capability of improved soft tissue differentiation. Particularly in the last decade, developments in MRI

hardware and software has made this imaging modality an especially valuable tool in diagnosing and

following patients with UC (Fig. 66-4).51

Figure 66-2. A: Erythema nodosum. B: Pyoderma gangrenosum. (Reproduced with permission from Goodheart HP. A Photoguide of

Common Skin Disorders: Diagnosis and Management. Baltimore, MD: Lippincott Williams & Wilkins; 1999.)

Figure 66-3. Abdominal x-ray of Megacolon Beck DE, Roberts PL, Saclarides TJ, et al. ASCRS. New York, NY: Springer; 2011.

Ultrasound and nuclear medicine may provide complementary information in addition to CT and MRI

but are currently used less commonly and are utilized only for specific situations.

Endoscopy

Endoscopic evaluation is the most useful tool in diagnosing UC. Often the first step is a flexible

sigmoidoscopy or rigid proctoscopy especially in cases of acute flare, when a full colonoscopy may pose

a significant risk of perforation. The macroscopic appearance of the colon through the endoscopy can

often differentiate between UC and CD. Biopsies are taken, in addition to stool samples to rule out

bacterial pathogens and ova/parasites.

Pathology

Macroscopic Appearance

UC always starts in the rectum and progresses proximally (Fig. 66-5). Although UC is a mucosal and

submucosal disease, in the acute setting of severe disease, the colon wall can be inflamed transmurally,

mimicking CD.

The mucosa is involved in a confluent manner, and unlike CD, fibrosis and strictures are uncommon

(Table 66-2). Most importantly, the presence of stricturing disease in UC represents the potential for

malignancy, which must be excluded. Superficial fissures are common, as are pseudopolyps. On

occasion, the rectum can appear to be spared, especially if topical medication has been used through

enema or suppository.

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Figure 66-4. MRI demonstration of active UC with rectal wall thickening, increased vascularity, and inner layer

hyperenhancement. Courtesy of Dr. William Reed.

Microscopic Appearance

UC is an inflammatory process, thus neutrophil infiltration is common, and crypt abscesses form, which

then coalesce to form ulcers (Table 66-2). Goblet cell mucin depletion and crypt distortion are common

in UC. In long-standing UC, special attention must be given to the presence of dysplastic lesions, though

these can be difficult to identify in cases of acute inflammation.

Differential Diagnosis

Bloody diarrhea can be a symptom of an infectious process. It is important to rule out pathogenic

bacteria, parasites, and viruses. Clostridium difficile should specifically be excluded. Other infectious

agents include Salmonella, Escherichia coli (0157:H7 strain), Camphylobacter, and Entamoeba.

In nearly 10% of the cases, it is impossible to definitively classify the colitis. Over time, a portion of

these indeterminate colitis cases will separate as either Crohn’s or UC. However some will remain as

indeterminate, especially if the serology assessment is inconclusive (for both ASCA and p-ANCA).52

MANAGEMENT

Medical Management

Corticosteroids

Corticosteroids are frequently used as the primary rescue medication in treatment of acute flares of UC.

Corticosteroid efficacy in inducing remission approaches 70%.53,54 Lack of improvement or disease

progression with corticosteroid treatment is followed by biologic agent treatment (as a secondary

rescue medication) or surgery.55 Overall, the use of corticosteroids is decreasing, largely due to the

increase in the number and treatment effectiveness of the biologic agents available. Corticosteroids

should not be used for maintenance of remission due to their side-effect profile. Topical corticosteroids

such as budesonide or rectal preparations can be effective and have a reduced side-effect profile.

However, these medications are not typically used in the acute setting. The side-effect profile of

systemic corticosteroids includes osteoporosis, diabetes, glaucoma, and infections, among others. Longterm use of corticosteroids is associated with an increase in mortality.56

Aminosalicylic Acid Compounds (5-ASA)

These compounds are most commonly used as first line medications in treating mild UC, and can be

used in maintenance of remission. Concomitant use of oral and rectal preparation is effective in

maintenance of UC remission.57 Noncompliance with 5-ASA maintenance therapy is associated with a

fivefold increase in disease recurrence.58,59 Cases of nephrotoxicity have been reported with use of 5-

ASA, though these cases are rare. Folate must be supplemented with treatment of 5-ASA as its

absorption is impaired by 5-ASA.

Immunomodulators (Nonbiologic)

Cyclosporine can be used as an effective first-line or second-line rescue medication (e.g., after failed

corticosteroid treatment) and is currently used at a limited number of centers. It is most commonly used

as first-line treatment, and serves as an option for those patients recalcitrant to corticosteroid

treatment.60 Close monitoring of cyclosporine levels is necessary. Cyclosporine toxicity profile includes

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hypertension, renal failure, and infections.61

Figure 66-5. UC endoscopic findings with A: Loss of normal vascular pattern. B: Contact bleeding. C: Granularity. D: Ulceration

and friability. E: Colonic stricture. (Reproduced with permission from Corman ML. Colon and Rectal Surgery, 5th ed. Philadelphia,

PA: Lippincott Williams & Wilkins; 2005.)

Mercaptopurine (6-MP). 6-MP and its prodrug azathioprine are thiopurine analogs and have been used

extensively in the treatment of UC. They are superior to 5-ASA treatment alone and are often clinically

used in combination with either 5-ASA or anti-TNF drugs in treating IBD.62 Skin cancers and lymphoma

have been reported with thiopurine.63 Severe infections have been reported with use of these

medications.64 Liver enzyme elevations, pancreatitis, and cholestasis have also been seen, and the most

commonly reported side effects are headaches, hypersensitivity, and abdominal pain.

Methotrexate. This medication is rarely used in UC, more commonly used in CD, although its sideeffect profile makes its use difficult even in CD. Hepatotoxicity bone marrow suppression and central

nervous system side effects limit the use of this medication.65

Biologic Immunomodulator Agents

Infliximab is the first anti-TNF medication that was used in treatment of CD in 1988, then shortly after

became FDA approved for use in UC. Infliximab is chimeric mouse–human monoclonal antibody.

Infliximab has been found to successfully induce remission in over 60% of the UC patients treated in the

ACT 1 and 2 trials.66 Extended follow-up of the patients in the trial found that 15% of patients who

initially responded to infliximab subsequently had to discontinue therapy due to side effects or loss of

efficacy.67 Approximately 9% of patients continued to be treated with infliximab for 3 years.

Adalimumab, certolizumab, and golimumab were then added to the list of the anti-TNF agents, a list

that is continually growing. Both infliximab and golimumab have been efficacious in inducing and

maintaining remission in UC patients.66,68,69 Among the biologic agents’ side-effect profile, infection

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remains a persistent concern.70,71 The data regarding malignancy risk with anti-TNF agents are mixed;

there appears to be an increased risk of lymphoma.72

SURGERY

Indications of Surgical Intervention

2 Approximately 20% to 30% of patients that develop UC will ultimately need an operation.73,74

Indications for surgery include fulminant colitis, toxic megacolon, uncontrolled bleeding, neoplasia,

recalcitrance to medical management, unrelenting extraintestinal manifestations, and development of

significant side effects of the treatment medications.

Toxic Megacolon

This is a life-threatening, surgical emergency. Toxic megacolon (Fig. 66-3) is not specific to UC; it can

occur in cases of infectious collidities (C. difficile, Shigella, Salmonella, etc.), or ischemic colitis. Patients

present with systemic toxicity, heralded by high fever, tachycardia, severe abdominal pain, leukocytosis

or leukopenia, and a distended, thickened colon. Immediate, aggressive resuscitation and broadspectrum antibiotics should be started, and all opiates, and antidiarrheal agents should be ceased. An

infectious cause should immediately be ruled out as treatment for UC includes corticosteroids, treatment

which would be detrimental to the management of infectious colidities. Toxic megacolon is seen most

often in new cases of UC, but acute exacerbations of chronic UC can also lead to toxic megacolon.

Nonoperative treatment can be attempted, however, any signs of instability, worsening of the clinical

condition, or lack of improvement within 3 to 5 days should be followed by prompt operative

treatment. In one study, nearly half of all patients with UC treated nonoperatively subsequently

required surgery, most under urgent or emergent circumstances.75 In the contemporary era of biologic

options, failure can occur in up to 30% in the short term (within 30 days), and it is unclear in the long

term how many of these patients will need a colectomy, and under what clinical circumstances.76

Fulminant Colitis

Patients presenting with tachycardia, fever, and surgical tenderness need aggressive resuscitation.

Intravenous steroids should be started promptly, and the patients should be offered surgical treatment

immediately if their condition deteriorates. In general terms, patients should improve within 3 to 5 days

on medical therapy. Early surgical intervention has shown a clear decrease in the mortality rate in

patients failing medical therapy.77,78

Uncontrolled Bleeding

Less than 5% of the patients affected with UC have life-threatening bleeding. In this rare circumstance

an abdominal colectomy is necessary. These cases represent approximately 10% of the emergent

colectomies performed in UC.79

Carcinoma/Dysplasia

Stage for stage, cancer in the setting of UC has the same prognosis, however, cancer is often detected at

a later stage in UC. Nearly 20% of the patients with colorectal carcinoma in the setting of UC are

unresectable at the time of diagnosis.80,81 The highest risk of colorectal cancer (CRC) is seen in those UC

patients with a long history of pancolitis, a risk that accrues after 8 to 10 years of UC. The absolute risk

of CRC development is less than 8% after 30 years of UC.82 Patients with over 8 years of UC,

particularly with extensive colitis, should undergo colonoscopy yearly, or every 2 years.83 It is often

difficult to identify dysplasia in inflamed colon, and thus at the time of colonoscopy, random biopsies

are obtained in addition to sampling any polyps, adenomas, or dysplasia-associated mass or lesions

(DALM). Undetected synchronous cancer can coexist in areas of low- and high-grade dysplasia.84 Thus,

high-grade dysplasia, nonadenoma-like DALMs, and multifocal dysplasia are indications for

proctocolectomy, though there is ongoing research in this area.

Recalcitrance to Medical Treatment

Some patients do not respond fully to medical treatment, and either have persistent symptoms despite

maximal medical treatment, or respond only to corticosteroids, and are thus subject to the side effects

of long-term corticosteroid treatment.

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