Increasing incidence of both juvenile-onset Crohn's disease and ulcerative colitis in Scotland.

OBJECTIVE: A previous study reported a three-fold rise in the incidence of juvenile-onset Crohn's disease in Scottish children and a marginal fall in ulcerative colitis between 1968 and 1983. The present study aimed to document the incidence of juvenile-onset inflammatory bowel disease between 1981 and 1995 and examine temporal trends between 1968 and 1995 in Scotland. SETTING: Scotland (latitude 55-60 degrees N) has a total area of 77 837 km2 (30 405 square miles) and includes four urban centres each with a population of over 100,000. PARTICIPANTS: The Scottish hospital discharges linked database was used to identify 1002 patients less than 19 years old who were coded as having inflammatory bowel disease between 1981 and 1997. All case notes were reviewed and diagnoses verified. Incident cases were defined as those with symptom onset before or at 16 years of age between 1 January 1981 and 31 December 1995. RESULTS: During the 15 year period 1981-1995, 438 incident cases of Crohn's disease and 227 of ulcerative colitis were identified, giving standardized incidences of 2.5 cases and 1.3 cases per 100,000 population per year for Crohn's disease and ulcerative colitis respectively. On 31 December 1995 there were 150 children < or = 16 years of age with Crohn's disease and 101 with ulcerative colitis, giving crude prevalences of 13.7 cases per 100,000 population for Crohn's disease and 9.2 for ulcerative colitis. The continuing rise in Crohn's disease incidence between 1981 and 1995 fits that predicted by linear trend analysis of the 1968-1983 data. The incidence of Crohn's disease in the 12-16 age range almost doubled between 1981 and 1995 and was greater for males than females. Ulcerative colitis incidence was thought to show a slight fall in the 1968-1983 data, but this is reversed in the 1981-1995 data. CONCLUSION: The incidence of juvenile-onset Crohn's disease continues to rise in Scotland and the prevalence has increased by 30% since 1983. Unlike the previous report from Scotland, the incidence of juvenile-onset ulcerative colitis also is apparently rising. Whether this represents a real rise in incidence, or merely the inclusion of milder cases which were not previously hospitalized remains uncertain.     

Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota

BACKGROUND & AIMS: The risk for colorectal cancer in Crohn's disease and ulcerative colitis patients from the United States currently is unknown. We estimated the risk for small-bowel and colorectal cancer in a population-based cohort of 692 inflammatory bowel disease patients from Olmsted County, Minnesota, from 1940 to 2001. METHODS: The Rochester Epidemiology Project was used to identify cohort patients with colorectal and small-bowel cancer. The cumulative probability of cancer and standardized incidence ratios (SIR) were estimated using expected rates from Surveillance, Epidemiology, and End Results, white patients from Iowa, from 1973 to 2000, and Olmsted County, from 1980 to 1999. RESULTS: Colorectal cancer was observed in 6 ulcerative colitis patients vs 5.38 expected (SIR, 1.1; 95% confidence interval [CI], 0.4-2.4), but 4 of these occurred among those with extensive colitis or pancolitis (SIR, 2.4; 95% CI, 0.6-6.0). Six Crohn's disease patients (vs 3.2 expected) developed colorectal cancer (SIR, 1.9; 95% CI, 0.7-4.1). Three Crohn's disease patients developed small-bowel cancer vs 0.07 expected (SIR, 40.6; 95% CI, 8.4-118). CONCLUSIONS: The risk for colorectal cancer was not increased among ulcerative colitis patients overall, but appeared to be increased among those with extensive colitis. The colorectal cancer risk was increased slightly among Crohn's disease patients, who also had a 40-fold excess risk for small-bowel cancer.     

Predictors of Crohn's disease

BACKGROUND & AIMS: Early intensive therapy in Crohn's disease should be considered only in patients with disabling disease. The aim of our study was to identify at diagnosis factors predictive of a subsequent 5-year disabling course. METHODS: Among the 1526 patients seen at our unit with Crohn's disease diagnosed between 1985 and 1998, we excluded patients operated on within the first month of the disease, patients with inadequate data, and patients with severe chronic nondigestive disease. In the 1188 remaining patients, Crohn's disease course within the first 5 years of the disease was categorized as disabling when at least 1 of the criteria of clinical severity, conventionally predefined, was present. RESULTS: Among the 1123 patients with follow-up data allowing full 5-year course classification, the rate of disabling disease was 85.2%. Independent factors present at diagnosis and significantly associated with subsequent 5-year disabling were the initial requirement for steroid use (OR 3.1 [95% CI: 2.2-4.4]), an age below 40 years (OR 2.1 [95% CI: 1.3-3.6]), and the presence of perianal disease (OR 1.8 [95% CI: 1.2-2.8]). The positive predictive value of disabling disease in patients with 2 and 3 predictive factors of disabling disease was 0.91 and 0.93, respectively. These values were 0.84 and 0.91, respectively, when tested prospectively in an independent group of 302 consecutive patients seen at our institution from 1998. CONCLUSIONS: At diagnosis of Crohn's disease in a referral center, factors predictive of subsequent 5-year disabling course are an age below 40 years, the presence of perianal disease, and the initial requirement for steroids.     

A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and IBD5

BACKGROUND & AIMS: A genome-wide association scan of nonsynonymous DNA polymorphisms identified association of a threonine-to-alanine substitution (T300A) in the autophagy-related 16-like gene ATG16L1 with Crohn's disease. We investigated this association in independent U.K. cohorts of Crohn's disease and ulcerative colitis. METHODS: The T300A variant (rs2241880) was genotyped in an independent sample of 727 Crohn's disease and 877 ulcerative colitis cases, and in 579 controls. We then performed an extension analysis combining these data with the U.K. data from the initial study to give a total of 1236 U.K. Crohn's disease cases and 1235 controls to estimate disease risk and test for interaction with the CARD15 and IBD5 risk loci and for association with disease subtypes. RESULTS: The association of T300A was replicated in the independent sample of 727 Crohn's disease cases (P = .001), and was strongly associated in the extended analysis of 1236 Crohn's cases (P = 2.4 x 10(-6)). The 300A/A genotype conferred a 1.65-fold risk of Crohn's disease, with a 2.2-fold risk of ileal disease. Analysis of the interaction of ATG16L1 with CARD15 and IBD5 indicated that all 3 loci contribute independently to disease risk. Homozygosity for the risk allele at all 3 loci conferred a combined risk of 20.4 (95% confidence interval: 8.71, 47.7) for Crohn's disease. The ATG16L1 risk genotype showed a modest but significant association with ulcerative colitis (P = .026). CONCLUSIONS: The association of ATG16L1 with Crohn's disease and possibly with ulcerative colitis supports a role for autophagy in the pathogenesis of inflammatory bowel disease.     

Increase in incidence and prevalence of inflammatory bowel disease in northern Denmark: a population-based study, 1978-2002

OBJECTIVES: Although incidence rates of inflammatory bowel disease have been reported worldwide, few long-term population-based studies with current time-trend analyses exist. We therefore examined time trends in the incidence rate of inflammatory bowel disease in a 25-year study period, and estimated the prevalence in 2002. All patients diagnosed between 1978 and 2002 were included as incident cases (n=2,326) and all patients living in North Jutland County on 31 December 2002 were used to estimate prevalent cases (n=2,205). METHODS: Medical records of all patients diagnosed with ulcerative colitis and Crohn's disease in the North Jutland County Hospital Discharge Registry were reviewed to examine if the diagnostic criteria were fulfilled. Age-specific and gender-specific standardized incidence rates were calculated. RESULTS: For ulcerative colitis, incidence rates in women increased from 8.3 (95% confidence interval (CI): 6.7-9.9) in 1978-1982 to 17.0 (95% CI: 14.7-19.3) per 100,000 person-years in 1998-2002. The corresponding figures for men were 7.7 (95% CI: 6.1-9.3) and 16.7 (95% CI: 14.4-18.8) per 100,000 person-years. For Crohn's disease, the incidence rates in women increased from 4.1 (95% CI: 3.0-5.2) in 1978-1982 to 10.7 (95% CI: 8.8-12.5) per 100,000 person-years in 1998-2002. The corresponding figures for men were 3.2 (95% CI: 2.1-4.2) and 8.5 (95% CI: 6.9-10.2) per 100,000 person-years. The prevalence of ulcerative colitis and Crohn's disease was 294 and 151 per 100,000 inhabitants, respectively. CONCLUSIONS: A marked and parallel increase was seen in both ulcerative colitis and Crohn's disease in both genders during the last 25 years, with a corresponding high prevalence of both diseases.     

Appendectomy is followed by increased risk of Crohn's disease

BACKGROUND & AIMS: Appendectomy is associated with a low risk of subsequent ulcerative colitis. This study analyzes the risk of Crohn's disease after appendectomy. METHODS: We followed-up 212,218 patients with appendectomy before age 50 years and a cohort of matched controls, identified from the Swedish Inpatient Register and the nationwide Census, for any subsequent diagnosis of Crohn's disease. RESULTS: An increased risk of Crohn's disease was found for more than 20 years after appendectomy, with incidence rate ratio 2.11 (95% confidence interval [CI], 1.21-3.79) after perforated appendicitis, 1.85 (95% CI, 1.10-3.18) after nonspecific abdominal pain, 2.15 (95% CI, 1.25-3.80) after mesenteric lymphadenitis, 2.52 (95% CI, 1.43-4.63) after other diagnoses. After nonperforated appendicitis, there was an increased risk among women but not among men (incidence rate ratio 1.37; 95% CI, 1.03-1.85, respectively, 0.89, 95% CI, 0.64-1.24). Patients operated on before age 10 years had a low risk (incidence rate ratio 0.48, 95% CI, 0.23-0.97). Crohn's disease patients with a history of perforated appendicitis had a worse prognosis. CONCLUSIONS: Appendectomy is associated with an increased risk of Crohn's disease that is dependent on the patient's sex, age, and the diagnosis at operation. The pattern of associations suggests a biologic cause.     

Fracture risk is increased in Crohn's disease, but not in ulcerative colitis

AIMS: To study fracture rates and risk factors for fractures in patients with Crohn's disease and ulcerative colitis. METHODS: 998 self administered questionnaires were issued to members of the Danish Colitis/Crohn Association, and 1000 questionnaires were issued to randomly selected control subjects. 845 patients (84.5%) and 645 controls (65.4%) returned the questionnaire (p<0.01). 817 patients and 635 controls could be analysed. RESULTS: Analysis was performed on 383 patients with Crohn's disease (median age 39, range 8-82 years; median age at diagnosis 26, range 1-75 years), 434 patients with ulcerative colitis (median age 39, range 11-86 years; median age at diagnosis 29, range 10-78 years), and 635 controls (median age 43, range 19-93 years, p<0.01). The fracture risk was increased in female patients with Crohn's disease (relative risk (RR) = 2.5, 95% confidence interval (CI) 1.7-3.6), but not in male patients with Crohn's disease (RR = 0.6, 95% CI 0.3-1.3) or in patients with ulcerative colitis (RR = 1.1, 95% CI 0.8-1.6). An increased proportion of low energy fractures was observed in patients with Crohn's disease (15.7% versus 1.4 % in controls, 2p<0. 01), but not in patients with ulcerative colitis (5.4%, 2p=0.30). The increased fracture frequency in Crohn's disease was present for fractures of the spine, feet, and toes and fractures of the ribs and pelvis. Fracture risk increased with increasing duration of systemic corticosteroid use in Crohn's disease (2p=0.028), but not in ulcerative colitis (2p=0.50). CONCLUSIONS: An increased risk of low energy fractures was observed in female patients with Crohn's disease, but not in male patients with Crohn's disease or in patients with ulcerative colitis.     

Influence of environmental factors on the onset and course of inflammatory bowel disease

Numerous environmental factors have been linked with inflammatory bowel disease. These include smoking, diet, hygiene, drugs, geographical and psychosocial factors. These factors may either increase the risk of or protect against developing this condition and can also affect the course of illness in a positive or negative manner. A number of studies have examined the influence of environmental factors on inflammatory bowel diseases as a whole as well as on ulcerative colitis and Crohn's disease separately. As there are differences in the pathogenesis of ulcerative colitis and Crohn's disease, the effect of environmental factors on their onset and course is not always similar. Some factors have shown a consistent association, while reports on others have been conflicting. In this article we discuss the current evidence on the roles of these factors on inflammatory bowel disease, both as causative/protective agents and as modifiers of disease course.     

Increased risk for demyelinating diseases in patients with inflammatory bowel disease

BACKGROUND & AIMS: Reports of multiple sclerosis (MS), demyelination, and optic neuritis (ON) associated with anti-tumor necrosis factor alpha therapy resulted in warnings on prescribing instructions for infliximab, etanercept, and adalimumab. However, the underlying relationship between IBD and these neurologic conditions has not been established. METHODS: We performed a retrospective cohort study and a retrospective cross-sectional study using 1988 to 1997 data from the General Practice Research Database. A total of 7988 Crohn's disease and 12,185 ulcerative colitis patients were matched for age, sex, and primary care practice to 80,666 randomly selected controls. In the cohort study, incident cases of MS, demyelination, and/or ON (MS/D/ON) had to occur at least 1 year after registration with the physician and after the diagnosis of IBD. In the cross-sectional study, the diagnosis of MS/D/ON could either precede or follow the IBD diagnosis. RESULTS: In the cohort study, the incidence of MS/D/ON was higher in patients with Crohn's disease and ulcerative colitis compared with their matched controls, reaching statistical significance for ulcerative colitis (ulcerative colitis incidence rate ratio [IRR], 2.63; 95% confidence interval, 1.29-5.15; Crohn's disease IRR, 2.12; 95% confidence interval, .94-4.50). In the cross-sectional study, MS/D/ON was more prevalent in patients with Crohn's disease and ulcerative colitis compared with their matched controls (Crohn's disease odds ratio, 1.54; 95% confidence interval, 1.03-2.32; ulcerative colitis odds ratio, 1.75; 95% confidence interval, 1.28-2.39). CONCLUSIONS: Demyelinating diseases occur more commonly among patients with IBD than among non-IBD patients. Future studies should clarify whether treatment with tumor necrosis factor alpha blockers results in further increased incidence of MS/D/ON among IBD patients.     

Geographic variation in the incidence of and mortality from inflammatory bowel disease

The geographic and temporal variations in mortality from Crohn's disease and ulcerative colitis were investigated. The validity of mortality data as indicators of morbidity was tested by comparing the death rates and incidences among different countries. Death rates from Crohn's disease and ulcerative colitis were high in England, Germany, and the Scandinavian countries, and low in the Mediterranean countries. There was a significant correlation between the incidence and mortality of both diseases among different countries. In addition, the incidence and mortality of Crohn's disease were correlated with those of ulcerative colitis. In countries with a low mortality rate from Crohn's disease, the death rates in men tended to be higher than those in women. In contrast, countries with high death rates from Crohn's disease showed female predominance. No such relationship existed for ulcerative colitis. The overall change in mortality rates during the last 20 to 30 years was characterized by a rise of Crohn's disease and a marked fall of ulcerative colitis. In countries with a high mortality rate from Crohn's disease, the death rates started to fall in recent times. The significant correlations between incidence and mortality show that the death rates from both diseases represent reliable indicators of the morbidity and that the severity of the two diseases is similar in different countries. The marked temporal and geographic variations in both incidence and mortality suggest that environmental factors play an important role in the etiology of both diseases. Supported by grant number So 172/1-1 from the Deutsche Forschungsgemeinschaft.     

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.     

Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn's disease

BACKGROUND AND AIMS: Recent studies on appendicectomy rates in ulcerative colitis and Crohn's disease have generally not addressed the effect of appendicectomy on disease characteristics. The aims of this study were to compare appendicectomy rates in Australian inflammatory bowel disease patients and matched controls, and to evaluate the effect of prior appendicectomy on disease characteristics. METHODS: Patients were ascertained from the Brisbane Inflammatory Bowel Disease database. Controls matched for age and sex were randomly selected from the Australian Twin Registry. Disease characteristics included age at diagnosis, disease site, need for immunosuppression, and intestinal resection. RESULTS: The study confirmed the significant negative association between appendicectomy and ulcerative colitis (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.14-0.38; p<0.0001) and found a similar result for Crohn's disease once the bias of appendicectomy at diagnosis was addressed (OR 0.34, 95% CI 0.23-0.51; p<0.0001). Prior appendicectomy delayed age of presentation for both diseases and was statistically significant for Crohn's disease (p=0.02). In ulcerative colitis, patients with prior appendicectomy had clinically milder disease with reduced requirement for immunosuppression (OR 0.15, 95% CI 0.02-1.15; p=0.04) and proctocolectomy (p=0.02). CONCLUSIONS: Compared with patients without prior appendicectomy, appendicectomy before diagnosis delays disease onset in ulcerative colitis and Crohn's disease and gives rise to a milder disease phenotype in ulcerative colitis.     

Incidence rates and disease course of paediatric inflammatory bowel diseases in Western Hungary between 1977 and 2011

BackgroundLimited data are available on paediatric inflammatory bowel diseases in Eastern Europe. Our aim was to analyse disease characteristics in the population-based Veszprem province database between 1977 and 2011.Methods187 (10.5%, ulcerative colitis/Crohn's disease/undetermined colitis: 88/95/4) out of 1565 incident patients were diagnosed with a paediatric onset in this population-based prospective inception cohort.ResultsThe incidence of Crohn's disease and ulcerative colitis increased from 0 and 0.7 in 1977–1981 to 7.2 and 5.2 in 2007–2011 per 100,000 person years. Ileocolonic location (45%) and inflammatory disease behaviour (61%) were most frequent in Crohn's disease, while azathioprine use was frequent (66%) and surgical resection rates were high (33% at 5 years) in cases with paediatric onset. In ulcerative colitis, 34% of patients were diagnosed with extensive disease, with high rates of disease extension (26% and 41% at 5 and 10 years), fulminant episodes (19.3%) and systemic steroid use (52.3%). The cumulative rate of colectomy was low (6.9%).ConclusionsThe incidence of paediatric inflammatory bowel diseases has rapidly increased in the last three decades in Western Hungary. Ileocolonic disease and a need for azathioprine were characteristic in paediatric Crohn's disease, while paediatric onset ulcerative colitis was characterised by extensive disease and disease extension, while the need for colectomy was low.     

Seasonal variations in onset of symptoms in Crohn''s disease

BACKGROUND: Seasonal variations in onset of symptoms have been reported in ulcerative colitis but not in Crohn's disease. AIM.: To investigate whether our inflammatory bowel diseases patients presented seasonal variations in onset of symptoms. PATIENTS AND METHODS: Patients with a diagnosis of inflammatory bowel diseases established between 1995 and May 2004, and consecutively observed from June 2003 to May 2004, were included in the study. Onset of symptoms (year, season and month) was recorded. Expected onsets with a uniform distribution during the year were calculated and compared to observed onsets. Statistical analysis: chi-square test, odds ratio (95% confidence interval). RESULTS: Overall 425 inflammatory bowel diseases patients were enrolled. Onset of symptoms (year and season) was established in 353/425 patients (83%; 150 Crohn's disease; 203 ulcerative colitis). Onset of symptoms in inflammatory bowel diseases patients as a whole occurred more frequently in spring-summer compared to autumn-winter (odds ratio 1.39; 95% confidence interval 1.03-1.87; p<0.03). This variation was observed in Crohn's disease (odds ratio 1.59; 95% confidence interval 1.00-2.51; p<0.05) and a similar trend, although not significant, was observed in ulcerative colitis (odds ratio 1.27; 95% confidence interval 0.86-1.88; p=0.27). CONCLUSIONS: These data indicate that onset of Crohn's disease symptoms occurred more frequently during spring-summer. A similar trend was observed in ulcerative colitis. Environmental factors, such as associated infections, smoking, use of drugs and seasonal changes in immune function may be responsible for triggering the clinical onset of inflammatory bowel diseases.     

Cancer in patients with ulcerative colitis, Crohn's disease and coeliac disease: record linkage study

OBJECTIVE: The objective of this study was to determine the risk of cancers in cohorts of patients with ulcerative colitis, Crohn's disease, or coeliac disease, compared with the risk in a control cohort. METHOD: The method used was the analysis of a linked statistical database of hospital and mortality data in an area in southern England. RESULTS: Rate ratios for cancer (excluding cases occurring within the first year of follow-up), compared with the value of 1 in the control cohort, were 1.25 [95% confidence interval (CI), 1.13-1.39] in patients with ulcerative colitis, 1.27 (95% CI, 1.11-1.45) with Crohn's disease, and 1.16 (95% CI, 0.94-1.43) with coeliac disease. In patients with ulcerative colitis or Crohn's disease, there was a significantly high risk of cancer of the colon [2.22 (95% CI, 1.71-2.83) and 1.64 (95% CI, 1.09-2.39), respectively]. In patients with ulcerative colitis there was a significantly high risk of cancer of the rectum [1.84 (95% CI, 1.27-2.58)]. In patients with ulcerative colitis or Crohn's disease, who did not undergo partial or total colectomy for it, the rate ratios for colon cancer were, respectively, 5.52 (95% CI, 4.39-6.71) and 4.81 (95% CI, 3.52-6.47). In ulcerative colitis, there was an elevated risk of cancer of the rectum, liver and ovary. The rate ratio for lung cancer was low, but of borderline significance [0.72 (95% CI, 0.50-0.98)]. In Crohn's disease, the rate ratio was high for cancer of the cervix [2.63 (95% CI, 1.12-5.29)]. In patients with coeliac disease, the high-risk cancer was non-Hodgkin's lymphoma [rate ratio 3.28 (95% CI, 1.49-6.28)]. CONCLUSION: All three diseases carry an increased risk of cancer overall when the first year cases are included, though fairly modest in scale, and the increased risk seen in coeliac disease reduces when first year cases are excluded. Each has a distinctive pattern of individual high-risk cancers.     

Ulcerative colitis: no rise in mortality in a European-wide population based cohort 10 years after diagnosis

BACKGROUND: Population based studies have revealed varying mortality for patients with ulcerative colitis but most have described patients from limited geographical areas who were diagnosed before 1990. AIMS: To assess overall mortality in a European cohort of patients with ulcerative colitis, 10 years after diagnosis, and to investigate national ulcerative colitis related mortality across Europe. METHODS: Mortality 10 years after diagnosis was recorded in a prospective European-wide population based cohort of patients with ulcerative colitis diagnosed in 1991-1993 from nine centres in seven European countries. Expected mortality was calculated from the sex, age and country specific mortality in the WHO Mortality Database for 1995-1998. Standardised mortality ratios (SMR) and 95% confidence intervals (CI) were calculated. RESULTS: At follow-up, 661 of 775 patients were alive with a median follow-up duration of 123 months (107-144). A total of 73 deaths (median follow-up time 61 months (1-133)) occurred compared with an expected 67. The overall mortality risk was no higher: SMR 1.09 (95% CI 0.86 to 1.37). Mortality by sex was SMR 0.92 (95% CI 0.65 to 1.26) for males and SMR 1.39 (95% CI 0.97 to 1.93) for females. There was a slightly higher risk in older age groups. For disease specific mortality, a higher SMR was found only for pulmonary disease. Mortality by European region was SMR 1.19 (95% CI 0.91 to 1.53) for the north and SMR 0.82 (95% CI 0.45-1.37) for the south. CONCLUSIONS: Higher mortality was not found in patients with ulcerative colitis 10 years after disease onset. However, a significant rise in SMR for pulmonary disease, and a trend towards an age related rise in SMR, was observed.     

Pancreatic disorders in inflammatory bowel disease

An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been rec-orded in patients with inflammatory bowel disease(IBD) compared to the general population.Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced,in some cases pancreatitis were defined as idiopathic,suggesting a direct pancreatic damage in IBD.Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn's disease and ulcerative colitis.This review will discuss the most common pancreatic diseases seen in patients with IBD.     

Non-calculus suppurative cholangitis in Danish patients with inflammatory bowel disease

BACKGROUND/AIMS: We examined the risk of non-calculus suppurative cholangitis in patients with inflammatory bowel disease in the entire Danish population. METHODOLOGY: The study included all patients discharged from Danish hospitals with a diagnosis of Crohn's disease or ulcerative colitis as registered in the Danish National Registry of Patients from January 1, 1977 to December 31, 1992. We compared the observed number of patients hospitalized with suppurative cholangitis with expected numbers on the basis of age, gender, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,317 eligible patients with inflammatory bowel disease were discharged during the study period. Among these were 52 cases of non-calculus suppurative cholangitis. The incidence rate of non-calculus suppurative cholangitis in the cohort with inflammatory bowel disease was 46.1 per 100,000 person-years. The standardized incidence ratio (SIR) for suppurative cholangitis was increased similarly for patients with Crohn's disease [SIR=6.7, 95% confidence interval (CI): 3.1-12.7] and for patients with ulcerative colitis (SIR=6.6, 95% CI: 4.7-9.1). The highest relative risk was found in male patients younger than 40 years of age, for both Crohn's disease and ulcerative colitis (SIR=70.5 and 78.7, respectively). CONCLUSIONS: Patients with inflammatory bowel disease have an increased risk of non-calculus suppurative cholangitis.     

The pregnane X receptor locus is associated with susceptibility to inflammatory bowel disease

BACKGROUND & AIMS: The pregnane X receptor (PXR) regulates an array of genes involved in the response to xenobiotics. Evidence from several studies suggests that xenobiotic metabolism may play a role in inflammatory bowel disease (IBD) and that low levels of PXR may be associated with disease expression. The aim of this study was to investigate the association of functional polymorphisms of the PXR encoding gene (NR1I2) with disease in IBD populations. METHODS: This was a case-control study examining 8 NR1I2 single nucleotide polymorphisms (SNPs) previously associated with altered activity of PXR-regulated genes in an Irish cohort including 422 patients with IBD and 350 ethnically matched controls. RESULTS: We showed significant associations of NR1I2 with IBD, Crohn's disease (CD), and ulcerative colitis (UC) groups compared with a control population for SNPs -23585 (IBD: P = .000008; odds ratio [OR], 1.62; 95% confidence interval [CI], 1.31-2.00) and -24381 (IBD: P = .0002; OR, 1.50; 95% CI, 1.21-1.84). SNPs 7635 (P = .0008) and 8055 (P = .007) were found to be associated with IBD and CD but not UC. Risk of IBD is strongly correlated to genotype at these sites, especially for the -25385CC genotype (P = .00001; OR, 2.92; 95% CI, 1.87-4.66). We also show specific correlations of IBD phenotype with genotypes and haplotypes in the patient group. CONCLUSIONS: These results show that genetic variation in the PXR encoding gene, which has been associated with altered activity of PXR, is strongly associated with susceptibility to IBD, CD, and UC.     

Appendicectomy has no beneficial effect on admission rates in patients with ulcerative colitis

BACKGROUND AND AIMS: Those who have had an appendicectomy have a reduced risk of developing ulcerative colitis. However, the effect of appendicectomy on disease activity in patients with ulcerative colitis has not been established. METHODS: We used the Danish National Patient Registry to identify all incident cases of ulcerative colitis in Denmark during the period 1981 to 1999. Of these, 202 had an appendicectomy after their first admission with ulcerative colitis. In these patients, we compared the incidence rate of hospitalisations with ulcerative colitis as first diagnosis during the period between the onset of ulcerative colitis and appendicectomy, with the rate of such hospitalisations after appendicectomy. To adjust for the clinical course of ulcerative colitis unrelated to appendicectomy, we extracted a reference cohort (n = 808), matched to the index subjects with respect to age, sex, and year of first admission, but with an intact appendix. RESULTS: The rate of admission with ulcerative colitis as first diagnosis decreased by 47% after appendicectomy (rate ratio 0.53 (95% confidence interval (CI) 0.36-0.80)). However, the reference cohort showed a similar decline in admission rate (rate ratio 0.51). Thus appendicectomy had no apparent beneficial effect on admission rate after adjustment for the clinical course of disease unrelated to appendicectomy (adjusted rate ratio 1.05 (95% CI 0.67-1.67)). CONCLUSIONS: Appendicectomy had no significant beneficial effect on admission rates in patients with ulcerative colitis.