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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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epidemiology and genetics
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
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
a day in clinic
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
your evaluation
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)
ulcerative colitis
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
crohn s disease9
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
uc vs cd
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
laboratory testing
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
panca and asca
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
extraintestinal manifestations
Extraintestinal Manifestations
  • Derm: erythema nodosum, pyoderma gangrenosum
extraintestinal manifestations14
Extraintestinal Manifestations
  • Ocular: episcleritis, anterior uveitis
  • MSK: arthritis, ankylosing spondylitis, sacroiliitis
  • Hepatobiliary: steatosis, cholelithiasis, primary sclerosing cholangitis
toxic megacolon
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
colon cancer
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
treatment of ibd
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
treatment of ibd18
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
treatment of ibd19
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
treatment of ibd20
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
treatment of ibd21
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
treatment of ibd22
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.
treatment of ibd23
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!
treatment of ibd24
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
treatment of ibd25
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
prognosis
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