Pre-diagnostic Changes in the Metabolome of Inflammatory Bowel Disease.

Does Consuming the Recommend Daily Level of Fiber Prevent Crohn's Disease?

Diagnosis and Management of Primary Sclerosing Cholangitis

Inflammatory bowel disease in children and adolescents: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Preclinical IBD: One more piece of the puzzle

Selected Summary

Inflammatory Bowel Disease: An Update on the Fundamental Biology and Clinical Management

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Elderly Patients: Expert Review

Background Accurate, early diagnosis of Inflammatory Bowel Disease (IBD) and stratification into Crohn’s disease (CD) and Ulcerative Colitis (UC) is crucial to limit delays in diagnosis and improve IBD management. Given the increasing recognition of humoral perturbations in IBD, we aimed to characterize and potentially utilize serological profiling of anti-microbial and auto-antibodies for the diagnosis and clinical classification of patients with IBD. Methods Sera from an adult (training n = 512; validation n = 1,596 [IBD=1,039; nonIBD=557]) and a pediatric (n = 240; 189 IBD, 51 non IBD) (validation) cohort of IBD and non-IBD subjects were profiled using a panel of well characterized, putative anti-microbial (ASCA IgA/IgG, anti-OmpC IgA, anti-CBir1 IgG, anti-Fla2 IgG and anti-FlaX IgG) and autoantibodies (atypical perinuclear anti-neutrophil cytoplasmic antibodies [pANCA] with DNAse sensitive pattern, anti-proteinase 3 [PR3] IgG, and anti-αvβ6 IgG [MBL, Tokyo, Japan]). Cutoffs for positive antibody status were defined as the 95th percentile of values observed in healthy adults for all anti-microbial antibodies, or according to manufacturer (pANCA and PR3). Cutoff for anti-αvβ6 was set at > 3.1 U/mL. We summed positive serological signals and trained logistic models to distinguish IBD from non-IBD controls (step 1) and to stratify UC vs CD (step 2). Model parameters from training cohort were applied to validation cohorts. The sensitivity, specificity and area under the curve (AUC) of the receiver operating characteristic curve were determined. Results In the training cohort, AUCs were 0.85 (IBD vs non-IBD) and 0.86 (CD vs UC). In the adult validation cohort, the sensitivity to distinguish IBD from non-IBD was 80% (834/1,039) and specificity was 79% (442/557) (AUC=0.85). Among the IBD-derived samples (n = 834; 420 UC and 414 CD), discrimination between UC and CD achieved a sensitivity of 91% (383/420) and specificity of 73% (301/414) (AUC=0.87). Anti-microbial antibody positivity strongly supported CD classification, while a combination of pANCA/PR3/avβ6 antibodies were enriched UC and colonic CD (Figure 1). Performance in the pediatric cohort revealed the sensitivity of IBD vs non-IBD as 80% (152/189) and specificity as 67% (34/51) (AUC=0.80). In the IBD derived pediatric samples (n = 152), the sensitivity of distinguishing UC from CD was 93% (42/45) while the specificity was 83% (89/107) (AUC=0.96). Performances in the adult and pediatric cohorts are presented in Figure 2. Conclusion Unique serological signatures identify IBD from controls and permit the classification of specific clinical phenotypes. Validation in prospective cohorts will enable the adoption of serological profiling to help for early diagnosis and classification of IBD.

East Meets West: The Increasing Incidence of Inflammatory Bowel Disease in Asia as a Paradigm for Environmental Effects on the Pathogenesis of Immune-Mediated Disease

BackgroundThe association of autoimmune liver disease (AILD) and inflammatory bowel disease (IBD) is well documented. IBD affects about 45% of children with autoimmune sclerosing cholangitis (AISC) and about 20% of...

A Genomewide Analysis Provides Evidence for Novel Linkages in Inflammatory Bowel Disease in a Large European Cohort

Background There are no prediction models for a diagnosis of inflammatory bowel disease (IBD) in primary care. An IBD risk prediction tool has the potential to reduce the length of time patients have undiagnosed IBD symptoms and improve IBD clinical outcomes. Therefore, our aim was to develop and validate a risk prediction model for the diagnosis of IBD, ulcerative colitis (UC) and Crohn’s disease (CD) in men and women separately. Methods A population-based retrospective open cohort study using Clinical Practice Research Datalink (CPRD) Aurum database was undertaken between 1st January 2010 and 31st December 2019, including patients aged 18 years or older. Patients were followed from first presentation with lower gastrointestinal (GI) symptoms potentially related to IBD to the earliest of IBD diagnosis, loss to follow-up, death or study end. 2,054,530 patients were in the model derivation cohort and 673,320 patients in the validation cohort. Cox proportional hazards models were used to derive separate risk equations in men and women for IBD, UC and CD. Candidate predictors included demographic factors (age, sex, smoking, body mass index, Charlson comorbidity score, loperamide use), family history of IBD, co-existing conditions (anxiety, depression, irritable bowel syndrome (IBS), haemorrhoids), extraintestinal manifestations (EIM) (mouth ulcers, ophthalmic, primary sclerosing cholangitis, dermatological), investigations (hemoglobin, mean corpuscular volume, platelets, albumin, vitamin B12, ferritin, C-reactive protein, erythrocyte sedimentation rate, calprotectin level). Measures of calibration and discrimination (C-statistic and D-statistic, higher values indicate better discrimination) were determined in men and women separately in the validation cohort at 1,2,3 and 5 years after symptom presentation. Results In the derivation cohort, 15,105 (0.7%) patients had an IBD diagnosis (10.014 UC (66.3%) and 5,088 CD (33.7%)). The IBD prediction model included 41 and 40 predictors, and the UC model 37 and 36 predictors, in women and men respectively; the CD model included 37 predictors in both men and women. C-statistics and D-statistics in men were as follows: IBD model 0.77 and 1.74; UC model: 0.81 and 1.95; and CD model: 0.77 and 1.95, respectively. Similar values were observed in women.The measures of discrimination showed that the prediction models reliably differentiated patients with and without IBD, UC and CD in both sexes. Model calibration was good, tending to overestimate at higher risk thresholds in validation cohort. Conclusion A risk model of patient demographics, symptoms and investigations performs well for IBD, UC and CD and may help in prioritising suspected IBD referrals in symptomatic subjects in primary care.

Background The IBD-Disk was adapted from the Inflammatory Bowel Disease –Disability Index as a tool to capture a patient’s functional status for Health Care Professionals to review. Patients complete this disk for ten symptoms with scores ranging from 0 to 10. Patients with higher scores have a significant burden of disease. We explore correlation of IBD disk score with faecal calprotectin, endoscopic scores, and a diagnosis of IBD in patients referred to our inception clinic service. Methods Patients with symptoms compatible with Inflammatory Bowel Disease (IBD) and a raised faecal calprotectin are fast tracked to our rapid access inception clinic service for further assessment. We prospectively collected data on demographics, faecal calprotectin levels and IBD disk scores. We assessed correlation between the total score and individual components of the IBD disk score with demographics, faecal calprotectin (F.Cal) at presentation and subsequent diagnosis of IBD and endoscopic scores. Descriptive and multivariate regression analysis was performed. Results 68 patients (47% female; median age 35.5 years [IQR 16.8]) attending the inception clinic were included in this analysis. Of these patients 17/68 (25%) were diagnosed with Crohn’s disease (CD), 18/68 (26%) with ulcerative colitis (UC) and 5/68 (7%) with indeterminate colitis. 33 (33.8%) had unclear diagnoses and are currently undergoing further investigation. IBD was excluded in 5/68 (7%) patients. Younger patients (age 15 – 30 years) and patients above 60 years of age had a relatively higher F.Cal at presentation (Figure 1). The total IBD disk score was significantly higher in younger patients (p=0.03). No correlation was seen between the eventual diagnosis of IBD and total score at presentation or individual components of the IBD disk score. Multivariate regression analysis, however, demonstrated significant correlation between regulated defecation and interpersonal interactions with F.Cal at baseline in patients with IBD (p<0.05). No correlation was seen with other variables of the IBD disk and faecal calprotectin levels. IBD Disk score as well as Harvey Bradshaw index correlated well with Simple Endoscopic Score in Crohn’s disease (SES-CD) (Figure 2). No significant correlation was seen between IBD Disk score and baseline F.Cal or Endoscopic Mayo Score. The simple Mayo score showed a better correlation between F.Cal and Endoscopic Mayo score than IBD Disk. Conclusion Correlation of F.Cal with certain elements of the IBD Disk tool highlights its utility in capturing both inflammatory and non-inflammatory related disability in patients with IBD. IBD Disk Scores correlate with CD endoscopic severity scores (ie SES-CD) but not UC scores (ie Endoscopic Mayo Score).

Objectives: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn’s disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature.Methods: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed.Results: We identified 31 patients with onset of MC after a median (range) of 20 (2–52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n = 16) or lymphocytic colitis (LC) (n = 5); nine CD patients developed CC (n = 5) or LC (n = 4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients.Conclusions: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.

BackgroundProton-pump inhibitors (PPI) have an impact on gut microbiome. The use of PPI has increased since the late 1980s and between 2007-2017, there were nearly 59 million PPIs dispensed annually in France.1 Considering that inflammatory bowel disease (IBD) affects persons of all races, a disease trigger for IBD may be a factor that can directly alter the intestinal immune response, or indirectly through changes in the gut microbiome. This raises the possibility that the advent use of PPI may be associated with the worldwide rise in IBD.PurposeWe investigated whether increased use of PPI was associated with a diagnosis of IBD.MethodThe University of Manitoba IBD Epidemiology Database includes all Manitobans diagnosed with IBD between 1984 to 2018 with age, sex and geography-matched controls and comprehensive prescription drug data from April 1995. Subjects were considered to be users if they received 2 prescriptions of PPI. We assessed PPI prescriptions pre-diagnosis and for 3-years post-diagnosis of IBD. The absolute and relative rates were calculated and compared for PPI use pre- and post-IBD diagnosis.Result(s)A retrospective analysis was completed by analyzing 5920 subjects that were diagnosed with IBD after April 1996. Rates of PPI use in controls increased gradually from 1.5 to 6.5% over 15-years. Persons with IBD have a higher rate of PPI use peaking up to 17% within 1-year of IBD diagnosis with a rate ratio (RR) of 3.1 [95% CI 2.9 – 3.3]. Furthermore, persons with Crohn’s disease (CD) [RR= 4.2; 95% CI 3.7 – 4.6] were more likely to have been PPI users pre-diagnosis than persons with ulcerative colitis [RR= 2.4; 95% CI 2.2 – 2.7]. Important predictors of increased PPI use were older age, year of data collection and CD diagnosis.Conclusion(s)This retrospective analysis showed an increase in PPI use over the past 20-years among all Manitobans. Persons with IBD have higher PPI use within 1-year of their IBD diagnosis. It is possible that persons with IBD have an increase in acid peptic diseases or alternatively, the use of a PPI alters the gut microbiome increasing the risk for IBD diagnosis, or that some IBD symptoms are treated with PPI whether warranted or not. Future studies are needed to delineate whether the indication for ongoing PPI use is appropriate.