestations result from activation of inflammatory cells and subsequent tissue injury.
  • Mechanism of diarrhea: excess fluid secretion and impaired absorption; bile salt malabsorption in inflamed ileum; steatorrhea; bacterial overgrowth
  • Multifactorial: Genetics, environmental triggers, commensal microbial antigens, and immunologic abnormalities result in inflammation and tissue injury.

  • 15% of CD patients have a first-degree relative with inflammatory bowel disease (IBD); first-degree relative of an IBD patient has 3- to 30-fold increased risk of developing IBD by age 28 years; >200 genes associated with IBD; >71 CD genes
  • Mutations in susceptibility loci
    • Ileal CD: IBD1 gene, NOD2
    • Early-onset CD (age ≤15 years): 5q31–33 (IBD5), 21q22, and 20q13
    • Extraintestinal manifestations of CD: mutations in HLA-A2, HLA-DR1, HLA-DQw5
    • Others: IL-10, IL-23 receptors, ATG16L1, IRGM
  • Associated genetic syndromes: Turner and Hermansky-Pudlak syndromes, glycogen storage disease type 1b

Risk Factors

  • Environmental factors
    • Cigarette smoking doubles the risk of CD; tobacco cessation reduces flares and relapses.
    • Dietary factors: higher incidence if diet high in refined sugars, animal fat, protein (meat, fish)
    • Salmonella or Campylobacter increases risk of developing IBD.
    • Clostridium difficile infection may trigger flare and make treatment more difficult.
  • Immunologic abnormalities: an aggressive immune response against commensal enteric bacteria
    • Tumor necrosis factor (TNF): upregulation of inflammatory Th1 cytokines

Commonly Associated Conditions

  • Extraintestinal manifestations
    • Arthritis (20%): seronegative, small and large joints; ankylosing spondylitis (AS) and sacroiliitis (SI)
    • Skin disorders (10%): erythema nodosum, pyoderma gangrenosum, psoriasis
    • Ocular disease (5%): uveitis, iritis, episcleritis
    • Kidney stones: calcium oxalate stones (from steatorrhea and diarrhea) or uric acid stones (from dehydration and metabolic acidosis)
    • Fat-soluble vitamin deficiency (A, D, E, K)
    • Osteopenia and osteoporosis; hypocalcemia
    • Hypercoagulability: venous thromboembolism prophylaxis essential in hospitalized patients
    • Gallstones: cholesterol stones resulting from impaired bile acid reabsorption
    • Primary sclerosing cholangitis (5%): more common in men with UC; asymptomatic, elevated alkaline phosphatase as marker; increased colon cancer risk (annual colonoscopy)
    • Autoimmune hemolytic anemia
  • Conditions associated with increased disease activity
    • Peripheral arthropathy (not SI and AS)
    • Episcleritis (not uveitis)
    • SI, AS, and uveitis are associated with HLA-B27.
    • Oral aphthous ulcers and erythema nodosum
    • Other complications: GI bleed, toxic megacolon, bowel perforation, peritonitis, malignancy, rectovaginal fistula

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