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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 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.
- 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
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.
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
- 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