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Ulcerative colitis: A practical approach

By Prof Anthony O’Connor - 21st Sep 2026

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Reference: September 2026 | Issue 9 | Vol 12 | Page 42

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Ulcerative colitis (UC) is an immune-mediated inflammatory disorder leading to chronic inflammation and ulceration of the lining of the colon and rectum. It is the most common form of inflammatory bowel disease (IBD). It is differentiated from Crohn’s disease (CD) by multiple pathologic factors and two key clinical phenotypes, namely disease location and behaviour.

As regards location, while CD can affect any part of the gastrointestinal (GI) tract, UC only affects the colon and rectum. In severe cases of the disease, where the entire colon is involved, the ileocaecal valve may become cicatrated and incompetent, allowing retrograde movement of faecal content, leading to a condition called backwash ileitis, where the terminal ileum becomes inflamed. Disease behaviour is the other principal clinical differentiating factor.

While the inflammation in CD is transmural, the inflammation in UC is superficial and thus rarely results in stenosis and fistulation, which are common features of CD. UC, however, may present with extraintestinal manifestations, such as arthritis, osteoporosis, erythema nodosum, episcleritis, uveitis, primary sclerosing cholangitis (PSC) and autoimmune hepatitis.

Epidemiology

UC affects about 500 per 100,000 people in Europe, with rates in Western Europe being twice those of Eastern Europe. In Ireland, it is estimated that, by the end of this decade, population prevalence of IBD will likely reach 1 per cent, with the clear majority of those being UC cases.

While UC can be diagnosed at any age, a bimodal incidence pattern is noted, with the most common age for onset of disease being between 15-30 years, with a smaller peak occurring between 50 and 70 years. In terms of gender, we observe a slight male predominance which is explained by a shifting risk as people age. At younger ages, men and women are diagnosed at relatively equal rates; however, in patients over the age of 45, men have a higher incidence rate of developing UC.

Individuals living in northern latitudes are at significantly increased risk than those living closer to the equator, with meta-regression analyses showing a distinct linear trend – for every 1,000km travelled away from the equator, there is an estimated 0.2 per cent increase in the incidence rate of UC.

While UC has historically been considered a disease of European and Jewish populations, in recent years there has been a huge increase in incidence rates in Asia, which correlates in close parallel with the spread of urbanisation and industrialisation across the region.

Aetiology

The aetiology of UC is a complex interplay of genetic and environmental factors. It is a polygenic disease with almost 250 identified genetic susceptibility loci. Approximately 7-11 per cent of patients diagnosed with UC have a first order relative with the condition. Concordance between monozygotic twins is estimated as being 6 to 18 per cent. Environmental factors including diet, stress, medications, and gut infections may then trigger the disease in genetically susceptible individuals.

Consumption of diets high in processed foods, increased intake of animal proteins, omega-6 fatty acids, and refined sugars may increase UC risk. Diets low in fibre lack protective benefits for the gut lining and may also increase risk. A paradoxical health benefit is observed for cigarette smoking, where non-smokers have a significantly higher risk of developing UC and the disease is not infrequently diagnosed in patients who have recently quit smoking. The inverse is true for CD. Other environmental triggers, such as specific viral or bacterial infections or medications like NSAIDs, may act as the catalyst that sets off the immune response in genetically vulnerable people

This causes the immune system to overreact and mistakenly attack the healthy lining of the colon and rectum, releasing harmful pro-inflammatory cytokines.

Diagnosis

The process of diagnosing UC begins in the consultation room. The most common presenting symptom is diarrhoea, but it is the presence of blood in the stool that is the cardinal hallmark of a likely UC diagnosis. Disorders of gut-brain interaction (DGBI), such as irritable bowel syndrome, occur in approximately 15-20 per cent of patients in western populations. The key task when a patient presents with lower GI symptoms is to differentiate those who require further investigation to rule out an organic disorder from those who can be positively diagnosed with DGBI.

It is important to note the differences between diarrhoea of large versus small bowel origin. Small bowel diarrhoea is more likely to be watery, of large volume, and accompanied by cramping, bloating, and gas. Fever is rare. By contrast, the features of large bowel diarrhoea, as one may see in UC, are those of frequent, regular, small volume stool, accompanied often by blood and mucus. Fever is much more common, as is pain.

Important differentials here include infections (salmonella, shigella, campylobacter, cytomegalovirus [CMV], adenovirus, entamoeba histolytica, C. difficile and E. coli O157:H7), colorectal cancer (CRC), ischaemic or diverticular colitis. History, therefore, should focus on factors such as symptom duration (UC is often more subacute, evolving over weeks to months), age of the patient, family history of IBD or CRC, travel history, and risk factors for ischaemia, and drug history. Diarrhoea occurring at night should also prompt further investigation.

Clinical examination is often more or less unremarkable. More common findings are mild tenderness, often localised to the left lower quadrant and maybe pallor or weight loss. In severe cases, signs such as peritonitis, distension, toxicity, tachycardia, and volume depletion should prompt concern for acute severe ulcerative colitis (ASUC). ASUC is a medical emergency that will be dealt with in more detail later. It is reported that 10-20 per cent of UC patients present initially with ASUC, and one third of all ASUC presentations occur in the first year post-diagnosis.

Investigations are dictated by clinical history. For patients with red flag symptoms, direct referral for colonoscopy is recommended These include unexplained rectal bleeding, weight loss, iron deficiency anaemia, perianal fistula or abscess, drainage, extraintestinal manifestations (inflammatory arthritis, uveitis, erythema nodosum, pyoderma gangrenosum), or diarrhoea, with a family history of IBD or CRC.

For patients under the age of 45 with diarrhoea and without red flags, a non-invasive investigation approach may be appropriate in the first instance, with CRP and faecal calprotectin tests. If CRP and faecal calprotectin are negative in this population, the yield at colonoscopy is less than 1 per cent and they can reasonably be treated for irritable bowel syndrome, assuming other conditions such as coeliac disease and thyroid dysfunction have been ruled out.

Colonoscopy findings include erythema, oedema, loss of vascular pattern, granularity, friability, erosion, and ulceration occurring in a continuous, symmetrical pattern that begins in the rectum and extends proximally into the colon. Histological features are of acute active inflammation with cryptitis and crypt abscesses, and chronic architectural changes including crypt distortion, Paneth cell metaplasia, and crypt atrophy.

UC is categorised into three classic anatomical distributions:

• Proctitis: Inflammation remains limited solely to the rectum.
• Left-sided/distal colitis/proctosigmoiditis: Inflammation extends from the rectum, through the left side of the colon, stopping at or before the splenic flexure.
• Extensive colitis/pancolitis: Inflammation extends past the splenic flexure. This form carries the highest risk of severe complications

Treatments

Treatment is based on the severity and location of the disease.

Proctitis or left-sided colitis is usually treated in the first instance with topical aminosalicylates, with suppositories favoured in rectal disease and enemas in disease extending beyond the rectosigmoid junction. In pancolitis, combined high dose (>4g/day) oral and topical aminosalicylates are initiated together.

In all cases, the patient should be reviewed after no more than four weeks. In proctitis or left-sided colitis, if the patient has not improved, high dose oral aminosalicylate is added. If no further improvement is seen in four weeks, oral corticosteroids are given. In pancolitis these are given at the first point of escalation.

Once remission has been achieved, it may be maintained with lower dose oral aminosalicylates (>2g/day and <4g/day). When this is not effective, immunomodulators or biologics may be used. Immunomodulators may be used for frequent relapses or steroid dependence include azathioprine, mercaptopurine, or methotrexate, but are limited in their use by side effect profile, the need for monitoring, and a lack of robust randomised clinical trial evidence. In practical terms, an increasing proportion of patients with moderate to severe UC are being treated with biologic therapy.

Biologic therapy

Biological therapies have revolutionised the management of UC in the last 25 years and can be categorised thus:

• Anti-TNF agents: These include infliximab, a monoclonal antibody against TNF-α. It was the first and still is the most commonly used biologic approved for UC treatment. It is available in both intravenous and subcutaneous forms and is approved for both induction and maintenance therapy. Combination therapy with a thiopurine has been shown to be effective in the most severe cases, albeit with a higher rate of adverse events. Other anti-TNF agents, including adalimumab, golimumab, and certolizumab, may also be used.
• Anti-integrin agents: These include vedolizumab, a monoclonal antibody against the α4β7 integrin. This is a gut specific agent with a very favourable adverse event profile. It is the favoured biologic in very elderly patients and those with active malignancy or specific concerns around immunosuppression.
• IL12/IL23 inhibitors: First-generation agents, such as ustekinumab, target the shared p40 subunit, blocking both IL-12 and IL-23 signalling, and are modestly efficacious in UC. However, in recent years, second-generation selective inhibitors, targetting the p19 subunit of IL-23, have become available. These agents, which include mirikizumab, guselkumab, and risankizumab, attenuate pathogenic pathways while preserving the wider immune system.
• Janus kinase (JAK) inhibitors: These are the first available oral small-molecule medications used to treat moderate to severe UC and disrupt the JAK-STAT pathway, interrupting IL-6 and IL-23. These agents are quite fast-acting and efficacious, in some cases, within days. This category includes tofacitinib, upadacitinib. and filgotinib. Their use is limited to patients aged under 65, non-smokers, and those without a history or risks for cardiac disease, due to a safety signal for major cardiac adverse events observed in arthritis indications that has thus far not been seen in the IBD population.

Monitoring

The holy grail in the management of UC is the achievement of so-called deep remission, consisting of resolution of symptoms (clinical remission), normal levels of CRP and faecal calprotectin (biochemical remission), and resolution of colonic inflammation and ulceration at endoscopy (mucosal healing). In recent years, the even more exacting goal of histologic remission, involving the resolution of histologic findings on biopsy, has been incorporated by some opinions into the definition of mucosal healing. In practical terms, though, the achievement of steroid-free clinical remission remains the principal aim for most patients.

Checking CRP and calprotectin every six months is a useful tool to help maintain remission and alert to the possible need to escalate therapy prior to the development of clinical symptoms. Regarding calprotectin, it is important to note that, when monitoring the progress of a patient with known UC, the cut-offs are different from those used when the test is deployed as a screening tool. Values under 250µg/g are considered by the European Crohn’s and Colitis Organisation to be consistent with remission, although some authorities advocate pursuing a lower level of 150µg/g. Further follow-up blood tests that should be performed every six months include full blood count, renal, liver, and bone profiles, and assessments of nutritional status including iron, vitamin B12, folate, and vitamin D.

Colonoscopy may be undertaken six-12 months after a change in therapy to ensure response. However, in reality, this is not acceptable to many patients or practical in all settings and systems, and a good calprotectin response may be an adequate surrogate. It is important to perform sigmoidoscopy/colonoscopy with biopsy in patients who are failing to respond to steroids or conventional treatments to ensure that alternative concurrent diagnoses are not present, such as CMV or other infectious colitis, pseudomembranous colitis, or CRC, all of which are more common in patients with UC.

In addition, it is worth remembering that rates of concurrent IBS among patients with UC are twice those observed in the broader population. Colonoscopy in these cases can reduce the risk of inappropriate escalation of therapy when symptoms are driven by DBGI rather than UC. Surveillance colonoscopy should begin eight years after the onset of symptoms (as opposed to diagnosis, which may be delayed) of UC.

Potential adverse effects

Patients with UC on immunosuppressants are at increased risk of infection, although this is frequently overstated. Clinical data show a roughly 19 per cent increase in the odds of non-serious infections (such as upper respiratory or minor bacterial issues) for patients on biologics compared to controls. Regarding severe infection, the risk is greater than the background population – 3-8 per 100 person-years on biologics compared to 1 per 100 person-years in the background population. The odds ratio (OR) for opportunistic infections can be elevated (up to 1.90). It is for this reason that pre-screening, such as for latent tuberculosis, HIV, viral hepatitis, EBV, CMV, and varicella are standard clinical practice.

Annual seasonal flu vaccination, pneumococcal, hepatitis B, tetanus, diphtheria, HPV, and polio vaccines are recommended. Recombinant zoster vaccines are recommended especially for patients on JAK inhibitor therapies or older age groups to prevent shingles. Live vaccines must be avoided in immunosuppressed patients.

Osteopenia and osteoporosis are common, and patients with more than three months of corticosteroid exposure should undergo bone density screening.

Cancer risk

CRC risk is increased in UC patients with greater disease extent than proctitis. The risk increases by 0.5 per cent per year, beginning eight years after onset of disease. This is why surveillance begins at this interval. Surveillance intervals depend on the extent of the disease, the severity of inflammation, concurrent colonic polyps (either UC-related or sporadic adenomas), family history of CRC, and co-existing diagnoses such as primary sclerosing cholangitis (PSC).

PSC patients require colonoscopy, a liver ultrasound, and/or MRI/MRCP at least annually. Controlling inflammation with medications and adhering to surveillance colonoscopy is the best means of reducing cancer risk. Large meta-analyses and population studies show that using biologics alone (such as anti-TNFs like infliximab or adalimumab, or gut-selective therapies like vedolizumab) does not raise the overall rate of malignancies compared to the general population or non-biologic control groups.

However, some studies have suggested increase rates of lymphoma and non-melanoma skin cancer in some patients, especially the over 65s. Hepatosplenic T-cell lymphoma is a rare but serious concern, particularly in EBV-naïve young males on combination therapy with thiopurines and anti-TNF. Skin protection measures such as high UV level sun block, wearing hats and long sleeves are advised.

Role for surgery

The proportion of patients requiring surgery for UC has declined significantly in the biological era, with the cumulative five-year probability of surgery for UC dropping from roughly 16 per cent in cohorts from the 1980s and 1990s, down to about 6 per cent in contemporary groups. The proportion of hospitalised UC patients requiring a colectomy fell by nearly half (from 5 per cent to 2.7 per cent) over a single decade from 2007 to 2017. Ileal pouch-anal anastomosis (IPAA), also known as J-pouch surgery, remains the commonest standard surgical procedure for treating severe or medication-resistant ulcerative colitis.

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