Clinical review of ulcerative colitis: epidemiology, diagnosis and management

Ulcerative colitis (UC) is a chronic relapsing and remitting inflammatory bowel disorder. It differs from Crohn's disease in that inflammation is limited to the colon, but may be associated with similar extra-intestinal manifestations (EIMs).

Ulcerative colitis: high incidence rates in the UK (Photo: SPL)
Ulcerative colitis: high incidence rates in the UK (Photo: SPL)

Section 1 Epidemiology and aetiology

In Europe, the highest incidence rates are in Scandinavia (20-26 per 100,000) and the UK (19 per 100,000). The lowest incidence rates are found in southern (0.7-7 per 100,000) and eastern (8.1 per 100,000) European countries. North America and Canada have among the highest incidence rates of inflammatory bowel disease (IBD) in the world.1,2

The incidence of UC is highest between the second and fourth decades of life.3

Aetiology and classification

The aetiology is unknown. Genetic factors contribute to disease pathogenesis. Patients with UC will have a first-degree relative with UC or IBD in up to 15% of cases. Several genes are linked to IBD, with different susceptibility among individuals.

Disease expression is determined by one or more of the environmental factors implicated in IBD - previous appendicectomy, smoking, dietary factors, improved sanitation, oral contraceptives, vitamin D levels and psychological stress.

The gut microbiota also plays a key part in the disease. No single organism is responsible, but there are reports of less diversity in the microbiota with IBD.

The prevailing hypothesis is that inflammation is generated by dysregulated immunological handling of microbial antigens. New molecular techniques are revealing microbiota differences with diet and geographical locations.3

Colonic disease is classified according to its distribution based on the Montreal classification: proctitis (E1), left-sided disease (E2) or pancolitis (E3).

Several classifications developed for clinical trials define mild, moderate and severe disease. The one most easily applied to clinical practice is shown in table 1.

Section 2 Making the diagnosis

UC classically presents with diarrhoea, rectal bleeding, mucus and abdominal pain, symptoms that reflect colonic inflammation. Weight loss can occur and may be due to dietary modifications instigated by patients to minimise symptoms.

The most common EIM presentations are arthralgia, arthritis, ankylosing spondylitis, scleritis, episcleritis and uveitis, erythema nodosum, pyoderma gangrenosum and primary sclerosing cholangitis.

Clinical examination may reveal little except for tachycardia and pallor with severe disease and features of associated EIM.

Rigid sigmoidoscopy is useful in examination because the characteristic feature of UC is rectal inflammation extending proximally in continuity. The features of rectal inflammation in increasing degrees of severity are loss of vascular pattern due to oedema, ulceration, exudates and various degrees of haemorrhage. Such findings are not diagnostic of UC and infectious colitis should be excluded before a diagnosis or relapse of UC is reached.

Investigations
Investigations depend on the setting. The aim in primary care is to make the diagnosis (new or relapse) and in secondary care, to confirm the diagnosis and assess the severity and extent of UC.

In primary care, tests must include stool specimens to exclude infectious colitis, namely salmonella, shigella, Escherichia coli, Clostridium difficile or campylobacter and giardiasis in some cases. A raised CRP and iron deficiency anaemia support the diagnosis. Raised faecal calprotectin can be helpful if rectal bleeding is absent and the presentation mimics irritable bowel syndrome.

Supporting findings include electrolyte disturbance due to fluid loss from the gut and dehydration, and abnormal LFTs, indicative of associated primary sclerosing cholangitis.

A tentative diagnosis can be made in young patients presenting with one or more of the above symptoms and consistent haematological and biochemical changes only after excluding infections.

In secondary care, the diagnosis is based on clinical, endoscopic and histological features. Diagnostic criteria are not routinely used, although the Copenhagen criteria (see box) can be helpful.

Copenhagen criteria

All criteria must be present

  • History of diarrhoea and/or rectal bleeding and pus for more than one week, or repeated episodes.
  • Characteristic endoscopic findings of continuous ulceration, vulnerability or granulated mucosa.
  • Histopathology consistent with ulcerative colitis (neutrophils within epithelial structures, cryptitis, crypt distortion, crypt abscesses).

Section 3 Managing the condition

The aim of therapy is to induce and maintain remission. The therapeutic approach, which depends on the extent and severity of the inflammation, is outlined in figure 1.

Mesalazine
Mesalazine preparations, containing the active moiety 5-aminosalicylic acid (5ASA), taken orally or topically, are first-line drugs with significant response rates and very few side- effects. The preparations differ in the release mechanism of 5ASA.

Response rates of 40-80% and remission rates of 25-35% have been reported.

Most oral preparations are also available as enemas or suppositories, used as monotherapy in left-sided colitis and as oral therapy in pancolitis.

Studies show a synergistic effect when oral and topical therapy are co-prescribed to induce remission.4

Prednisolone
Prednisolone is first-line therapy for severe acute UC or for an incomplete response to mesalazine after 10-14 days.

It is very effective at inducing remission, demonstrating complete remission rates of 58% and partial remission rates of 26% at 30 days. This efficacy is offset by short-term side-effects, particularly weight gain, acne and sleep disturbance.

Early assessment in secondary care is recommended for steroid-refractory and steroid-dependent patients (defined as more than two relapses per year), so steroid-sparing drugs can be prescribed.

The use of such drugs requires specialist monitoring because of the risk of potentially serious adverse events. These drugs include the thiopurines azathioprine and mercaptopurine, tacrolimus, and biological agents such as infliximab and adalimumab.

Once remission is achieved, maintenance therapy reduces the risk of future relapse. The therapeutic options are mesalazine preparations or thiopurines. Long-term maintenance therapy is generally recommended for left-sided and pancolitis, and proctitis that relapses more than once a year.

Surgery
Surgery offers a cure and is indicated for disease refractory to medical therapy or complicated by dysplasia or cancer.3 The options are proctocolectomy with long-term ileostomy, or subtotal colectomy, proctectomy and ileal pouch.

Pouch surgery can affect fertility and sexual function, although recent studies show that laparoscopic surgery reduces this risk.5

Section 4 Prognosis and follow-up

The prognosis is variable. In a five-year cohort follow-up study,6 more than half (59%) experienced one severe presentation followed by minor relapses and remission.

The remainder experienced regular relapses and remissions.

Patients should be educated about self-management and those on mesalazine maintenance therapy should have a twice-yearly renal function check.

Patients with left-sided UC and pancolitis have an increased risk of developing colon cancer. Those with an eight-year history of pancolitis or a 15-year history of left-sided colitis should be enrolled in an endoscopic cancer surveillance programme.

Section 5 Case study

A 32-year-old man presented to the urgent IBD clinic with symptoms of diarrhoea, with a stool frequency of seven times per day to loose watery stool, associated with fresh blood and tenesmus.

He had been diagnosed with UC three years ago, when his disease was limited to the rectum. He had stopped maintenance therapy and his last relapse was two years ago.

Rigid sigmoidoscopy showed inflamed rectum with oedema and bleeding, but no ulceration.

Oral therapy
Stool cultures were sent and the patient was started on oral mesalazine 2.4g twice daily. Stool cultures showed Campylobacter jejuni.

Mesalazine was continued and an antibiotic started. After 10 days, his diarrhoea had improved, but not completely resolved. Repeat stool culture was negative. Mesalazine suppository 1g daily was started.

A colonoscopy two weeks later showed mild pancolitis. The suppository was replaced by mesalazine enema 2g at night.

His symptoms settled after three weeks and the enemas were stopped. The patient remained on maintenance mesalazine 1.2g twice a day.

Remission
This case highlights a number of points. Patients with proctitis can maintain remission without therapy. In 25% of cases, the proctitis can extend to left-sided or pancolitis during the course of the disease. This has a bearing on the choice of first-line therapy.

In this case, because of the severity of his symptoms, he was started on oral therapy. Suppositories were avoided because of the patient's history of tenesmus.

One of the key learning points is that any relapses in UC may be due to an infection, and infection in patients with UC may trigger a relapse of the disease. Oral mesalazine was appropriate, provided the presence of campylobacter was not missed.

Persistent symptoms after successful treatment of campylobacter indicated UC relapse. Suppositories were initially used, based on the previous diagnosis of proctitis.

However, once disease extension was diagnosed by colonoscopy, they were replaced by an enema, to capture the synergistic effect of oral and topical mesalazine. Enemas can be stopped after two to three weeks. This patient should remain on long-term maintenance therapy.

Section 6 Evidence base

Clinical trials

  • Tursi A, Brandimarte G, Papa A et al. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol 2010; 105: 2218-27.

The main outcome was the reduction of a clinical activity index by at least 50% from baseline. A significant improvement in symptoms, but not remission, was observed.

The results suggest that VSL#3 has a role in clinical practice in mild to moderate UC as an alternative to increasing 5ASA drugs, which can induce or exacerbate renal failure.

  • Lobaton T, Rodriguez-Moranta F, Lopez A et al. A new rapid quantitative test for fecal calprotectin predicts endoscopic activity in ulcerative colitis. Inflamm Bowel Dis 2013; 19(5): 1034-42.

The outcome was the accuracy of calprotectin for the prediction of endoscopic activity and reliability of the rapid quantitative test, compared with the ELISA test.

The rapid test correlated more closely with the Mayo endoscopic subscore than clinical or biomarkers.

A cut-off of 280 microgram/g predicted endoscopic remission with strong correlation to a laboratory ELISA test, making it a useful tool for monitoring patients in primary care.

  • Frolkis AD, Dykeman J, Negron ME et al. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta- analysis of population-based studies. Gastroenterol 2013; 145(5): 996-1006.

The main outcome was the change in surgery risk for IBD over time.

The one-, five-, and 10-year risk of surgery was defined among patients with IBD diagnosed in the last half of the 20th century.

The main finding related to UC was a decrease in the oneand 10-year risk of surgery over the four decades. The reduction in surgery can be attributed to changes in clinical practice.

Guidelines

  • NICE. Ulcerative colitis. Management in adults, children and young people. CG166. London, NICE, June 2013.

This has a good algorithm on inducing remission in UC based on the extent of disease (page 39). It is also worth looking at the section on bone health (page 257).

  • Mowat C, Cole A, Windsor A et al on behalf of the IBD Section of the British Society of Gastroenterology. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011. doi:10.1136/gut.2010.224154

These guidelines include three key sections for GPs: safe prescribing of thiopurines in IBD and addressing patients' safety concerns, the importance of vaccination in IBD, and understanding surgery for UC.

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Further resources

  • Feldman M, Friedman LS, Lawrence J. Sleisenger and Fordtran's Gastrointestinal and Liver Disease (ninth edition). Philadelphia, Saunders, 2010. Volume two, chapter 112 covers UC.

Online resources

  • Crohn's and Colitis UK This charity offers, among other resources, a useful range of information sheets for patients, which are free to download.
CPD IMPACT: EARN MORE CREDITS

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Organise an audit of patients in your practice who have UC and review their repeat prescriptions for mesalazine.
  • Review NICE and British Society of Gastroenterology guidelines for updates on UC management.
  • Arrange a meeting with the consultant gastroenterologist and surgeon to discuss a protocol for referring patients with UC.

References

1. Burisch J, Munkholm P. Curr Opin Gastroenterol 2013; 29(4): 357-62.

2. Burisch J, Pedersen N, Cukovic-Cavka S et al. Gut 2013. doi: 10.1136/gutjnl-2013-304636

3. Ponder A, Long MD. Clin Epidemiol 2013; 5: 237-47.

4. Marteau P, Probert CS, Lindgren S et al. Gut 2005; 54(7): 960-5.

5. Beyer-Berjot L, Maggiori L, Birnbaum D et al. Ann Surg 2013; 258(2): 275-82.

6. Henriksen M, Jahnsen J, Lygren I et al. Scand J Gastroenterol 2006; 41(9): 1037-43.

  • Dr Naila Arebi, consultant gastroenterologist, The London Clinic and St Mark's Hospital, London.

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