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Inflammatory Bowel Disease Learning Zone

Understanding Crohn’s disease

Read time: 20 mins
Last updated:14th Oct 2021
Published:14th Oct 2021

Get to grips with Crohn’s disease, an increasingly common and debilitating form of IBD.

  • Discover how early intervention could slow or even prevent disease progression
  • Identify common symptoms experienced by patients with this condition
  • Check out the global incidence with our insightful world map


Prevalence and incidence

Crohn’s disease is an inflammatory bowel disease (IBD), characterised by chronic inflammation which can occur at any point along the gastrointestinal tract1. A growing body of evidence suggests that the prevalence and incidence of this debilitating condition is increasing globally, with some regional variation2–5.

While prevalence describes actual numbers of cases, incidence measures rates of new cases, and most epidemiological studies suggest that the incidence of IBD is increasing6.

Until recently, IBD was widely regarded as a disease of the western world4. The prevalence of IBD in westernised countries increased considerably over the course of the 20th century and today exceeds 0.3% in many regions of Europe, North America, and Oceania4. Interestingly, although this figure now appears to be stabilising or even decreasing in some of these countries, the beginning of the 21st century has seen a similar increase in the number of cases reported in newly industrialised nations, with incidence of IBD on the rise in South America, eastern Europe, Asia, and Africa (Figure 1)4. In Brazil, for example, an annual percentage increase in incidence of Crohn’s disease of 11.1% (95% confidence interval 4.8–17.8) has been reported 4.

T1 Crohns - Jan2021.Fig1.png

Figure 1. Worldwide incidence of Crohn’s disease per 100,000 person years, 1990–2016 (Adapted4).

Nevertheless, the results of a large systematic review suggest that the prevalence of Crohn’s disease remains highest in Europe (322 cases per 100,000 individuals in Germany) and North America (319 cases per 100,000 individuals in Canada)4,7. More recently, similar findings were reported by a study based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD)2. This revealed that between 1990 and 2017 the highest age-standardised prevalence rate of IBD was recorded in high-income North America (344.8 cases per 100,000 individuals [95% UI 331.7 – 359.3] in 1990; 422.0 cases per 100,000 individuals [95% UI 398.7 – 466.1] in 2017)2. Meanwhile, the lowest age-standardised prevalence rates were reported in the Caribbean (6.7 cases per 100,000 individuals [95% UI 6.3 – 7.2] in 2017)2. Other regions with low rates of IBD included Andean Latin America and parts of sub-Saharan Africa2.

Disease development

Among adults, Crohn’s disease affects more women than men8,9. It can develop at any point from early childhood but the median age of onset is 30 years6,10. Onset tends to occur in two peaks – mainly between 20 and 30 years of age, but also around 50 years10.


Genetic susceptibility

Though the exact aetiology of Crohn’s disease remains unknown, familial aggregation studies and twin studies indicate a strong genetic component11,12. A family history of the condition has been reported by approximately 12% of patients and concordance rates among monozygotic twins are estimated to be around 50%1,3

Further evidence of a genetic component can be found in differences in the prevalence of Crohn’s disease between ethnic groups. Caucasians and African Americans are among those most commonly affected, while individuals of Hispanic and Asian descent are considered to be at lower risk11. Of note, risk of developing Crohn’s disease is reportedly 3–fold higher in Jewish compared with non-Jewish individuals12.

To date, genome-wide association studies have identified over 200 susceptibility loci for IBD13. In Crohn’s disease, these include polymorphisms in the NOD2 gene, which is expressed in a range of cell types and encodes a protein with a role in innate immunity, as well as in autophagy-related genes14–16.

Gut flora

Dysbiosis is thought to play a key role in IBD pathogenesis, and Crohn’s disease is associated with the presence of specific pathogens in the gut microbiota and a reduction in gut microbial diversity compared to healthy individuals17. Alterations in the composition of the intestinal microbiota in patients with Crohn’s disease include changes in the relative abundance of Bacteroides and Firmicutes, and an increased proportion of Gammaproteobacteria and Enterobacteriales, as well as a decrease in Clostridiales17.

Environmental factors

A range of environmental factors influence the onset and progression of Crohn’s disease in genetically susceptible individuals1.

Cigarette smoking is the best-studied environmental risk factor. Among smokers, risk of developing Crohn’s disease is reportedly double that of non-smokers and smoking has been linked to an earlier onset of disease, need for immunosuppression, increased need for surgical intervention and higher rates of postoperative recurrence1,3.

Dietary changes and associated gut dysbiosis has also been implicated in the development of Crohn’s disease1. While high fibre diets are thought to reduce risk of Crohn’s disease, diets rich in sugar, fat, and meat have been shown to increase risk in several studies10.

Crohn’s disease risk is also held to be increased by exposure to certain drugs, including oral contraceptives, aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), as well as use of antibiotics such as penicillins, cephalosporins, metronidazole and fluoroquinolones, particularly during childhood1,10,18

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The pathogenesis of Crohn’s disease is not well understood, involving inflammatory processes of the intestinal tract, the origins of which are unknown19,20. This being said, it is thought that both the innate and adaptive immune responses play a role21. Indeed, massive infiltration of the mucosa by innate and adaptive immune cells is considered a key characteristic of active IBD in general22. This may be related to either overactivation of effector T cells and/or alteration of T cell-mediated tolerance22. An abnormal and sustained host immune response against intestinal microbiota is key to the development of IBD22.

In patients with Crohn’s disease, damage to the intestinal barrier leads to translocation of commensal microorganisms into the bowel wall. Innate immune cells respond to microbes and their mediators, resulting in immune cell activation and the production of cytokines and chemokines. Innate immunity is then activated as a result of disruptions to gut homeostasis and recruitment of additional immune cells to the bowel wall and causes activation of adaptive immune cells. Activated immune cells produce mediators, including cytokines, which, along with immune cells themselves, cause damage to epithelial cells, impair barrier function resulting in dysbiosis, and perpetuate gut inflammation (Figure 2)20 .

T1 Crohns - Jan2021.Fig2.png

Figure 2. Pathogenesis of Crohn’s disease (Adapted23).

Crohn’s disease is a chronic progressive disease, with half of all patients developing intestinal complications, including strictures and fistulae, within 10 years of diagnosis1.

IBD therapy

Crohn’s disease is characterised by patchy, transmural inflammation, known as “skip lesions”1,20. The lesions that typically occur in Crohn’s disease are “cobblestone appearance” and “longitudinal ulcers”24. It can occur at any point along the gastrointestinal tract, where it causes chronic, relapsing transmural inflammation, which is associated with a range of debilitating symptoms including diarrhoea, abdominal pain, fever, and fatigue1,10,20.

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Treatment goals

Evolution of treatment goals and treat-to-target

In the past, standard of care for patients with IBD was limited to managing their symptoms. Today, treatment goals in Crohn’s disease are evolving and a treat-to-target approach is now encouraged. This strategy promotes personalised care and early intervention27.

A treat-to-target approach involves careful monitoring of specific and objective improvement in measures of inflammation27,28.

Currently mucosal healing represents an important treatment target in Crohn’s disease and has been associated with improved patient outcomes1. In the future, transmural healing, which can be assessed using cross-sectional imaging techniques, is expected to become another key treatment target for patients with Crohn’s disease (Figure 3)1,29.

T1 Crohns - Jan2021.Fig4.png

Figure 3. Evolution of treatment targets in Crohn’s disease (Adapted30).

Consensus definition of targets in Crohn’s disease: STRIDE

The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) programme assessed potential treatment targets for patients with IBD to be used in a treat-to-target strategy31. For Crohn’s disease, the expert-consensus definition of treatment targets that was generated by STRIDE and published in 2015, combines clinical (patient-reported) remission and endoscopic (clinician-reported) remission31,32.

The original STRIDE statements define clinical remission as resolution of abdominal pain and normalisation of bowel habit, while absence of ulceration at ileocolonoscopy is used to confirm endoscopic remission31.

More recently, an updated version of the original STRIDE statements, STRIDE-II, has been made available28. Clinical response and remission, endoscopic healing, and normalisation of C-reactive protein/erythrocyte sedimentation rate and calprotectin were all listed as key therapeutic targets28.

As well as confirming the long-term treatment targets of clinical remission and endoscopic healing that were outlined in STRIDE I, STRIDE-II also introduced several additional targets including absence of disability, restoration of quality of life and normal growth in children28. Symptomatic relief and normalisation of serum and faecal markers were also identified as short-term targets28.

Role of early intervention

Although the majority of patients with Crohn’s disease initially present with uncomplicated disease, for many, chronic intestinal inflammation ultimately leads to the development of irreversible bowel damage and complications, which could necessitate surgery, leading to further permanent bowel damage3,20,33. Nevertheless, experts have now identified a “window of opportunity” in the early stages of the disease, during which appropriate therapeutic intervention has the potential to stop the inflammatory cascade and alter disease progression in many patients32,34.

It is therefore thought that early intervention with effective agents may allow many patients to achieve complete disease control by resolving local inflammation and potentially preventing disease progression and the associated irreversible bowel damage33,35–37.

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