Aims To describe the change in incidence of paediatric inflammatory bowel disease (IBD) observed at the National Centre for Paediatric Gastroenterology, Hepatology and Nutrition, and to determine whether the presenting disease phenotype and disease outcomes have changed during the past decade.
Methods The annual incidence of IBD in Irish children aged <16 years was calculated for the years 2000–2010. Two subsets of patients, group A (diagnosed between 1 January 2000 and 31 December 2001), and group B (diagnosed between 1 January and 31 December 2008) were phenotyped according to the Paris Classification. Phenotype at diagnosis and 2-year follow-up were then compared.
Results 406 new cases of IBD were identified. The incidence was 2.5/100 000/year in 2001, 7.3 in 2008 and 5.6 in 2010, representing a significant increase in the number of new cases of Crohn's disease (CD) and ulcerative colitis (UC). There were 238 cases of CD; 129 of UC; and 39 of IBD unclassified. Comparing groups A and B, no differences were found in disease location at diagnosis or, for CD, in its behaviour.
Conclusions There has been a substantial and sustained increase in the incidence of childhood UC and CD in Ireland over a relatively short period of time. However, disease phenotype at diagnosis has not changed. At 2 years follow-up, CD appears to progress less frequently than in some neighbouring countries. These variations remain unexplained. Prospective longitudinal studies will help to elucidate further the epidemiology of childhood IBD.
Statistics from Altmetric.com
Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC). A separate category, IBD unclassified (IBDU), or indeterminate colitis, is reserved for those who have clinicopathological features of IBD but whose diagnostic findings do not distinguish unequivocally between CD and UC. The peak age of onset is between 15 and 35 years,1 although IBD can occur as early as the first year of life.2 Data from the last decade of the twentieth century suggest that 10–25% of new patients with IBD are diagnosed before their 18th birthday.3 4 Careful assessment of reported epidemiological surveys shows that the incidence of paediatric IBD is rising internationally, although countries holding national data remain a minority.5
Ireland has a single National Centre for Paediatric Gastroenterology, Hepatology and Nutrition (NCPGHN) and our referral population closely approximates a national cohort, as has been shown previously.6 We have observed a marked increase in new cases of IBD since 2007. The aims of this study were to determine if the incidence or disease characteristics of IBD in Irish children had increased during the first decade of the twenty-first century.
What is already known on this topic?
▶ The incidence of paediatric inflammatory bowel disease (IBD), particularly Crohn's disease, has increased in many developed countries.
▶ Disease behaviour and extent can progress following initial diagnosis
What this study adds
▶ We provide evidence that the incidence of all forms of IBD increased in Ireland during the middle of the last decade.
▶ Disease behaviour in Irish children appears to be more stable than in other populations.
▶ The parallel rise in incidence of ulcerative colitis and Crohn's disease in Irish children is in contrast to reported global trends.
▶ The increasing prevalence of a chronic childhood illness has important implications for health policy decision-making in this area.
The NCPGHN comprises Our Lady's Children's Hospital, Crumlin and the National Children's Hospital, Tallaght and is the only provider of subspecialty paediatric gastrointestinal (GI) services in Ireland. The national census in Ireland is carried out every 4–5 years; annual population data do not exist. A census was held in 2011, but the results will not be available until summer 2012. There were 888 310 children aged 0–16 years in Ireland in 2002 and 922 767 children in 2006, a 3.9% rise in the population aged under 16 years. The 2006 census figure was used to calculate incidence for all years from 2000 to 2010.7
Children younger than 16 years with a diagnosis of IBD made between 1 January 2000 and 31 December 2010 were included in incidence calculations, which were standardised for age and sex and calculated per 100 000 of the at-risk population (ie, Irish children under 16 years of age). Children diagnosed with CD and UC in the period 1 January 2000 to 31 December 2001 (group A) were compared with those diagnosed between 1 January and 31 December 2008 (group B). Because of the increased number of new cases of IBD in 2008, new incident cases from 2 years were combined to create an earlier cohort of comparable size. Retrospective case ascertainment was by review of endoscopy records. A rural dwelling was defined as a house in a settlement of less than 4500 people.8 Approval for the use of patient data was given by the regional ethics committee. As a restrospective survey of historical data, patient consent was not deemed mandatory.
Diagnostic criteria and classification
IBD is diagnosed by paediatric gastroenterologists at NCPGHN using standardised criteria.9 10 All children with suspected IBD undergo oesophagogastroduodenoscopy, ileocolonoscopy and small bowel contrast radiography.
Clinical findings, treatment responses and endoscopy reports were extracted from hospital patient records, initially by a panel of senior authors and subsequently by CD and BH. Radiology, histology and laboratory results were also available electronically. This information was used to determine disease location and behaviour. The Paris criteria and preceding IBD classification have been reviewed by Levine et al.11 Data were entered into a standardised Microsoft Excel template. Any interpretative difficulties were resolved following discussion with the senior authors. The authors were not blinded to the year of diagnosis during data collection and entry.
Extraintestinal manifestations (EIMs) were defined as inflammatory activity in joints, eyes, skin or liver.12 Oral CD (including aphthous stomatitis) was not considered an EIM. The Paris definition of growth delay was used.11
Disease severity for patients with CD was measured by physician global assessment (PGA), based on patient symptoms and clinical findings at presentation.13 The derivation of the Paris S0 and S1 categories for UC is described in the reference article.11 When there was insufficient data to calculate a paediatric UC activity index score, a PGA was substituted.
Surgery was defined as segmental intestinal resection and did not include operative treatment of abscesses or perianal fistulas. Immunomodulator drugs included thiopurines and methotrexate, but not corticosteroids. Data on biological drugs are given separately.
The diagnosis of IBDU was reserved for children who had chronic active colitis with insufficient clinical, radiological or histological evidence to support firm categorisation as CD or UC.14 15 A small number of subjects had an initial diagnosis of IBDU which was revised to UC or CD, and in these cases the most up-to-date diagnosis was used. In total, 19 subjects in group A and 14 subjects in group B underwent clinical restaging of their disease within 2 years of the initial diagnosis.
The statistical analysis was performed using SPSS V.19. Pearson's χ2 test was used for comparison of proportions in both demographics and disease classification. The median ages were compared with the Mann–Whitney U test. Incidence trend analysis was by simple linear regression. Significance was defined as p<0.05.
There were 406 new cases of IBD between 1 January 2000 and 31 December 2010; 238 CD, 129 UC and 39 IBDU. Age-adjusted mean incidence rates per 100 000 were 3.9 for all IBD (95% CI 1.4 to 8.0), 2.3 for CD (0.6 to 5.6) and 1.1 for UC (0.2 to 3.7) (figure 1). Between 2000 and 2006, the incidence of IBD was relatively stable, ranging from 2.5 to 3.8/100 000/year. In 2007 there was a notable increase to 4.8 (95% CI 1.9 to 9.5)/100 000/year) in the number of children diagnosed with IBD. In 2008 the incidence rose sharply to 7.3 (3.5 to 13.1)/100 000/year. Data from 2009 and 2010 indicate that the higher rates of new cases of IBD have persisted (5.3 (05% CI 2.2 to 10.2) and 5.6 (2.5 to 11) per 100 000, respectively). Between 2000 and 2010 the mean annual increase in CD incidence was 0.153/100 000/year (p=0.04), and for UC the figure was 0.175 (p<0.01). The demographics and outcomes for groups A and B are compared in table 1, with a notable increase in the proportion of urban subjects in group B.
Table 2 shows Paris characteristics of two CD cohorts both at diagnosis and at 2-year follow-up.
The most common initial disease location was colon only (L2). For those aged <10 years, 10/19 (53%) had only colonic involvement at presentation. Isolated upper GI/proximal small bowel disease (L4a/b) was unusual at presentation (12% in group A and 3% in group B); after 2 years of follow-up most of these had progressed to develop distal disease. No statistically significant changes in disease location or behaviour occurred during the follow-up period for either group A or B.
Most children with UC had extensive colitis (Paris E4) at diagnosis (table 3).
There was a significant difference in colectomy rates by 2 years (38% for group A vs 7% for group B, p=0.05) (table 2).
The mean age at which UC was diagnosed was 9.4 years (group A) and 11 years (group B). The number of new cases of IBDU was one in 2000, 3 in 2001 and 12 in 2008.
This study shows that there has been a marked, sustained increase in the incidence of childhood onset IBD in Ireland over the past 5 years. The NCPGHN has provided diagnostic paediatric GI services in Ireland since 1991. A prospective 13-month survey by Sawczenko et al found that, in 1999, 86% of Irish children with IBD were seen by a paediatric gastroenterologist.6 The same survey calculated the overall incidence of IBD in Ireland at 4.4 per 100 000 (95% CI 3.2 to 6); this is a little higher than any of the next 7 years, but considerably lower than the incidence since 2007. Recently collated data from 2011 have confirmed 76 new cases of IBD between 1 January and 31 December, giving an incidence of 8.24 per 100 000 per year (95% CI 4.12 to 14.42). It is possible that a small number of older adolescents or children with mild IBD are not being referred to NCPGHN at any point in their management. As there is no centralised adult IBD database in Ireland, the exact numbers are not available. However, there is no evidence that national referral practices have changed, resulting in children now being seen at NCPGHN who would in the past have been managed solely by adult specialists or paediatric generalists elsewhere. Even if referral of children with IBD to NCPGHN had reached 100%, this would only account for a 14% increase in new cases, not the 87% increase observed between 2000 and 2008. It is therefore one of the strengths of the study that it approximates a national disease cohort, allowing the calculation of robust yet conservative incidence data using a well defined at-risk population.
To the best of our knowledge, this is the first published study to use the Paris Classification to determine whether changing IBD incidence is associated with changing disease phenotype. The Paris method was chosen because it is an up-to-date, paediatric-specific IBD classification system which is likely to become the standard for clinical and research practice. Data on EIMs were also collected to complete the phenotypic picture. The authors chose to compare smaller cohorts separated by a larger time interval, as this was considered the best way to look for differences between the lower and higher incidence eras. Significant changes in disease severity, location and behaviour at diagnosis were not detected, and other CD features such as the presence of perianal disease and EIMs also occurred with comparable frequency in both groups. Therefore the increase in new cases of IBD probably does not result from the emergence of a ‘new’ phenotype, rather the proliferation of an established one.
The genetic makeup of the population of Ireland is stable. The most significant demographic change of the past quarter century in Ireland has been the massive increase in gross domestic product, with associated changes in living standards, and internal migration from rural to urban locations. The proportion of new patients with CD living in urban areas increased between 2000 and 2008, although this may reflect urban migration rather than an undefined urban IBD risk factor; it is not currently known which, if any, aspects of daily life in developed nations predispose people to IBD.16
Internationally, there have been many reports of increases in the incidence of IBD.17,–,19 In a recent systematic review of epidemiology, Benchimol et al reported that CD has become more common, with the incidence of UC stable.5 Serial longitudinal studies from Wales showed a sustained rise in new cases of CD and UC between 1983 and 1993, although regional IBD incidence rates stabilised thereafter.20,–,22 In Scotland, the incidence of IBD is also rising and currently stands at 7.82/100 000/year.17 Regions with a particularly high IBD burden include northern Stockholm (10.5/100 000/year in 1999–2001)23 and Wisconsin (7.05/100 000/year in 2000–2001).24 The CD:UC ratio in this study was similar to other countries (2.3:1 in 2008). The parallel rise of UC and CD in Irish children is in contrast to the global trend perceived by Benchimol et al, although it has also been reported in neighbouring Scotland.17
The anatomic sites of CD activity at diagnosis were very similar for both cohorts, and progression of disease location (ie, new disease activity in a previously unaffected segment of bowel) during the first 2 years following diagnosis was rare. This contrasts with the disease extension described recently by groups from Scotland (39% at 2 years) and northern France (31% at median follow-up of 84 months),25 26 even allowing for their longer recruitment and follow-up periods. Interestingly Irish children also had more colonic disease (L2) than their French and Scottish counterparts. Further study is required to determine if these contrasts point to possible disease-modifying environmental or other factors at play in the Irish setting. CD in Irish children is predominantly inflammatory (B1) at diagnosis, consistent with findings from other centres.24,–,26 Progression of disease behaviour (ie, development of strictures or fistulas in patients with inflammatory disease at presentation) was only seen in two of our patients at maximal follow-up. The reason for the lower rate of complicated CD in our population is uncertain. It has been suggested that earlier use of immunomodulator therapy can favourably alter the course of CD in adults and children,27 28 but the frequency with which we introduce these drugs during the first year following diagnosis is similar to that reported by the French and Scottish groups. Van Limbergen et al found that exclusively colonic disease is associated with inflammatory behaviour, whereas those with ileocaecal CD are more likely to develop strictures and fistulas.25 Again, the higher rates of colonic CD among Irish children may therefore contribute to the low rates of complicated disease behaviour reported here. Repeat endoscopic and radiological assessments were only performed when clinically indicated. Therefore, unless there were changes in symptomatology, disease location was assumed to be stable. This may have led us to underestimate progression.
The total number of children with UC was quite small. Therefore while it is noteworthy that there were more children with severe disease in the earlier cohort (69% vs 43%) the differences do not reach statistical significance. We suspect that the marked decrease in colectomy rates for group B patients with UC reflects a change in clinical practice.
The incidence of IBD among Irish children has increased swiftly and substantially, a phenomenon that has been described internationally. The factors underlying this trend remain elusive. Despite the increase in incidence, the presenting phenotype in Ireland has not changed over the past decade. In contrast to some of our neighbouring countries, CD in Ireland is less likely to extend location or change behaviour during the first 2 years following diagnosis. Prospective research is now under way at NCPGHN which will further elucidate the Irish IBD phenotype, and investigate potential aetiopathogenic mechanisms.
Competing interests None.
Ethics approval Our Lady's Children's Hospital Ethics (Medical Research) Committee (reference number GEN/195/11).
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.