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 Crohns 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.     

Childhood hygiene is associated with the risk for inflammatory bowel disease: a population-based study

OBJECTIVES: The "hygiene hypothesis" postulates that individuals raised in a sanitary environment are more likely to develop inflammatory bowel disease (IBD). Several studies previously demonstrated contradictory results in this regard. We performed for the first time a population-based study on the association of surrogate markers of childhood hygiene with the risk for IBD.
METHODS: A cross-sectional population-based study was undertaken. Information on number of siblings, birth order, and living in an urban versus rural environment was obtained for 399,251 Jewish adolescents at the age of 17 yr from 1998 to 2004. The study population included only subjects born in Israel. In order to control for genetic confounding, subjects were also divided according to their ethnic group as being Ashkenazi, Sephardic, or Israeli in origin.
RESULTS: In total, 768 cases of inflammatory bowel disease (IBD) were diagnosed (0.19%), with 53.8% of the cases being of Ashkenazi origin. On multivariate analysis, variables significantly associated with IBD were male gender (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.24–1.67), Ashkenazi origin (OR 1.91, 95% CI 1.63–2.22), living in an urban environment (OR 1.38, 95% CI 1.02–1.78), small number of siblings in the family (for 1 sibling vs 5 or more, OR 2.63, 95% CI 1.49–4.62), and higher birth order (for birth order of 5 or higher vs 1, OR 2.35, 95% CI 1.47–3.77), showing for both variables an almost strictly highly significant monotonic association ( P value for trend <0.001).
CONCLUSIONS: Surrogate markers of childhood hygiene are associated with the risk for IBD, thus reinforcing the "hygiene hypothesis."     

Helicobacter pylori infection and inflammatory bowel disease in Asians: A meta-analysis

AIM: To investigate the relationship between Helicobacter pylori infection and inflammatory bowel disease (IBD) in an Asian population.METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched for observational studies published up until June 2014, without language restrictions. Additional references were obtained from reviewed articles.RESULTS: Ten studies involving 1299 IBD patients and 1817 controls were included in the meta-analysis (24.9% of IBD patients had H. pylori infection vs 48.3% of the controls). The pooled risk ratio for H. pylori infection in IBD patients compared with controls was 0.48 (95%CI: 0.43-0.54; P < 0.001). There was no significant heterogeneity in the included studies (I² = 21%). Egger’s linear regression indicated that there was no significant publication bias (P = 0.203).CONCLUSION: The H. pylori infection rate in Asian IBD patients is significantly lower than in non-IBD patients, indicating that infection protects against the development of IBD.     

Clostridium difficile infection in patients with inflammatory bowel disease: a case control study

Objective: Characterization of predisposing factors for Clostridium difficile infection recurrence (rCDI) and outcome in inflammatory bowel disease (IBD) patients.

Methods: Clinical characteristics of 167 inflammatory bowel disease patients with Clostridium difficile infection (IBD-CDI cohort) treated in Helsinki University Central Hospital were gathered. Medical history of the last three months preceding a toxin positive CDI test was recorded. Parameters, including ribotype of C. difficile, mortality and recurrence were compared with age and gender-matched C. difficile patients (CDI cohort).

Results: No difference was found in rCDI between IBD-CDI and CDI cohorts. As compared with IBD subtypes, rCDI was least common among patients with Crohn’s disease. The use of immunosuppressant therapy was higher in IBD patients with two or more CDI episodes. C. difficile ribotype 027 increased the rates for rCDI in IBD patients but not in non-IBD-CDI patients. The prevalence of 027 ribotype and mortality rates did not differ significantly among the cohorts. None of the IBD patients underwent colectomy upon CDI.

Conclusion: IBD patients are not more susceptible for rCDI than non-IBD patients. Predisposing factors for rCDI among IBD patients are associated with immunosuppressant treatments, colon affecting IBD and CDI caused by ribotype 027. CDI does not worsen the prognosis of IBD patients.     

Smoking and inflammatory bowel disease. A case control study.

A population case controlled study of smoking habits at the time of diagnosis was done in 260 patients with ulcerative colitis and 144 with Crohn's disease. Smokers had a decreased risk of acquiring ulcerative colitis in comparison with never smokers (relative risk 0.7) which appeared to be dose dependent. In former smokers a rebound effect was seen, especially in former heavy smokers, where the risk was sharply increased (relative risk 4.4). No sex difference was recorded. Smoking doubled the risk of acquiring Crohn's disease without any dose dependent pattern. In former smokers a non-significantly increased risk was observed. This might be caused by a carry over effect after stopping smoking, however, which possibly is reduced by time. No sex difference was seen.     

Environmental risk factors in paediatric inflammatory bowel diseases: a population based case control study

BACKGROUND: Environmental exposures in early life have been implicated in the aetiology of inflammatory bowel disease. OBJECTIVE: To examine environmental risk factors prior to the development of inflammatory bowel disease in a paediatric population based case control study. METHODS: A total of 222 incident cases of Crohn's disease and 60 incident cases of ulcerative colitis occurring before 17 years of age between January 1988 and December 1997 were matched with one control subject by sex, age, and geographical location. We recorded 140 study variables in a questionnaire that covered familial history of inflammatory bowel disease, events during the perinatal period, infant and child diet, vaccinations and childhood diseases, household amenities, and the family's socioeconomic status. RESULTS: In a multivariate model, familial history of inflammatory bowel disease (odds ratio (OR) 4.3 (95% confidence interval 2.3-8)), breast feeding (OR 2.1 (1.3-3.4)), bacille Calmette-Guerin vaccination (OR 3.6 (1.1-11.9)), and history of eczema (OR 2.1 (1-4.5)) were significant risk factors for Crohn's disease whereas regular drinking of tap water was a protective factor (OR 0.56 (0.3-1)). Familial history of inflammatory bowel disease (OR 12.5 (2.2-71.4)), disease during pregnancy (OR 8.9 (1.5-52)), and bedroom sharing (OR 7.1 (1.9-27.4)) were risk factors for ulcerative colitis whereas appendicectomy was a protective factor (OR 0.06 (0.01-0.36)). CONCLUSIONS: While family history and appendicectomy are known risk factors, changes in risk based on domestic promiscuity, certain vaccinations, and dietary factors may provide new aetiological clues.     

Low prevalence of Helicobacter pylori in inflammatory bowel disease: association with sulphasalazine.

The prevalence of IgG antibodies to Helicobacter pylori was examined in 110 patients with inflammatory bowel disease (IBD) (63 ulcerative colitis, 47 Crohn's disease) and compared with 100 age and sex matched control patients. The overall prevalence of H pylori seropositivity in the IBD patients was 22%, which was significantly less than that of 52% in the controls (p < 0.002). There was no difference in prevalence between ulcerative colitis and Crohn's patients. The low seropositivity in the IBD patients resulted from a very low prevalence of 10% in those currently receiving sulphasalazine (n = 40) and similarly low prevalence of 7% in those previously receiving sulphasalazine (n = 30). In those receiving olsalazine or mesalazine and who had never had sulphasalazine, the prevalence of seropositivity was 45%. Further studies using 14C urea breath test and microscopy of antral biopsy specimens confirmed that the negative serology in patients receiving sulphasalazine resulted from absence of the infection rather than absence of humoral immune response to it. In six control patients with H pylori infection, a two week course of sulphasalazine (500 mg four times daily) only caused slight suppression of the 14C urea breath test. In vitro studies failed to show any direct antibacterial effect of sulphasalazine on H pylori. These findings indicate that longterm treatment with sulphasalazine leads to eradication of H pylori infection and that this does not result from a direct antibacterial effect. It may be caused by the drug treating the gastritis and thereby depriving the bacterium of essential nutrients exuded by the inflamed mucosa.     

A case-control study of childhood environmental risk factors for the development of inflammatory bowel disease

OBJECTIVE : To clarify the relationship between childhood environment and the risk of subsequent development of Crohn's disease or ulcerative colitis. DESIGN AND OUTCOME MEASURES : A case-control study, assessing the risk of inflammatory bowel disease in relation to a series of historical and serological markers of childhood circumstance, analysed using the maximum likelihood form of conditional logistic regression. SETTING : District general hospital (secondary care institution). PARTICIPANTS : Subjects with Crohn's disease (n = 139) or ulcerative colitis (n = 137) aged between 16 and 45 years, each matched for sex and age with an outpatient control. RESULTS : Helicobacter seroprevalence was substantially reduced in Crohn's disease (OR 0.18; 95% CI, 0.06-0.52) but not in ulcerative colitis (OR 0.91; 95% CI, 0.38-2.16). In ulcerative colitis, a strong negative association with childhood appendectomy was confirmed (OR 0.05; 95% CI, 0.01-0.51). Crohn's disease was associated with childhood eczema (OR 2.81; 95% CI, 1.23-6.42) and the frequent use of a swimming pool (OR 2.90; 95% CI 1.21-6.91). There was no association between hepatitis A seroprevalence and either disease. CONCLUSION : The findings are consistent with the hypothesis that improved childhood living conditions are associated with increased risk of Crohn's disease. The study confirms that the negative association between appendectomy and ulcerative colitis relates primarily to events in childhood. Overall, the findings strongly support the assertion that childhood environment is an important determinant of the risk of inflammatory bowel disease in later life, with quite distinct risk factors for ulcerative colitis and Crohn's disease.     

Population‐based cases control study of inflammatory bowel disease risk factors

Background and Aim: The rapid increase in inflammatory bowel disease (IBD) incidence confirms the importance of environment in its etiology. We aimed to assess the role of childhood and other environmental risk factors in IBD. Methods: A population‐based case‐control study was carried out in Canterbury, New Zealand. Participants comprised 638 prevalent Crohn's disease (CD) cases, 653 prevalent ulcerative colitis (UC) cases and 600 randomly‐selected sex and age matched controls. Exposure rates to environmental risk factors were compared. Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CI) are presented. Results: A family history of IBD (CD OR 3.06 [2.18–4.30], UC OR 2.52 [1.90–3.54]), cigarette smoking at diagnosis (CD OR 1.99 [1.48–2.68], UC OR 0.67 [0.48–0.94]), high social class at birth (CD and UC trend, P < 0.001) and Caucasian ethnicity (CD OR 2.04 [1.05–4.38], UC OR 1.47 [1.01–2.14]) were significantly associated with IBD. City living was associated with CD (P < 0.01). Being a migrant was associated with UC (UC OR 1.40 [1.14–2.01]). Having a childhood vegetable garden was protective against IBD (CD OR 0.52 [0.36–0.76], UC OR 0.65 [0.45–0.94]) as was having been breast‐fed (CD OR 0.55 [0.41–0.74], UC OR 0.71 [0.52–0.96]) with a duration‐response effect. Appendicectomy, tonsillectomy, infectious monomucleosis and asthma were more common in CD patients than controls (P < 0.01). Conclusions: The importance of childhood factors in the development of IBD is confirmed. The duration‐response protective association between breast‐feeding and subsequent development of IBD requires further evaluation, as does the protective effect associated with a childhood vegetable garden.     

中国汉族炎症性肠病幽门螺杆菌感染状况分析

目的: 调查中国汉族IBD患者H pylori感染情况和IBD治疗药物及克罗恩病(CD)表型与H pylori感染的可能关系.方法: 收集106例IBD患者, 其中包括54例溃疡性结肠炎(UC)和52例CD, 对照组包括106例年龄和性别及社会经济状况与之匹配且接受了常规的体格检查的健康人. 采用H pylori IgG抗体胶体金免疫层析快速诊断试验比较了IBD患者和健康对照者H pylori的感染率.结果: IBD患者和对照组以及UC和CD患者之间H pylori感染率, 均具有显著性差异(31.1% vs61.3%, P<0.01;37.0% vs 25.0%, P<0.05). 在IBD患者中, 曾服用甲硝唑(22.3%)或喹诺酮类抗菌药(19.1%)的患者比对照组H pylori感染率显著降低, 而没有服用抗生素的患者也表明H pylori感染率显著低于对照组. IBD患者的表型特征与H pylori感染率没有显著的关系( P>0.05).结论: 中国汉族IBD患者, 特别是CD患者的H pylori感染率显著的低于正常对照者, 认为H pylori感染在IBD患者中可能是一种低危险因素.     

Urban–rural environmental exposure during childhood and subsequent risk of inflammatory bowel disease: a meta-analysis

Background: The relationship between living conditions in urban and rural areas during childhood and subsequent inflammatory bowel disease (IBD) remains controversial.

Aim: To explore the association between environmental exposures early in life and the subsequent risk of IBD.

Methods: Literature searches were conducted in the following databases: PubMed, EMBASE, and Conference Proceedings Citation Index. Studies were analyzed separately using rate ratios (RRs) or odds ratios (ORs) with 95% confidence intervals.

Results: The search strategy identified 15 studies. Of these, 9 studies explored the association between urban exposure during childhood and ulcerative colitis (UC), and 12 and 4 studies explored this relationship with Crohn’s disease (CD) and IBD, respectively. A meta-analysis showed that the pooled ORs estimated for the case–control studies of UC, CD, and IBD were 1.16 (0.83, 1.61), 1.45 (1.45, 1.85), and 1.34 (1.11, 1.62), respectively. The pooled RR estimated for the cohort studies of CD and IBD was 1.48 (1.17, 1.87). The stratified analysis and meta-regression showed significant relationships between CD and living conditions in case–control studies published during 2010–2017 and in non-European countries (P < 0.05).

Conclusions: Living conditions during childhood are positively associated with the subsequent development of IBD. Urban living environment is more common among those with CD than UC.     

Atopy,Helicobacter pylori and the hygiene hypothesis

It is uncertain whether the exposure to infections may decrease or increase the risk of allergy development in adult age. According to the hygiene hypothesis, an early childhood infection can down-regulate immunity, suppressing allergic and autoimmune disorders. Novel epidemiological data from a cross-sectional survey show that in subjects with active Helicobacter pylori infection the prevalence of asthma, eczema, allergic rhinitis is lower than in H. pylori-negative subjects. This information is supported by several mechanistic disease models, but is in contrast with previous reports on the association between H. pylori and atopic conditions. The public health relevance of both allergic disorders and H. pylori-related diseases calls for prospective and therapeutic studies. Studies able to show a cause-effect relationship are now essential to bring evidence that might make the case against H. pylori eradication in children and when such intervention is not highly recommended.     

Specificities of inflammatory bowel disease in childhood

In parallel with overall population trends, the incidence of paediatric ulcerative colitis (UC) has remained stable, whereas that of paediatric Crohn's disease (CD) has increased in recent decades. Still rare among preschool children, the incidence of both UC and CD rises steadily from middle childhood through adolescence. There is an unexplained preponderance of males with early-onset CD, and an equal gender distribution in paediatric UC. Observations on the familiality of paediatric inflammatory bowel disease (IBD) suggest that genetic susceptibility is particularly important to disease pathogenesis in young patients. In comparison to adult-onset disease, childhood UC is usually extensive but the anatomic localization of paediatric CD varies, as in adults. UC manifests uniformly as bloody diarrhea whereas the symptomatology of paediatric CD is much more diverse. Linear growth impairment frequently complicates chronic intestinal inflammation in paediatric CD. Key contributing factors have been defined; better immunomodulatory therapy and emerging biologic agents will potentially reduce its prevalence.     

Assessment of the prevalence of infection with Helicobacter pylori in patients with inflammatory bowel disease

OBJECTIVE: To determine the prevalence of Helicobacter pylori in patients with inflammatory bowel disease (IBD) and compare this to the prevalence in a control population with non-organic bowel symptoms, and to investigate the effect of sulphasalazine and other 5-aminosalicylic acid (5-ASA) drugs on the prevalence of H. pylori in IBD patients. DESIGN: Prospective, controlled trial. SETTING: Gastroenterology out-patient department, City General Hospital, North Staffordshire Hospitals NHS Trust, Stoke-on-Trent. PARTICIPANTS: The population comprised 51 patients with ulcerative colitis, 42 patients with Crohn's disease and 40 patients with irritable bowel syndrome as controls. Patients with X-ray- and/or biopsy-proven disease were eligible to be entered into the study. INTERVENTIONS: Subjects filled in a detailed questionnaire, were assessed for seropositivity of H. pylori and underwent a C13 urea breath test (UBT). MAIN OUTCOME MEASURES: Seropositivity for H. pylori and a positive C13 UBT result. RESULTS: A quarter of the irritable bowel syndrome controls were seropositive for H. pylori. Of the ulcerative colitis patients, 21.6% were currently H. pylori-positive on C13 UBT; 17.6% of the ulcerative colitis patients who had been previously treated with sulphasalazine were positive while 23.1% of the ulcerative colitis patients who had been treated with a non-sulphasalazine 5-ASA drug were positive. Of the Crohn's patients, 11.9% were currently H. pylori-positive; 3.6% of the Crohn's patients who had been previously treated with sulphasalazine were positive while 12.5% of the Crohn's patients who had been treated with a non-sulphasalazine 5-ASA drug were positive. CONCLUSIONS: Patients with IBD and Crohn's disease in particular were less likely to be H. pylori-positive than controls. Sulphasalazine treatment further decreased the prevalence of H. pylori, although the reduced prevalence of H. pylori in IBD patients could not be accounted for by this alone.     

Appendectomy, tonsillectomy, and risk of inflammatory bowel disease

PURPOSE: Appendectomy has been suggested as a possible protective factor in ulcerative colitis and as a risk factor in Crohn's disease. Tonsillectomy has also been associated with Crohn's disease. We performed a case-controlled study to investigate these associations in a homogeneous Greek population. METHODS: One hundred thirty-four consecutive cases of ulcerative colitis and 76 cases of Crohn's disease were included in the study. For each inflammatory bowel disease patient and a corresponding healthy control subject, matched for gender, age, and educational level, a standard record on various risk factors was completed by interview. The association between disease status and risk factors was assessed by Pearson's chi-squared test and the independent contribution of each risk factor was analyzed by means of logistic regression analysis. RESULTS: Appendectomy had been performed in 11 (8.2 percent) patients with ulcerative colitis, in 18 (13.4 percent) of their matched healthy control cases, in 19 (25.0 percent) patients with Crohn's disease, and in 10 (13.2 percent) of their matched healthy control cases. Odds ratio for development of ulcerative colitis after appendectomy was 0.6 (95 percent confidence interval, 0.26–1.27). Odds ratio for Crohn's disease was 2.2 (95 percent confidence interval, 0.94–5.12). Odds ratio for development of ulcerative colitis or Crohn's disease after tonsillectomy was 0.95 (95 percent confidence interval, 0.49–1.82) and 3.29 (95 percent confidence interval, 1.29–8.37), respectively. The logistic regression analysis showed that appendectomy and tonsillectomy have no independent association with the risk of developing ulcerative colitis, whereas in Crohn's disease both appendectomy and tonsillectomy have positive associations. Wellestablished risk factors, such as family history and smoking status, were also verified in this study. CONCLUSIONS: This case-control study, using multivariate logistic regression analysis, showed a less pronounced association between ulcerative colitis and appendectomy than previous reports. Our data also support the conclusion that tonsillectomy is a risk factor for developing Crohn's disease.Poster presentation at the World Congress of Gastroenterology, Vienna, Austria, September 6 to 11, 1998.