Crohn’s disease in adults: Observations in a multiracial Asian population

Abstract

AIM: To determine the demography and clinical presentation of CD and secondly to determine any differences in the prevalence between the different ethnic groups in a multiracial Asian population.

METHODS: Patients with CD who were seen in 2001–2003 in the University of Malaya Medical Centre (UMMC) were enrolled in this study. Prevalence of disease was calculated for the group as a whole and by race with hospital admissions per ethnic group as the denominator.

RESULTS: Thirty-four patients were diagnosed to have CD. Basic demographic data of patients; male:female 17:17; mean age 29.1 years (±13.5 years); ethnic group: Malays 5 (14.7%), Chinese 12 (35.3%) and Indians 17 (50%). Twenty-six (76.5%) were diagnosed under the age of 40 and 8 (23.5%) were diagnosed over the age of 40. Location of the disease was as follows: ileocolonic 13 (38.2%), terminal ileum only 9 (26.5%), colon only 8 (23.5%), and upper gastrointestinal 4 (11.8%). Sixteen (47.1%) had penetrating disease, 9 (26.5%) had stricturing disease and 9 (26.5%) had non-penetrating and non-stricturing disease. The hospital admission prevalence of CD was 26.0 overall, Indians 52.6, Chinese 6.9, and Malays 9.3 per 10⁵ admissions per ethnic group. The difference between Indians and Malays: [OR 5.67 (1.97, 17.53) P < 0.001] was statistically significant but not between the Indians and the Chinese [OR 1.95 (0.89, 4.35) P = 0.700]. The difference between the Chinese and the Malays was also not statistically significant. [OR 2.90 (0.95, 9.42) P = 0.063].

CONCLUSION: The clinical presentation of CD is similar to the Western experience. Although the overall prevalence is low, there appears to be a clear racial predominance among the Indians.

INTRODUCTION

Crohn’s disease (CD) and ulcerative colitis (UC) have long been recognized in the West, but is thought to be relatively uncommon in the Asia[1]. To illustrate this point, the prevalence rates of CD have been estimated to be 3.6 and 5.8 per 10⁵ in Singapore[2] and Japan[3], respectively compared to 144.1 per 10⁵ in Olmsted, Minnesota[4] and 147 per 10⁵ in North East Scotland[5]. However, the incidence appears to be increasing in this part of the world and is likely to become clinically more important in future. For example, in another Japanese study, the prevalence and the annual incidence were estimated to be approximately 2.9 and 0.6 per 10⁵ population, respectively in 1986, but this had increased to 13.5 and 1.2 per 10⁵ population in 1998[6]. Leong et al found a similar increase in the annual incidence of CD among the Chinese population in Hong Kong[7] and a study by Law et al found an increase in the number of admissions for CD among the Chinese population in Singapore[8].

Another interesting observation is that there appears to be ethnic differences in the prevalence of idiopathic inflammatory bowel disease[1,2,9-15]. This is particularly relevant in Malaysia which has a multiracial society mainly made up of three major Asian races: Malay, Chinese, and Indian. In particular, studies in neighboring Singapore which although has a predominantly Chinese population has a similar racial mix; significantly higher prevalence rates among the Indians for UC but not CD compared to the Chinese and the Malays have been found[2,9,10] These racial differences for UC were also seen in our own study in UMMC[15] The aim of this study is to determine the demography and clinical presentation of CD in a hospital setting in Malaysia and to determine any racial differences in prevalence.

MATERIALS AND METHODS

Patients with CD in UMMC as identified by International Classification Coding for Crohn’s disease from 2001 to 2003 were retrospectively included into the study. Patients under the age of 12 were excluded. The diagnosis of Crohn’s disease was made in accordance with previously accepted criteria based on a combination of clinical presentation as well as typical radiographic, endoscopic, histological, and laboratory findings[16]. Diagnosis was at least of 6 mo duration. Microscopic colitis, collagenous colitis, Behcet’s disease and infective enterocolitis were excluded. Stool microscopy and culture, bacterial and amoebic serology, acid-fast staining of biopsies were performed to exclude infectious enterocolitis. Baseline patient characteristics in particular race, date of diagnosis, clinical features, method of diagnosis, location of disease, complications and surgical intervention were documented. Phenotype of the disease was classified according to the Vienna classification[17]. Family history, smoking history and whether or not the patient had a previous appendectomy was also recorded.

The denominator were hospital admissions in UMMC in 2001-2003 as a whole and according to each of the major ethnic groups; Malays, Chinese, and Indians.

Statistical analysis

Data was analyzed using the SPSS 11.5 for Windows. Prevalence of the disease was calculated for the group as a whole with total hospital admissions for the same period of time and by race with hospital admissions per 100 000 ethnic group as the denominator. Prevalence rates were expressed with 95% confidence intervals.

RESULTS

Demographic characteristics

The demographics of the patients with CD are summarized in Table 1. There was no gender difference, 17 males and 17 females with a ratio of 1 : 1. The mean age was 29.1 years (±13.5 years). Twenty-six (76.5%) were diagnosed under the age of 40 and 8 (23.5%) were diagnosed over the age of 40. The breakdown according to ethnic group was as follows: ethnic group: Malays 5 (14.7%), Chinese 12 (35.3%), and Indians 17 (50%). None of the patients had a family history of IBD and only 5 (14.7%) were smokers whereas 2 (5.9%) were ex-smokers and the majority 27 (79.4%) were lifelong non smokers. Two (5.9%) patients had previous appendectomy.

Table 1.

Demographic characteristics of patients with CD in UMMC

		Allpatients
Number		34
Totalmales		17(50%)
Totalfemales		17(50%)
Age(range)		12-56years
Meanage		29±13.5years
Ethincgroup	Malay	5(14.7%)
	Chinese	12(35.5%)
	Indian	17(50%)
Familyhistory		0(0%)
Appendicectomy		2(5.9%)
Smokinghistory	Nonsmoker	27(79.4%)
	Exsmoker	2(5.9%)
	Currentsmoker	5(14.7)

Clinical features and disease location

In terms of clinical features, the commonest presenting complaints were diarrhea 29 (85.3%), abdominal pain 25 (73.5%), rectal bleeding 17 (50%), and weight loss 15 (44.1%). Other features included fever 8 (23.5%), vomiting 8 (23.5%), and abdominal mass 6 (17.6%). Perianal disease was seen in 10 (26.5%), and extraintestinal manifestations in 7 (20.6%). Thirteen (38.2%) presented with an acute abdomen and diagnosis was made following laparotomy.

Location of the disease was as follows: ileocolonic 13 (38.2%), terminal ileum only (with or without cecal overflow), 9 (26.5%), colon only 8 (23.5%), and upper gastrointestinal 4 (11.8%). Of the patients who had upper gastrointestinal disease (upper GIT), two had coexisting disease in the ileocolon, one in the terminal ileum only and one in the colon only.

Disease behavior and surgical rate

The median duration of follow up from the time of diagnosis till the date of recruitment into this study was 8 years (5-18.25). In terms of disease behavior, 16 (47.1%) had penetrating disease, 9 (26.5%) had stricturing disease and 9 (26.5%) had non-penetrating and non-stricturing disease. Of the 34 patients with CD, 16 (47.1%) of patients had undergone at least one operation. Seven (20.6%) had more than one operation.

Racial prevalence

The ethnic distribution of patients with CD were; Malays 5, Chinese 12, and Indians 17. Over the same period of time as the study, hospital admissions per ethnic group were as follows: Malays 53 906 Chinese 44 592, and Indians 32 330. The hospital admission prevalence of CD was 26.0 overall, Indians 52.6, Chinese 26.9, and Malays 9.3 per 10⁵ admissions per ethnic group (Table 2). The difference between Indians and Malays: OR 5.67 (1.97, 17.53) P < 0.001 was statistically significant but not between the Indians and the Chinese OR 1.95 (0.89, 4.35) P = 0.700. The difference between the Chinese and the Malays was also not statistically significant [OR 2.90 (0.95, 9.42) P = 0.063].

Table 2.

Prevalence of CD overall and according to ethnicity

	Malays	Chinese	Indians	Overall
CD (n)	5	12	17	34
Total admissions	53906	44592	32330	130828
Prevalence per 105	9.2	26.9	52.6	26.0
admissions

DISCUSSION

In terms of gender and typical age of presentation, CD in Malaysia appears similar to other Western studies[12,13] in that there was generally no major gender differences and most patients presented under the age of 40, mainly between the ages of 16 to 25. However, the majority of patients did not have any of the known risk factors identified from previous studies. For example, 79.4% of them were lifelong non smokers. As the number of patients with CD is less and there are no controls, this may not be a true finding although there have been other studies that have failed to identify smoking as a risk factor of CD[18,19]. None of our patients had a positive family history as with Leong et al study from Hong Kong[7]. This is in marked contrast to other published studies from the West , where a positive family history is found in 5-10% of patients with CD[20-22].

The commonest presenting complaints were also typical of CD. One interesting observation is that 38.3% of these patients presented with an acute abdomen requiring laparotomy and the diagnosis was subsequently made on histology. In terms of location of the disease, the distribution is also similar to the Western experience. For example, a study by Freeman looking at 877 patients in a single center in Vancouver, Canada found similar findings; CD was located in the ileocolon in 34.6% followed by colon alone in 27.2% and terminal ileum in 25.3% as divided according the Vienna Classification[21].

It is expected for most Crohn’s patients to develop either stricturing or penetrating (fistula, abscess, perforation) complications with time[23] As the median duration of follow up in our patients was fairly long (8 years [5-18.3]), it is not surprising that most of our patients either had stricturing or penetrating disease. Also demonstrated in this study was a high rate of surgery. Almost half the patients had undergone at least one operation.

Therefore, it appears that overall; the clinical presentation of CD in our patient population is similar to that seen in Western countries. Cohort studies looking at the clinical course of the disease in Asian patients suggest that like in the West, most will have chronic, intermittent disease although they may have a more favorable prognosis[24-27].

In terms of prevalence, however, this appears to be low, with CD making up only about 26.0 per 10⁵ admissions. The low frequency of diagnosis of CD had been previously reported in our center when only thirteen cases of CD were identified over an eight year period from 1982 to 1989[28]. Our present study was only able to look at the prevalence of hospital admission. The best epidemiological studies should be population based and in countries such as Japan, an IBD registry is available and incidence and prevalence rates are calculated based on the whole population. However, in most countries in Asia such registries are not established and studies are often made based on hospital statistics with the population of the “catchment area” as the denominator[2,7]. Our main limitation is identifying this catchment area to define the population served by our hospital.

Ethnic differences in IBD are intriguing as they point to either differences in host genetic susceptibility or exposure to environmental factors specific to an ethnic group. A recent study on UC carried out in our center showed the highest prevalence among the Indians followed by the Chinese and the Malays[15]. The hospital admission-based prevalence rates were significantly higher in the Indians compared to the Malays but not the Chinese. In Singapore however, there was a statistically significant difference showing a higher prevalence among the Indians compared to the Chinese[2] With respect to CD, the same Singaporean study showed an increased prevalence in CD among the Indians (4.9 per 10⁵ compared to 4.0 per 10⁵ in the Chinese and 2.9 per 10⁵ in the Malays) although this was not statistically significant. In our present study, the highest prevalence of CD was again found in the Indians.

Therefore, in a multiracial Asian country such as Singapore and Malaysia, IBD appears to be more common among the Indians. It is pertinent to note that all the three races have lived together for more than three generations and are exposed to similar environmental factors indicating that perhaps host genetic susceptibility play a more important role in the pathogenesis of IBD in this region.

In conclusion, in our hospital setting, the clinical features of CD are similar to the Western experience. Although the overall prevalence is low, there appears to be ethnic differences in the prevalence of the disease with a probable racial predominance among the Indians. Racial differences in prevalence may provide vital clues to the pathogenesis of the disease, particularly in the Asian setting.