Ulcerative Colitis

Aka: Ulcerative Colitis

1. Epidemiology
   1. Most common cause of chronic colitis
   2. Incidence: 2-7 cases per 100,000 per year
   3. Prevalence: 250,000 to 500,00 persons affected in United States
   4. Onset
      1. First peak onset at age 15-25 years (up to age 40 years)
      2. Second peak onset occurs after age 50 years
   5. Gender: Men and women affected equally
   6. Family History confers 10 fold risk
      1. Ashkenazi Jewish population afflicted more often
   7. Less common in ongoing Tobacco abuse but risk is higher after Tobacco Cessation
      1. Boyko (1987) N Engl J Med 316:707-10
2. Pathophysiology
   1. Etiology unknown
   2. Inflammation localized to mucosa only
      1. Crohn's Disease involves all layers of bowel wall
   3. Always involves rectum and extends proximally to contiguous sections of colon
      1. Ulcerative proctitis
         1. Involves Distal 12 cm colonic mucosa
      2. Proctosigmoiditis
         1. Involves rectum to splenic flexure
      3. Pancolitis
         1. Involves rectum to cecum
3. Symptoms: Classic Presentation
   1. Intermittent bloody Diarrhea
   2. Rectal urgency
   3. Tenesmus
4. Symptoms: General
   1. Abdominal Pain
   2. Rectal Bleeding
      1. Helps to differentiate from Crohn's Disease
   3. Diarrhea
   4. Tenesmus
   5. Fever
   6. Malaise
   7. Weight loss
5. Signs: Extraintestinal Manifestations
   1. Similar findings seen in Crohn's Disease
   2. Musculoskeletal
      1. Osteoporosis (15%)
      2. Colitic Arthritis or arthralgias (5-10% of cases)
   3. Ocular
      1. Episcleritis (parallels Ulcerative Colitis course)
      2. Uveitis (occurs in up to 3% of cases)
         1. Variable course
         2. Associated with Enteropathic Arthritis
      3. Recurrent Iritis
   4. Dermatologic
      1. Digital Clubbing (presence increases likelihood of Ulcerative Colitis)
      2. Erythema Nodosum
         1. Parallels Ulcerative Colitis course
      3. Pyoderma gangrenosum (up to 2% of cases)
      4. Lichen Planus
      5. Aphthous Ulcers (canker sore)
   5. Hepatobiliary
      1. Hepatic Steatosis
      2. Primary Sclerosing Cholangitis (4-5% co-Incidence)
      3. Cholelithiasis
      4. Pericholangitis
   6. Miscellaneous
      1. Nephrolithiasis
      2. Hypercoagulable state
         1. Deep Vein Thrombosis or Pulmonary Embolism in 0.3% of cases
6. Labs: Distinguish from infectious causes of colitis
   1. Stool Culture
   2. Stool for Ova and Parasites
   3. Clostridium difficile Toxin and culture
7. Labs: Markers of inflammation and malabsorption
   1. C-Reactive Protein (C-RP) or Erythrocyte Sedimentation Rate (ESR)
      1. Mildly increased in moderate to severe cases
   2. Electrolyte abnormalities related to Chronic Diarrhea (e.g. Hypokalemia)
   3. Serum Albumin
      1. Decreased in moderate to severe cases
   4. Hemoglobin or Hematocrit
      1. Decreased in moderate to severe cases
8. Labs: Diagnosis
   1. Biopsy of colon wall (via Colonoscopy as described below)
      1. Diffuse, shallow, mucosa Ulceration
      2. Crypt abscess and branching
      3. Muscularis mucosal thickening
      4. Inflammatory cell infiltration
   2. Experimental markers: pANCA with ASCA
      1. Combination is sensitive but not specific (pending further study)
      2. Labs
         1. Perinuclear antineutrophilic cytoplasmic antibodies (pANCA) and
         2. Anti-Saccharomyces cerevisiae antibodies (ASCA)
      3. References
         1. Reese (2006) Am J Gastroenterol 101:2410-22
9. Diagnosis: Colonoscopy Findings (gold standard for diagnosis)
   1. General
      1. Mucosal inflammation begins at rectum
      2. Inflammation extends without interruption
      3. Inflammation ends in a distinct proximal margin
   2. Mild disease
      1. Erythematous mucosa
      2. Decreased vascular pattern visualization
      3. Fine mucosal friability
   3. Moderate disease
      1. Diffuse edema and erythema
      2. Loss of vascular pattern
      3. Superficial Erosions
      4. Mucosa bleeds with minimal trauma
   4. Severe disease
      1. Frank Ulceration
      2. Spontaneous bleeding
10. Imaging
    1. Not recommended for diagnosis unless endoscopy not available
    2. Double contrast Barium Enema and Small Bowel follow-through
       1. Haustra loss
       2. Contiguous inflammation from rectum proximally
          1. Contrast with non-contiguous and Small Bowel lesions of Crohn's Disease
    3. Abdominal XRay (long-standing disease signs)
       1. Bowel shortening
       2. Haustra loss
       3. Lumen narrowing and rigid appearance
11. Differential Diagnosis
    1. See Inflammatory Bowel Disease
12. Grading: Severity
    1. Mild Cases: Criteria below are normal
    2. Moderate to severe cases
       1. Serum Albumin <3.5 mg/dl (Severe: <3.0 mg/dl)
       2. Body temperature >99 F or 37.2 C (Severe: >100 F or 37.8 C)
       3. Bowel Movements >4 per day (Severe: >6 per day)
       4. ESR >20 mm/hour (Severe: >30 mm/hour)
       5. Hematocrit <40% (Severe: <30%)
       6. Heart Rate >90 beats per minute (Severe: >100 beats per minute)
       7. Weight loss >1% (Severe: >10%)
    3. References
       1. Chang (2004) Gastroenterol Clin North Am 33:236
13. Management: Mild to Moderate disease
    1. Agents: 5-Aminosalicylic Acid Derivatives (5-ASA agents)
       1. No Sulfa Allergy
          1. Sulfasalazine (Azulfidine)
       2. Sulfa Allergy
          1. Mesalamine (Asacol, Pentasa)
          2. Olsalazine (Dipentum) 500 mg PO bid
          3. Balsalazide
    2. Duration of medication use: 6-12 weeks
       1. Taper preparations to prevent rebound
    3. Route
       1. Rectal suppositories are preferred for proctitis
       2. Use oral and rectal agents together for pancolitis
14. Management: Moderate to Severe disease
    1. Corticosteroids: Oral
       1. Agents
          1. Prednisone 40-60 mg/day orally
          2. Methylprednisolone (Medrol) 35-40 mg/day orally
          3. Hydrocortisone (Cortef) 200-300 mg/day orally
          4. Methylprednisolone (Solu-Medrol) 40 mg IV daily
       2. Taper Corticosteroids gradually to prevent rebound
          1. Continue starting dose until clinical response (typically 10-14 days)
          2. After response, reduce dose by 5mg per week
       3. Efficacy
          1. Systemic Corticosteroids do not maintain remission and have serious side effects
    2. Corticosteroids: Rectal (for distal Ulcerative Colitis)
       1. Hydrocortisone Enema (Cortenema) 100 mg qd to bid
       2. Hydrocortisone Acetate rectal foam (Cortifoam)
    3. Disposition
       1. Hospitalization required when cases refractory to oral steroids
       2. Cyclosporine (Sandimmune) is used in acute cases refractory to IV Corticosteroids
15. Management: Immunosuppressants for Refractory disease
    1. Agents
       1. Infliximab (Remicade)
       2. Azathioprine (Imuran) 50-100 mg/day
       3. 6-Mercaptopurine (Purinethol)
    2. Indications:
       1. Poor control with Corticosteroids
       2. Serious Corticosteroid complications
       3. Steroid dependent to control symptoms
    3. Duration
       1. For long term therapy only
       2. Ineffective for acute dx
       3. Onset of action: 2-6 months
    4. Complications
       1. Pancreatitis
       2. Infection risk
       3. Hepatitis
       4. Bone Marrow suppression (Follow Complete Blood Count)
16. Management: Surgery
    1. Surgical management of Ulcerative Colitis is curative
    2. Indications
       1. Medical failure
       2. Corticosteroid intolerance
       3. Growth retardation in children
       4. Dysplasia or malignancy
       5. Fulminant colitis with or without Megacolon
          1. Perforation
          2. Peritonitis
          3. Hemorrhage
    3. Procedures
       1. Total proctocolectomy (Brooke ileostomy)
          1. Completely cures Ulcerative Colitis
          2. Entire colorectal mucosa is excised
          3. Results in gas or stool Incontinence
          4. Requires external collecting bag
       2. Ileal pouch anal anastomosis
          1. Patient maintains anal function and continence
          2. Pouchitis occurs in 30-50% of patients
    4. Complications
       1. Colonic stricture and increased risk of Bowel Obstruction
       2. Pouchitis or Pouch dysfunction
    5. References
       1. Cima (2005) Arch Surg 140:300-10
17. Complications
    1. Colon Cancer (Adenocarcinoma)
       1. See monitoring below
       2. Colon Cancer risk is not increased in disease limited to proctitis or proctosigmoiditis
       3. Risk increases with duration since diagnosis
          1. First 10 years: 2% risk
          2. First 20 years: 8% risk
          3. First 30 years: 18% risk
       4. References
          1. Eaden (2001) Gut 48:526-35
    2. Toxic Megacolon
    3. Bowel Perforation
    4. Colonic Stricture
    5. Gastrointestinal Bleeding
18. Monitoring: Colon Cancer
    1. General Colonoscopy approach
       1. Biopsies taken from cecum to rectum every 10 cm
    2. Pancolitis
       1. Colonoscopy every 1-2 years after 8-10 years of disease
    3. Left-sided Colitis
       1. Colonoscopy every 3 years after 12-15 years of disease (British use 15-20 years)
19. Course: Following initial attack of Ulcerative Colitis
    1. Continuous active Ulcerative Colitis: 75%
    2. Remission for 15 years: 10%
    3. Mortality within 1 year of initial attack: 5%
    4. Undergo total proctocolectomy within 5 years: 25%
20. Prevention
    1. Probiotic E. coli Nissle 1917
       1. As effective as Mesalamine in relapse prevention
       2. Not commercially available as of Spring 2005
       3. Kruis (2004) Gut 53:1617-23
21. References
    1. Carter (2004) Gut 53:V1-16
    2. Kornbluth (2004) Am J Gastroenterol 99:1371-85
    3. Langan (2007) Am Fam Physician 76:1323-31