ULCERATIVE COLITIS

ULCERATIVE COLITIS - Venu G. Pillarisetty, MD; Ruben Peralta, MD, FACS
BASICS
DESCRIPTION
An idiopathic inflammatory disease of the colon mucosa, affecting the rectum and usually extending proximally to involve the entire colon in a continuous manner.
• At least 95% have rectal involvement
• 50% limited to rectum and sigmoid.
• 30-40% of patients have disease beyond the sigmoid, but not of the entire colon.
• 20% have pancolitis.
EPIDEMIOLOGY
• Predominant age: 15-35. 2nd and smaller peak in the 7th decade.
• Predominant sex: Female slightly > Male
Incidence
US population: 5-12 new cases per 100,000
Prevalence
70-150/100,000
ALERT
Pediatric Considerations
Twenty percent of patients are 21 years
Pregnancy Considerations
• Outcome of pregnancy similar to general population. 1 study showed 30% of those with inactive disease at onset of pregnancy relapsed and 14% did so in 1st trimester.
• Treatment with sulfasalazine does not seem to affect outcome of pregnancy.
• Recommend that patient delays pregnancy until time when disease is inactive.
RISK FACTORS
• Better sanitation, artificial work environments (e.g., indoors), and fatty food increase risk
• NSAIDs can activate disease
• Appendectomy is protective against later development of disease
• Negative association with smoking (relative risk of smokers is 40% of nonsmokers)
Genetics
Family history in 5-10% in population surveys and 20-30% in referral-based studies. More common in the Jewish population.
ETIOLOGY
Unknown; major hypotheses include allergy to dietary components and abnormal immune responses to bacterial or self-antigens; final outcome is mucosal inflammation secondary to immune cell infiltration (1)[B]).
ASSOCIATED CONDITIONS
• Extracolonic manifestations in 10-15%
• Arthritic conditions including large joint arthritis, sacroiliitis, and ankylosing spondylitis. Infliximab has had a favorable response in treating these conditions.
• Pyoderma gangrenosum and other skin conditions; infliximab has helped.
• Episcleritis and uveal tract disease
• Sclerosing cholangitis; ursodeoxycholic acid is helpful


DIAGNOSIS
SIGNS AND SYMPTOMS
• Bloody diarrhea (watery stool accompanied by blood, pus, and mucus)
• Tenesmus
• Abdominal pain; tenderness in severe disease
• Rectal urgency, occasional fecal incontinence
• Fever
• Weight loss
• Arthralgias and arthritis: 15-20%
• Spondylitis: 3-6%
• Ocular: 4-10% include episcleritis, uveitis, cataracts, keratopathy, marginal corneal ulceration, and central serous retinopathy
• Erythema nodosum
• Pyoderma gangrenosum
• Aphthous ulcers of mouth: 5-10%
• Asymptomatic fatty liver (common); occasional hepatomegaly
• Pericholangitis (uncommon)
• Primary sclerosing cholangitis: 1-4%
• Cirrhosis of liver: 1-5%
• Bile duct carcinoma
• Thromboembolic disease: 1-6%
• Pericarditis (rare)
• Amyloidosis (rare)
TESTS
Lab
• Anemia may reflect chronic disease as well as iron deficiency from blood loss.
• Leukocytosis during exacerbation
• Elevated ESR and C-reactive protein
• Electrolyte abnormalities, especially hypokalemia
• Hypoalbuminemia
• Elevated liver function tests
• Perinuclear antineutrophil cytoplasmic antibody is elevated in 85% of cases of ulcerative colitis and 15% of Crohn disease.
• Antiglycan antibody is elevated in 75% of Crohn disease and 5% of ulcerative colitis cases.
Imaging
• Plain abdominal films
- Invaluable in management of acute complications of ulcerative colitis and should be immediately available in all patients who show tenderness of the colon, fever, and leukocytosis
- Permit the early diagnosis of toxic megacolon and perforation and treatment planning; toxic megacolon is most severe near the cecum and is present when diameter >12 cm.
• Barium enema
- Mucosal irregularities, effacement of haustra, pseudopolyposis
• Upper gastrointestinal series with small bowel follow-through to rule out Crohn disease
Diagnostic Procedures/Surgery
• Sigmoidoscopy; may include biopsy
- Should be sufficient to make initial diagnosis
• Colonoscopy; may include biopsy for evaluation for premalignant features
- To differentiate from Crohn disease
- To investigate suspected stricture or mass
- To define the extent and location of involvement and specific segments
- Full colonoscopy contraindicated in active disease or colonic dilatation because of risk of perforation
Pathological Findings
Inflammation of the colonic mucosa with ulcerations
• Ulcerations are hyperemic and hemorrhagic.
• Rectum is involved 95% of the time.
• The inflammation extends proximally in a continuous fashion but for a variable distance.
• May affect terminal ileum, so-called backwash ileitis.
DIFFERENTIAL DIAGNOSIS
• Other sources of rectal bleeding, including hemorrhoids, neoplasms, colonic diverticula, arteriovenous malformation, Crohn disease
• Infectious diarrhea including bacterial (enterotoxigenic Escherichia coli, E. coli 0157:H7, Salmonella, Shigella, Aeromonas, Plesiomonas) and parasitic (Entamoeba histolytica)
• Herpes simplex, Chlamydia trachomatis, Cryptosporidium, Isospora belli, cytomegalovirus
• Antibiotic-associated diarrhea
• Radiation proctitis
• Ischemic proctitis and colitis
TREATMENT
STABILIZATION
Hospitalization for severe exacerbations
GENERAL MEASURES
Control inflammation, prevent complications, and replace nutritional losses and blood volume.
Diet
No specific diet; milk products not withheld unless an associated lactase deficiency exists
Activity
Full activity as tolerated
MEDICATION (DRUGS)
First Line
• Sulfasalazine is treatment of choice both for mild exacerbations and for chronic treatment. Used to decrease the frequency of relapses (dosage range 2-6 g/d).
• Proctitis or proctosigmoiditis may be treated topically with steroid enemas or mesalamine (5-aminosalicylic acid [5-ASA]) enemas and suppositories.
• Oral or parenteral corticosteroids are used for more severe exacerbations (e.g., prednisone 40-60 mg/d, gradual taper over 2 months).
• 10% of patients have chronic disease and require continuous low to moderate steroid doses.
• Newer agents include oral 5-ASA derivatives.
• Immunomodulators, such as azathioprine, mercaptopurine (6-mercaptopurine), methotrexate, and cyclosporine, used in patients unresponsive to steroids and 5-ASA drugs or who cannot be weaned from high-dose steroids.
- Most experience is with azathioprine and mercaptopurine.
- Daily plain films of the abdomen are obtained until improvement occurs.
- If dilatation of colon increases or treatment has failed to attain reversal in 72 hours, emergency colectomy is indicated.
• Antimicrobial agents (antimycobacterials and metronidazole) are sometimes useful in Crohn disease, but not in ulcerative colitis.
• Antidiarrheal agents such as diphenoxylate-atropine and loperamide may be used to help control diarrhea, but require careful monitoring because they may precipitate toxic megacolon.
• Precautions: Use of antidiarrheal agents in severe disease could precipitate toxic megacolon.
Second Line
• Budesonide is a less toxic steroid almost totally cleared by the liver; it may help avoid steroid risks.
• Several preparations of 5-ASA exist, but results seem best with sulfasalazine in full dose.
• Infliximab recently was found to improve long-term outcomes in patients with moderate to severe disease despite treatment with other medications. (2)[B]
SURGERY
• Emergency surgery for massive hemorrhage, perforation, and toxic dilatation of the colon
• Surgery indicated for cancer, persistent multisite mucosal dysplasia, and patients refractory to all other forms of therapy.
• Total colectomy with ileostomy pouch is curative.
• Many patients prefer a continent ileostomy (J-pouch) emptying through the rectum.
• With the continent ileostomy operations, "pouchitis" occurs in ~10% with erratic partial response to antibiotics.
• Subtotal colectomy with the ileum connected to the rectal stump also may be performed.
• Regular proctoscopic surveillance is required because colonic mucosa is retained, thereby leaving a risk of future cancer development.
FOLLOW-UP
PROGNOSIS
• Variable course; mortality for initial attack is ~5%. 75-85% experience relapse, and up to 20% eventually require colectomy.
• Colon cancer risk is the single most important risk factor affecting long-term prognosis.
• Left-sided colitis and ulcerative proctitis have favorable prognosis with probable normal lifespan.
ALERT
Geriatric Considerations
Increased mortality if 1st presentation after 60 years of age
COMPLICATIONS
• Perforation
• Toxic megacolon
• Liver disease
• Stricture formation (less than Crohn disease)
• Colon cancer (may occur in as many as 30% of those with pancolitis for 25 years). Incidence of cancer is cumulative over time and begins after 7-8 years of the disease; risk may be considerably less in left-sided disease.
PATIENT MONITORING
• Colonoscopy for cancer surveillance with biopsy of the mucosa for evidence of dysplasia every 1-2 years after the disease has been present for 7-8 years. This is particularly important in pancolitis. Low-grade dysplasia warrants more frequent evaluation (e.g., every 3-6 months), and high-grade dysplasia (or low-grade dysplasia within a mass) warrants consideration of colectomy.
• Magnification chromoendoscopy has been shown to be capable of detecting significantly more intraepithelial neoplasias than conventional colonoscopy. (3)[B]
• Annual liver tests
• Cholangiography for cholestasis
Pediatric Considerations
Cancer surveillance is important because occurrence of cancer relates to the duration and extent of disease, whether frequently symptomatic or not.
REFERENCES
1. Hanauer SB. Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006;12:S3-S9.
2. Rutgeerts R, Sandborn WJ, Feagan BG. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462-2476.
3. Kiesslich R, Hoffman A, Neurath MF. Colonoscopy, tumors, and inflammatory bowel diseasenew diagnostic methods. Endoscopy 2006;38(1):5-10.