Diarrhea usually mixed with blood, with or without mucus
Constipation in some cases of severe proctitis
Extraintestinal (about 10 % of patients )
Related to disease activity
Deep vein thrombosis
Unrelated to disease activity
Primary sclerosing cholangitis
Acute lower gastrointestinal hemorrhage
Abdominal examination is often unremarkable apart from mild tenderness. Significant tympanitic distension or any evidence of peritonism are of great concern and need urgent attention. During acute attacks the patient may become dehydrated, hypokalemic (from diarrhea), and anemic (from GI blood loss).
A relapsing and remitting course is the usual pattern of illness; about 50 % of patients with UC have a relapse in any given year.
Symptoms and signs can be formally scored using validated disease activity scores for UC (e.g., Lichtiger score; see Table 14.2).
Activity score for ulcerative colitis (Lichtiger et al.) 
0 = 1–2 times/day
3 = 6–9 times/day
1 = 3–4 times /day
4 = ≥10 times /day
2 = 5–6 times /day
Nocturnal bowel movement
0 = No
1 = Yes
0 = None
2 = ≥50 % of time
1 = <50 % of the time
3 = Every time
0 = No
1 = Yes
0 = None
1 = Mild; minimal interference with daily activity
2 = Moderate; interferes with daily activity
3 = Severe; incapacitating
0 (Excellent) to 5 (terrible)
Antidiarrheal or opioid drugs
0 = No
1 = Yes
0 = None
1 = Mild to moderate but localized
2 = Mild to moderate but diffuse
3 = Severe or evidence of peritonism
14.4.1 Colorectal Cancer
Colorectal cancer (CRC) is the most common neoplastic complication of UC, with an incidence of 3 per 1,000 person-years of disease and a prevalence of 3–7 % . It is more likely to be multiple, have a higher grade, and be nonpolypoid than sporadic noncolitic cancers.
Particular risk factors for CRC among people with UC are:
Diagnosis of PSC
History of colitis for >8 years
Severity of colitis (particularly the first attack)
Young age at onset of colitis
Family history of CRC
Considering all patients with UC, the risk of cancer increases with the duration of the disease:
Two percent at 10 years
Ten percent at 20 years
Twenty percent at 25 years
The risk in the subgroup of those with extensive colitis is significantly greater:
Five percent at 10 years
Twenty percent at 20 years
Forty percent at 25 years
Dysplasia in UC is the most reliable marker of an increased risk of CRC, but it can be difficult to detect. It is divided into four categories:
Low grade (LGD)
High grade (HGD)
Dysplasia presents as two main patterns: flat lesions and elevated lesions. Flat dysplasia is often identified incidentally in surveillance biopsies from unremarkable mucosa, although dye-spraying may improve the detection of flat dysplasia. Elevated lesions can be either adenoma-like – essentially sporadic adenomas, as in people without UC – or non-adenoma-like. This latter group is more heterogeneous, the lesions are less demarcated, and the surrounding flat mucosa is more likely to be dysplastic. Hence biopsy of the surrounding mucosa of any elevated lesion in UC is essential. Adenoma-like dysplasia can essentially be treated like any other adenoma if the surrounding mucosa is nondysplastic.
A proctocolectomy with or without ileal pouch formation should be recommended to all patients with the following conditions [13, 14]:
Any elevated lesion with surrounding flat dysplasia
A non-adenoma-like elevated lesion
It should also be considered in patients with flat LGD. Patients should be told that their risk of CRC is nine times greater than that in patients without LGD, and the risk increases with a more distal location of the cancer in the colon/rectum. A colectomy with ileorectal anastomosis could in exceptional circumstances be considered in colonic cancer/HGD with careful postoperative surveillance (see below Sect. 14.11.2: Colectomy and ileorectal anastomosis). Given these risks in UC, screening for colorectal cancer is obviously important. Screening guidelines have been developed :
Ideally, screening should be performed when a patient is in remission.
The first surveillance colonoscopy should be performed after 6–8 years from the onset of symptoms. It is at this colonoscopy that the extent of disease is accurately documented .
The frequency of surveillance is guided by the risk of CRC in any individual and is normally categorized into high risk (yearly colonoscopy), intermediate risk (every 3 years), and low risk (every 5 years) . The risk stratification is based on how extensive the colitis is, the severity of inflammation, the presence of pseudopolyps, and a family history of CRC.
Ideally, pancolonic dye-spraying should be used with targeted biopsies of abnormal areas. If this is not available, however, two to four random biopsies should be taken every 10 cm along the entire colon and rectum. Additional biopsies should be taken in suspicious areas.
Patients diagnosed with PSC should have annual colonoscopies irrespective of the state of the liver disease.
In patients with LGD at one site, colonoscopy should be performed every 6 months until two successive colonoscopies are negative.
The risk of cholangiocarcinoma is increased in patients with UC on account of the relationship between UC and PSC. About 4 % of patients with UC develop PSC during their lifetime, and in this population the lifetime risk of cholangiocarcinoma is about 10 %. The risk of cholangiocarcinoma, like PSC, is not influenced by the disease activity of UC.
14.4.3 Toxic Megacolon
This is a nonobstructive dilatation (>6 cm) of colon in conjunction with extensive colitis (rarely just left-sided disease) and systemic disturbance. The incidence is falling and currently occurs in less than 4 % of patients with UC. Patients are at greatest risk early after diagnosis, especially during the first attack. It often follows a prolonged attack of drug-resistant acute colitis, and hypokalemia, opioid analgesics, drugs causing constipation, anticholinergics, and possibly superadded infections such as Clostridium difficile and cytomegalovirus are believed to be precipitants. Examination reveals mild tympanitic distension, but any evidence of localized or generalized peritonism should be an indication for emergency surgery. Medical management of toxic acute UC is permissible at the first instance (see Sect. 126.96.36.199), but any deterioration or failure to improve should again lead to emergency surgery.
The criteria for diagnosis of toxic megacolon are :
Diagnosis of colitis
Radiographic evidence of colonic distension >6 cm
Fever >38 °C
Heart rate >120 bpm
Neutrophilia >10 × 109
One of the following:
Glasgow Coma Scale score <15
The dilatation is accompanied by and possibly the result of inflammation of the bowel wall extending beyond the mucosa into the muscle. This leaves the bowel prone to perforation, which is why the condition is so dangerous. Perforation of a toxic megacolon carries a mortality of 40 %.
14.4.4 Acute GI Hemorrhage
Severe GI bleeding occurs in less than 5 % of all patients with UC but accounts for about 10 % of the emergency colectomies performed for UC . The risk of significant hemorrhage increases with the extent of the disease.
14.4.5 Benign Strictures
These occur in about 4 % of all patients with UC, predominantly in the left colon. Treatment depends on the degree of symptoms and the extent of disease elsewhere in the colon. Total colectomy is the usual surgical option.
UC is diagnosed based on a suggestive history and examination leading to a combination of endoscopic, histological, and microbiological investigation.
The gold standard for diagnosing colitis is flexible sigmoidoscopy/colonoscopy. This shows acute inflammation starting in the rectum and extending proximally, and allows biopsies to be taken for histology. Care is required because the risk of perforation is high in acute disease, and colonoscopy should be reserved for assessing the extent of disease after the acute attack has been treated. Extent of disease is defined by the Montreal classification (Table 14.3). About 20 % of patients have extensive disease at presentation  (Fig. 14.1).
Disease limited to the rectum
Disease limited to the colorectum distal to the splenic flexure
Disease beyond the splenic flexure
Proportion of people with varying extents of disease at presentation
In active disease, the mucosa is erythematous, granular, friable, and demonstrates contact bleeding. Pseudopolyps, which are islands of mucosa within an area of extensive ulceration, may be present in severe disease. In quiescent chronic disease, the mucosa usually shows signs of chronic injury, with loss of the normal vascular pattern, and may appear featureless. Inflammatory polyps may be present.
Biopsies should be taken from multiple sites along the colon (including areas that appear normal), always including the rectum . The contiguous nature of the disease is one of the major features that distinguishes UC from Crohn’s colitis, although this is not always apparent macroscopically. However, even when there is variation in the severity of the colitis between different segments of the bowel, which can give a false impression of skip lesions, biopsies from the apparent “skip” area usually show features of chronic inflammation typical of UC, highlighting the importance of multiple biopsies. In chronic disease and in patients who have received topical therapy, the rectum can often appear normal, giving the impression of rectal sparing. Again, biopsy is crucial in the diagnosis. Another area of confusion is near the ileocecal valve, where the “cecal patch” can give the impression that it is a focus of inflammation distant from a more distal area of colitis and therefore a “skip lesion.” This can be seen even in normal asymptomatic individuals.
Once colitis is established as a cause of the patient’s symptoms, histology and microbiology help confirm the diagnosis of UC.
All patients with colitis should have stool sent for microbiological assessment to exclude an infectious cause of their colitis. This should include virology, parasitology, and C. difficile toxin.
UC is confined to the large bowel, although up to 30 cm of terminal ileum can be involved with “backwash ileitis.” Reports of biopsies taken during ileocolonoscopy should describe whether the tissue shows features of UC to distinguish it from other common causes of colitis such as Crohn’s disease, pseudomembranous colitis, and diverticular disease. They should also comment on disease activity and on any dysplasia seen within the specimen.
The severity of the inflammatory reaction correlates well with the clinical course of the disease. Cardinal features of UC include:
Inflammation limited to the mucosa and superficial submucosa, although deeper layers can be involved in fulminant colitis
Diffuse and severe distortion of crypt architecture, although this can take 6 weeks to develop
Diffuse and severe reduction in crypt density
Heavy infiltration of inflammatory cells in the lamina propria, especially basal plasmocytosis. Neutrophils are prevalent in active disease, and these can form crypt abscesses, which are a reliable indicator of disease severity.
Severe mucin depletion
Superficial ulceration in active disease
14.6 Additional Useful Diagnostic Procedures
Blood tests often show a chronic or acute-on-chronic inflammatory response:
High C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white cell count
Low hemoglobin, albumin
Renal function in all patients presenting with severe acute colitis
Liver function tests to assess progressive PSC
Perinuclear anticytoplasmic antibody (pANCA) serology is commonly positive in UC, whereas Crohn’s disease is often negative for pANCA but positive for anti–Saccharomyces cerevisiae mannan antibodies. Patients who are pANCA positive and anti–Saccharomyces cerevisiae mannan antibody negative are far more likely to have UC than Crohn’s disease.
Fecal calprotectin is sensitive for GI inflammation.
Plain abdominal radiography is vital in cases of severe acute colitis to exclude toxic dilatation of the colon. If there is any suspicion of toxic megacolon clinically or radiologically, plain abdominal radiography should be repeated daily until the clinical condition improves. Edema of the bowel wall can be seen as “thumbprinting.”
Computed tomography (CT) is useful in assessing the extent of inflammation in UC, although this is nonspecific and does not help in separating the various possible etiologies of the inflammation. CT colonography (virtual colonoscopy) is not a good substitute for colonoscopy in colitis, but it may be used to assess strictures where endoscopy has failed.
An erect chest radiograph is also useful in cases of suspected perforation.
Contrast enemas are not commonly used and are reserved for stricture assessment where endoscopy has failed and CT colonography is not available.
UC should be managed jointly by physicians and surgeons.
14.7.1 Conservative Treatment
No evidence that elemental diets or any other treatment other than pharmacological or surgical treatment is of benefit in either the induction or maintenance of remission in UC.
14.7.2 Medical Treatment
The medical treatment of UC is divided into treatment of acute disease, treatment of chronic active disease, and maintenance of remission. Following ileal pouch formation (see Sect. 14.11.4), patients can develop pouchitis. This is discussed here.
188.8.131.52 Acute Colitis
Patients with mild/moderate disease can be managed as outpatients, whereas those with severe disease require inpatient care. Severe attacks are defined by a modernized version of the Truelove and Witts criteria  and can be characterized by:
Stool frequency (>6 per day)
Plus any one of the following:
Temperature >37.8 °C
Pulse >90 bpm
Hemoglobin <10.5 g/dL
CRP >30 g/L
Specific monitoring and treatment apply are required for patients experiencing severe attacks :
Frequent clinical evaluation, including stool charts
Daily blood assessment (full blood count, CRP, electrolytes, albumin)
Stool culture, including C. difficile analysis
Daily abdominal radiography if any suspicion of colonic dilatation is present
High-dose intravenous (e.g., hydrocortisone 100 mg four times daily) and topical steroids administered rectally (e.g., hydrocortisone liquid enemas four times daily)
Intravenous cyclosporine in thiopurine-naïve patients if there is no significant improvement after 3 days, followed by oral cyclosporine when in remission (2 mg/kg intravenously and 4–9 mg/kg orally)  or oral azathioprine (1.5–2.5 mg/kg/day). This has been shown to reduce the colectomy rate in patients who do not respond to steroids, although there is a high relapse rate once the cyclosporine is stopped.
Infliximab may be used as an alternative to cyclosporine .
Intravenous electrolyte-rich fluid with or without blood, as required (maintain hemoglobin >8–10 g/dL)
Anticoagulation (e.g., subcutaneous low-molecular-weight heparin daily) is essential in UC given the increased risk of deep vein thrombosis in these patients.
Avoid antidiarrheal drugs (e.g., loperamide, codeine), opioids, anticholinergics, and, if possible, nonsteroidal anti-inflammatory drugs, all of which increase the risk of perforation. Remember that significant pain may indicate perforation.
Oral 5-aminosalacylic acid (5-ASA) compounds provide no advantage in acute colitis.
Broad-spectrum antibiotics can be used in those showing signs of septic complications.
After 3 days of treatment, patients with stool frequency >8/day or a Units of CRP are mg/L >45 are unlikely to improve without a colectomy .
Failure to improve within 7 days of treatment or deterioration within that period indicates that surgery is required.
Once the clinical condition has improved, patients should convert to oral treatment (as used for mild/moderate acute attacks).
Patients should be encouraged to eat and drink during severe attacks. A low-fiber diet is usually recommended.
Mild/Moderate Acute Colitis
Specific treatment applies for patients with mild or moderate acute colitis :
First-line treatment should be with an oral and topical 5-ASA compound (mesalazine). The oral dose should be >2 g daily and the rectal dose, 1 g daily. These can be reduced slowly as symptoms improve.
When symptoms do not improve within 2 weeks, oral steroids can be administered, with a reducing dose starting at 40 mg prednisolone daily and titrating over 6 weeks until treatment is stopped.
If symptoms deteriorate during the reducing regimen then the steroids should be increased again until symptoms settle.
Initially administer oral mesalazine 2–4 g daily, which should be continued after remission is established, and then reduced to half this dose after 2 months (see Sect. 184.108.40.206).
220.127.116.11 Chronic Active Disease
For patients with chronic active disease :
A 5-ASA such as mesalazine 4 g daily initially, forms the basis of treatment. These are used in conjunction with 5-ASA enemas (e.g., mesalazine 1 g daily) as for mild/moderate acute colitis.
Failure to wean completely from steroids should lead to the consideration of azathioprine as a steroid-sparing agent (aim for a maintenance dose of 1.5–2.5 mg/kg/day)..
Anti–tumour necrosis factor (TNF) therapy should be considered in thiopurine-intolerant patients (ACT I and ACT II trials) . Tacrolimus has also been shown to reduce the level of steroid maintenance in refractory disease.
Appendicectomy may have some effect in the management of ulcerative proctitis, but more studies are needed .
18.104.22.168 Maintenance of Remission in Quiescent Disease
The chance of maintaining remission can be maximised by following some key principles :
Lifelong treatment should be administered, if tolerated by the patient.
5-ASA compounds are the mainstay of treatment (e.g., mesalazine 1–2 g/day).
For distal disease, treatment with topical 5-ASA therapy alone (e.g., mesalazine 500 mg daily) is acceptable if tolerated by the patient.
For those with frequent relapses despite or for those intolerant to 5-ASA compounds, consider azathioprine 1.5–2.5 mg/kg/day. Anti-TNF therapy is an alternative.
Appendicectomy has been suggested as a possible adjunct in the maintenance of remission of UC .
Antibiotic therapy is the first-line treatment for pouchitis: commonly metronidazole (400 mg three times daily) or ciprofloxacin (500 mg twice daily) for 2 weeks.
There is some evidence that combined ciprofloxacin and metronidazole for 4 weeks is superior to either agent alone in reducing remission .
Long-term low-dose antibiotics can be used for those with frequent relapses.
Topical mesalazine or steroids are used when antibiotics fail to improve the pouchitis.
Chronic pouchitis is a common cause of pouch failure. Treatment with concentrated preparations of probiotic bacteria (e.g., VSL#3) has had some success both in maintaining remission in chronic pouchitis [32, 33] and as prophylaxis . Budesonide and infliximab have also been used in the treatment of chronic pouchitis.
The 2015 European consensus guidelines  provide a review of the evidence for surgical decision making in UC. Despite advances in medical treatment, up to 30 % of patients with UC will ultimately require a colectomy. The indications for surgery are:
Development of complications (e.g., perforation, hemorrhage, dysplasia, cancer)
Failure of medical treatment
Frequent relapses or steroid resistance
Drug side effects, including steroid dependence
In both situations there are those who require emergency surgery (eg severe acute colitis not responding to medical treatment (Fig. 14.2), colonic perforation) and those who can have their surgery planned electively.
Severe acute colitis (Courtesy of Illustration Services, Cellular Pathology, John Radcliffe Hospital, Oxford, UK)
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Emergency surgery involves total colectomy and end ileostomy as a life-saving procedure. Management of the retained rectum is discussed below. Patients presenting with severe acute colitis as their first attack are the most likely to require colectomy (up to 25 %).
Following recovery from a total colectomy, the fate of the remaining rectum must be considered, as it can continue to cause bloody anal discharge if the inflammation fails to subside, and it remains a site of potential cancer, although the risk is about 5 % over 20 years. There are four options for the residual rectum:
Progression to restorative proctocolectomy, if suitable (see Sect. 14.8.1 Completion proctectomy)
Completion proctectomy (see Sect. 14.8.1 Completion proctectomy)
In elderly patients with significant rectal disease in whom the rectum was divided at the level of the levators during emergency surgery, knowing that a pouch or ileorectal anastomosis would never be considered. This technique is rarely used.
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