Gastroenterology Book

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Crohn's DiseaseAka: Terminal Ileitis, Regional Enteritis, Crohn's Colitis

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  1. See Also
    1. Inflammatory Bowel Disease
    2. Gynecologic Manifestations of Crohn's Disease
  2. Epidemiology
    1. Incidence: 1-10 cases per 100,000
    2. Peak onset: 15-25 years (onset up to age 40)
    3. Women more often affected than men
    4. Familial aggregation
      1. First degree relative confers 2-4 fold risk
      2. Second degree relative confers less increased risk
  3. Pathophysiology
    1. Etiology unknown
    2. Related genetic mutation: NOD2 (Chromosome 16 in IBD1)
      1. Associated with increased Crohn's relative risk
        1. One NOD 2 mutation: 2 fold relative risk
        2. Two NOD 2 mutations: 15-35 fold relative risk
      2. Proposed mechanism
        1. Related to defective bacterial sensing by Monocytes
        2. Results in hyper-immune response to bacterial LPS
      3. References
        1. Ahmad (2002) Gastroenterology 122:854
    3. Chronic granulomatous inflammation
      1. Transmural extension to entire bowel wall
      2. Ulcerative Colitis only affects mucosa
    4. Effects entire Gastrointestinal tract, mouth to anus
      1. Distal ileum and proximal colon most often involved
      2. Isolated colonic involvement in 25% of cases
    5. Irregular involvement ("Skip lesions")
  4. Symptoms
    1. Fever
    2. Weight loss
    3. Fatigue
    4. Nausea
    5. Anorexia
    6. Abdominal Pain (Low abdominal ache or cramp)
    7. Diarrhea (85%)
    8. Rectal bleeding
      1. Much less prominent than in Ulcerative Colitis
      2. Non-bloody Diarrhea is typical for Crohn's Disease
  5. Signs
    1. See Gynecologic Manifestations of Crohn's Disease
    2. Stool Occult Blood positive
    3. Anal Disease(20%)
      1. Perirectal fistula
      2. Anal Skin Tag
      3. Anal Ulceration or Anal Fissure
      4. Perirectal Abscess
    4. Right Lower Quadrant abdominal palpable mass (common)
    5. Extra-abdominal manifestations
      1. Similar to manifestations in Ulcerative Colitis
  6. Signs: Extra-abdominal Manifestations (10% Incidence)
    1. Similar findings in Ulcerative Colitis
      1. See Ulcerative Colitis extraintestinal manifestations
    2. Minimal increased Colon Cancer risk
  7. Labs: Complete Blood Count (CBC)
    1. Mild Anemia
      1. Chronic blood loss
    2. Mild Leukocytosis
      1. Mild Leukocytosis
        1. Crohn's disease exacerbation
      2. Marked Leukocytosis
        1. Severe colitis
        2. Toxic Megacolon
        3. Intra-abdominal abscess
  8. Diagnosis: Colonoscopy with Ileoscopy
    1. Focal Ulcerations: aphthous, stellate, or linear
    2. Skip areas
    3. Rectal sparing
    4. Cobblestone appearance
    5. Strictures
  9. Differential Diagnosis
    1. See Inflammatory Bowel Disease
  10. Imaging
    1. Small Bowel follow-through
    2. Barium Enema with retrograde terminal ileum filling
      1. May show classic thumbprinting
        1. Defect protrudes into lumen
  11. Management
    1. General
      1. No immunosuppressants if infectious colitis possible
      2. Consider concurrent vitamin supplementation
        1. Folic Acid
        2. Vitamin B12
        3. Fat soluble vitamins
        4. Calcium Supplementation
    2. Mild to Moderate (Weight loss <10%, tolerating P.O.)
      1. Step 1: Start Salicylate (5-ASA preparations)
        1. Mesalamine (Rowasa, Pentasa, Asacol) or
        2. Sulfasalazine (Azulfidine)
      2. Step 2: Anaerobic agent if Salicylate not effective
        1. Metronidazole 10-20 mg/kg/day or
        2. Ciprofloxacin 1 gram/day
      3. Step 3: Treat as moderate to severe if refractory
      4. Step 4: Maintenance therapy for remission
        1. Mesalamine (Rowasa) 3.2 to 4 grams per day
    3. Moderate to Severe (Significant systemic symptoms)
      1. Step 1: Systemic Corticosteroids
        1. Prednisone 40 mg PO qd for 8-12 weeks
          1. Consider Budesonide instead of Prednisone
          2. Budesonide (Entocort) has minimal absorption
        2. Methylprednisolone IV for severe fulminant disease
        3. Taper once control is achieved
          1. Initial: Taper by 5-10 mg weekly
          2. Below 20 mg: Taper by 2.5 to 5 mg weekly
      2. Step 2: Consider immunosuppresant for maintenance
        1. Start while tapering Corticosteroid off
        2. Azathioprine 2-2.5 mg/kg/day or
        3. 6-Mercaptopurine 1.5 mg/kg/day
      3. Step 3: Infliximab (Remicade)
        1. Indicated if refractory to Steps 1 and 2
      4. Step 4: Consider other immunomdoulator if refractory
        1. Methotrexate 25 mg weekly
        2. Tacrilimus and Cyclosporine have also been used
    4. References
      1. Knutson (2003) Am Fam Physician 68(4):707
      2. Wall (1999) Pharmacotherapy 19:1138
      3. Hanauer (2003) Gastroenterology 125:906
  12. Management: Available preparations
    1. Similar to Ulcerative Colitis Management
    2. Antiinflammatory agents
      1. Corticosteroids
      2. Oral 5 ASA preparations
        1. Not effective for small bowel Crohn's Disease
        2. Sulfasalazine (Azulfidine)
          1. Inexpensive but significant side effects
        3. Olsalazine (Dipentum)
          1. Diarrhea commonly occurs
        4. Mesalamine (Asacol, Pentasa, Canasa, Rowasa)
        5. Balsalazide (Colazal)
      3. Immunosuppressive agents
        1. 6-Mercaptopurine
        2. Azathioprine
        3. Methotrexate
    3. Fish Oil (Enteric Coated)
      1. Dose: 2.7 g qd
      2. Marked reduction in relapse in 1 year (28% vs 69%)
      3. Serum markers of inflammation also reduced
      4. Reference
        1. Belluzzi (1996) N Engl J Med 334:1557
    4. Metronidazole (Flagyl)
      1. Effective for Crohn's Disease and perianal disease
    5. Monoclonal Antibody
      1. Infliximab (Remicade): Anti-tumor necrosis factor
      2. Natalizumab: Alpha 4 integrin Antibody (experimental)
    6. Other agents currently being researched
      1. Thalidomide (not used in women who can conceive)
      2. Mycophenalate (Cellcept)
      3. Tacrolimus
      4. IL-10, 11 and 18
      5. Probiotics
  13. Management: Intestinal resection (75% of patients)
    1. Efficacy
      1. Not Curative (unlike for Ulcerative Colitis)
      2. Symptoms nearly always recur after surgery
        1. Five years: 30% symptoms recur
        2. Ten years: 50% symptoms recur
        3. Fifteen years: 70% symptoms recur
      3. Surgery associated with improved quality of life
        1. Delaney (2003) J Am Coll Surg 196:714
    2. Indications
      1. Colon obstruction
      2. Intractable pain or other symptoms
  14. Complications
    1. Colon Cancer
      1. Much lower risk than with Ulcerative Colitis
    2. Rectal disease (50% of Crohn's Disease patients)
      1. Rectal Fissure
      2. Rectocutaneous fistula
      3. Perirectal Abscess
  15. Prognosis: Risk for intestinal resection
    1. Poor prognostic indicators (relapse)
      1. Crohn's involving small intestine
      2. Perianal fistulas
    2. Favorable prognostic indicators
      1. Ileocecal disease
      2. Colorectal disease
      3. Relapse-free period of 10 years
    3. References
      1. Bernell (2000) Ann Surg 231:38
  16. Monitoring: Colon Cancer screening
    1. Annual Colonoscopy after 15 years of disease
  17. References
    1. Botoman (1998) Am Fam Physician 57(1):57
    2. Moses (1998) Postgrad Med 103(5):77
    3. Sands (2000) Gastroenterology 118(2 Suppl 1):S68
    4. Stein (2001) Surg Clin North Am 81(1):71
      1. Entire issue devoted to Crohn's Disease

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