Inflammatory
Bowel Disease

A modern diagnostic perspective

By Associate Professor Louise Smyth
Published December 2020

Chronic, diarrhoeal disease of unidentifiable aetiology is described as early as ancient Greek medical tracts and, in retrospect, both Fabry and Morgagni probably describe cases prior to Matthew Baillie’s 1793 report of lethality of an ulcerative colitis. Following that description, many of the chronic diarrhoeal disorders of unknown aetiology were described as ulcerative colitides. After the description by Sir Samuel Wilks, in 1859, of the autopsy changes found in a 42-year-old woman who died after several months of intractable diarrhoea and fever, the term gained prominence. When Sir William Hale White published a series of cases in 1888, “Ulcerative Colitis” (UC) entered the lexicon. However, a review of Wilks’ case using modern diagnostic criteria, would prefer Crohn Disease (CD) but the seminal paper of Burrill Crohn, that differentiated his eponymous, idiopathic, chronic inflammatory disease of the bowel wall, with extra-enteric involvement, did not appear until the October, 1932, edition of JAMA, just 88 years ago, despite several earlier references to the differing patterns of disease and associated pathological findings. Nevertheless, the clinical presentation may not always be clear, especially during the first months of symptoms, and some cases may remain as undifferentiated colitis while others are otherwise resolved. The association between UC and colorectal carcinoma had already been reported, following the introduction of safe sigmoidoscopy, in 1909 by John Lockhart-Mummery (Mulder, Noble, Justinich, & Duffin, 2014).

The mean Australian annual incidence rate for IBD reported to EpiCom (European Crohn’s and Colitis Organization– Epidemiological Committee) in two independent cohorts from 2010 and 2011 was 30.3/100,000 (Vegh. et al. 2014). The prevalence in Australia is expected to increase by approximately 250% from 2010 to 2030. Furthermore, while still predominantly a disease affecting young adults, where the incidence may be reaching a plateau in Western countries (Weimers & Munkholm, 2018), both paediatric and elderly patients are increasingly being diagnosed (Gower-Rousseau, et al., 2013). In addition, these special groups and others may present with different disease phenotypes and require different treatment regimens. In this Northern French population, of similar size to that of Victoria, the incidence rate of CD increased from 5.3 to 7.6 per 105 over the study period (1988-2008) while UC remained stable. Strikingly, the incidence of CD in patients under 20 years old nearly doubled, a finding replicated in Italy, Ireland, Scotland and Scandinavia. Importantly, the extent of disease and the inflammatory phenotype was shown to be more severe in younger patients. In fact, the Montreal criteria for the evaluation of adult IBD has been supplemented by the Paris criteria for paediatric disease.

Table 1 - Montreal and Paris Classifications for Crohn’s Disease (CD)

*In both the Montreal and Paris Classification systems, L4 and L4a/L4b may coexist with L1, L2, L3, respectively.(After Levine et al., 2011)

Table 2 - Montreal and Paris Classifications for Ulcerative Colitis (UC)

*Severe defined by Pediatric Ulcerative Colitis Activity Index (PUCAI) ≥65.(After Levine et al., 2011)

In this French, community-based study, the increased severity of early onset disease was evident despite greater use of immune suppression and biological anti-inflammatories, in this group.

“ … clinical symptoms on diagnosis were more subtle in the elderly than in the younger age groups with less diarrhoea, abdominal pain, weight loss, fever and extra-intestinal manifestations (EIMs) in CD and less rectal bleeding and abdominal pain in UC. … As for phenotypes, elderly onset CD was characterised by the predominance of pure colonic disease (L2) and inflammatory behaviour (B1) in accordancewith the literature and in sharp contrast with the youngest age-group. On the other hand, UC location on diagnosis was more alike in the young-onset and elderly onset groups with more extensive disease than in the middle-age group.” (Gower-Rousseau, et al., 2013)

In the same study there was significantly more disease extension, stricturing and perforating behaviour in patients <17 years at diagnosis compared to those >60 years.

Elsewhere, an association with Primary Immune Deficiency (especially NOD2 gene & IL10 pathway) has been established in up to 20% of children with very early onset disease (<5 years) and these children should be assessed by a paediatric Clinical Immunologist (Kelsen & Sullivan, 2017). In all age groups, intestinal infection should be excluded as a cause of presenting symptoms, especially in high-risk groups but, infection is also an important complication of IBD (especially penetrating CD) and presents a risk to patients who require immune suppression.

While the aetiology and pathogenesis of IBD remains unclear, it is ever more clear that they represent a complex interaction of genetic susceptibility and environmental factors resulting in abnormal immune responses directed against the gut microbiota of affected individuals. The changing epidemiology, detailed by Kaplan and Windsor (Kaplan & Windsor, 2020), underlines the association with increasing Westernisation/industrialisation. Diagnosis is predicated upon endoscopy, imaging and histology butfeatures may change in serial small biopsies of bowel and a significant proportion of diagnoses are only secured after colectomy. Selection of patients for diagnostic endoscopy or follow-up assessment of disease activity can be enhanced by the measurement of blood and faecal biomarkers, which may also favour one disease over the other, minimising expensive, invasive, higherrisk investigation. It is especially useful to identify patients without evidence of bowel wall inflammation at presentation, who are more likely to have Irritable Bowel Syndrome (IBS). The usefulness of biomarkers has been established in adults (Kochhar & Lashner, 2017) and in children (Elitsur, Lawrence, & Tolaymat, 2005).

UK Guidelines suggest the following approach to differentiate patients presenting with symptoms that may be attributable to IBD or IBS.

Figure 1. Use of Faecal Calprotectin Test in Primary Care.

Table 3 . Usefulness of tests available at Clinical Labs for the assessment of possible or established IBD, other than biopsy.