Ulcerative colitis (UC) is an idiopathic, remitting and relapsing, chronic inflammatory bowel disease (IBD) that starts in the rectum and extends proximally.

UC

Inflammatory bowel disease (IBD)

Idiopathic proctocolitis

Pancolitis

• Patients with UC often present with acute onset of bloody diarrhea accompanied by tenesmus, fever, and dehydration. At presentation 40% of adults have proctitis, 40% have left-sided colitis, and 20% have pancolitis. Diarrhea is not always present in UC patients with proctosigmoiditis and proctitis, and patients may have constipation.
• Abdominal pain is not usually a prominent symptom. Abdominal distention and tenderness may indicate the presence of complications such as toxic megacolon.
• The onset of symptoms is typically acute and is generally followed by periods of spontaneous remission and frequent relapses.
• Fever, evidence of dehydration may be present during the acute flare-up.
• Evidence of extraintestinal manifestations may be present in nearly 25% of patients: Liver disease, sclerosing cholangitis, iritis, uveitis, episcleritis, arthritis, erythema nodosum, pyoderma gangrenosum, aphthous stomatitis. Box 1 summarizes common extraintestinal manifestations of UC.

Accumulating evidence suggests that it may result from an inappropriate inflammatory response to environmental triggers and immune dysregulation involving CD4+ T-cell Th2 response in a genetically susceptible host.

• Crohn disease
• Bacterial infections:
  1. Acute: Campylobacter, Yersinia, Salmonella, Shigella, Chlamydia, Escherichia coli, Clostridioides difficile, gonococcal proctitis
  2. Chronic: Whipple disease, tuberculosis, enterocolitis
• Irritable bowel syndrome
• Protozoal and parasitic infections (amebiasis, giardiasis, cryptosporidiosis)
• Neoplasm (intestinal lymphoma, carcinoma of colon)
• Ischemic bowel disease
• Diverticulitis
• Celiac sprue, lymphocytic or collagenous colitis, radiation enteritis, endometriosis
• Solitary rectal ulcer
• Acute self-limited colitis
• Medication (NSAIDs, chemotherapy)

An accurate diagnosis of UC should define the extent and severity of inflammation. Diagnostic workup includes:

• Comprehensive history, physical examination
• Laboratory tests (see “Laboratory Tests”)
• Colonoscopy to establish the presence of mucosal inflammation; typical endoscopic findings in UC are areas of continuous friable mucosa; diffuse, uniform erythema replacing the usual mucosal vascular pattern (Table 2); and pseudopolyps. The transition from abnormal to normal tissue tends to be abrupt. Rectal involvement is invariably present if the disease is active. Pathologic findings suggestive of UC include crypt abscesses and atrophy, mucin depletion, basal plasmacytosis, basal lymphoid aggregates, increased lamina propria cellularity, and Paneth cell metaplasia

• Anemia and high erythrocyte sedimentation rate (in severe colitis) are common, but normal levels do not rule out the disorder.
• Potassium, magnesium, calcium, and albumin may be decreased.
• Antineutrophil cytoplasmic antibodies (ANCA) with a perinuclear staining pattern (pANCA) can be found in >45% of patients; there is an increased frequency in treatment-resistant left-sided colitis, suggesting a possible association between these antibodies and a relative resistance to medical therapy in patients with UC.
• Calprotectin is a protein that is measured in feces as a marker of intestinal mucosa leukocyte activity that may be useful for screening of patients with suspected IBD. Trials have shown that based on a pretest probability of IBD of 32% in adults, an abnormal fecal calprotectin test would increase the posttest probability to 91% and a normal result would reduce the probability to 3%.
• Fecal lactoferrin is also a sensitive marker of intestinal inflammation.
• Stool examinations for ova and parasites, stool culture, and testing for C. difficile toxin and E. coli O157:H7 may be useful to eliminate other causes of diarrhea in selected patients with risk factors.

Image studies (plain radiography, CT scan [Fig. E1]) are generally reserved for suspected complications such as perforation of bowel or toxic megacolon.

• Correct nutritional deficiencies; total parenteral nutrition with bowel rest may be necessary in severe cases. Folate supplementation may reduce the incidence of dysplasia and cancer in chronic UC.
• Avoid oral feedings during acute exacerbation to decrease colonic activity; a low-roughage diet may be helpful in early relapse.
• Psychotherapy is useful in most patients. Referral to self-help groups is also important because of the chronicity of the disease and the young age of the patients.

The therapeutic options (Table 3) vary with the degree of disease (mild, severe, fulminant) and areas of involvement (distal, extensive).

• Mild disease can be treated with 5-aminosalicylate agents (mesalamine, olsalazine, balsalazide, sulfasalazine). It can be administered as an enema (40 mg once daily at bedtime for 3 to 6 wk) or suppository (500 mg bid) for patients with distal colonic disease. Oral forms in which the 5-acetyl salicylic acid is in a slow-release or pH-dependent matrix (Pentasa 1 g qid, Asacol 800 mg PO tid) can deliver therapeutic concentrations to the more proximal small bowel or distal ileum. Olsalazine can be useful for maintenance of remission of UC in patients intolerant to sulfasalazine. Usual dose is 500 mg bid taken with food. Balsalazide is indicated for mild to moderately active UC. Usual dose is three 750-mg capsules tid. Probiotics may also be helpful in inducing remission in mild-to-moderate UC.
• Mild-to-moderate UC is often treated with a combination of rectal and oral 5-aminosalicylate. Refractory patients are candidates for oral glucocorticoids or immunosuppressive agents (e.g., cyclosporine).
• Severe disease usually responds to oral corticosteroids (e.g., prednisone 40 to 60 mg/day); the FDA has recently approved an extended-release formulation of the corticosteroid budesonide for induction of remission in mild to moderate UC. Corticosteroid suppositories or enemas are also useful for distal colitis. The immunosuppressant azathioprine or mercaptopurine also provides effective long-term treatment for Crohn disease. In patients with moderately to severely active disease, a tumor necrosis factor (TNF) inhibitor (infliximab, adalimumab, golimumab), an integrin receptor antagonist (vedolizumab), or an interleukin (IL) 12-23 antagonist (ustekinumab) are useful for both induction and maintenance of remission. In patients with moderately to severely active ulcerative colitis who cannot tolerate or respond poorly to TNF inhibitors oral Janus kinase inhibitors (tofacitinib or upadacitinib) may be effective. The FDA has also approved ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator for treatment of adults with moderately to severe active ulcerative colitis who had an inadequate response to or would not tolerate other drugs.
• Fulminant disease generally requires hospital admission and parenteral corticosteroids (e.g., IV hydrocortisone 100 mg q6h). When bowel movements have returned to normal and the patient is able to eat normally, PO prednisone is resumed. IV cyclosporine can also be used in severe refractory cases; renal toxicity is a potential complication.
• Surgery is indicated in patients who do not respond to intensive medical therapy. Fig. 2 illustrates the surgical management of chronic UC.
• Proctocolectomy is usually curative in these patients and also eliminates the high risk of developing adenocarcinoma of the colon (10% to 20% of patients develop it after 10 yr with the disease). Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the procedure of choice for most patients who require elective surgery, since it preserves anal sphincter function. Continent ileostomy is an alternative procedure.

Figure 2 Surgical management of chronic ulcerative colitis.

From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.

• Colonoscopic surveillance and multiple biopsies should be instituted approximately 10 yr after diagnosis because of the increased risk of colon carcinoma.
• Erythropoietin is useful in patients with anemia refractory to treatment with iron and vitamins.
• In patients on long-term steroid therapy, periodic bone density scans are recommended to screen for glucocorticoid-induced osteoporosis.

• The natural history of the disease is one of remission and episodic flares.
• The clinical course is variable. ∼66% of patients will achieve clinical remission with medical therapy, and nearly 80% of treatment-compliant patients maintain remission. 15% to 20% of patients eventually require colectomy. Pouchitis is the most common long-term complication of IPAA (up to 40% of patients). >75% of patients treated medically will experience relapse.

• GI consultation for initial diagnostic sigmoidoscopy/colonoscopy in suspected cases.
• Surgical referral for patients with severe disease unresponsive to medical therapy. Indications for surgery in patients with UC are summarized in Box 3.

Ulcerative Colitis (Patient Information)