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ULCERATIVE COLITIS (UC)

[Source:  Outlines in Clinical Medicine  on Physicians' Online 1999]

SX:  

  1. Presents with (secreatory) diarrhea, hematochezia, little pain, tenesmus
  2. Typically with sudden onset of symptoms
  3. Begins in colon at mucucutaneous line (dentate line) at ano-rectal junction
  4. Proximal progression with no skip areas
  5. Overall Involvement:  Left sided colitis ~ 50%, pancolitis ~20%, proctitis ~30%
  6. Numerous extra-colonic manifestations
  7. Frequency of exacerbations is reduced in smokers

Intracolonic Sx  

  1. Colon Adenocarcinoma     
    1. Original data suggested high risk of progression to cancer in UC patients
    2. Previously, most patients were advised to have total colectomy
    3. Risk of colon cancer may be decreased in UC patients with UC taking medications
    4. Risk increases in UC patients after 10 years of disease
    5. Prior to aggressive treatment, colon cancer risk was >40% at 24 years
    6. Frequent colonoscopy with biopsies is recommended for surveillance
  2. Obstruction       
  3. Leakage - perforation
  4. Iron deficiency - hemorrhage
  5. Toxic Megacolon (see below)
  6. Inanition
  7. Strictures, Fistulas (rare in UC), perirectal abscess
  8. Mnemonic is "COLITIS"

Extracolonic SX:

  1. Urinary Calculi - oxalate stones      
  2. Liver Disease: Sclerosing Cholangitis       
  3. Cholelithiasis       
  4. Erythema nodosum (pyoderma gangrenosum)       
  5. Retardation of growth
  6. Arthritis       
    1. Proximal Arthritis associated with IBD most common in HLA-B27+ patients
    2. Distal polyarthritis also seen in IBD
    3. Incidence of true ankylosing spondylitis is elevated in IBD (B27+)
  7. Thrombophlebitis
  8. Iatrogenic: glucocorticoids, blood transfusions, operations
  9. Vitamin Deficiency (Malabsorption)      
  10. Eyes: uveitis, chorioretinitis, iridocyclitis, episcleritis
  11. Mnemonic is "ULCERATIVE"

Patterns of Ulcerative Colitis - 70% Chronic Relapsing, 20% Chronic Continuous, 10% Fulminant Colitis; includes toxic megacolon (nerve destruction and distension) with sepsis

Medical RX:       

  1. Sulfasalazine
    1. Remitting, maintenance agent of choice in tolerant patients
    2. Fairly high incidence of side effects with nausea, rash, pancreatitis, etc.
    3. Dose: 500mg bid-tid then increase to maximum 1.5 gm tid (should be titrated to effect)
    4. Requires weeks to see effect
  2. Olsalazine
    1. May be more effective than mesalazine in prevention of relapses in UC
    2. 5-ASA @ 2gm/day similar efficacy to sulfasalazine, better tolerated, mild-moderate UC
    3. Doses >2gm/day of olsalazine is better than placebo
    4. May cause diarrhea (rate may be increased over sulfasalazine)
  3. Mesalamine (oral, Asacol®; enema and suppositories, Rowasa®)
    1. Effective in maintaining or improving UC (mild-moderate)
    2. Well tolerated in UC but may cause watery diarrhea
    3. Oral dose is 2.4g/d, should be started low with increase over 1-3 weeks
    4. Mesalamine 0.8-1.6gm/day reduced exacerbations >50% over a 6 month period
    5. Proctocolitis may respond to Rowasa enamas without requirement for other agents
  4. Glucocorticoids      
    1. Steroid enemas - distal colitis / proctocolitis only (effective to ~28cm)
    2. Inpatient: moderate dose iv medication, eg. methylprednisolone 30-50mg iv q8° or drip
    3. Oral glucocorticoids at 60mg/day, with slow taper over weeks
  5. 6-MP and AZA (Imuran®)
    1. Effective for reducing glucocorticoid doses ("steroid sparing agent")
    2. Helps induce and maintain remissions in UC
    3. Reduces remissions in ~65% of patients with chronic refractory UC
  6. Cyclosporine   
    1. Effective at moderately high doses in glucocorticoid resistant exacerbations
    2. Reduces requirement for surgical intervention in steroid-resistant exacerbations
    3. Given IV for acute UC flares and is rapidly effective within 3-7 days
    4. Generally reserved as bridge therapy to prevent emergent collectomy
    5. Increased risk of infection       
  7. Fish Oils
    1. High in eicosapentainoic acids, compete for 5-lipoxygenase activity forming LTB5
    2. Fish oils reduce inflammation
    3. Fish oils demonstrate some adjunctive effect in UC treatment
  8. Nicotine
    1. Nicotine Patch may reduce exacerbations in combination with mesalamine
    2. Patient show smoke intermittently note reduction in UC exacerbations during smoking
    3. Nicotine patch had no effect on prevention of UC exacerbations during maintenance
    4. However, activity of patch (22mg/day) was confirmed in active UC
    5. Side effects in most patients included nausea, dizziness, local reactions
    6. Overall, nicotine may provide some benefit in the setting of active UC
  9. Methotrexate has not been shown to have substantial effects in UC to date

Surgical RX for Ulcerative Colitis       

  1. Nearly all cases are performed for medical therapy failures
  2. Some cases are performed to reduce risk of developing colon cancer or for polyps
  3. Many patients may have proctocolectomy with anal anastomosis (continant sphincter)
  4. Stool frequency and C-reactive protein levels correlated strongly with colectomy
  5. Surgical morbidity with the procedure was 26% for elective surgery, 44% for urgent

Toxic Megacolon      

  1. Occurrance
    1. Most commonly found in patients with IBD, usually ulcerative colitis
    2. Also associated with infections and Kaposi Sarcoma
    3. The incidence is declining due to better treatments, earlier recognition
  2. Defined as colonic dilatation with inflammatory colitis, septic symptoms
    1. Severe inflammation occurs down to smooth muscle layer
    2. Result is paralysis of colonic smooth muscle
    3. This leads to colonic dilatation
    4. Myenteric plexus nerves are not consistently damaged
    5. Nitric oxide, cytokines, leukotrienes, and proteolytic enzymes all paralyze muslce
  3. Bacterial Infections (all associated with bloody diarrhea)       
    1. Clostridium difficle pseudomembranous colitis. Salmonella - typhoid and non-typhoid, Shigella
    2. Campylobacter, Yersinia
  4. Parasitic:  Entamoeba histolytica, Cryptosporidium
  5. Viral:  Cytomegalovirus colitis,  Culture negative colitis
  6. Diagnostic Criteria
    1. Radiographic Evidence of colonic distension
    2. Three of: Fever >38°C (101.5°F), Heart Rate >120/min, WBC >10.5K/µL, anemia
    3. One of: dehydration, altered consciousness, electrolyte imbalance, hypotension
  7. Treatment
    1. Blood cultures should be obtained
    2. Nothing per mouth, insert nasogastric tube or intestinal tube
    3. Reduce severity of colitis with broad spectrum antibiotics
    4. Intensive supportive management
    5. Blood counts, electrolytes, serial abdominal films every 12 hours
    6. Parenteral nutrition is of benefit in Crohns Disease but not in Ulcerative colitis
    7. Prophylaxis for stress ulcers and deep vein thromboses is recommended
    8. Glucocorticoids recommended in IBD toxic megacolon to prevent Addisonian reactions
    9. Medical therapy is effective in ~50% of cases
    10. Surgery may be required after 48-72 hours of distension which is not improving

Indications for Surgical Rx       

  1. Bleeding - usually in Ulcerative Colitis
  2. Obstruction
    1. More common in Crohn's Disease
    2. Acute obstruction with edema is contraindication to operate
  3. Perforation / Fistula / Peritonitis / Abscess
  4. Failed medical therapy
  5. Remove grossly involved bowel; ~50% of CD patients recur
  6. For UC, removal of entire colon completely eradicates the intestinal disease

Novel Therapies      

  1. Specific Cytokine Blockers
    1. IL-1 receptor antagonist (IL-1RA)
    2. TNFa blockers (see below)
  2. Other immunosuppressive agents may be effective
    1. Cyclosporine is being evaluated in specific settings
    2. Rapamycin
    3. FK506 and other immunosuppressives
    4. CTLA-4Ig blocks T cell activation, is being evaluated in various autoimmune diseases
  3. 5-Lipoxygenase Inhibitor - Zileuton 600mg po qid has shown some efficacy in CD
  4. Fish Oil
    1. May reduce production of inflammatory leukotrienes and thromboxanes
    2. Suppresses IL-1 and TNF production
    3. Free Radical Scavanger activity
    4. High dose enteric coated (2.7gm/d) reduced CD exacerbations at 1 year
  5. Interferon alpha
    1. Some reduction in disease symptoms in early studies
    2. No effect on endoscopic appearance

Ref:
Outlines in Clinical Medicine  on Physicians' Online 1999

       

2009