Crohn Disease

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Basics

Description

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

  • Hallmark features of Crohn disease (CD)
    • Transmural inflammation which can result in fibrotic strictures, fistulas, fissures, or abscesses
    • Noncaseating granulomas (30%)
    • Skip lesions: diseased mucosa interspersed with normal mucosa; can 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, aphthous ulcers
    • Perianal disease (pain, anal fissures, perirectal abscess) may precede intestinal disease.
  • Developed disease
    • Mucosal cobblestoning, luminal stenosis, creeping fat, strictures, or fistula
    • May present as wasting illness or anorexia

Epidemiology

Incidence
  • 3 to 20 cases per 100,000 person-years in North America; incidence rising globally
  • Bimodal age distribution: Predominant age is 15 to 30 years, with a second smaller peak at 50 to 80 years.
  • Women slightly more affected than men; increased incidence in northern climates
  • Increased risk in whites versus nonwhites: 2- to 5-fold

Prevalence
247 cases per 100,000 persons

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.

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.
  • 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, or protein
  • Salmonella or Campylobacter increases risk of developing IBD.
  • Clostridioides difficile infection may trigger flare and make treatment more difficult.

Commonly Associated Conditions

  • Extraintestinal manifestations
    • Arthritis (20%): seronegative, small and large joints (ankylosing spondylitis [AS] or sacroiliitis [SI], associated with HLA-B27)
    • Skin disorders (10%): erythema nodosum, pyoderma gangrenosum, psoriasis
    • Ocular disease (5%): uveitis (associated with HLA-B27), 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 (PSC) (5%)
    • Autoimmune hemolytic anemia
  • Conditions associated with increased disease activity
    • Peripheral arthropathy (not SI and AS)
    • Episcleritis (not uveitis)
    • Oral aphthous ulcers and erythema nodosum
  • Complications: GI bleed, toxic megacolon, bowel obstruction, bowel perforation, peritonitis, malignancy, intra-abdominal fistula, perianal disease

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Basics

Description

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

  • Hallmark features of Crohn disease (CD)
    • Transmural inflammation which can result in fibrotic strictures, fistulas, fissures, or abscesses
    • Noncaseating granulomas (30%)
    • Skip lesions: diseased mucosa interspersed with normal mucosa; can 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, aphthous ulcers
    • Perianal disease (pain, anal fissures, perirectal abscess) may precede intestinal disease.
  • Developed disease
    • Mucosal cobblestoning, luminal stenosis, creeping fat, strictures, or fistula
    • May present as wasting illness or anorexia

Epidemiology

Incidence
  • 3 to 20 cases per 100,000 person-years in North America; incidence rising globally
  • Bimodal age distribution: Predominant age is 15 to 30 years, with a second smaller peak at 50 to 80 years.
  • Women slightly more affected than men; increased incidence in northern climates
  • Increased risk in whites versus nonwhites: 2- to 5-fold

Prevalence
247 cases per 100,000 persons

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.

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.
  • 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, or protein
  • Salmonella or Campylobacter increases risk of developing IBD.
  • Clostridioides difficile infection may trigger flare and make treatment more difficult.

Commonly Associated Conditions

  • Extraintestinal manifestations
    • Arthritis (20%): seronegative, small and large joints (ankylosing spondylitis [AS] or sacroiliitis [SI], associated with HLA-B27)
    • Skin disorders (10%): erythema nodosum, pyoderma gangrenosum, psoriasis
    • Ocular disease (5%): uveitis (associated with HLA-B27), 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 (PSC) (5%)
    • Autoimmune hemolytic anemia
  • Conditions associated with increased disease activity
    • Peripheral arthropathy (not SI and AS)
    • Episcleritis (not uveitis)
    • Oral aphthous ulcers and erythema nodosum
  • Complications: GI bleed, toxic megacolon, bowel obstruction, bowel perforation, peritonitis, malignancy, intra-abdominal fistula, perianal disease

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