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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
- 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