Inflammatory bowel disease in Asia

Inflammatory bowel diseases (IBD) were rare in Asia until two decades ago. For those Asian countries in which epidemiological, case series or hospital resource use data exist, there has been a consistent rise in the incidence and prevalence rates for both Crohn's disease (CD) and ulcerative colitis (UC).^1,2 This relatively rapid increase, such as the six-fold increase of UC in Hong Kong over a relatively short period of time, is considered to be the result of environmental changes.³ The increase in inflammatory bowel diseases parallels these countries' economic growth and increasing affluence, which has mostly occurred after the 1970's.

The increasing incidence of IBD has been recognized for both CD and UC, indicating that this rise did not result simply from a reclassification from one to the other. Overall, UC still predominates over CD in most parts of Asia.¹ The difficulty in the study of IBD in Asia arises from the lack of population-based registries in most countries, some patients' preference to present to traditional and alternative health practitioners or therapists, the limited availability of diagnostic facilities or difficulties in accessing them, and low awareness of IBD among doctors due to their previous rarity. Despite these difficulties, single centre studies and collective multi-centre studies, and in the case of Japan, population-based studies, have shown rising rates of IBD all around the same time.

Genotyping studies in Asia are of interest as they differ distinctly from Caucasians. The NOD2 gene polymorphisms found to be associated with the development of CD in Caucasians are not apparent in Asians.^4,5 Less data are available on the other genes and most studies have been of small scale. A polymorphism of the interleukin 23 receptor (IL23R) gene on chromosome 1p31 confers significant protection against the development of CD in Caucasians⁶ but not in the Japanese population.⁷ Further, the latter study did not demonstrate an association between the genetic variants of the autophagy-related 16-like 1 (ATG16L1) gene or the chromosome 5p13.1 locus and the development of CD in the Japanese population.⁷ The tumor necrosis factor superfamily member 15 (TNFSF15) gene of chromosome 9q32 contributes towards the risk of developing Crohn's disease in both Japanese and European populations.^8,9 In summary most genetic variants linked to IBD discovered so far through fine-mapping in regions of genetic linkage, the candidate gene approach, and in genome-wide association studies, vary according to ethnicity. While there is a lower rate of familial clustering of both CD and UC in Asia in comparison with Caucasians,^3,10 this is most likely related to the overall low disease prevalence rates, and is expected to increase as the IBD prevalence rises. The overall attributable risk of a positive family history in Asians is likely to be similar to that of Caucasians.¹¹

Within individual Asian countries, ethnic-racial differences influence the rates of IBD. In Malaysia and Singapore, two multi-ethnic countries, the incidence of UC is consistently higher in Indians than in the Chinese and Malays, whereas Malays are relatively protected against the development of CD.^12–14 Not only do Indians have a higher prevalence of UC, but severity of disease, prevalence of extra-intestinal manifestations and trend towards more extensive disease are also higher.¹⁴ Ethnicity combines genetic, social, socioeconomic, cultural and dietary factors so the exact reasons for these differences remain, as yet, undefined. However, geographical, climatic and infective etiologies are less likely to be important determinants given that these incidence rates differ within the same limited areas.

Migration studies have also demonstrated the interaction between genes and the environment. The background prevalence and incidence of UC is high in the Punjab region of north India.¹⁵ Second generation South Asian immigrants to the United Kingdom, however, have demonstrated even higher incidence and prevalence rates than local Caucasians, indicating that under certain changing environmental conditions the emergence of IBD is favoured.¹⁶ Alternatively, certain environmental factors in Asia, no longer active after migration to the West, may be suppressing the clinical development of IBD.

In this issue of the Journal of Gastroenterology and Hepatology, the Asia Pacific Inflammatory Bowel Disease Working Group publishes consensus statements in UC.¹⁷ These statements cover the epidemiology, diagnosis, and medical and surgical management of UC, but with emphasis on several points of interest to Asian countries. These statements were initially developed through a focus group followed by two rounds of anonymous voting through the Delphi method. Participants of the voting were gastroenterologist and surgical specialists with a particular interest in IBD, with representatives from throughout the Asia-Pacific region. The first round of voting was conducted anonymously through email and the second round of voting face-to-face after reviewing the available regional and international literature.

The statements were selected to be simple, useful and relevant. The regional epidemiology data were reviewed, confirming that the impression of rising incidence and prevalence is based on robust data. Modern diagnostic tests were recommended. Differentiating infective enterocolitis from UC was emphasized. The management guidelines were updated from the previous JGH publication¹⁸ by including recent advances, especially the use of biologic agents in countries with high background prevalences of latent tuberculosis. These statements are not designed to be all-encompassing. Importantly, the definitions, classification and nomenclature of IBD need to be standardized according to established international criteria, to ensure uniformity of descriptive and comparative epidemiology. To ensure that a ‘common language’ is used, the internationally-accepted Montreal Classification¹⁹ was used.

Another research-focused group, the Inflammatory Bowel Disease—Asia Pacific Working Party, recently convened in Guangzhou, China (March 7–8, 2009). The purpose of the meeting was to establish clinical and scientific research priorities, after reviewing the epidemiology, disease phenotype, and genetic and environmental risk factors of IBD relevant to Asia. During the first day, experts presented the latest IBD research findings, followed by the formation of discrete research groups. On the second day of the conference, the chairperson of each session presented their recommendations and established directions for further studies (Table 1).

Obtaining robust epidemiology data was recognized to be difficult in some Asian countries due to the sheer population size of some cities, and the high population flux resulting from rural to urban shifts. However, research into the environmental risk factors in Asian areas, that are only now seeing an increase in IBD, may help identify which factors are the most important in allowing these diseases to emerge.

Affluence appears to be a central factor, or cofactor, in the increasing incidence of IBD in Asia. Affluence, however, has multiple components. Changes in breast-feeding, exposure to environmental organisms and pathogens, the use of antibiotics, changes in the intestinal micro biota, and altered diet have all been postulated to be important. The rising rate of IBD in Asia offers an opportunity to explore the similar increase that was noted in Western countries half a century previously. Research in environmental risk factors may generate important hypotheses relating to pathogenesis, immunological function and host-bacteria interaction long considered major components in the development of IBD in genetically-susceptible individuals. Research in the field of environmental risk factors complements the rapidly-evolving field of IBD genetics and genome wide association studies. Exploring racial differences in susceptibility genes may also generate hypotheses to explain the differential rates of IBD within multi-ethnic countries with similar environmental risk factors. Ultimately the rapidly evolving field of research in IBD needs to involve and engage the region of the world containing 60% of the human population, a rapidly expanding economy, huge social change, and an increasing incidence of diseases previously confined to the West.