SEARCH

SEARCH BY CITATION

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

Background

We have tested the hypotheses that compared with local white Caucasians, UK-resident patients of Bangladeshi descent develop inflammatory bowel disease (IBD) at a younger age; more often have Crohn's disease than ulcerative colitis (UC); and have a more aggressive disease course.

Aim

To test the hypotheses that compared to white Caucasian patients of English, Scottish or Welsh descent, patients of Bangladeshi descent develop IBD at a younger age; more often have Crohn's disease; and have a more aggressive disease course by screening case-records of these patients.

Methods

We screened the case-records of 132 Bangladeshi and 623 white Caucasian consecutive out-patients. We then matched each Bangladeshi to a patient of white Caucasian descent for age at diagnosis and disease duration. Data on migration status, phenotype, disease course, treatments and extra-intestinal manifestations and complications were obtained.

Results

No differences were seen in the adjusted age at diagnosis of IBD between Bangladeshi and white Caucasian patients. More Bangladeshis than white Caucasian patients (P < 0.01) were diagnosed with Crohn's disease than UC. Crohn's phenotype at diagnosis was similar in both groups. However, multivariate Cox logistic regression analyses showed that Bangladeshis developed perianal complications (HR [95% confidence interval CI] 8.6 [1.4, 53.1], P = 0.02), and received anti-TNFs (HR [95% CI] 3.0 [1.2, 7.7], P = 0.02) earlier and underwent surgery later (HR [95% CI] 0.4 [0.2, 0.9], P = 0.03) than white Caucasians. More Bangladeshis with UC had extensive disease (24/40 [60%]) than white Caucasians (16/49 [33%], P = 0.02). Overall, more Bangladeshis were anaemic and vitamin D deficient.

Conclusions

Bangladeshi patients with IBD more frequently have Crohn's than UC. Bangladeshis with Crohn's more frequently develop perianal disease, have earlier medication escalation and undergo surgery later than white Caucasians. Bangladeshis have more extensive UC than white Caucasians. The relative contributions of genotype and environmental factors, including vitamin D, to these phenotypic differences require additional study.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

The incidence of inflammatory bowel disease (IBD) in Asian ethnic minorities in the UK has risen in recent years.[1] Data from patients of mainly Indian descent living in the UK suggest that, compared with Northern Europeans, South Asians are more frequently diagnosed with extensive ulcerative colitis (UC) than with Crohn's disease[2, 3] and that the latter is typified by a more benign inflammatory non-stricturing, non-penetrating phenotype.[3] This, however, has not been our impression when looking after Bangladeshi patients in East London and so we have tested the hypotheses that compared to white Caucasian patients of English, Scottish or Welsh descent, patients of Bangladeshi descent (i) develop IBD at a younger age; (ii) more often have Crohn's disease; and (iii) have a more aggressive disease course.

Methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

Study design and clinical setting

We conducted a retrospective case-controlled study to evaluate the phenotype and disease course of IBD patients of Bangladeshi descent, comparing it to that in white Caucasian patients matched for age at diagnosis and disease duration. Barts and the London NHS Trust is a tertiary referral centre in East London, UK, that serves approximately 2000 paediatric, adolescent and adult patients with IBD from the local catchment area and beyond.

Screening

The self-reported ethnicity, as well as age at diagnosis, disease duration and postcode of each consecutive patient attending our specialist IBD out-patient clinics between March and August 2010 were recorded. To avoid tertiary referral bias we included only patients with postcodes from the surrounding boroughs of Tower Hamlets, City and Hackney, and Newham, which make up our immediate catchment area.

Defining age at diagnosis

To test if Bangladeshi patients develop IBD at a younger age than white Caucasians, we assessed age at diagnosis in all of the patients from our catchment area, regardless of whether or not they were subsequently matched. Because the age distribution of our local Bangladeshi population is skewed towards a younger age than that of the white Caucasians, for this part of the study we adjusted the comparison of age at diagnosis in these groups using their respective age distributions in our local (healthy) population as the denominator.[4]

Matching

For the second part of the study, all patients of Bangladeshi descent living in our catchment area with an established diagnosis of IBD, based on endoscopic, histological and radiological findings,[5, 6] were included. To compare the natural history of IBD in the two groups, each index case was then matched on the grounds of age at diagnosis (to within 3 years) and then disease duration (to within 5 years) to a white Caucasian patient of English, Scottish or Welsh descent, to control for the higher prevalence of Crohn's disease and the increased severity and extent of both forms of IBD when it is diagnosed in childhood.[7-9] Where more than one potential match on the grounds of age at diagnosis was available, the individual with the closest disease duration was included.

Demographic and socio-economic data

Demographic data, including place of birth and year of migration, were obtained from the Trust's electronic patient record (EPR) and our IBD database. Socio-economic data were obtained from the ACORN database[10]: based on an individual's postcode, this online database segments the UK population into 56 ordinal socio-economic types: where 1 is categorised as “affluent mature professionals, living in large houses” and 56 as “multi-ethnic populations living in crowded flats”.

IBD phenotype and disease course

Inflammatory bowel disease was phenotyped according to the Montreal Classification.[11] When radiological or endoscopic tests were undertaken to re-stage disease and changes in location and/or behaviour for Crohn's disease, and extent for UC, respectively, were found, the date of the relevant investigation was used to calculate the time to change of Montreal classification. The natural history of UC and Crohn's disease were assessed by comparing the time to change in Montreal Classification; the treatments used including numbers of courses of steroids, and use of and time to use of immunosuppressant treatments and surgeries. Researchers collecting data on the Bangladeshi patients (JRG and NMJ) were blinded to the results of the white Caucasian (NK and MW) patients.

Extra-intestinal manifestations and complications

We recorded the occurrence of organ-specific extra-intestinal manifestations (EIMs) of IBD including: arthropathy, cutaneous involvement, ocular involvement and primary sclerosing cholangitis (PSC), as well as the prevalence of anaemia and vitamin D deficiency at last follow-up.

Anaemia was defined according to WHO criteria[12]; in men as Hb <13 g/dL, in nonpregnant women <12 g/dL, in pregnant women <11 g/dL, in children aged 12–13 years <12 g/dL, and in children aged 5–11 years <11.5 g/dL. Iron deficiency was defined as a ferritin <30 µg/L when the corresponding CRP was <10 mg/L, or a ferritin <100 µg/L when C-reactive protein (CRP) was >10 mg/L and/or transferrin saturation (TNSat) <16%.[13] Anaemia of chronic disease was defined as anaemia in the presence of a CRP-adjusted, normal or increased serum ferritin and/or a low plasma iron and iron-binding capacity.[14] Checks were made for co-existing haemoglobinopathies. B12 deficiency was defined as <191 ng/L and folate deficiency as serum folate <3.8 mcg/L. Blood test results were obtained from the EPR.

The normal range for serum vitamin D3 in our Trust is 80–150 nmol/L. We recorded the number of patients with serum levels below the lower limit of normal.

Statistical methods

Statistical analyses were conducted using spss (version 16, San Diego, CA, USA) and Prism (version 4, Chicago, IL, USA) software. All analyses were two-tailed and P-values <0.05 were considered significant. Univariate analysis of baseline demographic data comparing patients of Bangladeshi descent and white Caucasians was carried out using chi-squared test for categorical data and Student's t-test for continuous normally distributed variables and Mann–Whitney U-tests for discrete or nonparametric data. Univariate survival analyses using Kaplan–Meier curves and the log-rank test were used to identify differences in the proportions of patients and the time to change in Montreal Classification, escalation in therapy and need for surgery between the ethnic groups. Where ethnicity was found to influence disease progression, multivariate Cox regression analyses taking into account factors that have previously been linked to a worse prognosis, including age at diagnosis,[7, 8] socio-economic status,[15] smoking,[16] extensive and/or perianal disease involvement[17, 18] the use of steroids at diagnosis and thiopurines[19] were used to test whether ethnicity independently influenced disease progression.

Ethical consideration

Because we were evaluating the course of disease in patients using our IBD service, we did not require formal ethical approval according to the guidelines of the UK National Research Ethics Service.[20]

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

Screening

We screened 2449 scheduled appointments in 1247 patients: 192 patients were excluded because they did not have a confirmed diagnosis of IBD. Thirteen per cent [132/1055] and 59% [623/1055] patients reported being of Bangladeshi and white Caucasian descent respectively: of these, significantly more people of white Caucasian descent (62% [389/623] vs. 8% [11/132], P < 0.0001) lived outside our catchment area (see Figure 1).

image

Figure 1. STROBE[42] diagram outlining the screening, matching and inclusion of Bangladeshi and white Caucasians. Each index case was matched on the grounds of age at diagnosis (to within 3 years) and then disease duration (to within 5 years) to a white Caucasian patient of English, Scottish or Welsh descent. Where more than one potential match on the grounds of age at diagnosis was available, the individual with the closest disease duration was included.

Download figure to PowerPoint

Age at diagnosis

Among the population available for matching, only 7% (9/121) Bangladeshis compared with 26% (60/234) Caucasians had IBD diagnosed at age >40 years (P < 0.001). However, after adjusting for the age distributions in the Bangladeshi compared with the local white Caucasian population, no differences were seen in the age at diagnosis (see Figure 2).

image

Figure 2. Age at diagnosis of the Bangladeshis and white Caucasians in the screening population. Amongst the population available for matching only 7% (9/121) Bangladeshis, compared with 26% (60/234) Caucasians, had IBD diagnosed at age >40 years (P < 0.001). However, having adjusted for differences in the demographics of the same ethnic group in our local population, no differences were seen in the age at diagnosis (Chi-squared test for trend, P = 0.52) between our Bangladeshi and white Caucasian patients.

Download figure to PowerPoint

Matching

We were unable to match 2% [2/121] of the Bangladeshi patients because their disease durations were less than 4 months and a similar white Caucasian match was unavailable (see Figure 1). As a consequence of our matching there was no difference in the mean [S.E.M.] age at diagnosis (23.4 [1.0] vs. 24.0 [1.1] years, P = 0.69) or disease duration (6.1 [0.43] vs. 6.9 [0.43] years, P = 0.43) between the Bangladeshi and white Caucasian groups respectively (Table 1).

Table 1. Demographic characteristics, disease duration and type of the included patients
CharacteristicsBangladeshi 119White Caucasian 119P-value
  1. Differences between parametric continuous variables and in nonparametric and/or discrete variables were sought using Student's t-test and the Mann–Whitney U-test respectively. Differences between categorical variables were sought using Chi-squared analyses.

  2. a

    The denominator is stated for a variable where there was missing data.

SexMale [%]72 [61%]57 [48%]0.05
AgeMean [S.E.M.] age (years)29.6 [1.1]30.9 [1.1]0.37
Cigarette smokingaLifelong non-smoker [%]73/103 [71%]65/98 [66%]0.55
 Smoker [%]15/103 [15%]13/98 [11%] 
 Ex-smoker [%]15/103 [15%]20/98 [20%] 
 Median [range] pack years3.1 [0.7–15.0]4.5 [0.3–42]0.18
ACORN typeMedian [range] ACORN type55 [9–56]21 [1–56]<0.001
DurationMean [S.E.M.] age at diagnosis (years)23.4 [1.0]24 [1.1]0.69
 Mean [S.E.M.] disease duration (years)6.1 [0.4]6.9 [0.4]0.16
 Median [range] time to diagnosis (months)5 [0–172]5 [0–134]0.59
Disease typeCrohn's disease [%]79 [66%]62 [52%]0.004
 Ulcerative colitis [%]40 [34%]49 [41%] 
 Inflammatory bowel disease unclassified [%]8 [7%] 

Baseline demographics

There was no difference in the mean age between groups (Table 1). Overall, more patients of Bangladeshi descent were male patients than female patients (Table 1). There were no differences in the proportions of patients who were ex- or current smokers or in the duration of smoking between groups. However, and allowing for missing data, more Bangladeshi men (41% [26/63]) than women (10% [4/40]) were or had been smokers; in contrast, there was no difference in smoking status of patients according to gender in the white Caucasians (P < 0.001) (Table 1). Based on their postcodes and according to the ACORN classification type (median [range]), patients of Bangladeshi (55 [9–56]) descent lived in more socio-economically deprived areas of East London than patients of white Caucasian (21 [1–56]) descent (P < 0.0001).

Disease type and time to diagnosis

More patients of Bangladeshi descent were diagnosed with Crohn's disease than UC or inflammatory bowel disease of uncertain type (IBDU) than their matched patients of white Caucasian descent (Table 1). There was no difference in the time to diagnosis between Bangladeshis or white Caucasians for either UC or Crohn's disease (Table 1).

Phenotype and natural history of Crohn's disease

There were no differences in the phenotype of Crohn's disease according to the Montreal Classification between Bangladeshis and white Caucasians at diagnosis (Table 2). Over the period of follow-up (equivalent to the disease durations above), there were no differences in the time to, or the proportions of, patients whose Crohn's disease became more extensive [increased Location (L) or developed upper gastrointestinal disease + L4] or changed behaviour (increased B) between groups. However, patients of Bangladeshi descent (Hazard ratio (HR) [95% CI] 8.6 [1.4, 53.1], P = 0.02) were more likely to develop perianal disease earlier in their disease course than white Caucasians (Figure 3a).

Table 2. Crohn's disease phenotype and disease course in patients of Bangladeshi and white Caucasian descent
CharacteristicsBangladeshi N = 79White Caucasian N = 62P-value
  1. Differences between parametric continuous variables and in nonparametric and/or discrete variables were sought using Student's t-test and the Mann–Whitney U-test, respectively. Differences between categorical variables were sought using Chi-squared analyses.

  2. a

    Survival analyses using Kaplan–Meier curves and the log-rank test.

Crohn's disease (Montreal classification)A1: Age ≤1633 [42%]29 [48%]0.74
 A2: 17–4043 [54%]29 [48%]
 A3: >403 [4%]2 [3%]
 L1: Ileal26 [33%]20 [32%]0.47
 L2: Colonic19 [24%]14 [23%]
 L3: Ileocolonic30 [38%]26 [42%]
 + L4: Upper gastrointestinal (GI)14 [18%]13 [21%]0.39
 B1: Inflammatory50 [63%]34 [55%]0.93
 B2: Stricturing12 [15%]7 [11%]
 B3: Penetrating16 [20%]9 [15%]
 + p: Perianal18 [23%]10 [16%]0.46
Disease courseIncrease in Montreal classification location (L)3 [4%]4 [6%]0.92a
 Median [range] time to increase in L (months)55 [6–227]92 [17–251]
 New upper GI disease (+L4)4 [5%]1 [2%]0.09a
 Median [range] time to develop L4 (months)56 [6–324]79 [13–312]
 Increase in Montreal classification behaviour (B)17120.81
 Median [range] time to increase in B (months)56 [6–324]64 [1–311]
 New perianal disease (+p)13 [16%]2 [3%]0.002a
 Median [range] time to develop +p (months)61 [6–324]88 [1–312]
Medications ever5-ASA74/79 [94%]49/57 [86%]0.13
 Budesonide25/78 [32%]15/53 [28%]0.65
 Prednisolone52 [66%]38 [61%]0.35
 Number of courses of steroids1 [0–5]0 [0–7]0.02
 Thiopurines60/79 [76%]39/62 [63%]0.01a
 Median [range] time to thiopurines (months)20 [1–199]37 [0–312]
 Methotrexate14 [18%]6 [10%]0.12a
 Median [range] time to methotrexate (months)54 [6–324]77 [8–312]
 Anti-TNF26/79 [33%]13/60 [22%]0.01a
 Median [range] time to anti-TNF (months)20 [1–199]37 [0–312]
SurgeryIntestinal surgery18 [30%]27 [44%]0.03a
 Median [range] time to intestinal surgery (months)47 [0–190]42 [0–312]
 Perianal surgery16 [20%]5 [8%]0.04a
 Median [range] time to perianal surgery51 [0–324]75 [1.5–312]
image

Figure 3. Kaplan–Meier curves and univariate log-rank (graphs) and multivariate simultaneous Cox hazard regression (Tables) survival analyses of the time to new perianal disease (a), time to thiopurine (b), time to anti-TNF therapy (c) and time to intestinal surgery (d) of patients with Crohn's disease. The solid lines represent the disease course in the Bangladeshi and the broken lines the white Caucasian patients, respectively; the tags denote censored data. Variables were entered into each model simultaneously and checks for co-linearity defined by a standard error >5. HR, hazard ratio; 95% CI, the 95% confidence interval.

Download figure to PowerPoint

Bangladeshis were given more courses of steroids than white Caucasians (Table 2), and tended to receive thiopurines (HR [95% CI] 1.7 [1.0, 3.0], P = 0.06) (Figure 3b) and anti-TNF (HR [95% CI] 2.4 [1.1, 5.4], P = 0.04) (Figure 3c) medications, but not methotrexate, earlier in their disease course than white Caucasians.

White Caucasian patients who had undergone surgery had their first intestinal resection earlier in their disease course, most having had a right hemi-colectomy, than patients of Bangladeshi descent (Figure 3d). Bangladeshis were more likely to have undergone perianal surgery than the white Caucasians (Table 2).

Phenotype and natural history of ulcerative colitis

Bangladeshi patients diagnosed with UC had more extensive disease than white Caucasian patients (Table 3). Similar proportions of Bangladeshis and white Caucasian patients developed more extensive disease over follow-up (Table 3). There were no differences in the number of courses of steroids, use of 5-ASAs, or the time to, or proportions of patients who were prescribed thiopurines between groups. Similarly, there was no difference in the time to, or proportions of patients who underwent a colectomy between groups (Table 3).

Table 3. Ulcerative colitis (UC) phenotype and disease course in patients of Bangladeshi and white Caucasian descent
CharacteristicsBangladeshi descent (N = 40)White Caucasian descent (N = 49)P-value
  1. Differences between parametric continuous variables and in nonparametric and/or discrete variables were sought using Student's t-test and the Mann–Whitney U-test, respectively. Differences between categorical variables were sought using Chi-squared analyses. Survival analyses were undertaken using Kaplan–Meier curves and the log-rank test. Differences between categorical variables were sought using Chi-squared analyses.

  2. a

    The denominator is stated for a variable where there was missing data.

  3. b

    Survival analyses using Kaplan–Meier curves and the log-rank test.

UC Montreal classificationaE1: Proctitis1 [2%]15/45 [31%]0.002
 E2: Left15 [37%]14/45 [29%]
 E3: Total24 [60%]16/45 [33%]
Disease courseExtension of UC2 [5%]6 [12%]0.61
 Median [range] time to extension of UC (months)40 [9–239]48 [5–288]
Medications ever5-ASA34 [85%]47 [96%]0.07
 Prednisolone29 [43%]38 [78%]0.58
 Number of courses of steroids2 [0–6]1 [0–13]0.86
 Thiopurines25 [63%]24 [49%]0.23b
 Median [range] time to thiopurines (months)25 [3–239]54 [3–288]
 Methotrexate9 [23%]7 [14%]0.34b
 Median [range] time to methotrexate (months)49 [9–239]56 [5–288]
 Calcineurin inhibitor3 [8%]6 [12%]0.55b
 Median [range] time to calcineurin inhibitor (months)52 [0–239]56 [3–288]
SurgeryIntestinal surgery350.68b
 Median [range] time to intestinal surgery (months)48 [9–239]56 [3–288]

Extra-intestinal manifestations and complications

Organ-specific EIMs of IBD (arthropathy, cutaneous involvement, ocular involvement, PSC) were equally distributed between the two groups (Table 4). At last follow-up, significantly more of the patients of Bangladeshi (39% [47/119]) than white Caucasian (20% [24/119]) descent were anaemic (P < 0.001), regardless of differences in disease type. Furthermore, of anaemic patients, haematinics consistent with iron deficiency were more common among the Bangladeshi patients (P = 0.03). Similarly, where the result was available, vitamin D deficiency was significantly more prevalent among the patients of Bangladeshi than in patients of white Caucasian descent (Table 4).

Table 4. Extra-intestinal manifestations and complications of inflammatory bowel disease in patients of Bangladeshi and white Caucasian descent
CharacteristicsBangladeshi descent (119)White Caucasian descent (119)P-value
  1. Differences between parametric continuous variables were sought using Student's t-test and differences between categorical variables were sought using Chi-squared analyses. Differences between categorical variables were sought using Chi-squared analyses.

  2. a

    The denominator is stated for a variable where there was missing data.

EIMPrevalence18 [15%]25 [21%]0.2
Type EIMArthropathy16 [13%]15 [13%]1
 Cutaneous1 [1%]6 [5%]0.12
 Ocular1 [1%]3 [3%]0.62
 Primary sclerosing cholangitis0 [0%]1 [1%]1
Vitamin D deficiencyaPrevalence78/84 [93%]46/56 [82%]<0.05
 Mean vitamin D3 (nmol/L) [S.E.M.]34.2 [2.5]53.3 [3.5]<0.001
AnaemiaPrevalence47 [39%]24 [20%]0.001
 Mean haemoglobin (g/dL) [S.E.M.]12.6 [0.2]13.4 [0.1]<0.001
 Mean haematocrit (L/L) [S.E.M.]0.38 [0.005]0.4 [0.004]0.01
 Mean cell volume (fL) [S.E.M.]84.1 [0.6]88.6 [0.6]<0.001
Anaemia typeIron deficiency38 [81%]12 [50%]0.03
 Anaemia of chronic disease7 [15%]9 [38%]
 Undetermined2 [4%]3 [13%]

Influence of migration status on disease phenotype in Bangladeshis

Migration data were available for 84% [100/119] Bangladeshi patients. Overall, 44% [44/100] patients of Bangladeshi descent were born in Bangladesh; the median [range] age at migration to the UK was 14 years [0.1–34]. All the Bangladeshi patients were diagnosed in the UK. The mean [S.E.M.] of the age at diagnosis of Bangladeshis born in the UK was 17 [5.9] years compared with 31 [11.4] years (P < 0.001) for those born in Bangladesh; the mean [S.E.M.] duration of residence in the UK of the latter group prior to diagnosis was 18.2 [1.9] years. There were no differences in Crohn's disease phenotype at diagnosis or at maximal follow-up between Bangladeshis born in the UK or in Bangladesh (data not shown). However, and allowing for the differences in age at diagnosis, Bangladeshis born in the UK more frequently had extensive UC than those born in Bangladesh (100% [11/11] vs. 60% [12/20] respectively, P = 0.02).

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

Few studies evaluating IBD phenotype or disease course according to ethnicity have been published.[2, 3, 21-23] Such studies are methodologically difficult to design, in part because they require large sample sizes, which are frequently not available at single centres. To our knowledge, there are no other published reports of the phenotype and natural history of IBD in patients exclusively of Bangladeshi descent either living in Bangladesh or abroad. The incidence of IBD in Bangladeshis living in Bangladesh has historically been low[24]; however, we have previously reported that the incidence of IBD in Bangladeshi immigrants to the UK, and their children is increasing.[1]

Key results and interpretation

Age at diagnosis

Analysis of the population demographics of our local catchment area showed that Bangladeshis are on average younger than white Caucasians. Having adjusted for this observation, there was no difference in the age at diagnosis of IBD in patients of Bangladeshi and Caucasian descent screened for inclusion.

Disease type

We report herein that, compared with patients of white Caucasian descent, patients of Bangladeshi descent are more likely to be diagnosed with Crohn's disease than UC or IBDU. Our findings contrast with previous reports of IBD phenotype in Indians living in Leicester in the UK, and in a large group of mixed South Asian patients, the majority of whom were of Indian descent, from Northwest London: these two ethnic groups, when compared to non-matched Northern European control patients, tended to be more frequently diagnosed with UC.[3, 25] Although Indians and Bangladeshis share similar genetic backgrounds,[26-28] the two ethnic groups may have differences in exposure to environmental factors relevant to the aetiology of IBD, in part as a consequence of differences in religion: these include diet, alcohol consumption and smoking habits.

More men than women in our Bangladeshi group were diagnosed with Crohn's disease; whereas and in keeping with data from large epidemiological studies,[29] there was no difference in disease type according to gender in the white Caucasian group. Bangladeshi men, as we report herein, are more frequently tobacco smokers than Bangladeshi women, who very rarely smoke.[30] Furthermore, healthcare utilisation is perceived to be less in women than in men of Bangladeshi descent and it is conceivable, but unproven, that there are a group of Bangladeshi women with Crohn's disease who have not presented with their symptoms to appropriate healthcare services.[31] Despite including only patients who lived at addresses within our local catchment area, Bangladeshi patients in this series lived in more socio-economically deprived areas than white Caucasians: however, socio-economic status did not account for the differences in Crohn's disease course reported herein.

Crohn's phenotype and natural history

Previous reports of the phenotype of Crohn's disease in Indians in India[32] and in South Asians living in Northwest London suggest that colonic non-stricturing, non-penetrating disease is the predominant phenotype.[3] We found no differences in the phenotype of Crohn's disease between patients of Bangladeshi and white Caucasian descent at diagnosis; however, more Bangladeshis developed perianal disease than white Caucasians. Overall, the progression of Crohn's disease to a stricturing or penetrating phenotype, regardless of ethnicity and allowing for the duration of disease, appears similar to that frequently cited from Northern Europe.[33] Although there were no differences in the proportions of patients who ultimately underwent intestinal surgery, intestinal surgery was more frequently delayed in patients of Bangladeshi descent. The reasons for this are unknown. We initially hypothesised, based on our clinical experience, that patients of Bangladeshi descent would have more extensive disease with more extensive small bowel involvement, which would negate limited surgery: however, in both patient groups the proportion of patients with extensive small bowel disease (+L4) was similar. Although, in the setting of ileal disease without co-existing perianal disease, surgery is frequently the most appropriate treatment option, when there is co-existing perianal disease medical treatment with thiopurines and anti-TNF medications maybe more appropriate. In this context, it is possible that the tendency to earlier use of immunomodulators and the earlier use of anti-TNF agents in the natural history of Bangladeshi patients prevented the need for intestinal surgery. Lastly, Bangladeshi patients may be more reluctant than patients of white Caucasian descent to undergo surgery, but we have no quantitative or qualitative data to support this assertion.

The proportion of white Caucasians progressing to perianal disease was lower than has been reported previously.[33-35] There are a number of possible reasons for the differences between our data and what is perceived to be characteristic IBD phenotypic data. Firstly, much of the classical phenotypic data come from tertiary centres in Northern Europe where cigarette smoking is more common than in our population in the UK.[33-35] Secondly, by restricting our inclusion criteria to include patients living in our local catchment area to exclude tertiary referral bias, we are likely to have excluded patients referred to our specialist colorectal surgeons for fistula surgery. Finally, the low prevalence of perianal disease in our dataset may reflect our infrequent use of corticosteroids as induction agents in patients with Crohn's disease.[19]

UC phenotype and natural history

In agreement with other studies of South Asian migrants to the UK,[3, 36] but interestingly not with data reporting the extent of UC in Indian patients from Chandigarh[37] and Punjab,[38] our Bangladeshi patients had more extensive UC than white Caucasians. Despite this, therapeutic requirements, including colectomy rates, were similar in the two groups.

Extra-intestinal manifestations and complications

As has been previously reported, ethnicity did not seem to influence the prevalence of organ-specific EIMs in our patient groups.[3, 37, 39] However, using WHO criteria, anaemia, and specifically iron deficiency anaemia, was more common in the Bangladeshi patients. Iron deficiency anaemia is usually a consequence of persistently active IBD,[13] but, dietary deficiency, perhaps as a consequence of lower socio-economic status, and non-adherence to oral iron treatment maybe more common in Bangladeshi than in white Caucasian patients.[40, 41]

Perhaps unsurprisingly, and allowing for the possibility of detection bias, given the climate in the UK and in the differences in skin tone, vitamin D deficiency was more prevalent among the Bangladeshi than among white Caucasian patients. Of note, there were no differences in the time of year that vitamin D levels were assessed, and there was no difference in the prevalence of vitamin D deficiency within the Bangladeshi group according to gender (data not shown).

Strengths and limitations

Strengths

Our matched study has several strengths. Firstly, because early age at diagnosis is an adverse prognostic factor for the outcome of IBD,[7-9] by carefully matching our cohort according to age at diagnosis we have avoided this potential selection bias. Secondly, unlike previous studies which have published differences in phenotype according to ethnicity, we have controlled for disease duration and therefore the duration of follow-up in which to compare disease course. Thirdly, we have studied only patients of Bangladeshi descent and not a mixed South Asian population. Fourthly, because this is a single centre cohort from a tertiary centre for IBD care, the patients were each accurately phenotyped, allowing us to look for differences among demographic characteristics, disease phenotype and treatment regimens. Lastly, by restricting the inclusion of patients to our local catchment area, we have avoided tertiary centre bias.

Limitations

Conversely, this work has a number of limitations. Because of our retrospective data collection, in particular for the Montreal classification, our results are potentially subject to interpretation bias, and bias because of missing data, for example, for smoking habits. We acknowledge too, that the sample size is relatively small and consequently that our conclusions may be subject to a type II error, especially when sub-stratified by disease type. Because we did not stratify our patients by postcode at diagnosis, it is conceivable, although unlikely, that patients may have relocated to our area to be closer to their tertiary treatment centre.

Conclusions

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

Compared with patients of white Caucasian descent matched for age at diagnosis and disease duration, Bangladeshi patients with IBD more frequently have Crohn's disease than UC. Contrary to previous reports of the phenotype of Crohn's disease in Indians and South Asians, we found no differences in Crohn's disease phenotype at diagnosis between Bangladeshis and white Caucasians; Bangladeshis with Crohn's disease did, however, have more courses of steroids and progressed more quickly to perianal disease, thiopurines and anti-TNF therapy. Patients of Bangladeshi descent had more extensive UC than white Caucasians. Overall, Bangladeshis were more frequently anaemic and vitamin D deficient. Carefully designed genotypic, immunological and environmental studies are needed to elucidate the reasons for the differences in disease type, phenotype and course, observed between patients of Bangladeshi and white Caucasian descent, and may contribute to furthermore understanding of the aetiopathogenesis of IBD.

Acknowledgements

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

Declaration of personal interests: Prof. David Rampton has served as a speaker, a consultant and advisory board member for Shire, Ferring and Abbott, and has received research funding from MSD. Dr James Lindsay has served as a speaker, a consultant and advisory board member for MSD UK, Ferring UK, Ferring worldwide, Warner Chilcott, Shire UK, Abbott UK, Abbott International, Atlantic Healthcare, and has received research funding from Shire, Schering Plough/MSD. Dr Nick Croft has served as a speaker, a consultant and advisory board member for MSD, Shire, Ferring, Schering Plough and Dr Falk, and has received research funding from Abbott, Shire, Johnson and Johnson. Declaration of funding interests: None.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References