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Inflammatory Bowel Disease. Michael Tuggy. MD. Epidemiology and Genetics. Prevalence approx. 100/100,000 Incidence 10,000 per year UC=CD, M=W Bimodal distribution, peaks between ages 15-25 and 55-65 Highest incidence in whites of North America and Ashkenazi Jews. Pathogenesis.

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Inflammatory bowel disease l.jpg

Inflammatory Bowel Disease

Michael Tuggy. MD


Epidemiology and genetics l.jpg
Epidemiology and Genetics

  • Prevalence approx. 100/100,000

  • Incidence 10,000 per year

  • UC=CD, M=W

  • Bimodal distribution, peaks between ages 15-25 and 55-65

  • Highest incidence in whites of North America and Ashkenazi Jews


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Pathogenesis

  • 3 theories:

    • Genetic: 10% IBD pt.s with + family hx

    • Infectious vs. Environmental: L. monocytogenes, M. paratuberculosis, stress, smoking, NSAIDs

    • Immunologic: imbalance between pro- and anti-inflammatory cytokines in gut lumen


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A day in clinic…

  • 45 y.o. AA male with painless rectal bleeding. Hx of anxiety and depression, on disability.

  • History of 3-4 years of “hemorrhoids”

  • + Urgency of bowel movement

  • + crampy abdominal pain

  • + diffuse joint pains, no swelling or redness


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Your evaluation?

  • Exam - + stool guaiac, normal rectal exam

    • Small flecks of blood on anoscopy, normal mucosa

    • HEENT – no injection of conjunctiva or sclera

    • MSK – no joint swelling or redness, no edema

    • Labs: CBC – Hct = 42, ESR – 44

  • Colonoscopy - + segment of inflamed bowel about 25 cm up from the pectinate line (5 cm long and circumferential)


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Ulcerative Colitis

  • Superficial mucosal inflammation of colon only

  • Begins at rectum and spreads continuously

  • 30% proctitis, 40% L sided colitis, 30% pancolitis

  • Sxs: bloody diarrhea, fecal urgency, tenesmus, abdominal cramping




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Crohn’s Disease

  • Transmural inflammation of any part of GI tract, presence of “skip” lesions and noncaseating granulomas

  • Rectum often spared

  • 30% small bowel (usually terminal ileum), 40% ileum/colon, 25% colon, 5% stomach/duodenum

  • Sxs: non-bloody diarrhea, weight loss, fever, RLQ pain and/or mass, perianal disease with abscess and/or fistulas


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Continuous/superficial

Colon only w/ rectum

++Rectal bleeding

Rare fistulas/strictures

Surgery curative

“Skip”/Deep

Mouth to anus+rectum

+Rectal bleeding

++fistulas/strictures

Surgery palliative (high rate of recurrence, >50%)

UC vs. CD


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Laboratory testing

  • CBC (high rate of anemia, due to chronic inflamm., blood loss, B12 malabsorption)

  • ESR, CRP often elevated

  • Albumin (often low due to chronic inflamm., blood loss, malabsorption)

  • Stool studies to rule out infection

  • Noncaseating granulomas on biopsy suggest CD


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pANCA and ASCA

  • Antineutrophil cytoplasmic antibodies found in 65% UC and 5-10% CD

  • Antibodies to yeast S. cerevisiae found in 60-70% CD and 10-15% UC

  • 10-20% of pt.s w/ IBD, unable to distinguish btwn UC and CD

  • Combo of -pANCA/+ASCA 50% sens and 97% spec for CD

  • Combo of +pANCA/-ASCA 57% sens and 97% spec for UC


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Extraintestinal Manifestations

  • Derm: erythema nodosum, pyoderma gangrenosum


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Extraintestinal Manifestations

  • Ocular: episcleritis, anterior uveitis

  • MSK: arthritis, ankylosing spondylitis, sacroiliitis

  • Hepatobiliary: steatosis, cholelithiasis, primary sclerosing cholangitis


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Toxic Megacolon

  • Occurs in 1-3% of pt.s w/ IBD

  • Colonic dilatation >6cm and signs of toxicity (fever, hypotension, tachycardia, leukocytosis)

  • High risk of perforation

  • Medical management w/ broad-spectrum antibx, urgent surgical consultation if no response


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Colon Cancer

  • Risk for colon cancer UC=CD

  • Risk factors: disease duration, disease extent, dysplasia on bx, presence of PSC

  • 1-2% risk per year if IBD >10 years

  • Colon cancer not preceded by adenomatous polyps

  • Colonoscopy with surveillance biopsies recommended q1-2 years after disease for 10 years


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Treatment of IBD

  • Aminosalicylates

    • 5-ASA reduces inflammation

    • Sulfasalazine (Azulfadine) oldest/cheapest

    • Newer agents comprised of Mesalamine bound to carrier molecules to prevent degradation in the proximal small bowel (Rowasa, Asacol, Pentasa)

    • Oral, enema, and suppository forms available


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Treatment of IBD

  • Corticosteroids

    • Topical tx w/ Hydrocortisone foam or enemas tried first

    • Systemic tx w/ Prednisone or Methylprednisolone if pt fails topical tx

    • Steroids should not be used to maintain remission, only for acute flares

    • Significant side effects: growth retardation, osteoporosis, HTN, hyperglycemia, cataracts

    • Budesonide recently approved in US, fewer systemic side effects and less adrenal suppression


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Treatment of IBD

  • Immunomodulatory drugs

    • Mercaptopurine, Azathioprine, Methotrexate often used as long-term tx

    • 3-6 month onset of action

    • Significant side effects: bone marrow suppression, pancreatitis, hepatic toxicity


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Treatment of IBD

  • Antibiotics

    • Primarily for treatment of CD, high risk of small intestinal bacterial overgrowth due to enteral fistulas

    • Metronidazole and Ciprofloxacin commonly used, considered to have broad bactericidal activity with immunosuppressive properties


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Treatment of IBD

  • Cyclosporine

    • Used in pt.s with severe UC refractory to corticosteroids

    • Often used as a bridge to surgery or onset of action of immunomodulatory drugs – only has short term benefit.

    • Significant side effects: nephrotoxicity, electrolyte or liver chemistry abnormalities, HTN, paresthesias, anaphylaxis, sz


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Treatment of IBD

  • Biologic therapy

    • Infliximab (Remicade): a chimeric IgG anti-TNF antibody (about as good as steroids in UC).

    • Certolizumab – may be more effective.

    • Antagonizes activity of TNF-alpha, cytotoxic to immune cells, induces T-cell apoptosis

    • Approved for use w/ CD and UC

    • Significant side effects: risk of infusion-related reactions, hypersensitivity reactions, lupus-like syndrome, infections-sepsis.


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Treatment of IBD

  • Other possible txs:

    • Omega-3 FA’s – reduces relapses for patients in remission. (CD)

    • Probiotics may reduce relapses in adults (UC)

      • Lactobacillus, E. coli

      • VSL #3 (induced remission in children AND adults

        • $47 per month!


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Treatment of IBD

  • Surgical tx for UC

    • Total proctocolectomy curative, eliminates risk of colon cancer

    • Required in 25% of pt.s

    • Indications: severe hemorrhage, perforation, carcinoma, fulminant colitis, toxic megacolon not improving with medical tx


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Treatment of IBD

  • Surgical tx for CD

    • >50% of pt.s will require at least one surgery

    • Palliative, >50% recurrence rate at surgical site

    • Indications: fistulas or perianal disease refractory to medical management, intra-abdominal abscess, obstruction related to strictures, carcinoma


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Prognosis

  • Flare-ups and recurrence common

  • Increased recurrence rate with smoking

  • Quality of life an issue as many complications with disease

  • Crohn’s and Colitis Foundation of America www.ccfa.org


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