Annemarie Broderick

Rapid rise in incidence of Irish paediatric inflammatory bowel disease

Aims To describe the change in incidence of paediatric inflammatory bowel disease (IBD) observed at the National Centre for Paediatric Gastroenterology, Hepatology and Nutrition, and to determine whether the presenting disease phenotype and disease outcomes have changed during the past decade. Methods The annual incidence of IBD in Irish children aged <16 years was calculated for the years 2000–2010. Two subsets of patients, group A (diagnosed between 1 January 2000 and 31 December 2001), and group B (diagnosed between 1 January and 31 December 2008) were phenotyped according to the Paris Classification. Phenotype at diagnosis and 2-year follow-up were then compared. Results 406 new cases of IBD were identified. The incidence was 2.5/100 000/year in 2001, 7.3 in 2008 and 5.6 in 2010, representing a significant increase in the number of new cases of Crohns disease (CD) and ulcerative colitis (UC). There were 238 cases of CD; 129 of UC; and 39 of IBD unclassified. Comparing groups A and B, no differences were found in disease location at diagnosis or, for CD, in its behaviour. Conclusions There has been a substantial and sustained increase in the incidence of childhood UC and CD in Ireland over a relatively short period of time. However, disease phenotype at diagnosis has not changed. At 2 years follow-up, CD appears to progress less frequently than in some neighbouring countries. These variations remain unexplained. Prospective longitudinal studies will help to elucidate further the epidemiology of childhood IBD.

Outcome in Cystic Fibrosis Liver Disease

OBJECTIVES:Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD.METHODS:This is a 7-year follow-up of 42 children with CFLD and their age- and sex-matched controls. Participants were reviewed clinically, biochemically, and radiologically at follow-up.RESULTS:Overall, 85% (72 of 84) of the original cohort were included, 36 CFLD participants and 36 CF controls. There was no significant difference in the number of deaths/transplants between groups (7 of 36 (19.4%) CFLD participants, 3 of 36 (8.3%) CF controls). There was a tendency for participants with CFLD to die younger than their respective CF controls. There was no difference in height, weight, body mass index, or pulmonary function between the groups. Nutritional parameters (sum skinfold thickness 31.6 vs. 42.3, P=0.03; mean upper arm fat area 15.08 vs. 10.59, P=0.001; Shwachman score 43.7 vs. 32.1, P=0.001) were worse among CFLD participants than among CF controls. Cystic fibrosis-related diabetes was more common in CFLD participants (11 of 27 (40.7%) vs. 5 of 33 (15.2%), P=0.02). Eight children (22.2%) with evidence of CFLD at baseline had no clinical evidence of liver disease as adults.CONCLUSIONS:Patients with CFLD have a more severe CF phenotype than do CF patients without liver disease. However, a subgroup of children with CFLD will not manifest clinically significant liver disease as adults.

The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long‐term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long‐term outcome. We identified 781 patients, median age 12 years, with 4,277 person‐years of follow‐up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event‐free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma‐glutamyltransferase, and aspartate aminotransferase‐to‐platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC–inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5‐0.9, and 0.7, 95% confidence interval 0.5‐0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long‐term outcome. Conclusion: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma‐glutamyltransferase, and aspartate aminotransferase‐to‐platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC–inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518–527).

Disease outcome for children who present with oral manifestations of Crohn's disease.

BACKGROUND: At the time of diagnosis of Crohn’s disease there may be oral manifestations. The aim of this study was to describe the outcome for children with oral Crohn’s disease (OCD) at diagnosis, and to determine if there was a difference in the Paediatric Crohn’s Disease Activity Index (PCDAI) scores between those with and those without oral lesions at follow-up. METHODS: Thirty-one patients with OCD who had enrolled in two previous studies were invited to participate. Clinical and laboratory data were collected to calculate the PCDAI. Details of the management of Crohn’s disease were also recorded. RESULTS: Twenty-four of 31 patients participated (77%), of whom 17 were boys (M:F = 2.4:1). Mean age at follow-up was 15.7 years (SD 1.98, range 11.9–19.7 years). Mean duration of follow-up was 55 months (SD 22, range 20–97 months). Oral manifestations were present at follow-up in 7 (29%) of 24 patients. There were no differences between patients with and without OCD at follow-up with regard to medical treatments received or intestinal disease location. There was no difference in median PCDAI scores between those who had and those who had not oral lesions at follow-up. CONCLUSIONS: OCD resolved in the majority of children treated for intestinal Crohn’s disease. The occurrence of mouth lesions during follow-up of children who had oral manifestations at initial diagnosis was not a marker for Crohn’s disease activity elsewhere in the intestinal tract.

Outcome in patients with cystic fibrosis liver disease

BACKGROUND Liver disease is an important complication in CF. AIMS To determine if CFLD is a risk factor for mortality in CF, and which baseline characteristics predict all-cause mortality. METHODS Irish children with CFLD, and their age and gender matched controls were enrolled at baseline and reviewed after 10years to determine which characteristics predict mortality. RESULTS 72/84 (85.71%) participants were followed, (mean age Cases 21.71yrs SD 6.5, CF controls 23.62 SD 5.6, 22 (61%) males), with no difference in duration of follow-up. Nineteen participants (26.4%) died, 38.9% (14/36) with CFLD and 13.89% (5/36) CF controls (Odds Ratio (OR) 3.94 95% CI:1.23-12.56 p=0.005). In logistic regression, liver disease (OR 4.28 95% CI 1.07-17.16) female gender (OR 12.25 95% CI 2.37-63.24), reduced pulmonary function, (OR 5.11 95% CI 1.09-23.81) were each independent risk factors for mortality in CF. CONCLUSIONS Liver disease is an independent risk factor for mortality in CF.

A rising incidence and poorer male outcomes characterise early onset paediatric inflammatory bowel disease

The incidence of paediatric inflammatory bowel disease diagnosed before age 10 years is reportedly increasing, but national data are limited.

Cryptogenic, Multifocal, Ulcerous, and Stenosing Enteritis as a Manifestation of Enterocolic Venopathy

Cryptogenic, multifocal, ulcerous and stenosing enteritis (CMUSE) is a poorly understood and exceptionally rare disease typically characterized by the presence of multifocal persistent small bowel ulceration and stenosis (1). Some of the features of CMUSE point to a vascular etiology, although to da

Cyclical vomiting syndrome in children: a prospective study.

Background  Cyclical vomiting syndrome (CVS) is a disorder that affects all ages and is characterized by episodes of severe nausea and vomiting with symptom‐free intervals between episodes. The incidence in children is 3.15/100 000 children per year. Our objective was to evaluate the natural history of CVS and examine factors that predict symptom resolution.

Giant inflammatory polyposis coli as a manifestation of Crohn's disease in patients with coexistent cystic fibrosis.

Crohns disease (CD) arising in children with cystic fibrosis (CF) is well recognized. Indeed, reports suggest that CD is significantly more common in patients with CF than in the general population. Giant inflammatory polyposis is a rare manifestation of idiopathic inflammatory bowel disease and may complicate both ulcerative colitis and CD. Giant inflammatory polyposis has not been specifically reported in patients with coexistent CF and CD. Herein, we report the occurrence of giant inflammatory polyposis in 2 boys attending a tertiary care hospital, with an established diagnosis of CF who subsequently developed CD. Both boys required surgical treatment for CD. In addition to classical features of CD, both colonic resection specimens showed giant inflammatory polyposis. The appearances were modified by the presence of a layer of thick mucus. It is suggested that the coexistence of CF in patients with CD may predispose to the development of giant inflammatory polyposis. In addition to contributing to their development, it also appears that there is a propensity for CF to alter the morphological appearance of giant inflammatory polyposis. This may lead to diagnostic confusion when examining endoscopic biopsies.

Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long‐term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event‐free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver‐related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P= not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P= 0.002), but 5‐year event‐free survival was similar (74% versus 77%, P= NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5‐year event‐free survival was better (91% versus 67%, P< 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5‐year event‐free survival 88% versus 61%, P= 0.005). Conclusion:A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5‐year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.