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Understanding ulcerative colitis

Declaration of sponsorship Takeda
Read time: 20 mins
Last updated:14th Oct 2021
Published:14th Oct 2021

Improve your ability to support patients with ulcerative colitis.

  • Visualise the pathogenesis with our diagrammatic overview
  • Discover how disease severity is determined with endoscopic imagery
  • Get to grips with the ongoing evolution of therapeutic targets
In this section

Epidemiology

Prevalence and incidence

Ulcerative colitis has a higher prevalence than Crohn’s disease in adults1,2. It is a chronic, progressive, relapsing and remitting condition characterised by continuous inflammation of the colonic mucosa3–5. As in Crohn’s disease, there are regional variations in the prevalence and incidence of ulcerative colitis, but an overall global increase has been consistently reported6–9.

A systematic review investigating the worldwide prevalence and incidence of ulcerative colitis revealed that the prevalence was highest in Europe (505 cases per 100,000 individuals) and North America (249 cases per 100,000 individuals) (Figure 1)10. Within these regions, the highest prevalence values have been reported in Norway and the United States11.

T2 UC - Jan2021.Fig1.png

Figure 1. Worldwide ulcerative colitis prevalence per 100,000, 1990–2016 (Adapted11).

Overall, incidence of ulcerative colitis is increasing globally, though there is substantial variation between different populations and geographical regions, with estimates ranging from 0.5–31.5 cases per 100,000 individuals each year9,12,13. In recent years, newly industrialised countries have experienced a particular surge in the number of new cases reported annually. In Brazil, for example, the annual percentage change has recently been calculated at 14.9% (95% confidence interval 10.4–19.6)11.

Disease development

In contrast to Crohn’s disease, ulcerative colitis is generally thought to be equally as common in males as in females across all age groups5. It can develop at any age from infancy onwards, but most frequently presents in adolescents and other patients under 30 years of age3. Interestingly, there is a second, albeit less pronounced peak between the ages of 50 and 80 years old, with incidence of ulcerative colitis on the rise in patients over the age of 65 years3,14.

Aetiology

Though the exact causes of ulcerative colitis are not well understood, experts have identified several important factors that are thought to contribute to the development of this disease5,15.

Genetic susceptibility

A family history of IBD is considered the most important risk factor for developing ulcerative colitis and has been reported in 8–14% of patients16,17. Indeed, first-degree relatives of patients with IBD are four times more likely to develop ulcerative colitis17. Rates of ulcerative colitis also vary between different ethnic groups and, like Crohn’s disease, it is particularly prevalent among Ashkenazi Jews, providing further evidence of a genetic component18.

In a 2017 review, it was reported that genome-wide associated studies (GWAS) have now identified over 200 susceptibility loci for IBD. Of these, 137 confer a higher risk of developing both ulcerative colitis and Crohn’s disease, while a further 27 are specific to ulcerative colitis19. These susceptibility loci include human leukocyte antigen and genes associated with barrier function17. However, these “identified genetic factors” can only account for around 8% of the disease variance and therefore have poor predictive capacity and are of little use in a clinical setting17,19.

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Pathophysiology

Pathogenesis

The exact pathogenesis of ulcerative colitis is not well understood; however, it is thought to be similar to that of Crohn’s disease, though some important differences have been identified17.

In ulcerative colitis, thinning of the mucus layer contributes to impairment of the epithelial mucosal barrier21.

A range of different factors contribute to ulcerative colitis pathogenesis5.

Following increased intestinal epithelial permeability, innate immune cells, such as macrophages, recognise bacterial antigens via toll-like receptors (TLRs) and NOD-like receptors (NLRs) and become activated28. This leads to increased production of pro-inflammatory cytokines – tumour necrosis factor α (TNFα), interleukin (IL)-1β, IL-6, IL-12 and IL-2328,29. Processed antigens are presented to T helper (Th) cells via T cell receptors (TCRs), facilitating an adaptive immune response and production of IL-4, while natural killer T (NKT) cells produce IL-13 and IL-5, further disrupting the epithelial barrier29. Furthermore, leucocyte recruitment increases through mechanisms such as upregulation of pro-inflammatory chemokines (CXCL) and binding of integrin (α4β7)-bearing T cells to colonic endothelial cells via mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) (Figure 2)30.

T2 UC - Jan2021.Fig2.png

Figure 2. Pathogenesis of ulcerative colitis (Adapted29). α4β7, Integrin α4β7; CXCL, Chemokine (C-X-C motif) ligand; HLA-2, Human leukocyte antigen 2; IL, Interleukin; MAdCAM-1, mucosal vascular addressin cell adhesion molecule 1; NF-κB, Nuclear factor- κB; NKT, Natural killer cell; TCR, T cell receptor; Th2, T helper 2 cell; TLR, Toll-like receptor; TNFα, Tumour necrosis factor α; Treg, Regulatory T cell.

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Treatment goals

Evolution of treatment goals and treat-to-target

In the past, the goal of treatment in IBD was to achieve symptomatic relief, preferably without the need for glucocorticoids35. More recently, it has been established that absence of symptoms does not necessarily indicate absence of inflammation, leading to the introduction of more stringent treatment targets35,36.

The concept of a treat-to-target approach in ulcerative colitis is still relatively new, having first been defined in 201537. The treat-to-target strategy involves adjusting therapy based on whether or not patients meet predefined treatment response targets, encouraging personalisation of care and earlier intervention36,38.

Despite being met with enthusiasm by experts around the world, many physicians have been slow to adopt this new disease management style and still consider symptomatic control an adequate treatment target36.

Consensus definition of targets in ulcerative colitis: STRIDE

The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) programme assessed potential treatment targets for patients with IBD to facilitate a treat-to-target strategy. As in Crohn’s disease, the expert-consensus definition of treatment targets in ulcerative colitis combines clinical (patient-reported) remission and endoscopic (clinician-reported) remission. In ulcerative colitis, clinical/patient-reported outcome (PRO) remission is defined as resolution of rectal bleeding and diarrhoea or altered bowel habit, while endoscopic remission is defined as a Mayo endoscopic sub-score of 0–1 (Figure 4)37,39.

AdobeStock_174230725_1920x.jpeg

Figure 4 . Understanding Mayo endoscopic sub-scores (a) Score 0, normal mucosa; (b) Score 1, mild disease with erythema, decreased vascular pattern and mild friability; (c) Score 2, moderate disease with marked erythema, absent vascular pattern, friability and erosions; (d) Score 3, severe disease with spontaneous bleeding and ulceration40.

The STRIDE statements were recently updated to reflect new evidence regarding treatment optimisation in IBD39. STRIDE-II provides confirmation of the long-term treatment targets identified in STRIDE-I, with the addition of absence of disability, restoration of quality of life and normal growth in paediatric patients39. STRIDE-II also lists symptomatic relief and normalisation of serum and faecal markers as suitable short-term targets39.

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