A subtype of inflammatory bowel disease (IBD), Crohn's disease (CD) is believed to result from a complex interplay between genetic susceptibility and one or more environmental triggers. The disease is characterized as a chronic immune-mediated disorder of the gastrointestinal tract which may or may not be accompanied by a variety of extraintestinal or systemic complications. Disease presentation and severity are known to vary between individuals, having important implications for disease management [1], [2]. Thus, in recent years, issues of CD sub-classification by phenotype have been reviewed, and the Montreal classification system [2] (revised Vienna) is the accepted standard.

Crohn's disease is found in all racial groups worldwide. However, historically, the highest prevalence rates have been reported in white populations, particularly those of North America and Europe, with significantly lower rates seen in black and Asian populations within these or any other foreign country [3]–[12]. As such, the majority of reports contributing to our understanding of disease presentation and clinical course originate primarily from Western populations, leaving a paucity of literature regarding the racial variability of CD phenotype [5], [12]–[14].

Earlier epidemiological observations have suggested that CD presents in a more severe form in African American and Asian populations compared to their white counterparts [15]–[17], yet findings have been inconsistent, often limited by small sample size and variations in disease classification methods. Recently however, reports indicate that the incidence of IBD in both African American and Asian populations has been steadily rising over the decades [18]–[22]. This increase in incidence may be attributed to one of several factors namely, changes in utilization and accessibility of hospital care (suggesting an underreporting of previous incidence rates), selection bias of IBD centers, or a true rise in the incidence among these racial groups [23]. Therefore, aspects surrounding the racial variations in CD phenotype should continue to be explored and include all non-white populations in order to further contribute towards our understanding of the environmental and genetic factors involved in the disease etiology.

The aim of our study was thus to provide a preliminary and descriptive view on disease phenotype of the racial groups in Cape Town, South Africa.

The study protocol and questionnaire were reviewed and approved by the Senate Research Ethics Committee of the University of the Western Cape (Reg no. 11/3/16), the Human Research Ethics Committee of the University of Cape Town (HREC REF: 122/2011) and the Provincial Department of Health. All participants gave written informed consent. http://dx.doi.org/10.6084/m9.figshare.1041586.

Population based epidemiological studies remain of paramount importance in piecing together the complex pathogenesis underlying CD, particularly in terms of inter-racial variations of disease phenotype. In South Africa, while a number of earlier reports are available, no such recent data exists for the population; a population broadly classified into three ethnic groups: black south African, white and Cape Coloured.

This study included all consecutive state-sector adult CD patients within the Western Cape, South Africa seen over a seventeen month period. Comparing Cape Coloured subjects with their white counterparts, a significant difference in the development of ‘complicated’ CD (60% vs. 9%) over time was noted. One possible explanation is the high prevalence of ongoing active smoking in Cape Coloureds at study enrolment. Cigarette smoking is a well described risk factor for the development of complicated and aggressive CD over time [28]. The rate of complicated CD in our white subjects was lower compared to that described in other populations. It is possible that the discrepancy in disease course can be attributed to differences in treatment strategies, patient compliance to medical management, or true microbial differences between populations, but these factors were not investigated. In addition, recent reports indicate that prevalence of systemic lupus erythematosus, particularly among the black and Coloured females in Cape Town, South Africa is higher than previously thought [29], [30]. However in this present study, no concomitant diagnosis of CD and systemic lupus erythematosus was found, suggesting that different factors contribute to the etiology of the two diseases.

In keeping with reports from Asia [31]–[44], among our Cape Coloured subjects, ileo-colonic appeared to be the most common location at diagnosis. Interestingly in contrast to white patients, Cape Coloured subjects appeared to have a shorter duration of presenting symptoms in years until diagnosis. These findings are at odds with the widely held belief that the disease is frequently overlooked in this population due to the high rates of tuberculosis and infectious diarrhea, or poor access to health care. Notably, the public-sector health care system in South Africa predominantly caters to those who are of lower socioeconomic standing. In this study, findings are likely not attributed to inter-racial differences in access to healthcare or medical treatment as there was no significant inter-racial difference in the level of income. Moreover education is considered to be a good marker of socioeconomic status and in our cohort, there was no significant inter-racial difference in the level of education.

Family history of IBD is considered one of the strongest predisposing risk factors in CD. However in our cohort 6% of the Cape Coloured and none of the black patients reported having a first degree family member with IBD. In contrast 14% of the white subjects had a positive family history, the latter compatible with Western data (10–25%) [43], [45], [46]. This finding may reflect racial differences in CD susceptibility mutations. A study of South African Coloureds failed to demonstrate an association with 3 nucleotide oligomerization domain (NOD-2) mutations commonly seen in the West [47]. Moreover, significant differences of allele and genotype frequencies in the -237C→T promoter polymorphisms of the SCL11A1 gene, a gene implicated in CD susceptibility [48], were observed in South African Coloured CD patients, but not in their white and black counterparts [49]. Similar discrepancies have been observed in Japanese [50], [51], Han Chinese [52]–[54], Korean [55], Indian [56] and Malaysian [57] populations [58], [59].

A five year retrospective study [60] based on the GSH gastrointestinal clinic patient lists, found an increasing CD incidence in the Coloured population; from 0.4/100 000 per year during 1970–1974 [61] to 1.3/100 000 per year during 1975–1980. Of the 117 CD patients reviewed; 32 were Coloured and only 1 was black. In contrast, we found 152 Cape Coloured and 7 black, consecutive CD state sector patients. Given the significant socioeconomic, dietary and lifestyle changes that have taken place over the past two decades, it is likely that our findings indicate an epidemiological transition among these racial groups, a trend noted in developed and developing countries alike [5], [18]. These observed trends in our Cape Coloured and black subjects lend support to both different susceptibility genes and variable environmental interactions between racial groups, implying distinctions in disease pathogenesis or risk.

Our study was limited by the small number of black subjects. It is possible that over a longer period, including patients from both, the state and private sector, a larger sample size would be drawn. Data regarding medication use has been poorly captured in the past, as this was a retrospective study, details on the type medical treatment used, duration of treatment, dosage and adherence was difficult to determine, and may have contributed to the identified inter-racial differences. Similarly, given the retrospective nature of the study, the exact parameters used to exclude tuberculosis diagnosis (i.e., histological, radiological, endoscopic), were not available to report in this paper. Our cohort may have included a higher proportion of patients with ‘complicated’ disease as GSH and TBH are both referral based IBD centers. Poor socioeconomic status is associated with helminth infection and in South Africa helminth infection has been shown to be protective against IBD development [62]. Therefore it is entirely possible that within our cohort this may have influenced the severity of CD between the racial groups however this was not one of the variables evaluated in the present study. The ethnic diversity of our cohort was also not representative to that of the Western Cape, as 2011 provincial estimates approximate (N = 5,822,734) 15.7% of the population as white, 48.8% as Colored and 32.9% as black (excluding Indian and Asian ethnicities) [63]. We also did not verify the self-reported race using genetic markers. However, validity of self-reported racial status has been previously acknowledged, as very low rates of discordance between self-reported racial status and genetic markers have been described [25], [64], [65].