Ulcerative Colitis

George Clement, MD and Elise Leisinger, DO Reviewed 06/2017

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Subject: Ulcerative Colitis

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  • Chronic relapsing and remitting inflammatory disease of the bowel causing recurrent episodes of diarrhea that is often bloody and accompanied by abdominal pain, incontinence, fever, and weight loss

  • Marked by inflammatory colonic mucosal changes

  • Colonic involvement is universal but may be accompanied by large joint arthritis, ocular inflammation, skin lesions, biliary disease, liver disease, thromboembolic disease, and (rarely) pulmonary complications



  • North America: 19.2 per 100,000 person-years 1

  • Europe: 24.3 per 100,000 person-years 1

  • Asia and Middle East: 6.3 per 100,000 person-years 1


  • North America: 249 per 100,000 persons 1

  • Europe: 505 per 100,000 persons 1

Pregnancy Considerations

  • Increased risk of preterm delivery and small for gestational age birth

  • 30% with inactive disease relapse in pregnancy

  • Management with gastroenterologist and/or maternal-fetal medicine specialist/obstetrician is recommended.


  • Idiopathic; hypothesized association with autoimmune dysfunction, genetic predisposition, diet, and colonic microbiome

  • Almost universally involves terminal colon, >95% of patients have rectal involvement, 50% have disease limited to rectum and sigmoid; 20% have pancolitis.


Moderate heritability. Specific genetic markers have not been identified. 


  • Age: variable, peak incidence among ages 15 to 40 years

  • First-degree relative with ulcerative colitis (UC)

  • Theorized risk factors include disruption of colonic microbiome by diet or infection; dietary factors (Western diet in particular), antibiotic use, lack of breastfeeding in infant, obesity, and NSAID use.


No known preventive measures 

Pediatric Considerations

  • Breastfeeding may protect against pediatric inflammatory bowel disease (IBD).

  • UC more likely pancolonic at onset and shorter time from diagnosis to colectomy (median 11.1 years)


  • Arthritis: large joint, sacroiliitis, ankylosing spondylitis

  • Pyoderma gangrenosum (rare)

  • Erythema nodosum (common)

  • Aphthous ulcers

  • Episcleritis and uveitis (rare)

  • Autoimmune liver disease (rare)

  • Fatty liver (common)

  • Liver cirrhosis (rare)

  • Primary sclerosing cholangitis (rare)

  • Bile duct carcinoma (rare)

  • Thromboembolic disease (rare)

  • Colon cancer (rare)

  • Anemia (rare)

  • Pulmonary diseases (very rare)



  • Frequent diarrhea, may be bloody or include mucus

  • Frequent, small bowel movements, associated with tenesmus, colicky abdominal pain, urgency, and fecal incontinence

  • Onset is gradual and progressive over weeks.

  • Episodes are sometimes accompanied by fever, weight loss, fatigue, and anemia.

  • Predominant age of onset: 15 to 40 years; smaller peak in ages 50 to 80 years


  • Often normal

  • Abdominal tenderness

  • Presence of blood on rectal exam

  • In severe disease: fever, hypotension, tachycardia, pallor, loss of subcutaneous fat, muscle atrophy, peripheral edema


  • Crohn disease

  • Infectious colitis: bacterial, parasitic, or viral (cytomegalovirus [CMV])

  • Diverticular colitis

  • Diversion colitis in patients with prior bowel surgery

  • Medication-induced colitis

  • Radiation colitis

  • Graft versus host disease

  • Celiac disease


  • Stool examination to rule out infectious cause.

  • Sigmoidoscopy or colonoscopy with biopsy to confirm colitis.

Initial Tests (lab, imaging)

  • CBC: leukocytosis and anemia support diagnosis

  • BMP: urea and electrolyte abnormalities; hypokalemia supports diagnosis

  • LFTs: liver function abnormalities; low albumin indicates severe disease 2

  • ESR or CRP elevation supports diagnosis and can help define severity 2

  • Ferritin and transferrin if anemic to determine iron deficiency versus chronic disease

  • Vitamin B12 and folate levels

  • Fecal calprotectin: indicates colonic inflammation 3

  • Stool studies to rule out infectious cause: Clostridium difficile toxin (four samples), stool cultures, shiga toxin, ova and parasite microscopy, Giardia antigen

  • STI testing to rule out proctitis, particularly in MSM: chlamydia, gonorrhea, HSV, syphilis 3

  • Perinuclear antineutrophil cytoplasmic antibody (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) are commonly present in patients with UC, but testing for these is not currently recommended for diagnosis 3.

  • Abdominal x-ray to exclude dangerous colonic dilation and assess disease severity 3

Diagnostic Procedures/Other

  • Colonoscopy with at least two biopsies from each of five sites along the entire colon is an initial diagnostic step 3.

  • Complete colonoscopy in severe UC may be contra-indicated due to risk of perforation or precipitation of toxic megacolon 3.

Test Interpretation

  • Endoscopic findings that support UC include mucosal engorgement with vascular markings, mucosal erythema, and mucosal granularity. Affected areas will extend proximally and continuously.

  • Histologic findings that support UC include mucosal separation, distortion, and atrophy of the crypts, chronic inflammatory cells in lamina propria, lymphocytes and plasma cells in crypt bases 4[C]

  • If only rectal biopsy, villous mucosal architecture and Paneth cells metaplasia support UC 4[C]

  • Mild ileal inflammation (“backwash ileitis”) may be present in UC 4[C].


Treatment strategies are determined by functional status, degree of colonic involvement, course of illness, frequency of relapses, extraintestinal manifestations, response to prior treatments, and side effect profile. 


First Line

  • Proctitis/distal colitis with mild or moderate severity: 5-ASA (e.g., mesalamine 1g/day) suppository; 5-ASA foam enemas are an alternative but less effective 5[C].

  • Left-sided UC with mild to moderate severity: topical 5-ASA (e.g., Mesalamine 1 g/day) PLUS >2 g/day oral mesalamine 5[C]

  • Left-sided severe UC: hospital admission and systemic steroids (e.g., prednisone 40 to 60 mg/day) in addition to mesalamine/5-ASA 5[C]

  • Extensive UC of mild to moderate severity: oral sulfasalazine titrated up to 4 to 6 g/day OR a combination of topical and oral 5-ASA (above) 5[C]

  • Severe UC: necessitates hospitalization for intensive treatment and surveillance for complications; IV steroids (methylprednisolone 60 mg/day or hydrocortisone 400 mg/day) with or without 2 to 6 g/day oral mesalamine 5[C]

Second Line

  • Proctitis/distal colitis with mild to moderate severity: first-line therapy PLUS 2 to 6 g/day oral mesalamine. Topical corticosteroids (budesonide 2 to 8 mg/day or hydrocortisone 100 mg/day) may be added 5[C].

  • Left-sided UC with mild to moderate severity: first-line therapy PLUS topical corticosteroids (budesonide 2 to 8 mg/day or hydrocortisone 100 mg/day) may be added. Persistent rectal bleeding despite this regimen can be treated with systemic prednisone at 40 to 60 g/day with a prolonged taper 5[C].

  • Left-sided severe UC: first-line therapy PLUS prednisone at 40 to 60 g/day and long taper; if refractory, azathioprine 2.5 mg/kg/day OR 6-mercaptopurine (1.5 mg/kg/day) for induction and maintenance 5[C]

  • Severe UC: TNF-α-blocker IFX (adalimumab, Infliximab, golimumab) combined with methotrexate or thiopurine. Patients with severe UC will often need timely colectomy 5[C].

  • Infliximab adult dose: 5 mg/kg IV at weeks 0, 2, and 6 for induction and then maintenance of 5 mg/kg IV is given every 8 weeks.

  • Adalimumab: 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 6[C]

  • Other second-line therapies, particularly in refractory disease, include CsA 4 mg/kg/day and tacrolimus 0.1 to 0.2 mg/kg/day PO or 0.01 to 0.02 mg/kg/day IV. Trough concentrations with tacrolimus should be 10 to 15 ng/mL.

  • TNF-α-blockers can help maintain remission in steroid-dependent patients with severe UC.

  • Immunosuppressive therapy increases risk of opportunistic infections. Chronic steroid use can cause adrenal suppression gastrointestinal bleeding, heart disease, osteoporosis, thinning of skin, and compromised vascular wall integrity. Infusion of biologics carries the risk of anaphylactic reactions during treatment.

Pediatric Considerations

Pediatric growth and development can be affected due to malabsorption. 


  • Surgery is indicated for medically refractory disease (particularly with high-dose steroids).

  • Emergent surgery (typically total or subtotal abdominal colectomy with end ileostomy) for massive hemorrhage, perforation, and toxic dilatation

  • 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% 4[C].


  • There is ongoing research into the role of probiotics, dietary changes, and fecal microbiota transplant as treatment for UC. The current evidence is insufficient to support the efficacy of any particular alternative therapy for achieving or maintaining remission.

  • Tobacco cessation is associated with 65% reduction in relapse 3[C].


  • Admission for UC or its complications warrants gastroenterology consultation.

  • Severe UC may require emergent surgical intervention. Consultation with surgery is indicated.

  • Imaging studies help assess disease activity and colon size.

  • Initiate IV corticosteroids and rule out infectious etiologies (C. difficile, CMV, shigella/amoeba)



Patient Monitoring

  • Regular surveillance colonoscopy in patients with prolonged (8 to 10 years) active disease 4

  • Initiate annual surveillance immediately in patients with primary sclerosing cholangitis.

  • Annual LFTs and cholangiography for cholestasis

  • Annual BUN/creatinine for patients on long-term mesalamine

Pediatric Considerations

Cumulative risk of cancer increases with duration of disease-ensure regular surveillance 


  • NPO during acute exacerbations

  • There are otherwise no specific dietary recommendations. Dietary research is ongoing.


Crohn and Colitis Foundation of America (CCFA): http://www.ccfa.org/ 


  • Chronic disease with variable severity and rate of recurrence

  • 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.

  • 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.


  • Perforation: Treat toxic megacolon with prompt surgery. Limit colonoscopies in severe disease.

  • Obstruction

  • Anemia

  • Fulminant colitis

  • Toxic megacolon

  • Liver disease

  • Stricture formation

  • Osteoporosis

  • Colorectal cancer


Molodecky  NA, Soon  IS, Rabi  DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology.  2012;142(1):46. e42–64.e42.  [View Abstract]
Silverberg  MS, Satsangi  J, Ahmad  T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol.  2005;19(Suppl A):5A–36A.  [View Abstract]
Mowat  C, Cole  A, Windsor  AI, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut  2011;60:571–607.  [View Abstract]
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.  [View Abstract]
Meier  J, Sturm  A. Current treatment of ulcerative colitis. World J Gastroenterol.  2011;17(27): 3204–3212.  [View Abstract]
Bressler  B, Marshall  JK, Bernstein  CN, et al. Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus. Gastroenterology.  2015;148: 1035.e3–1058.e3.  [View Abstract]


Algorithm: Hematemesis (Bleeding, Upper Gastrointestinal) 



  • K51.90 Ulcerative colitis, unspecified, without complications

  • K51.919 Ulcerative colitis, unspecified with unspecified complications

  • K51.80 Other ulcerative colitis without complications

  • K51.00 Ulcerative (chronic) pancolitis without complications

  • K51.40 Inflammatory polyps of colon without complications

  • K51.50 Left sided colitis without complications

  • K51.30 Ulcerative (chronic) rectosigmoiditis without complications

  • K51.20 Ulcerative (chronic) proctitis without complications


  • 556.9 Ulcerative colitis, unspecified

  • 556.8 Other ulcerative colitis

  • 556.3 Ulcerative (chronic) proctosigmoiditis

  • 556.6 Universal ulcerative (chronic) colitis

  • 556.5 Left-sided ulcerative (chronic) colitis


  • 64766004 Ulcerative colitis (disorder)

  • 444546002 chronic ulcerative colitis (disorder)

  • 52506002 Chronic ulcerative rectosigmoiditis

  • 444548001 Ulcerative pancolitis (disorder)

  • 52231000 chronic ulcerative proctitis (disorder)


  • Diffuse, uninterrupted colonic mucosal inflammation

  • Hallmark symptom is bloody diarrhea.

  • Annual or biannual surveillance colonoscopy after 8 to 10 years of colitis due to increased risk of colorectal cancer.