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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

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    1. Inflammatory Bowel Disease Michael Tuggy. MD

    2. 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

    3. 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

    4. 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

    5. 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)

    6. 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

    7. Ulcerative Colitis

    8. Crohn’s Disease

    9. 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

    10. 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

    11. 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

    12. 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

    13. Extraintestinal Manifestations • Derm: erythema nodosum, pyoderma gangrenosum

    14. Extraintestinal Manifestations • Ocular: episcleritis, anterior uveitis • MSK: arthritis, ankylosing spondylitis, sacroiliitis • Hepatobiliary: steatosis, cholelithiasis, primary sclerosing cholangitis

    15. 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

    16. 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

    17. 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

    18. 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

    19. 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

    20. 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

    21. 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

    22. 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.

    23. 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!

    24. 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

    25. 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

    26. 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