Trends in Inflammatory Bowel Disease-Comparison Between the Arab and Jewish Population in Israel

Introduction: Genetic and environmental factors have a major influence on the pathophysiology of inflammatory bowel disease (IBD). Older studies reported a very low prevalence of IBD among the Arab population in Israel. Objective: Evaluate the current prevalence and disease characteristics of IBD in the Israeli-Arab population and to compare them to the Jewish population in the same area. Methods: Electronic medical records of all patients insured in the Sharon-Shomron district of Clalit Health Services were reviewed until December 2012. Files of all adults (> 18 years) with a diagnosis of IBD were retrieved. Results: 616,338 patients were insured in the district 185,510 Arabs and 430,828 Jews. 2050 Jewish and 263 Arab patients met the criteria for IBD (prevalence of 0.48% and 0.14% respectively, p < 0.001). Arab patients were younger at diagnosis (35.6 ± 16.2 vs. 41 ± 18.8y, p < 0.001), had more exacerbations (58.6% vs. 39.5%), anemia (52.1% vs. 39.5%), hypoalbuminemia (33.5% vs. 25.7%) and hypocholesterolemia (53.6% vs. 44%) (all p < 0.01). The Arab patients received more oral steroids (46% vs. 36%, p < 0.01). More Jewish patients underwent colonoscopy and bone densitometry (43% vs. 32% and 20% vs. 12%, respectively, p < 0.01). Arab patients had more IBD-related hospitalizations (37% vs. 28%, p < 0.01), but had the same rate of IBDrelated surgery compared to the Jewish patients. Conclusions: Prevalence of IBD among the Israeli-Arab population is increasing, but remains lower than among the Jewish population. Arab patients are younger and have more active disease. Our findings support the central role of genetic and environmental factors in the phenotypic expression of IBD, while underscoring ethnic and cultural differences.


Introduction
The prevalence of IBD in Israel [1], and in the rest of the world [2,3] is increasing.Genetics [4] and the environment [5] are both includes the largest population studied in Israel on the topic of IBD [1,9,12,16].The subjects studied belong to two stable ethnic groups living in the same area in Israel, with similar access to the same healthcare system.With this in mind, we think that the differences found between the two groups, can be explained by a combination of genetic differences and socio-cultural effects.
Traditionally, IBD is reported as more prevalent in developed countries with a north-to-south gradient [17].However, in the last three decades, geographic distinction has become less prominent, with reports of high incidence of IBD in southern Europe and Australia [18][19][20].Ethnicity is another important factor.IBD has been reported as more prevalent in Jews, especially those of Ashkenazi ancestry and less prevalent among other ethnic groups such as Arabs, Spanish, African-American and Chinese [7,9,21].An increase in the overall incidence and prevalence of IBD is reported worldwide [22,23], with a concomitant increase among ethnic groups previously believed to be of low prevalence, such as Hispanics and Asians [24][25][26].Past reports, have documented lower prevalence of IBD in Ashkenazi Jews in Israel compared to those in North America [27,28], and very low to zero prevalence among the Arab-Israeli population [9,10,11].Other recent studies from Israel confirmed the increasing prevalence among the Jewish population [16] with continuing low prevalence in the Arab population [12].The present study demonstrated an increasing prevalence of IBD among the Jewish population, approaching that reported in Europe and North America [26].However, we also found increasing prevalence among the Arab-Israeli population, reaching 140/100,000 compared to 54/100,000 noted in a previous study [12].These differences may be attributed, at least in part, to much smaller [16] and less homogenous [12] populations studied.The significant increase in the prevalence of IBD among the Arab population could be explained by Westernization of their life style, including improved sanitation, consumption of industrialized food, urbanization of the environment and increased availability of medical care [14,15,26].Chicago, USA.Student's t-test, and the χ 2 test, was used.Data are shown as mean ± standard deviation (SD).A P value < 0.05 was considered statistically significant.

Results
A total of 616,338 patients were registered as insured by Clalit Health Services in the district until December 2012.Of these, 184,510 (29.9%) belonged to the Arab population and the rest were Jewish (Table 1).Altogether, 2,050 Jewish and 263 Arab patients met the criteria for IBD in adults (prevalence of 0.48% and 0.14%, respectively, p < 0.001).Age at diagnosis was 41.1 ± 18.8 years and 35.6 ± 16.2 years among the Jewish and Arab populations, respectively (p < 0.001).Of these 1,056 (51.5%)Jewish patients and 132 (50.2%)Arab patients were women (p = 0.68).BMI was similar among the Jewish and Arab patients (25.3 ± 6 and 25 ± 5.1, respectively) (p = 0.64).CD was found in 1,070 (52%) of the Jewish patients and in 134 (51%) of the Arab patients, the rest had UC (p = 0.7).The Arab patients had more anemia, hypoalbuminemia, hypocholesterolemia and disease exacerbations than the Jewish patients (Table 2).The Arab patients underwent fewer colonoscopies and bone density studies after diagnosis, but there was no difference in the percentage undergoing small bowel imaging between the two groups.The Arab patients had more IBD related hospitalizations than the Jewish patients (37.6% vs. 28%, respectively, p < 0.001), but no difference was noted between the groups regarding IBD related surgery (Table 2).The Arab patients were treated more often with steroids (46% vs. 36.5%,respectively, p < 0.01), but there was no difference between the two groups regarding treatment with 5ASA, immunomodulators, Budesonide or anti-TNF (Figure 1).Jewish patients had lower rates of diabetes, higher rates of dyslipidemia and thus received more lipid lowering drugs than Arab patients.No difference was noted between the two groups in terms of aspirin and NSAID's consumption (Table 1).

Discussion
The present study demonstrated an increasing prevalence of IBD in both the Jewish and the Arab populations in Israel.However, important differences were noted between these two ethnic groups.The Arab population demonstrated lower prevalence, younger age at presentation, more exacerbations and hospitalizations and increased prescription of steroids.To the best of our knowledge, this study   Several previous studies have investigated IBD among various ethnic groups.[29][30][31].These studies found differences in IBD phenotype, in the minority population, in terms of disease location, behavior and extra intestinal manifestations.The current study found that the Arab patients were younger at diagnosis and had more parameters indicating disease activity such as higher rate of anemia, hypoalbuminemia and hypocholesterolemia.In addition, they had, higher disease exacerbation rates, and more IBD related hospitalizations.While previous studies have compared either native to immigrant populations or patients living in different locations, we studied two native ethnic groups living in the same district in Israel who were exposed to the same health care system.Our findings suggest more aggressive disease among the Arab population, although lack of adherence to medical treatment and follow-up cannot be excluded.
Genetic variability has been noted in ethnic groups with IBD around the world [32-34].Genetic differences between Jewish and Arab IBD patients in Israel were described by Karban, et al. [35,36].They found a significantly lower rate of NOD2/CARD15 mutation and higher frequency of GSTT1-null in Arab compared to Jewish IBD patients.Although, the Jews and Arabs, observed in this study, originate from similar geographic areas, they share few genetic similarities [37].This might explain the earlier onset of IBD in the Arab population.
In addition to environmental and genetic factors, we suggest that behavioral factors play a role in the differences found between the two populations.Recent studies have investigated the causes of lack of adherence to medical treatment in Arab populations both in Israel and North America.They found decreased compliance rate due to lower awareness of the disease and lack of access to medical care as well as cultural differences leading to reliance on traditional medications [38][39][40].Low socioeconomic status has also been found to affect the effectiveness of IBD management [41].The Arab population in Israel has, for the most part, a lower socioeconomic status than the Jewish population [14], supporting this theory.Fewer colonoscopies and bone-density spectrometrys among the Arab patients supports the lack of adherence theory.We found a higher rate of corticosteroid use and more IBD related hospitalizations in the group of Arab patients.Nevertheless, this group did not have a higher rate of IBD related surgeries.The higher steroid use, usually prescribed by the family physician as an urgent short term treatment, and the higher hospitalization rate may be secondary to lower compliance with long term medical therapy and follow up.Much disease exacerbation is treated during admission, hence the equal rates of surgery between the two groups.
Other than steroids, there was no difference in medications use including 5ASA, immunomodulators and anti-TNF, between the groups.Most studies report lower rates of immunomodulators and biologic therapy in IBD patients from minority ethnic groups [29,42,43].Our findings support the basic assumption of equal access to medical attention among both populations.
The main limitation of this study is its retrospective nature, with potentially incomplete information.The disease activity was defined from laboratory data alone and not from the disease activity index, since the data was retrieved electronically from the laboratory information.However, this HMO database is one of the largest of its kind providing an opportunity to compare these two permanent, stable ethnically different populations who reside in the same geographic area.
In summary, this study compared large populations of Jewish and Arab IBD patients in Israel.Both ethnic groups are stable, live in the same area and have equal access to medical attention and facilities.The data for both populations support the global increase in IBD prevalence.This increase is occurring both in high prevalence populations and in an ethnic group once thought to have very low to no risk for the disease.We found a difference in disease phenotype manifested as more active disease in the Arab group.Apart from objective genetic and environmental differences, which should be further investigated, ethnic and cultural differences probably have a very important contribution.Our findings suggest that investing in medical education and close patient guidance by culturally sensitive

Figure 1 :
Figure 1: Medications use among Jewish and Arab-Israeli populations.

Table 1 :
Characteristics and demographics of the study populations.

Table 2 :
Laboratory and imaging data.