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Summary: Background: The incidence and short‐term outcome of anaemia in inflammatory bowel disease (IBD) are largely unknown. Aim: To determine the incidence, prevalence and clinical outcome of anaemia in terms of resolution of anaemia within 12 months. We also planned to assess risk factors for anaemia in IBD. Methods: A random sample of 342 patients was obtained from the population‐based IBD cohort of Örebro University Hospital, Sweden, consisting of 1405 patients diagnosed between 1963 and 2010. Haemoglobin measurements recorded from 1 January 2011 to 31 December 2013 were extracted from the Clinical Chemistry data system. Results: In Crohn's disease, the incidence rate of anaemia was 19.3 (95% CI: 15.4‐23.7) per 100 person‐years and the prevalence was 28.7% (CI: 22.0‐36.2), compared with 12.9 (CI: 9.8‐16.5) and 16.5% (CI: 11.2‐22.9) for ulcerative colitis. Crohn's disease was associated with an increased incidence (OR = 1.60; CI: 1.02‐2.51) and prevalence of anaemia (OR = 2.04; CI: 1.20‐3.46) compared to ulcerative colitis. Stricturing disease phenotype in Crohn's disease (HR = 2.59; CI: 1.00‐6.79) and extensive disease in ulcerative colitis (HR = 2.40; CI: 1.10‐5.36) were associated with an increased risk of anaemia. Despite a higher probability of receiving specific therapy within 3 months from the diagnosis of anaemia, Crohn's disease patients had a worse outcome in terms of resolution of anaemia within 12 months (56% vs 75%; P = 0.03). Conclusions: Anaemia is a common manifestation of IBD even beyond the first years after the diagnosis of IBD. Crohn's disease is associated with both an increased risk and a worse outcome. [ABSTRACT FROM AUTHOR]

Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn’s disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T) allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T) allele, relative to homozygous carriers of the minor (C) allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The characteristic clinical symptoms of collagenous colitis are non-bloody diarrhoea, urgency and abdominal pain. Treatment is aimed at reducing the symptom burden and the disease impact on patients’ health-related quality of life. The objective of this study was to analyse health-related quality of life in patients with collagenous colitis. Methods: In a cross-sectional, postal HRQL survey, 116 patients with collagenous colitis at four Swedish hospitals completed four health-related quality of life questionnaires, two disease-specific (Inflammatory Bowel Disease Questionnaire and Rating Form of IBD Patient Concerns), and two generic (Short Form 36, SF-36, and Psychological General Well-Being, PGWB), and a one-week symptom diary. Demographic and disease-related data were collected. Results for the collagenous colitis population were compared with a background population controlled for age and gender (n =8931). Results: Compared with a Swedish background population, patients with collagenous colitis scored significantly worse in all Short Form 36 dimensions (p <0.01), except physical function. Patients with active disease scored worse health-related quality of life than patients in remission. Co-existing disease had an impact on health-related quality of life measured with the generic measures. Lower education level and shorter disease duration were associated with decreased well-being. Conclusion: Health-related quality of life was impaired in patients with collagenous colitis compared with a background population. Disease activity is the most important factor associated with impairment of health-related quality of life. Patients in remission have a health-related quality of life similar to a background population. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ∼20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease. [ABSTRACT FROM AUTHOR]

Objective. Disease-related worries constitute an important dimension of patient-reported perception of health status in inflammatory bowel disease (IBD). The Rating Form of IBD Patient Concerns (RFIPC) questionnaire is purported to measure IBD-related worries. This study evaluated the psychometric properties of a Swedish translation of RFIPC in an unselected population of Crohn's disease (CD) patients. The degree and nature of the worries were characterized and predictive factors for outcome of RFIPC and underlying dimensions were identified. Material and Methods. The RFIPC was completed by 447 CD patients in conjunction with regular visits. A physician global assessment of disease activity and four other health-related quality of life (HRQL) questionnaires were used for construct validity. Reliability and responsiveness were evaluated with follow-up visits. Underlying dimension and predictive factors were identified with factor analysis and multiple linear regression analysis. Results. Test-retest reliability was 0.90, correlation with corresponding HRQL measures 0.60–0.80 and responsiveness ratio 0.84. Median RFIPC sum score was lower than in previous studies. Top three concerns were ostomy, energy level and bowel control. Four dimensions were identified in descending order of concern: disease-related complications, daily-life achievements, intimacy, and stigmatization. Predictors of RFIPC score were disease activity, gender, and BMI ( p < 0.001–0.008). Conclusions. The Swedish version of RFIPC exhibited an adequate psychometric performance in CD patients, but was less sensitive to change in disease activity. The patients were more concerned about complications and achievement than intimacy and stigmatization. The strongest predictors of more worry were active disease, female gender and higher BMI. [ABSTRACT FROM AUTHOR]

The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention. [ABSTRACT FROM AUTHOR]

Objective. Selective leukocyte apheresis is a new type of non-pharmacological treatment for patients with active ulcerative colitis and Crohn's disease. Preliminary data have indicated that this type of therapy is safe and efficacious, and large sham-controlled studies are currently in progress. In Scandinavia, a substantial number of patients with chronic inflammatory bowel disease have already received leukocyte apheresis on a compassionate use basis and the aim of this study was to report the clinical outcome and adverse events in the first patients treated. Material and methods. Clinical details of the first consecutive 100 patients with inflammatory bowel disease treated with granulocyte, monocyte/macrophage (Adacolumn) apheresis in Scandinavia were prospectively registered. Median length of follow-up was 17 months, (range 5–30). Results. The study population comprised 52 patients with ulcerative colitis, 44 patients with Crohn's disease and 4 patients with indeterminate colitis. In 97 patients the indication for Adacolumn treatment was steroid-refractory or steroid-dependent disease. Clinical remission was attained in 48% of the patients with ulcerative colitis, and an additional 27% had a clinical response to the apheresis treatment. The corresponding figures for patients with Crohn's disease were 41% and 23%, respectively. Complete steroid withdrawal was achieved in 27 out of the 50 patients taking corticosteroids at baseline. Adverse events were reported in 15 patients and headache was most frequently reported (n=7). Conclusions. Granulocyte, monocyte/macrophage apheresis treatment seems to be a valuable adjuvant therapy in selected patients with refractory inflammatory bowel disease. The risk for toxicity or severe adverse events appears to be low. [ABSTRACT FROM AUTHOR]

Objective. Health-related quality of life (HRQoL) is an important measure of inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the validity, reliability and responsiveness of the Swedish translation of the IBDQ in patients with Crohn's disease (CD). Material and methods. Four hundred and forty-eight patients with CD completed the IBDQ and three other HRQoL questionnaires (Rating Form of IBD Patient Concerns; Short Form-36; and the Psychological General Well-Being Index) in connection with their regular visit at the outpatient clinic. Disease activity was assessed by the physician on a 4-point Likert scale. Thirty-two patients who were stable in remission completed the questionnaires a second time, 4 weeks later. A total of 418 patients repeated all measurements after 6 months. Results. The dimensional scores were highly correlated with other measures of corresponding aspects of HRQoL and were significantly better in remission than in relapse. High test–retest correlations indicated good reliability. Responsiveness was confirmed in patients whose disease activity changed over time. However, high correlations between the dimensions, poor correlations between items within each dimension, and factor analysis all indicated that the original grouping of the items is not valid for Swedish CD patients. Conclusions. Although the Swedish IBDQ has good external validity, reliability and responsiveness for patients with CD, our results did not support the original grouping of the items. [ABSTRACT FROM AUTHOR]

Summarizes clinical studies on the genetic predisposition to Crohn's disease and focuses on the clinical characteristics of familial Crohn's disease. Familial aggregation of inflammatory bowel disease; Clinical data supporting a genetic predisposition in inflammatory bowel disease; Genetics and clinical characteristics of Crohn's disease.

Background & Aims: The composition of the gastrointestinal microbiota is thought to have an important role in the etiology of inflammatory bowel diseases (IBDs) such as Crohn''s disease (CD) and ulcerative colitis (UC). Interindividual variation and an inability to detect less abundant bacteria have made it difficult to correlate specific bacteria with disease. Methods: We used 454 pyrotag sequencing to determine the compositions of microbial communities in feces samples collected from a cohort of 40 twin pairs who were concordant or discordant for CD or UC, and in mucosal samples from a subset of the cohort. The cohort primarily comprised patients who were in remission, but also some with active disease. Results: The profiles of the microbial community differed with disease phenotypes; relative amounts of bacterial populations correlated with IBD phenotypes. The microbial compositions of individuals with CD differed from those of healthy individuals, but were similar between healthy individuals and individuals with UC. Profiles from individuals with CD that predominantly involved the ileum differed from those with CD that predominantly involved the colon; several bacterial populations increased or decreased with disease type. Changes specific to patients with ileal CD included the disappearance of core bacteria, such as Faecalibacterium and Roseburia, and increased amounts of Enterobacteriaceae and Ruminococcus gnavus. Conclusions: Bacterial populations differ in abundance among individuals with different phenotypes of CD. Specific species of bacteria are associated with ileal CD; further studies should investigate their role in pathogenesis. [Copyright &y& Elsevier]

Background: A history of appendectomy is rare in patients with ulcerative colitis. This suggests a protective effect of appendectomy or that appendicitis and ulcerative colitis are alternative inflammatory responses. We sought to characterize this inverse relation further. Methods: We studied a cohort of 212,963 patients who underwent appendectomy before the age of 50 years between 1964 and 1993 and a cohort of matched controls who were identified from the Swedish Inpatient Register and the nationwide census. The cohort was followed until 1995 for any subsequent diagnosis of ulcerative colitis. Results: Patients who underwent appendectomy for appendicitis and mesenteric lymphadenitis had a low risk of ulcerative colitis (for patients with perforated appendicitis, the adjusted hazard ratio was 0.58 [95 percent confidence interval, 0.38 to 0.87]; for those with nonperforated appendicitis it was 0.76 [95 percent confidence interval, 0.65 to 0.90]; and for those with mesenteric lymphadenitis it was 0.57 [95 percent confidence interval, 0.36 to 0.89]). In contrast, patients who underwent appendectomy for nonspecific abdominal pain had the same risk of ulcerative colitis as the controls (adjusted hazard ratio, 1.06; 95 percent confidence interval, 0.74 to 1.52). For the patients who had appendicitis, an inverse relation with the risk of ulcerative colitis was found only for those who underwent surgery before the age of 20 years (P<0.001). Conclusions: Appendectomy for an inflammatory condition (appendicitis or lymphadenitis) but not for nonspecific abdominal pain is associated with a low risk of subsequent ulcerative colitis. This inverse relation is limited to patients who undergo surgery before the age of 20 years. (N Engl J Med 2001;344:808-14.) [ABSTRACT FROM AUTHOR]