Iranian Registry of Crohn's and Colitis: study profile of first nation-wide inflammatory bowel disease registry in Middle East.

BACKGROUND/AIMS: A recent study revealed increasing incidence and prevalence of inflammatory bowel disease (IBD) in Iran. The Iranian Registry of Crohn's and Colitis (IRCC) was designed recently to answer the needs. We reported the design, methods of data collection, and aims of IRCC in this paper. METHODS: IRCC is a multicenter prospective registry, which is established with collaboration of more than 100 gastroenterologists from different provinces of Iran. Minimum data set for IRCC was defined according to an international consensus on standard set of outcomes for IBD. A pilot feasibility study was performed on 553 IBD patients with a web-based questionnaire. The reliability of questionnaire evaluated by Cronbach's α. RESULTS: All sections of questionnaire had Cronbach's α of more than 0.6. In pilot study, 312 of participants (56.4%) were male and mean age was 38 years (standard deviation=12.8) and 378 patients (68.35%) had ulcerative colitis, 303 subjects (54,7%) had college education and 358 patients (64.74%) were of Fars ethnicity. We found that 68 (12.3%), 44 (7.9%), 13 (2.3%) of participants were smokers, hookah and opium users, respectively. History of appendectomy was reported in 58 of patients (10.48%). The most common medication was 5-aminosalicylate (94.39%). CONCLUSIONS: To the best of our knowledge, IRCC is the first national IBD registry in the Middle East and could become a reliable infrastructure for national and international research on IBD. IRCC will improve the quality of care of IBD patients and provide national information for policy makers to better plan for controlling IBD in Iran.

Emerging Epidemic of Inflammatory Bowel Disease in a Middle Income Country: A Nation-wide Study from Iran.

BACKGROUND: The burden of inflammatory bowel disease (IBD) hasn't been reported in Iran. We aimed to estimate the prevalence and incidence of IBD and its trend in Iran at national and subnational level from 1990 to 2012. METHODS: We conducted a systematic review of English and Persian databases about the epidemiology of IBD. We also collected outpatient data from 17 provinces of Iran using almost all public and private referral gastroenterology clinics. Prevalence and incidence rate was calculated at national and subnational levels. The Kriging method was used to extrapolate provinces with missing data and GPR model to calculate time trends of rates at subnational level. RESULTS: We found 16 case series, two population-based studies, and two review articles. We collected 11,000 IBD cases from outpatient databases. Among them, 9,269 (84.26%) had ulcerative colitis (UC), 1,646 (14.96%) had Crohn's disease (CD), and 85 had intermediate colitis (IC). A total of 5,452 (49.56%) patients were male. Mean age at diagnosis was 32.80 years (CI: 13 - 61) for UC and 29.98 years (CI: 11 - 58) for CD. Annual incidences of IBD, UC, and CD in 2012 were 3.11, 2.70, and 0.41 per 100,000 subjects respectively. Prevalence of IBD, UC, and CD in 2012 were 40.67, 35.52, and 5.03 per 100,000 subjects respectively. The incidence of UC and CD showed a significant increase during the study period (P for trend < 0.05). CONCLUSIONS: The incidence and prevalence of IBD are increasing in Iran. Establishing a national IBD registry seems necessary for comprehensive care of IBD patients in Iran.

Target antigens for perinuclear antineutrophil cytoplasmic antibodies in Iranian patients with ulcerative colitis.

UNLABELLED: BACKGROUND Patients with ulcerative colitis (UC) carry autoantibodies such as perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). OBJECTIVE: The aim of the present study was to evaluate the target antigens for p-ANCA in Iranian patients with UC. METHODS p-ANCA target antigens including elastase, lactoferrin, cathepsin G, myeloproxidase, lysozyme, and bactericidal permeability increasing protein (BPI) were determined in 113 patients with UC using enzyme-linked immunosorbent assay (ELISA). RESULTS 59.2% of the patients were positive for at least one antigen and p-ANCA directed against lactoferrin, elastase, lysozyme, cathepsin G, Bactericidal permeability increasing protein, and myeloproxidase in 31.5%, 25.9%, 8.3%, 7.4%, 5.6%, and 0% of the patients, respectively. CONCLUSION The highest prevalence of p-ANCA was observed against lactoferrin and elastase. Also, myeloproxidase was not an antigen for p-ANCA among our patients.

NOD2 exonic variations in Iranian Crohn's disease patients.

PURPOSE: The NOD2 gene is known to have a strong association with Crohn's disease, but different trends were reported in occurrence of NOD2 variants in distinct ethnicities. The aim of this study was to assess all exonic sequences of the NOD2 gene in Iranian Crohn's disease patients and healthy controls to identify any existing variation and evaluate their association with Crohn's disease. METHODS: A total of 90 non-related Crohn's disease patients and 120 sex- and age-matched healthy controls of Iranian origin were enrolled in this study. The participants were referred to a tertiary center in a 2-year period (2006-2008). The exonic regions of the NOD2 gene were amplified by polymerase chain reaction and evaluated by direct sequencing. RESULTS: A total of 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. 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. CONCLUSIONS: 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.

Diagnostic value of antineutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibody in Iranian patients with inflammatory bowel disease.

BACKGROUND AND STUDY AIMS: Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) and anti-Saccharomyces Cerevisiae antibody (ASCA) are potential markers for diagnosis of inflammatory bowel disease (IBD). The aim of the present study was to evaluate the diagnostic value of pANCA and ASCA in Iranian patients with IBD. PATIENTS AND METHODS: Serum samples were collected from 144 patients with IBD (113 ulcerative colitis and 31 Crohn's disease) and patients with non-IBD problems were assayed for ASCA by Enzyme-Linked Immunosorbent Assay (ELISA) and for pANCA by indirect immunofluorescence assay. RESULTS: Sensitivity and specificity of pANCA in UC were 39.8% and 82.1%, respectively. For CD, pASCA test provided the sensitivity of 58% and specificity of 70%. A combination of pANCA+/ASCA- for diagnosis of UC showed a sensitivity of 31.9% and specificity of 89.1%. In addition the combination of pANCA-/ASCA+ showed a sensitivity of 35.5% and specificity of 79.8% for diagnosis of CD. CONCLUSION: Due to low sensitivity of pANCA and ASCA alone or in combination, they are not valuable serological markers for diagnosis of UC or CD.

Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease.

BACKGROUND AND AIMS: The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be linked to inflammatory bowel disease (IBD). Many studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about the genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms (Apa I, Taq I, Bsm I, Fok I) with IBD in Iran. METHODS: In this case control designed study 150 patients with ulcerative colitis, 80 patients with Crohn's disease and 150 Age and Sex matched healthy controls from Iranian origin were enrolled. These patients were referred to a tertiary center during a two-year period (2004-2006). Assessment of VDR gene polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype-phenotype association for these polymorphisms was analyzed. RESULTS: Only the frequency of the Fok I polymorphism was significantly higher in ulcerative colitis and Crohn's groups. The frequency of the polymorphic allele f was higher in ulcerative colitis and Crohn's patients comparing with controls (P = 0.011 and P < 0.001, respectively). The f/f genotype was also significantly more frequent (P < 0.001), while the F/F genotype was less presented in Crohn's patients compared to controls (P < 0.001). No genotype-phenotype association was observed with any mutations. CONCLUSIONS: This study suggests a probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population.

Frequency of three common mutations of CARD15/NOD2 gene in Iranian IBD patients.

BACKGROUND: The CARD15/NOD2 gene, located on the pericentromeric region of chromosome 16 (IBD1) has been reported to have an association with IBD, especially Crohn's disease. Three common mutations of CARD15 are variably associated with Crohn's disease in different ethnic groups. We evaluated the frequency of these mutations (R702W, G908R and 1007fsinsC) in Iranian IBD patients and compared it with the healthy control population. METHODS: One hundred patients with ulcerative colitis, 40 patients with Crohn's disease, and 100 sex- and age-matched controls were enrolled from a tertiary center during a one-year period (2005-2006). The three mutations were assessed in DNA of leukocytes by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of R702W mutation was significantly higher in Iranian patients with Crohn's disease (p< 0.001; OR 19.21; 95% CI 4.23-87.32) compared to healthy controls. No association was observed between the other mutations and Crohn's disease and none of these mutations was associated with ulcerative colitis. CONCLUSION: The R702W mutation of CARD15 gene was associated with Crohn's disease in the Iranian population.

The frequency of C3435T MDR1 gene polymorphism in Iranian patients with ulcerative colitis.

BACKGROUND AND AIMS: The MDR1 (multidrug resistance) gene, located on chromosome 7, is in one of the inflammatory bowel disease susceptibility loci. It produces P-glycoprotein, a transmembrane efflux pump, transferring drugs and toxins from intracellular to extracellular domains. In the human gastrointestinal (GI) tract, P-glycoprotein is found in high concentrations on the epithelial cells of the colon and small intestine. MDR1 gene polymorphisms such as C3435T are associated with lower P-glycoprotein expression, and thus it is suggested to have an association with ulcerative colitis. We tried to determine the frequency of C3435T polymorphism of the MDR1 gene in Iranian patients with ulcerative colitis and to compare it with a healthy control population. MATERIALS AND METHODS: In this case-control-designed study, 300 unrelated ulcerative colitis patients and 300 sex-and-age-matched healthy controls were enrolled. They were visited at a tertiary center during a 2-year period (2003-2005). DNA of patients and controls was amplified by polymerase chain reaction with specific primers, and C3435T polymorphism was detected by the restriction fragment length polymorphism method. RESULTS: The frequency of the 3435T allele was significantly higher in ulcerative colitis patients compared to the controls (p < 0.001). The frequency of homozygote T/T and heterozygote C/T genotypes were also significantly higher in Iranian patients with ulcerative colitis (p = 0.044 and 0.041, respectively). CONCLUSION: This study suggests that C3435T polymorphism of the MDR1 gene has an association with ulcerative colitis in Iranian population as previously reported in western countries.

Abdominal pain due to lead-contaminated opium: a new source of inorganic lead poisoning in Iran.

Although the incidence of occupational and adult lead poisoning has declined, the problem still exists. We encountered three patients with lead poisoning in Iran, all of whom associated with presented with diffuse abdominal pain, which was at times colicky in nature, anemia, constipation, nausea, vomiting, and slightly abnormal liver biochemistries. A history of opium ingestion was present in each of these patients. None of the patients reported known occupational exposure to toxins. Diagnoses of lead poisoning were confirmed through the detection of elevated blood lead levels. The cause of lead poisoning was attributed to the ingestion of contaminated opium. Opium adulterated with lead had not been previously recognized as a source of lead poisoning in Iran. It is, therefore, pointed out that lead poisoning should be considered as a differential diagnosis for acute abdominal colic of unclear cause in patients with opium addiction.

Bone mineral density in Iranian patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk of developing osteopenia and osteoporosis. The aim of the study was to investigate the prevalence of decreased bone density and related risk factors in Iranian IBD patients. A total of 126 ulcerative colitis (UC) and 39 Crohn's disease (CD) patients were enrolled. Dual-energy x-ray absorptiometry technique was used to measure bone density, and blood samples were obtained to measure biochemical markers. To find predictive variables for bone mineral density (BMD), stepwise regression analysis was carried out. A total of 53 IBD patients (32.1%) had diminished bone mineral density at either lumbar spine (L1-L4) or femoral neck. Of these, 9 (5.4%) had osteoporosis; however, 44 (26.7%) were osteopenic. Femoral neck bone density was significantly decreased among CD patients (p<0.04). There was no significant difference in BMD between men and women. We have found significant differences in BMD T scores at lumbar L1-L4, L2-L4, and femoral neck in corticosteroid ever-users (p<0.002, p<0.001, p<0.003, respectively). There was no significant difference in biochemical markers between UC and CD patients, except that more CD patients were hypocalcemic (p<0.001). Stepwise regression analysis has revealed lumbar spine T score was predicted by age (p<0.0001), corticosteroid use (p<0.002), and body mass index (BMI) (p<0.005); however, femoral neck was predicted by age (p<0.0001), BMI (p<0.0001), smoking (p<0.009), and corticosteroid use (p<0.028). Low bone density in Iranian UC and CD patients is in accordance with Western societies. Treatment with corticosteroid has increased this possibility in both groups. Corticosteroid use, age, smoking, and BMI are predictive factors for low bone density.

Appendectomy, tonsillectomy, and risk of inflammatory bowel disease: a case control study in Iran.

There is some controversy about the prevalence of appendectomy and tonsillectomy among patients with Crohn's disease and a lower rate of appendectomy among patients with ulcerative colitis (UC). The objective of this study was to elucidate the role of appendectomy and tonsillectomy in Iranian patients with inflammatory bowel disease (IBD). Three hundred and eighty-two consecutive cases of UC and 46 cases of CD were included. Age and sex-matched controls were randomly selected. A total of 382 controls for UC and 184 controls for CD were enrolled. A standard record concerning smoking habit, history of appendectomy and tonsillectomy, OCP, and NSAID use was completed. Logistic regression analysis was used to evaluate potential confounding variables. Twelve patients (3.1%) with UC reported a previous history of appendectomy compared with 30 controls (7.9%) (OR=0.38, 95%CI=0.19-0.76, P<0.004). Appendectomy was reported by five patients (10.9%) with CD compared with four controls (2.2%) (OR=5.49, 95%CI=1.41-21.34, P<0.02). The logistic regression analysis showed that appendectomy is a risk factor in CD but has a modest protective effect for development of UC. No association with tonsillectomy was found for either disease. A statistically significant protective effect for smoking in UC was found (OR=0.2, 95%CI=0.13-0.32, P<0.0001). We have found an inverse association between OCP and NSAID use with UC, but not CD (P<0.0001 and P<0.001, respectively). 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.

Inflammatory bowel disease in Iran: a review of 457 cases.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) was believed to be infrequent in Iran; however, unofficial reports have confessed the continuing rise in IBD in our country. METHODS: Demographic and clinical features, extraintestinal manifestations, extension of disease and complications of 401 patients with ulcerative colitis (UC), 47 with Crohn's disease (CD), and nine with indeterminatn colitis (IC) were assessed retrospectively. The exact course of physicians' visits of 250 IBD patient was asked through face-to-face interview. RESULTS: Mean age at diagnosis was 31.9 years in UC and 30.5 years in CD patients. The male to female ratio was 0.8 for UC and 1.3 for CD. The percentage of CD and UC patients who were non-smokers was 82.9 and 84.5%, respectively. Patients with UC presented with rectal bleeding (41.9%), whereas those with CD complained of abdominal pain (46.9%). Among UC patients, proctosigmoid was affected in 51.9%. Colorectal cancer was diagnosed in two patients. The mean lag time between the onset of symptoms and definite diagnosis was 13.9 and 17.7 months for UC and CD patients, respectively. A total of 32.4% of patients with IBD had at least one of the five major extra-intestinal diseases. CONCLUSION: The demographic and clinical picture of IBD is more or less the same as that of other developing countries; however, the rarity of CD in Iran is noted. Although the true epidemiologic profile of IBD in Iran is still unknown, it is not as rare as previously thought, and it seems as if gradual adoption of a Western lifestyle may be associated with the continuing rise in IBD.