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Crohn Disease

Crohn Disease is a topic covered in the 5-Minute Clinical Consult.

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Basics

Description

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

  • Hallmark features of Crohn disease (CD)
    • Transmural inflammation resulting in fibrosis, stricture, and fissures with sinus tract, abscess, or fistula formation
    • Noncaseating granulomas (30%), crypt abscesses
    • Skip lesions: segmental distribution of disease; may affect multiple bowel segments, interspersed with areas of normal mucosa; can also be continuous, mimicking ulcerative colitis (UC)
    • Diverse presentations: ileocolitis (50%); isolated colitis (20%) are most common.
  • 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/adhesions and/or fistulae.

Epidemiology

Incidence
  • 8 to 15 cases/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

Prevalence
U.S. adults: 100 to 200 cases/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 fluid absorption; bile salt malabsorption in inflamed ileum, with steatorrhea, bacterial overgrowth
  • Multifactorial: Genetics, environmental triggers, commensal microbial antigens, and immunologic abnormalities result in inflammation and tissue injury.

Genetics

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 different genes associated with IBD

  • Mutations in susceptibility loci
    • Ileal CD: IBD1 gene (chromosome 16)
    • Early-onset CD (age ≤15 years): mutations in 5q31 to 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
    • Tissue inflammation may result from increased secretion of cytokines.

Commonly Associated Conditions

  • Extraintestinal manifestations
    • Arthritis (20%): seronegative, primarily involving large joints; axial arthritis or 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
    • 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, sclerosing cholangitis, rectovaginal fistula

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Citation

Stephens, Mark B., et al., editors. "Crohn Disease." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116824/all/Crohn_Disease.
Crohn Disease. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116824/all/Crohn_Disease. Accessed April 18, 2019.
Crohn Disease. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116824/all/Crohn_Disease
Crohn Disease [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 18]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116824/all/Crohn_Disease.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Crohn Disease ID - 116824 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116824/all/Crohn_Disease PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -