> Table of Contents > Ulcerative Colitis
Ulcerative Colitis
Jason E. Domagalski, MD, FAAFP
image BASICS
DESCRIPTION
  • Chronic idiopathic inflammatory disease of the colonic mucosa that can affect any section of the colon starting at the rectum with variable extension towards the cecum
  • >95% of patients have rectal involvement, 50% have disease limited to rectum and sigmoid; 20% have pancolitis.
EPIDEMIOLOGY
Incidence
  • United States: 9 to 12 new cases/100,000 persons/year
  • Incidence stable over the past 5 decades
  • Predominant age: 15 to 35 years; second and smaller peak in the 7th decade
  • Predominant sex: female > male (slight)
Prevalence
205 to 240/100,000 persons
Pregnancy Considerations
  • Increased risk of preterm delivery and small for gestational age birth
  • 30% with inactive disease relapse in pregnancy
  • Patients should delay pregnancy until disease is inactive for at least 3 months.
ETIOLOGY AND PATHOPHYSIOLOGY
Unknown; hypotheses include allergy to dietary components and abnormal immune responses to bacterial or “self” antigens; final common path is mucosal inflammation secondary to immune cell infiltration.
Genetics
  • Family history in 5-10% in population surveys and 20-30% in referral-based studies
  • 50-60% concordance rate in identical twin studies
  • Associations with interleukin 23/Th17 pathway, interleukin 10, and interferon gamma genes
RISK FACTORS
  • Better sanitation, indoor work environments, and fatty foods increase risk.
  • NSAID use > 15 days per month associated with increased risk
  • Appendectomy protects against late disease onset.
  • Negative association with smoking: Relative risk of smokers is 40% of nonsmokers.
GENERAL PREVENTION
  • Increased risk for colon cancer w/o colectomy
  • Aspirin (≥300 mg/day) and ursodeoxycholic acid (10 mg/kg/day) are preventive.
Pediatric Considerations
  • Breastfeeding may protect against pediatric inflammatory bowel disease (IBD).
  • More likely pancolonic at onset and shorter time from diagnosis to colectomy (median 11.1 years)
COMMONLY ASSOCIATED CONDITIONS
  • Extracolonic manifestations in 10-15%
  • Arthritides, including large joint arthritis, sacroiliitis, and ankylosing spondylitis
  • Pyoderma gangrenosum
  • Episcleritis and uveitis
  • Asymptomatic fatty liver (common)
  • Primary sclerosing cholangitis: 1-4%
  • Cirrhosis of liver: 1-5%
  • Bile duct carcinoma
  • Thromboembolic disease: 1-6%
image DIAGNOSIS
PHYSICAL EXAM
  • Arthralgias and arthritis: 15-40%
  • Spondylitis: 3-6%
  • Ocular: 4-10%; includes uveitis, cataracts, keratopathy, and central serous retinopathy
  • Dermatologic: erythema nodosum, pyoderma gangrenosum
  • Pulmonary: pleuritis
  • Aphthous ulcers of mouth: 5-10%
DIFFERENTIAL DIAGNOSIS
  • Hemorrhoids, neoplasms, colonic diverticula, arteriovenous malformation, Crohn disease
  • Infectious diarrhea, including bacterial (enterotoxigenic Escherichia coli), Clostridium difficile colitis, and parasitic (Entamoeba histolytica)
  • Herpes simplex, Chlamydia trachomatis, Cryptosporidium, Isospora belli, cytomegalovirus
  • Radiation proctitis; ischemic colitis
DIAGNOSTIC TESTS & INTERPRETATION
  • Anemia (chronic disease ± iron deficiency)
  • Leukocytosis during exacerbation
  • Elevated ESR and CRP
  • Electrolyte abnormalities, especially hypokalemia
  • Hypoalbuminemia, elevated LFTs
  • Perinuclear antineutrophil cytoplasmic antibody (pANCA) is elevated in 60-70% of cases, also found in 40% of patients with Crohn disease. Sensitivity 33%, specificity 97%
Initial Tests (lab, imaging)
  • Plain abdominal films
    • Obtain immediately if significant abdominal tenderness, fever, and leukocytosis for early diagnosis of toxic megacolon and perforation.
  • Upper GI series with small bowel follow-through to rule out Crohn disease.
  • Ultrasound, MRI, scintigraphy, and CT may have similar accuracy in diagnosis of IBD (1)[A].
  • Stool culture and stool testing for parasites to rule out infectious colitis (2)[C]
  • C. difficile antigen if recent antibiotics
Diagnostic Procedures/Other
  • Sigmoidoscopy (may include biopsy) is often sufficient to make initial diagnosis.
  • Colonoscopy (may include biopsy)
    • Evaluate premalignant features; differentiate from Crohn disease; investigate stricture/mass; define extent and location of disease.
  • Full colonoscopy contraindicated in severe, active disease/colonic dilatation (risk of perforation)
Test Interpretation
Inflammation of the colonic mucosa with ulcerations:
  • Ulcerations are hyperemic and hemorrhagic.
  • Mucosal separation, distortion, and atrophy of the crypts on histology (2)[C]
  • Extends proximally, without skips
  • May affect terminal ileum, so-called backwash ileitis
image TREATMENT
Management involves acute treatment of inflammatory symptoms, followed by maintenance of remission; therapeutic approach is determined by symptom severity and the extent of colonic involvement.
  • 5-aminosalicylic acid (5-ASA) is effective for inducing remission in mild to moderate disease (NNT = 6) and preventing relapse in quiescent disease (NNT = 4) (3)[A]:
    • Topical mesalamine is superior to oral aminosalicylates and topical steroids for proctitis (3)[A].
    • Combination of oral and topical aminosalicylates is more effective than either alone.
  • Corticosteroid therapies are effective for inducing remission in active disease (NNT = 3) (3)[A].
  • Azathioprine or 6-mercaptopurine (6-MP) reduce relapse in patients with quiescent disease (NNT = 4) (3)[A].
  • Maintenance of remission in mild to moderate distal disease with the following: mesalamine suppositories for proctitis or enemas for distal colitis, sulfasalazine, balsalazide, or combination oral and topical mesalamine (3)[A]
  • Maintain remission in mild to moderate extensive disease with sulfasalazine, olsalazine, mesalamine, and balsalazide (3)[A].
  • Infliximab is effective at inducing remission in ambulatory patients with moderate to severely active disease (NNT = 4) (3)[A].
GENERAL MEASURES
Control inflammation, prevent complications, and replace nutritional losses and blood volume.
MEDICATION
First Line
  • Sulfasalazine
    • Uncoated tablets. Adults: initial: 1 g PO q6-8h; maintenance: 500 mg PO q6h; children ≥6 years: initial: 40 to 60 mg/kg/day PO in 3 to 6 divided doses; maintenance: 30 mg/kg/day PO divided q6h (max 2 g/day)
    • Enteric-coated tablets. Adults: initial: 3 to 4 g/day PO in divided doses q6-8h; maintenance: 2 g/day PO in divided doses; children ≥6 years: initial: 40 to 60 mg/kg/day PO in 3 to 6 divided doses; maintenance: 30 mg/kg/day PO in 4 divided doses (max 2 g/day)
  • Mesalamine
    • Oral delayed-release tablets (Asacol HD) to induce remission; adults: 800 mg PO TID for 6 weeks
    • Oral controlled-release tablets (Pentasa) for maintenance of remission; adults: 1 g PO QID
    • Single daily dose available for mesalamine (Lialda; acute therapy 4.8 g once daily or 2.4 g once daily for maintenance) and (Apriso; 1.5 g once daily; approved in the United States ONLY for maintenance)
    • Once daily dosing is as effective as conventional TID dosing for mild to moderately active UC treatment and to maintain remission (4)[A]
  • 5-ASA (e.g., mesalamine) enemas and suppositories to treat proctitis/proctosigmoiditis:
    • Suppositories: (Canasa) adults: 1,000 mg per rectum at bedtime for 3 to 6 weeks
    • P.1079

    • Enemas: adults: 4 g per rectum, retained for 8 hours each night; use for 3 to 6 weeks or until remission is achieved.
  • Balsalazide: adults: 2.25 g PO TID for total daily dose of 6.75 g for 8 to 12 weeks; children/adolescents: 2.25 g PO TID for total daily dose of 6.75 g or 750 mg PO TID for total daily dose of 2.25 g for 8 weeks
  • Olsalazine: adults: 500 mg PO BID (up to 3 g/day); children >2 years old: 30 mg/kg/day in 2 divided doses (up to 2 g/day), primarily used for maintenance
Second Line
  • Prednisone for severe exacerbations: adult dosage: initial: 40 to 60 mg/day PO (max 1 mg/kg/day) for 7 to 10 days; taper over 2 to 3 months; can be given IV in hospitalized patients
  • Infliximab is effective in patients whose disease is refractory to conventional treatment (3,5)[A]:
    • Adult dose: 5 mg/kg IV at weeks 0, 2, and 6 for induction, then maintenance of 5 mg/kg IV is given every 8 weeks
  • Adalimumab: for moderate to severe ulcerative colitis refractory to steroids and azathioprine/6-MP. Initial dose: 160 mg SC (given as four injections on day one or two injections daily over 2 consecutive days; limit injections to 40 mg per injection); 2nd dose 2 weeks later: 80 mg, and maintenance: 40 mg every other week thereafter; should only be continued if evidence of remission by 8 weeks (5)
Pediatric Considerations
  • Infliximab can increase the risk of cancer in children; weigh risks versus benefits.
  • Immunomodulators can be used in children unresponsive to steroids and aminosalicylates or who cannot be weaned from high-dose steroids:
    • Daily abdominal plain films until improvement
    • If dilatation of colon increases or treatment has failed to attain reversal in 72 hours, surgical consultation for emergency colectomy is indicated.
SURGERY/OTHER PROCEDURES
  • Indicated for medically refractory disease (particularly with high-dose steroids)
  • May be emergent for massive hemorrhage, perforation, and toxic dilatation of the colon. The emergency surgery of choice is total or subtotal abdominal colectomy with end ileostomy.
  • Surgery is also indicated for cancer/multisite mucosal dysplasia.
  • Total colectomy with ileostomy is curative.
  • Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the most common surgery and an appropriate alternative to ileostomy. Common complications include pouchitis (50%) and need for reoperation in up to 30% (2)[C].
  • Regular proctoscopic surveillance is required if a colonic mucosal cuff is retained.
COMPLEMENTARY & ALTERNATIVE MEDICINE
  • Insufficient evidence supports the efficacy of probiotics for maintaining remission (6)[A].
  • Encouraging results in limited studies for aloe vera gel, wheat grass juice, Andrographis paniculata extract (HMPL-004), topical Xilei-san, curcumin, Boswellia serrata gum resin, Plantago ovata seeds, evening primrose oil, wormwood, and Tripterygium wilfordii (7)[A]
  • Fecal microbiota transplant associated with nonsignificant increase in remission rate (8)[B].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Obtain imaging studies to assess disease activity.
  • Initiate IV corticosteroids and rule out infectious etiologies (C. difficile, cytomegalovirus, shigella/amoeba).
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Surveillance colonoscopy. Recommendations vary. Most begin a surveillance program after 8 years of disease with involvement beyond the splenic flexure with colonoscopy every 1 to 2 years including multiple random biopsies or targeted biopsies using chromoendoscopy.
  • Initiate annual surveillance immediately in patients with primary sclerosing cholangitis.
  • Magnification chromoendoscopy may detect significantly more intraepithelial neoplasias than conventional colonoscopy.
  • Nonadenomatous dysplastic lesions or masses are associated with cancer in 33-83% of cases and warrant total colectomy.
  • Annual LFTs and cholangiography for cholestasis
  • Annual BUN/creatinine for patients on long-term mesalamine
Pediatric Considerations
Cancer surveillance is important because cumulative risk of cancer increases with duration of disease.
DIET
  • NPO during acute exacerbations
  • Lactose-free diet is often recommended.
  • Omega-3 fatty acids, seal and cod liver oil, dietary lactulose, wheat grass juice, vitamin D, and diets with decreased meat and alcohol have been recommended to reduce relapses and improve systemic symptoms (inconsistent evidence) (7)[A].
PATIENT EDUCATION
  • Adherence to drug therapy is important to induce and maintain remission.
  • Crohn and Colitis Foundation of America (CCFA): http://www.ccfa.org/
PROGNOSIS
  • Variable; mortality for initial attack is ˜5%; 75-85% experience relapse; up to 20% require colectomy.
  • Colon cancer risk is the single most important factor affecting long-term prognosis.
  • Primary sclerosing cholangitis increases the risk of colon cancer in patients with ulcerative colitis.
  • Left-sided colitis and ulcerative proctitis have favorable prognoses with probable normal lifespan.
Geriatric Considerations
  • Increased mortality if first presentation occurs after 60 years of age.
  • Consider lower medication dosages and slower titration due to risks of polypharmacy.
REFERENCES
1. Horsthuis K, Bipat S, Bennink RJ, et al. Inflammatory bowel disease diagnosed with US, MR, scintigraphy, and CT: meta-analysis of prospective studies. Radiology. 2008;247(1):64-79.
2. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105(3):501-523.
3. Talley NJ, Abreu MT, Achkar JP, et al. An evidencebased systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol. 2011;106(Suppl 1):S2-S25.
4. Feagan BG, MacDonald JK. Once daily oral mesalamine compared to conventional dosing for induction and maintenance of remission in ulcerative colitis: a systematic review and meta-analysis. Inflamm Bowel Dis. 2012;18(9):1785-1794.
5. Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142(2):257.e3-265.e3.
6. Jonkers D, Penders J, Masclee A, et al. Probiotics in the management of inflammatory bowel disease: a systematic review of intervention studies in adult patients. Drugs. 2012;72(6):803-823.
7. Ng SC, Lam YT, Tsoi KK, et al. Systematic review: the efficacy of herbal therapy in inflammatory bowel disease. Aliment Pharmacol Ther. 2013;38(8):854-863.
8. Moayyedi P, Surette MG, Kim PT, et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology. 2015;149(1):102.e6-109.e6.
Additional Reading
&NA;
  • Huang X, Lv B, Jin HF, et al. A meta-analysis of the therapeutic effects of tumor necrosis factor-&agr; blockers on ulcerative colitis. Eur J Clin Pharmacol. 2011;67(8):759-766.
  • Racine A, Cuerq A, Bijon A, et al. Isotretinoin and risk of inflammatory bowel disease: A French nationwide study. Am J Gastroenterol. 2014;109(4):563-569.
See Also
&NA;
Algorithm: Hematemesis (Bleeding, Upper Gastrointestinal)
Codes
&NA;
ICD10
  • K51.90 Ulcerative colitis, unspecified, without complications
  • K51.919 Ulcerative colitis, unspecified with unspecified complications
  • K51.80 Other ulcerative colitis without complications
Clinical Pearls
&NA;
  • UC always involves the colon and has continuous areas of inflammation with shallow mucosal ulcerations, and crypt granulomas are not seen on biopsy (differentiating features from Crohn colitis).
  • Treat proctitis with 5-ASA suppositories.
  • Colectomy is curative.
  • Routine surveillance colonoscopy is recommended every 1 to 2 years after patients have had UC for 8 years.