GASTROENTEROLOGY
INFLAMMATORY BOWEL DISEASE
Definition
• Ulcerative colitis (UC): idiopathic inflammation of the colonic mucosa
• Crohn’s disease (CD): idiopathic transmural inflammation of the GI tract, skip areas
• Indeterminate colitis: in 5–10% of chronic colitis, cannot distinguish UC vs. CD even w/ bx
Epidemiology & pathophysiology (NEJM 2009;361:2066; Gastro 2011;140:1785)
• 1.4 million people in U.S.; prev 1:1000 UC & 1:3000 CD; ↑ incidence in Caucasians, Jews
• Age of onset 15–30 y in UC and CD; CD is bimodal and has second peak at 50–70 y
• Smokers at ↑ risk for CD, whereas nonsmokers & former smokers at ↑ risk for UC
• Genetic predisposition + disruption of intestinal barrier (epithelial or ↓ defenses) ± Δ in gut microbiota → acute inflam w/o immune downregulation or tolerance → chronic inflam
ULCERATIVE COLITIS (NEJM 2011;365:1713; Lancet 2012;380:1606)
Clinical manifestations
• Grossly bloody diarrhea, lower abdominal cramps, urgency, tenesmus
• Severe colitis (15%): progresses rapidly over 1–2 wk with ↓ Hct, ↑ ESR, fever, hypotension, >6 bloody BMs per day, distended abdomen with absent bowel sounds
• Extracolonic (>25%): erythema nodosum, pyoderma gangrenosum, aphthous ulcers, uveitis, episcleritis, thromboembolic events (esp. during a flare; Lancet 2010;375:657), AIHA, seroneg arthritis, chronic hepatitis, cirrhosis, PSC (↑ risk cholangio CA, CRC)
Diagnosis
• Colonoscopy: involves rectum (95%) & extends proximally and contiguously within colon
• Classify by location: proctitis (25–55%), left-sided colitis (50–70%) and pancolitis (20%)
• Appearance: granular, friable mucosa with diffuse ulceration; pseudopolyps
• Microscopy: superficial chronic inflammation; crypt abscesses & architectural distortion
Complications
• Toxic megacolon (5%): colon dilatation (≥6 cm on KUB), colonic atony, systemic toxicity, & ↑ risk of perf. Rx w/ IV steroids & broad-spectrum abx; surgery if fail to improve w/in 48–72 h
• Stricture (5%): occurs in rectosigmoid after repeated episodes of inflammation
Prognosis
• 50% of Pts in remission at any given time; intermittent exacerbations in 90%; continual active disease in ~18%. Rate of colectomy at 10 y is 24%.
• Mortality rate of severe UC flare is <2%, & overall life expectancy in UC = non-UC Pts
CROHN’S DISEASE (Lancet 2012;380:1590)
Clinical manifestations
• Abdominal pain, fever, malaise, wt loss
• Mucus-containing, nongrossly bloody diarrhea; N/V, bloating, obstipation
• ↓ albumin, ↑ ESR/CRP, ↓ Hct (due to Fe, B12, folate deficiency; chronic inflammation)
• Extracolonic as in UC
Diagnosis
• EGD/colonoscopy + small bowel imaging (eg, video capsule endoscopy [if no stricture] or CT/MR-enterography); CD can affect any portion of GI tract with skip lesions
• Classify by location: small bowel (47%), ileocolonic (21%), colonic (28%); upper tract rare
• Appearance: nonfriable mucosa, cobblestoning, aphthous ulcers, deep & long fissures
• Microscopy: transmural inflammation with mononuclear cell infiltrate, noncaseating granulomas (seen in <25% of mucosal biopsies), fibrosis, ulcers, fissures
Complications
• Perianal disease: fissures, fistulas, perirectal abscesses (up to 30% of Pts)
• Stricture: small bowel, postprandial abd pain; can lead to complete SBO
• Fistulas: perianal, enteroenteric, rectovaginal, enterovesicular, enterocutaneous
• Abscess: fever, tender abd mass, ↑ WBC; steroids mask sx, ∴ need high-level suspicion
• Malabsorption: ileal disease/resection: ↓ bile acids abs → gallstones; ↓ fatty acid abs → Ca oxalate kidney stones; ↓ fat soluble vitamin abs → vit Δ deficiency → osteopenia
Prognosis
• Variable at 1 y: ~50% in remission, ~20% flared, ~20% low activity, ~10% chronic active
• At 20 y, majority will have required some surgery; overall life expectancy is slightly ↓
MANAGEMENT (Gastro 2011;140:1827)
Initial evaluation
• H&P (✓ for intestinal & extraintestinal manifestations) and endoscopy as above
• Laboratory: ESR, CRP, CBC, LFTs, Fe, B12, folate, vit D. Fecal calprotectin appears useful for Ddx IBD vs. IBS & may predict IBD flare (Infl Bowel Dis 2012;18:2218).
• Exclude other etiologies: infectious/ischemic colitis, med adverse effect, intestinal lymphoma/carcinoma, colon cancer, IBS, vasculitis, Behçet’s, celiac disease, SIBO
• Rule out infection before treating with immunosuppressants and biologics
Goals of treatment
• Avoid NSAIDs (both UC and CD)
• Induce remission of acute flare → maintain remission; mucosal healing 1° goal
• Convention has been step up Rx (least → most toxic). Recent shift to early and/or combined immunomodulation to improve disease outcome (Lancet 2008;371:660; NEJM 2010;362:1383).
Complications of therapy (Clin Gastro Hep 2009;7:874)
• Anti-TNFα: reactivation TB; must doc 
PPD prior to Rx. Exclude viral hepatitis. Small ↑’d risk of NHL. Other: infusion rxn; lupus-like rxn, psoriasis, MS, CHF.
• 6MP/AZA: BM suppression, lymphoma, pancreatitis, hepatitis; ✓ TPMT genotype prior to dosing to ↓ risk of generation of toxic metabolites
• 5-ASA: diarrhea, abd pain, pancreatitis. If sx, consider 3-d holiday.
Cancer screening (Gastro 2010;138:738)
• Colon cancer: risk in UC ~2% at 10 y, ~8% at 20 y, ~18% at 30 y. Similar for colonic CD, plus risk of small bowel cancer as well. Dysplasia best marker for risk. Other risk factors include: PSC, 
FHx, greater extent of disease, stricture, & pseudopolyps.
• Surveillance: colonoscopy w/ random bx 8 y after dx to eval for dysplasia, q1–3y thereafter based on risk factors. If high-grade dysplasia or dysplasia assoc. lesion/mass → colectomy. Chemoprophylaxis: 5-ASA & ursodeoxycholic acid (if PSC) ? beneficial (AJG 2011;106:731; Aliment Pharmacol Ther 2012;35:451).