Inflammatory Bowel Disease

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Inflammatory Bowel Disease

• Michael Tuggy. MD

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Epidemiology and Genetics

• Prevalence approx. 100/100,000
• Incidence 10,000 per year
• UCCD, MW
• 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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Ulcerative Colitis
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Crohns Disease
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Crohns 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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UC vs. CD

• Continuous/superficial
• Colon only w/ rectum
• Rectal bleeding
• Rare fistulas/strictures
• Surgery curative

• Skip/Deep
• Mouth to anusrectum
• Rectal bleeding
• fistulas/strictures
• Surgery palliative (high rate of recurrence, gt50)

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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 gt6cm 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 UCCD
• Risk factors disease duration, disease extent,
  dysplasia on bx, presence of PSC
• 1-2 risk per year if IBD gt10 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 FAs 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
• gt50 of pt.s will require at least one surgery
• Palliative, gt50 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
• Crohns and Colitis Foundation of America
  www.ccfa.org

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