Crohn Disease

Description

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

• Hallmark features of Crohn disease (CD)
  • Transmural inflammation that can result 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.

Epidemiology

• 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
• Increased risk in Ashkenazi Jews: 3- 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.

• 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.
• 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) 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