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Epidemiology of Inflammatory Bowel Diseases (IBD) in Iran: A Review of 740 Patients in Fars Province, Southern Iran


1 Gastroenterohepatology Research Center, Nemazi hospital, Shiraz University of Medical Sciences, Shiraz, IR Iran
2 Colorectal Research Center, Faghihi hospital, Shiraz University of Medical Sciences, Shiraz, IR Iran
3 Laparoscopy Research Center, Faghihi hospital, Shiraz University of Medical Sciences, Shiraz, IR Iran
4 Pharmacy school, International brunch of Shiraz University of Medical Sciences, Shiraz, IR Iran
5 Nutrition and Health school, Shiraz University of Medical Sciences, Shiraz, IR Iran
*Corresponding author: Ali Reza Safarpour, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran.Tel.: +98-7112357282, Fax: +98-7112307594, E-mail: asafarpour@sums.ac.ir.
Annals of Colorectal Research. 1(1): 17-22. , DOI: 10.17795/acr-11477
Article Type: Research Article; Received: Feb 26, 2013; Revised: Mar 3, 2013; Accepted: Apr 3, 2012; epub: Jun 30, 2013;
Running Title: Epidemiology of IBD in Southern of Iran

Abstract


Background: Although the prevalence and incidence of Inflammatory Bowel Disease (IBD) are reaching a stable status in most of the industrialized countries, Asian countries have faced with an increasing number of IBD patients in the last two decades. However, due to the lack of national registry system, a limited amount of data is available on the epidemiology of IBD in Iran, particularly the southern parts of the country.

Objectives: The aim of this retrospective analytic study is clarification of multiple aspects of epidemiological factors of IBD patients in area of southern Iran.

Patients and Methods: Between 1989 and 2010, 740 patients with IBD, 620 ones with ulcerative colitis (UC) and 120 ones with crohn’s diseases (CD) were diagnosed as IBD cases and referred to our center. Then, their demographic characteristics, disease-related manifestations, complications, and their chief complaints were analyzed, retrospectively.

Results: The mean age at diagnosis was 34.68 ± 1.44 (range: 8 – 79 years) for UC patients and 32.97 ± 1.34 (range: 9 – 80 years) for CD ones. The male/female ratio was 0.9/1 and 0.98/1 for UC and CD patients, respectively. In comparison to rural patients, more urban ones with both UC and CD were registered (86.4 % with UC and 91.74% with CD). No significant change was detected in onset-diagnosis lag time in IBD patients during the study.
In this study, a significant positive relationship was found between the type of the disease and positive family history, CD > UC, (χ2(6df) = 14.56, P = 0.024). Furthermore, bloody diarrhea (69.4%) and abdominal pain (54.3%) were the most prevalent presentations in UC and CD patients, respectively. Besides, massive bleeding was the most prevalent complication for both UC and CD patients (32.9% and 19.8% respectively). In addition, 289 UC (46.6%) and 39 CD (33.7%) patients had experience at least one relapse during their course of disease. Nevertheless, no significant correlation was observed between the season of the onset and the type of the disease in UC and CD patients (χ2(6df) = 6.09, P = 0.41). Also, no significant relationship was detected between smoking and the type of disease (χ2(2df) = 3.79, P = 0.13).

Conclusions: An obvious increase in the number of IBD patients has been detected in our population during the past decades. This can be attributed to either improvement in the patients’ and the physicians’ knowledge and availability of diagnostic tools or a real increase in the incidence rate of the disease. In either case, this alarming increase should be taken into consideration by both the health authorities (regarding the significant burden) and the researchers of the field in our society.

Keywords: Inflammatory Bowel diseases (IBD); Southern Iran; Epidemiology

1. Background


Inflammatory Bowel diseases (IBD), including Crohn’s Disease (CD), Ulcerative Colitis (UC), and indeterminate colitis (IC), are multi-factorial diseases. Although both genetic and environmental factors are involved in the pathogenesis, the certain causes of these diseases are still unclear (1). Based on the recent epidemiologic data, IBD which was considered as a rare disease in many countries is turning to a global disease over time (2). Because of the low mortality rate associated with IBD, almost equal to normal population, the prevalence of the disease is also increasing along with its incidence (3). Although the prevalence and incidence of IBD are reaching a stable status in most of the industrialized countries (4), Asian countries have been faced with an increasing incidence of the disease in the last two decades. In the same line, the data from Japan (5), China (6), Hong-Kong (7), Singapore (8), India (9), Lebanon (10), and Kuwait (11) showed significant increase in IBD incidence in the recent years. Although the prevalence and incidence of IBD have not been properly studied in Iran, our country is located in the list of the countries with an increasing rate of IBD (12). Moreover, since the previous studies (13, 14) did not use the national registry system’s data and were more hospital-based and retrospective, no clear epidemiological data is available on the prevalence of IBD in Iran. In fact, the review of the literature showed that hospital-based studies, especially for rare diseases, usually show a lower prevalence rate (15). The present retrospective descriptive-analytical study aims to clarify different demographic (especially for new cases in the past decades) and clinical characteristics of IBD patients in Fars province, South of Iran.

2. Objectives


The aim of this study is to clarify multiple aspects of epidemiological factors of IBD patients in area of southern Iran.

3. Patients and Methods


In the present study, we used the files of 744 patients diagnosed with IBD, which were collected during 21 years (1989-2010) in Gastroenterohepatology’s IBD Registry between 1989 and 2009, Shiraz, Fars province, Iran. The data were collected through questionnaires containing the demographic data, signs and symptoms at the onset of the disease, date of the beginning of the disease, time interval between the onset of the disease and the date of diagnosis, and information regarding other clinical and surgical events. The questionnaires were completed by trained paramedical personnel for all the patients. IBD was diagnosed based on histological, clinical, endoscopic, and radiologic criteria determined by Lenard-jones (16). Each diagnosis was also confirmed by two gastroenterologists. Of course, in case the diagnosis changed during the follow-up period (each follow-up period was 6 or 12 month during the study period), the final situation was considered for the patients. Relapse was defined as change in the patients’ normal bowel habit accompanied with rectal bleeding with colonoscopic documentation. Because of the low number of the cases (only 4 patients), indeterminate colitis was excluded from this study. Extra Intestinal Disease was diagnosed based on the related specialists’ opinions as well as the histological and laboratory data (if needed).


All the information was recorded in the patients’ electronic files by trained staff. The subject and the objectives of the study were explained to all the patients and written informed consents were obtained from all the participants. This study was approved by the Ethic Committee of Shiraz University of Medical Sciences, Shiraz, Iran.


In the present study, Chi-square test was performed in order to determine the relationship between two categorical variables. Moreover, descriptive analysis of the data was done through the software, version 16 ( Inc. Chicago, IL.). Also, P-value < 0.05 was considered as statistically significant.

4. Results


According to the documentations, among the 783 patients whose information about the first time IBD diagnosis was registered in Gastroenterohepatology’s IBD Registry between 1989 and 2009, 740 patients fulfilled the diagnostic criteria. In addition, the number of UC and CD patients were 620 (83.8%; Male: 297(47.9%), female: 323(52.1%) and 120 (16.2%; Male: 59(49.3%), female: 61(50.7%), respectively. The mean age at diagnosis was 34.68 ± 1.44 (range: 8 – 79 years) for UC patients and 32.97 ± 1.34 (range: 9 – 80 years) for CD patients. Moreover, the age range of 20-29 years was considered as the peak range in the related chart (Figure 1) and no second peak was detected. Furthermore, the male and female ratio was 0.9/1 and 0.98/1 for UC and CD patients, respectively. In addition, in comparison to rural patients, more urban ones had been registered for both UC (86.4%) and CD (91.7%). Among the UC patients, 4%, 81.6%, and 14.4% were uneducated, had under diploma degrees, and had university degrees, respectively. In CD patients, however, 1.7% was uneducated, 88.8% had under diploma degrees, and 9.5% had university degrees.


Figure 1
Age-specific distribution for UC and CD patients

Moreover, 4.8% of UC and 5.1% of CD patients had positive family history of IBD in their first degree relatives. A positive significant correlation was also found between the type of the disease and positive family history which is more in CD than in UC, (χ2(6df) = 14.56, P = 0.024). In addition, bloody diarrhea (69.4%) and abdominal pain (54.3%) were the most prevalent presentations in UC and CD patients, respectively (Table 1). The frequency of arthritis, as the most prevalent Extra Intestinal manifestation was 8.2% and 12.1% among UC and CD patients respectively (Table 2). Besides, after massive bleeding, which was the most prevalent complication for UC and CD patients (32.9% and 19.8%, respectively), toxic mega colon (2.9%) and fistula (10.3) were common complications in UC and CD patients, respectively (Table 3).


Table 1
Frequency of symptoms at first presentation in IBD patients

Table 2
Extra Intestinal manifestations (EIMs) in IBD patients

Table 3
Frequency of complications in IBD patients

As shown in Table 4, the extent of the disease was analyzed by total colonoscopy in all IBD patients.


Table 4
Extension of the disease in IBD patients.

A total of 289 UC (46.6%) and 39 CD (33.7%) patients had experience at least one relapse during their course of disease. Analysis of the number of the new cases (according to their files, retrospectively) revealed an increase in the number of new IBD patients diagnosed each 10 years during the past three decades. In addition, Figures 2 and 3 reveal a five-fold increase in patients whose symptoms had appeared and IBD was diagnosed during 1970-2010.


Figure 2
Dates of diagnosis in IBD patients

Figure 3
Dates of onset of symptoms in IBD patients

In order to determine whether this annual increase was due to a real increase of new cases or an increased detection rate over time caused by improvement in diagnostic tools or more easier access to them, the lag time between the onset of the symptoms and the date of diagnosis was analyzed as an indirect indicator of “better” diagnosis. Nevertheless, comparison of years of diagnosis and onset-diagnosis lag times showed no significant changes in the lag times during the 30 years (Figures 2 and 3). Furthermore, comparison of the mean onset-diagnosis lag time and the number of newly diagnosed IBD cases during 1970-2010 revealed a dramatic increase in cases, while it showed no decrease in the lag time (Figure 4). The Mean time interval between the onsets of the symptoms and the diagnosis time was 14.36 ± 13.1 months in the UC group and 16.56 ± 14.3 month in the CD group. Moreover, appendectomy rate was 2.9% (18 patients) and 7.6% (9 patients) in UC and CD patients, respectively. In addition, the frequency of tonsillectomy was 29 (4.7%) and 5 (4.1%) in UC and CD groups, respectively. UC patients mostly consumed 5ASA-preparations (71.7%) and corticosteroids (55.4%), while the most consumed drugs in the CD group were 5ASA-preparations (72.7%) and Infleximab (57%). Other drugs which were consumed by both groups included Metotrexate, Antibiotics, and immunosuppressive medications (Azathioprine, 6-mercaptopurine). In this study, no significant relationship was found between the season of the onset and the type of the disease in UC and CD patients (χ2(6df) = 6.09, P = 0.41). Disease onset in spring, summer, autumn, and winter was 48.5%, 22%, 12.9%, and 6.16% for UC patients, and 47.8%, 26.1%, 8.7%, and 17.4% for CD patients. Besides, the disease onset in spring was more common for both UC and CD (Figure 5.


Figure 4
Comparison of mean onset-diagnosis lag time (month) with the number of newly diagnosed IBD cases between 1970 and 2010

Figure 5
Seasonal variation in the onset of the symptoms in IBD patients (Spring: 1, summer: 2, Fall: 3, Winter: 4)

Finally, the frequency of smoking (cigarette and water pipe) was 5.2% (32) and 7.4% (9) in UC and CD patients, respectively. However, no significant correlation was detected between smoking and the type of the disease (χ2(2df)= 3.79, P = 0.13).

5. Discussion


Along with the significant increase of IBD all over the world, the results of the present study revealed increasing trends for both UC and CD in the past 3 decades in Iran (Figures 2 and 3). Moreover, an obvious increase has been observed in the new cases of IBD in the past three decades in our population. A portion of this increase may be due to the enhancement of the availability of the diagnostic services as well as an increase in the public knowledge regarding this type of disease. The present study showed no significant decrease in “lag time” between the onset of the symptoms and diagnosis in the study period. According to this finding, the increase of incidental cases is probably the main cause of the obvious increase of IBD patients in Iran. It is still not clear whether this increase in Iran and other Asian countries is due to the environmental factors emerging from industrialization or other unknown factors (2). The peak age at diagnosis in our study showed a pattern similar to other Asian countries, such as India (9) and Japan (17). In this pattern, only one peak at the age range of 20-40 was documented and no second peak (> 60 years old), usually observed in developed countries (18), was detected. On the other hand, two studies in South Korea (19) and Hong Kong (20) demonstrated small second peaks in their elderly population. In other studies conducted in Iran, the male/female ratio was reported to be 0.8/1 (13) and 0.7/1 (14) for UC and 1.4/1 (21) and 1.2/1 (22) for CD patients. In addition, the female predominance for UCin those studies was similar to the present one (0.9/1), it is in contrast to equal gender distribution in UC in other Asian countries (23-25). Regarding CD, the results of this study showed an equal sex distribution which was on the contrary to the male predominance reported in studies conducted in Hong Kong (20), Korea (19), and one other study performed in Iran (22). This may be related to a more health-conscious behavior in women, lead to a higher detection rate in this gender. In the present study, a positive significant relationship was found between the type of the disease (UC vs. CD) and family history of IBD. In two other Iranian studies (13, 14), the number of UC patients with a positive family history was more than that of the CD patients, which is in contrast to the findings of the present study (4.8% of UC and 5.1% of CD). Lower positive family history for UC patients in our study as well as Asian countries (1.6-4.5%) is in contrast with the results of the studies conducted in industrial countries (8-14%) (26, 27). In similar studies in Singapore (8) and South Korea (28), the percent of familial occurrence for CD was 0-3% which is lower than our study results (5.1%).


In our study, diarrhea (mostly bloody) for UC and abdominal pain for CD patients were the most prevalent presentations at the onset of the disease. Despite the similarity between our results and two other studies conducted on CD in Iran (13, 14), a clear difference was observed between Iranian (14) and other Asian (29) UC patients regarding their first complaint (Diarrhea vs. rectal bleeding). Along with other similar studies conducted in Iran (14, 22) and Kuwait (11), arthritis was the most prevalent extra-intestinal manifestation (EIMs) for both UC (18.2%) and CD patients (12.1%) in the present study, as well. Furthermore, the frequency of other EIMs in our study as well as other Iranian (30), Indian (31), and Chinese (6) studies was reported as 8-16%. Only in one study performed in Iran, EIMs was reported above 60% for both CD and UC (22). It is possible that the lower rate of EIM in Iran and other Asian countries might be due to the lack of long time cohort studies rather than a real difference. Left sided colitis was the most prevalent (31.3%) colon-related disorder in our study and one other Iranian report (22). Other Iranian reports, however, reported proctitis as the most prevalent colonic involvement (13, 14). Most studies conducted in Asian countries have shown a high rate of left sided colitis among the UC patients. The prevalence of this form of colonic extension in China (6) and Korea (25) was reported as 92.7% and 35.1%, respectively. However, pancolitis, with the prevalence rate of 37.6%, was shown as the most prevalent type in Singapore (32). Along with the results of a study conducted in Netherland (33), the findings of the present study revealed no relationship between the seasons and the onset of IBD. This is in contrast with a report from Norway showed a significant peak in the onset of UC during December (χ2(11df) = 21.6, P = 0.028); however, no seasonal variation was detected in CD (34). It is well accepted that cigarette smoking is protective against UC and probably a risk factor for CD (35, 36). However, no significant correlation was found between smoking (cigarette or water pipe) and IBD in the present study. Malekzadeh et al. also showed no significant correlation between CD and smoking, but confirmed the protective effect of cigarette smoking against UC (36). The retrospective nature of data collection for a portion of our population and incomplete cooperation of the private practices are the limitations of this study and should be considered in future. On the other hand, the large study population was one of the advantages of this study. Finally, it can be concluded that a significantly increased rate of IBD either due to the people’s and the physicians’ knowledge improvement and newer diagnostic tools or a real increase in the incidence rate is well documented in our population and should serve as a focus for the health authorities as well as the researchers of this field.

Acknowledgments

The authors would like to thank Gasrtoenterohepatology and Colorectal research centers for their cooperation in the process of data collection. Research Improvement Center of Shiraz University of Medical Sciences and Ms. Afsaneh Keivanshekouh are also appreciated for improving the use of English in the manuscript.

Footnotes

Implication for health policy/practice/research/medical education It should be written by author. For more information, please refer to the previous issue.
Please cite this paper as Taghavi SA, Safarpour AR, Hoseini SV, Safarpour M, Noroozi H. Epidemiology of Inflammatory Bowel Diseases (IBD) in Iran: A review of 740 patients in Fars province, Southern Iran. Annals of colorectal research journal. Ann Colorectal Res: 2013;1(1):in press. DOI: 10.5812/acr.11477
Authors’ Contribution Main idea was proposed by Seyed Alireza Taghavi, Ali Reza Safarpour and Seyed Vahid Hoseini. Study design and writing was done by Ali Reza Safarpour, Seyed Alireza Taghavi, Maral Safarpour and Hesameddin Noroozi. Data collecting was done by Maral Safarpour, Hesameddin Noroozi and Salar Rahimikazerooni. Data Analysis was done by Ali Reza Safarpour and Hesameddin Noroozi.
Financial Disclosure None declared.
Funding/Support None declared.

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Table 1

Frequency of symptoms at first presentation in IBD patients

Symptoms Ulcerative colitis, % Crohn’s Disease, %
Bloody Diarrhea 69.4 47.4
Rectorrhagia 56 44
Abdominal pain 51.9 54.3
Constipation 19.2 16.4
Non – Bloody Diarrhea 9.4 13.8
Steatorrhea 8.4 6

Table 2

Extra Intestinal manifestations (EIMs) in IBD patients

EIMs Ulcerative colitis, % Crohn’s Disease , %
Arthritis 8.2 12.1
Eye Involvement 5.0 7.8
Skin Involvement (EN,PG)a 5.3 9.5
Liver & Billiary Involvement 4.8 5.2
Total 23.3 34.6
a Abbreviations: EN; Erythema Nodosum, PG; PyodermaGangranosum

Table 3

Frequency of complications in IBD patients

Complication Ulcerative colitis (n = 620), No. (%) Crohn’s Disease (n = 120), No. (%)
Massive Bleeding 204(32.9) 23(19.8)
Toxic Mega colon 18(2.9) 2(1.7)
Fistula   12(10.3)
obstruction 8(1.3) 5(4.3)
Perforation 4(0.6)  
Stricture 1(0.2) 1(0.9)
Colorectal CA 7(1.1)  
Small Intestinal CA    
Protein losing EntroPathy 1(0.2)  
Total 243(39.2) (43) 37

Table 4

Extension of the disease in IBD patients.

Disease Pancolitisa, (%) Proctitisb, (%) Left sided colitisc, (%) Small Intestine, (%)
UC ( n = 620 ) 160(25.8) 152(24.5) 194(31.3)  
CD ( n = 120 )   2(1.7)   28(24.1)
a Pancolitis: disease involved complete parts of colon
b Proctitis: disease limited to rectum
c Left sided colitis: disease below the splenic flexure

Figure 1

Age-specific distribution for UC and CD patients

Figure 2

Dates of diagnosis in IBD patients

Figure 3

Dates of onset of symptoms in IBD patients

Figure 4

Comparison of mean onset-diagnosis lag time (month) with the number of newly diagnosed IBD cases between 1970 and 2010

Figure 5

Seasonal variation in the onset of the symptoms in IBD patients (Spring: 1, summer: 2, Fall: 3, Winter: 4)