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Inflammatory Bowel Disease in Iran

Inflammatory Bowel Disease in Iran. Inflammatory bowel disease IBD. Including Ulcerative Colitis (UC) and Crohn’s Disease (CD), is a chronic and recurrent disease triggered by genetic, environmental, and immunologic factors.

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Inflammatory Bowel Disease in Iran

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  1. Inflammatory Bowel Disease in Iran

  2. Inflammatory bowel disease IBD • Including Ulcerative Colitis (UC) and Crohn’s Disease (CD), is a chronic and recurrent disease triggered by genetic, environmental, and immunologic factors. • UC can be histologicaly distinguished from CD by the localized inflammation in the superficial layer of the colonic mucosa.

  3. Inflammatory bowel disease IBD Considerable variation in the epidemiology of IBD has been observed around the world, with a wide range of both within and between geographic regions. IBD is reported more common in developed countries than developing countries according to previous articles. With the highest incidence and prevalence rates in North America and Europe.

  4. Evolution in Epidemiology of IBD • As developing nations have become more industrialized, the incidence of IBD has increased. • Several studies have reported that the incidence of IBD has increased markedly over the latter part of the 20th century.

  5. Evolution in Epidemiology of IBD • Studies have shown that individuals emigrating from low prevalent regions (eg, Asia) to higher prevalent countries eg, England, are at increased risk for developing IBD, particularly among first-generation children. • The emergence of IBD in traditionally low prevalent regions (eg, in Hispanic and Asia) suggests that the development of IBD may be influenced by environmental risk factors.

  6. Geographic Patterns • In the developing world, defining incidence and prevalence is considerably more difficult because many countries lack health care systems administrative databases. • Also, care is centralized in hospitals; • thus, hospitalization records may more accurately reflect prevalence of disease as compared with hospitalization records from the developed world.

  7. Geographic Patterns • Where outpatient management of IBD is more common. • To properly interpret the incidence or prevalence data and evaluate time trends, a systematic review of all population- based studies is needed.

  8. Time trend in IBD • Since The etiology and pathogenesis of IBD is not fully understood. • Insight into the worldwide epidemiology of IBD is important : • To identify Geographic patterns and time trends • To highlight the burden of IBD globally, • To determinant Possible environmental role in IBD

  9. Epidemiology of IBD in Iran • The objectives of our study were to conduct a time trends patterns of IBD in Iran. • To evaluate the change in incidence . • Compare with systematic review of the worldwide incidence and prevalence of UC and CD ,

  10. Prevalence Rate for UC and CD • in Europe ,the UC estimates ranged from 4.9 to 505 per 100,000, • in Asia and the Middle East, 4.9 to 168.3 per 100,000 • in North America, 37.5 to 248.6 per 100,000 • The CD estimates ranged from 0.6 to 322 per 100,000 in Europe, • 0.88 to 67.9 per 100,000 in Asia and the Middle East, and 16.7 to 318.5 per 100,000 in North America

  11. Epidemiology of IBD in Iran • 1985- Ulcerative colitis in Iran: a review of 112 cases, by Mir-Madjlessi et al. 1973-1982 They reported the extreme rarity of Crohn's disease in Iran. 2005- Inflammatory bowel disease in Iran: A review of 457 cases, by Aaghazadeh , Zali, et al. Including 401 UC, 47 CD and 9 IC • 2008- Epidemiology of Inflammatory Bowel Disease in Iran: A review of 803 cases by Derakhshan et al. Gastroenterology and Hepatology from bed to bench. 2008;1(1):19-24 • 1992-2007 Including 671 UC, 109 CD and 23 IC

  12. Epidemiology of IBD in Iran 2009- Epidemiologic Characteristics of 500 Patients with IBD in Iran Studied from 2004 through 2007, by Vahedi et al. Arch Iranian Med . • 2012- Epidemiology of Pediatric Inflammatory Bowel Diseases in Southern Iran, by Dehghani et al. 2001-2007 36 IBD including 26 UC and 9 CD • 2013- Epidemiological and Clinical Characteristics of Inflammatory Bowel Disease in Patients from Northwestern Iran, by Masnadi Shirazi et al. Middle East Journal of Digestive Diseases, Vol.5, No.2, April 20132005-2007 200 IBD patients including 183 UC and 17 CD

  13. IBD Registry and epidemiological research in RCGLD • IBD Registry in • Taleghani Hospital, Shahid Beheshti University, Tehran, Iran • Private clinic

  14. IBD Registry and epidemiological research in RCGLD (cont.) • During 10 years, between 1992 and 2012 we recorded patient’s data in a questionnaire • Demographic information • Medical, familial and habitual history • Diagnosis identification • Signs and symptoms at onset and visit date • Extra-intestinal manifestations • Complications • Colonoscopy reports

  15. IBD Registry and epidemiological research in RCGLD (cont.) • The interview was performed face to face by trained practitioners. • General information was retrieved from medical records of patients by gastroenterologists. • The patients were followed up by telephone who required proper information. • Gastroenterologists confirmed IBD in patients based on clinical, radiological, endoscopic and pathological criteria.

  16. IBD Registry and epidemiological research in RCGLD (cont.) • The data base were updated through referring IBD patients for determining any other changes such as; • Hospitalization • Drug use • Colonoscopy • Pathology • Laboratory tests • New disease

  17. Results of IBD registry studies in RCGLD • From 1992 to 2012, 2257 patients with IBD were confirmed in this study. • The result of the data registry system concluded • 1914 with UC (84.8 %) • 343 with CD (15.2 %)

  18. Prevalence of IBD • The prevalence of UC was 5 times higher than CD. • Similar to the fourfold higher incidence of ulcerative colitis than Crohn's disease in Japanese, Korean, and Chinese cohorts • According to recent studies, both diseases have been reported with an increase in number in eastern countries. • the demographic finding of UC in Iran shows a slight female predominant, but in western and Asian studies there is an equal sex distribution in UC.

  19. Male to female graph in IBD (%)

  20. Mean age at onset

  21. Mean age at diagnosis

  22. Characteristics of IBD • CD was diagnosed at a younger age than UC and IC. • The peak age of onset in this study appears to be in the 2nd and 3rd decades of life in UC and CD patients, consistence with findings in the West and Asia for IBD.

  23. Results of IBD registry studies in RCGLD • Never smoked • 93.5% patients with UC • 90.2% with CD • Current smokers • 6.5% patients with UC 10.8% with CD • Appendectomy was carried out in • 4.4% UC patients, • 14.2% CD patients

  24. Level of Education and IBD

  25. Results of IBD registry studies in RCGLD • UC presented with • diarrhea (75.3%) • hematochesia (73%) • bloody diarrhea (64.8%) • abdominal pain (57.4%) • weakness (56.8%) • tenesmus (55.8%)

  26. UC presentation

  27. Results of IBD registry studies in RCGLD • CD patients complained of • abdominal pain (72.6%) • diarrhea (62.3%) • weakness (52.1%) • weight loss (55.8%)

  28. CD presentation

  29. Results of IBD registry studies in RCGLD • Extension of disease was evaluated with colonoscopy procedure in UC patients as follows: • 10.9% proctitis • 14.3% proctosigmoiditis • 13.8% left side colitis • 5.9% pancolitis • Colonoscopy was performed in CD patients in which 71.8% were categorized as having ileocolitis and terminal ileum was affected in 21.8% of patients.

  30. Extension of disease in UC

  31. Results of IBD registry studies in RCGLD • Major complications of UC were • severe bleeding (3.4%) • dysplasia (1.1%) • pouchitis (0.2%) • intestinal perforation (0.5%) • toxic mega colon (0.4%) • stenosis (0.9%)

  32. Results of IBD registry studies in RCGLD • Extraintestinal manifestations were reported in • 59.9% of UC patients • 64.2% of CD • Musculoskeletal (26.8%) and skin (18.2%) disorders were the most common affected sites in IBD patients. • Sclerosing cholangitis was diagnosed in 8.1% of IBD patients

  33. Results of IBD registry studies in RCGLD • The mean lag time between age of onset and age of diagnosis was • 8 months in UC • 20 months in CD • In CD patients 25.6% had documented fistula. • Colectomy rate was 2.8% UC patients and 15.8% CD patients . • Colorectal cancer was determined in 1% of IBD patients (UC and CD patients).

  34. Previous study on appendectomy and tonsillectomy in Iranian IBD patients • 2006- Appendectomy, tonsillectomy, and risk of inflammatory bowel disease: a case control study in Iran. Int J Colorectal Dis (2006) 21: 155–159. • 382 UC and 46 CD were studied. • 382 controls for UC and 184 controls for CD were enrolled. • Appendectomy is protective in UC, but a risk factor in CD among Iranian population. • Tonsillectomy was not associated with either UC or CD disease. UC, but not CD, is a disease of non- smokers. • The inverse association between ulcerative colitis and OCP or NSAID in the Iranian population is noted.

  35. Results of IBD registry studies in RCGLD • Familial history of IBD was presented in • 14.2% UC patients, of whom 57.9% had a positive family history in first-degree and 42.1% in second-degree relatives. • IBD was affected 15.8% cases of CD patients, identifying 57.1% in first- and 42.9% in second-degree relatives.

  36. IBD Genetics research in RCGLD • 2007- The frequency of C3435T MDR1 gene polymorphism in Iranian patients with ulcerative colitis. Int J Colorectal Dis. 2007 Sep; 22(9):999-1003. • 300 UC and 300 controls • C3435T polymorphism of the MDR1 gene has an association with UC in Iranian population as in western countries. • 2008- Frequency of three common mutations of CARD15/NOD2 gene in Iranian IBD patients. Indian journal of Gastroenterology, 2008, Vol. 27, No 1: 9-11. • 100 UC, 40 CD and 100 controls • R702W mutation of CARD15/NOD2 gene was more frequent in CD patients than controls

  37. IBD Genetics research in RCGLD (cont.) • Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease. J Gastroenterol. Hepatol. 2008 Dec;23(12):1816-22. • 150 UC, 80 CD and 150 controls • A probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population was observed.

  38. IBD Genetics research in RCGLD (cont.) • 2011- NOD2 exonic variations in Iranian Crohn's disease patients. Int J Colorectal Dis (2011) 26:775–781. • 90 CD and 120 controls • 21 sequence variations were identified among all exonic regions of the NOD2 gene, of which eight had an allele frequency of more than 5%. • Eight new mutations (one in exon 2 and seven in exon 4) were observed.

  39. IBD Genetics research in RCGLD (cont.) • The three main variants (R702W, G908R, and 1007fs) showed allele frequencies of 13.3%, 2.2%, and 1.7%, respectively. • Three new variations (P371T, A794P, and Q908H) and R702W mutation were significantly more frequent in Crohn's disease patients compared to controls. • Eight novel mutations were identified in the NOD2 exons, but the pathophysiological importance of these variants remains unclear. • Iranian patients with their different genetic reservoirs may demonstrate some novel characteristics for disease susceptibility.

  40. Genetic Factors • Among the 100 IBD genes and loci defined, • only nucleotide binding oligomerization domain protein 2 (NOD2) (5% penetrance or 20-fold risk in mutation homozygotes, has a meaningful contribution to CD risk alone. • All remaining genes and loci contribute • modestly to IBD risks, However, the exact relationship between genetic susceptibility and the role of the environment in the pathogenesis of IBD still largely remains a mystery

  41. Time Trends of IBD types In Iran

  42. Changing Environment • The clinical picture of a patient with IBD results from a complex interaction of • genetic, • environmental, • developmental and disease course factors, • such as the patient’s age, nutritional status and presence of co-morbidities.

  43. Genetic Factors • Genetic susceptibility plays a key role in IBD development. • 8- to 10-fold greater risk of IBD among relatives of ulcerative colitis ,and Crohn’s disease. • To be involved in the ethiology of IBD, • Are associated with immune functions, • Mucosal transport functions, or bacterial recognition.

  44. Environmental Factors • Given the patho-physiologic complexity inherent in IBD, • it is unlikely that genetics alone will provide • sufficient information for time trend in IBD. • Rates of appendectomies have decreased in developed countries, whereas the incidence of UC has remained constant.

  45. Health Care Improvement • The rising incidence of IBD during the 20th century may be explained by environmental exposures that result from increasing • urbanization; • For example, IBD occurs more commonly in urban versus rural regions.

  46. Environmental Risk Factors • Individuals raised in urban areas are exposed to considerably different environmental risk factors than those living outside these regions., • microbial exposures, • sanitation, • occupations, • Diet, lifestyle behaviors, medications, and • pollution exposures, which have all been implicated as potential environmental risk factors for IBD.

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