Inflammatory bowel disease (IBD), including CD and UC, are common chronic GI diseases in Western countries [1-4]. IBD has been increasing in both incidence and prevalence in many newly industrialized countries since the beginning of the 21st century [1,3,5-8]. The reason for the global increase in this initially Western-prevalent disease has not been established but is most likely related to environment factors, including improved hygiene, civilization, and the spread of Western lifestyles and diets [1].

Longitudinal studies of Western populations performed within the past 50 years have revealed a pattern of initial increases in UC incidence, followed by increases in CD incidence at various intervals over the specified decades [3,9]. For example, a study in Denmark [10] reported a steady increase in CD incidence but stable UC incidence from 1981 to 1992. In Japan, which was one of the first among Eastern countries to adopt aspects of Western lifestyles, researchers reported a rapid rise of the incidence rate of UC beginning in 1970, with a peak in in 1974, followed by a peak in the CD incidence rate in 1979 [11]. This trend was also observed in other low-incidence Asian countries such as Hong Kong (from 8.94 in 1981–1985 to 1.03 in 2011–2014) [12], South Korea (from 6.8 in 1986–1990 to 2.3 in 2001–2005) [13], and Malaysia (from 8:1 in 1990–2000 to 3.6:1 in 2000–2010) [14].

Western studies have reported that CD and UC are more prevalent among female patients or that no intersex difference exists [15]. By contrast, the data from our study as well as reports from other Asian countries have indicated that IBDs, especially CD, are more prevalent among male patients [5]. Although the exact reason for these disparate patterns is unknown, a difference in genetic background between Asian and Western populations [16] may be a contributing factor, and the male-preference culture in Asian countries may lead to differences for male and female babies regarding breastfeeding, antibiotic use in childhood, and subsequent development of IBDs [17].

In Taiwan, the first case of IBD was diagnosed in 1969 as UC at the National Taiwan University Hospital [18]; however, no reliable nationwide descriptive epidemiology data [19] from the 20 century regarding IBD in Taiwan is available [5]. Since 1997, IBDs, including CD and UC, have been registered as catastrophic illnesses due to their potential to cause repeated admissions and their requirements for chronic, sensitive care. Accordingly, medical costs are covered by insurance for patients registered with relevant diagnoses. Submission of a clinical diagnosis, pathological report, and possibly endoscopic or radiologic image studies for formal review by experts is required to validate and register the patient’s diagnosis of CD or UC. In our previous study, we demonstrated that CD and UC increased in both incidence and prevalence in Taiwan from 1998 to 2008, according to the nationwide insurance registration data [5,8]. In this study, we used the same nationwide database and now provide an updated report on the incidence, prevalence, and epidemiological trend of IBD in Taiwanese patients since the beginning of the 21st century.

Analyzing data from the nationwide insurance registration system, we demonstrated that the incidence and prevalence of IBD increased steadily from 2001 to 2015 in Taiwan. Globally, the incidence level of IBD is highest in Western countries, with annual rates as high as 24.3 people per 100,000 for UC and 29.3 people per 100,000 for CD [1,2,7]. The present study revealed that the incidence rates of UC (0.95/100,000) and CD (0.47/100,000) have been increasing in Taiwan since the beginning of the 21st century. The incidence rates in Taiwan are low compared with those in Japan, South Korea [19], and Hong Kong [7,12] but are similar to those in other Asian countries such as Singapore, Malaysia, and Thailand [1]. Differences in degree of urbanization and socioeconomic status among the populations of these regions may have contributed to the described variation [5]. In the present study, incidence levels may have been underestimated, because we used relatively stringent criteria for analysis. In studies of other countries, most incidence and prevalence levels have been calculated using clinical-diagnosis data only. By contrast, incidence and prevalence levels in this study were based on numbers of patients who had completed catastrophic-illness registration, which requires clinical records, endoscopic images, and pathology results.

In this study, we first demonstrated a decrease in the UC-to-CD incidence ratio in Taiwan. Decreases have also been observed in other low-incidence Asian countries such as Hong Kong (from 8.94 in 1981–1985 to 1.03 in 2011–2014) [12], South Korea (from 6.8 in 1986–1990 to 2.3 in 2001–2005) [13], and Malaysia (from 8:1 in 1990–2000 to 3.6:1 in 2000–2010) [14]. By contrast, the UC-to-CD ratio has remained steady in Western countries (Fig. 7) [9,12,13,19,22-24]. Consistent with other studies from developing countries, we demonstrated that UC remains the predominant IBD in Asia and is twice as common as CD. Historically, the incidence of UC has usually increased first, followed by that of CD [2]. For instance, a study conducted in Denmark [10] revealed a steady increase in CD incidence alongside a stable UC incidence from 1981 to 1992. In Japan, the incidence rate of UC peaked in 1974 whereas that of CD peaked in 1979 [11]. A similar trend was observed in the present study: in Taiwan, UC-to-CD ratio significantly decreased during the study period, from 4.32 (2001–2005) to 4.17 (2006–2010) to 2.03 (2011–2015).

The reason for the catch-up of CD incidence between Taiwan and countries with higher incidence levels is not clear, but the trend may reflect common risk factors for CD and UC among various populations, such as improved social economic status and diet. The time lag between increases in UC and CD incidences may imply that the pathogeneses of the diseases differ [12] or may reflect improvements in CD-diagnosis accuracy [9]. The diagnosis of UC is usually straightforward and based on endoscopic findings from sigmoidoscopy [20]. By contrast, the diagnosis of CD is more complex and sometimes requires multiple evaluations, including enteroscopic, pathologic, and radiologic evaluations [21]. We speculate that the improved endoscopic technology of the 21st century—that is, capsule endoscopy and deep enteroscopy [25]—may have enabled earlier diagnosis of CD. This phenomenon may partially explain the relatively steep increases in the CD incidence rate in most Asian countries in the 21st century [26].

In the present study, the most common age of registration of patients with CD was between 20 and 39 years, whereas that for UC was between 40 and 59 years. The mean age of patients registered with CD and UC was compared with that from reports conducted in other countries in Asia [20,21]. Although the results of the present study revealed that the median age of patient IBD registration did not significantly change during 2001 to 2015, a significant increase in the CD incidence rate was discovered among 20 to 39-year-old. Additionally, we found that the previously identified male predominance continued, with the male-to-female ratio not changing from 2001 to 2015.

Our findings may have several implications for medical practice in Taiwan as well as in other Asian countries with low IBD incidence. First, similar to the increased incidence of IBD, an increased incidence of colorectal cancer has been observed in Taiwan, and the need for colonoscopy screening has increased [27]. Thus, endoscopists must learn to diagnose colorectal neoplasm and IBD early to improve patient outcomes. Specifically, endoscopists with experience in IBD care must diagnose IBD early, differentiate among instances of IBD and infectious colitis, and help patients manage IBD-related complications. The Taiwan Society of Inflammatory Bowel Disease (TSIBD) was founded in 2013 with the aim of improving awareness, quality of care, and outcomes for patients with IBD in Taiwan [20,21]. Second, the high cost of caring for patients with IBD combined with the increased incidence of IBD may have a considerable financial effect on the health care system [28]. The use of biologic therapy has been suggested to reduce requirements for surgery and hospitalization and to improve quality of life and work productivity among patients with IBD [29,30]. However, the Taiwan health insurance criteria for biologic-therapy coverage and coverage period are more stringent than those for most other countries discussed herein, such as Japan and South Korea [30]. Therefore, the TSIBD multicenter IBD registry study [31] was initiated to obtain precise data on IBD patient clinical information, disease phenotype, and treatment strategies and outcomes. These data may eventually prompt the health care system to cover more expenses for patients with TBD.

Some of the factors associated with IBD incidence may also be associated with changes in disease severity over time. For example, IBD in Western countries may still be more severe than in Asia. Analyzing the incidence trend of IBD may provide clues regarding IBD pathogenesis [3]. Policy planners and taxpayers should understand the global burden of IBD. Proof that IBD has a considerable disease burden may affect research funding allocated by national authorities.

This study has some intrinsic limitations from registration data. First, it is possible that a portion of IBD patients were not registered with catastrophic illness and not included in the current study. Second, our catastrophic illnesses registration permitted either UC or CD but not IBD-unclassified. Third, there was also no detail data regarding the disease location, activity, patterns of drugs used for patients included in this study. Fourth, there is no firm diagnostic criteria of UC and CD in Taiwan. The NHI reviewer usually give certification of IBD with reference to the Taiwan consensus for UC [20] and CD [21].

In conclusion, using Taiwan’s nationwide insurance database to identify patients with IBD, the present study revealed that the incidence and prevalence of IBD in Taiwan steadily increased from 2001 to 2015. The number of patients with CD increased more rapidly than that of patients with UC. Although the incidence of IBD remains low in Taiwan, the upward trend in CD incidence in Taiwan as well as other developed countries suggests that requirements for IBD care will be greater in the future.