Simon Chin

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

Inflammatory bowel disease (IBD) encompasses two related but distinct disorders of as yet unknown cause. Ulcerative colitis (UC) is a chronic, idiopathic, diffuse inflammation of the rectum that frequently may extend continuously over variable lengths of more proximal colon. The inflammation is usually restricted to the mucosa and submucosa. Crohn’s disease (CD) is a chronic, idiopathic, transmural inflammation that can affect one or several segments of the digestive tract. The predominant sites of disease are the terminal ileum, colon, and perianal region. The inflammation is often focal with involved areas adjacent to normal areas (skip lesions). In most cases, these two conditions can be distinguished after clinical, endoscopic, histopathologic, and radiologic examinations. The term indeterminate colitis is reserved for cases of colitis in which findings are not sufficient to allow differentiation between Crohn’s colitis and UC. Whether these entities represent different disease processes with related phenotypic expressions or a single disease entity with variable phenotypic expression remains to be determined. The first description of UC dates from 1859. The landmark paper by Crohn et al describing a series of patients including a 17-year-old boy dates to 1932, but patients with chronic ileitis had been previously described. The symptoms of IBD are protean, but commonly include intestinal symptoms such as abdominal pain, bloody diarrhea, poor appetite, and weight loss, and at times a wide range of extraintestinal manifestations including fever, arthritis, skin rashes, renal calculi, and hepatobiliary disease, all of which are not significantly different from adults. There are, however, distinct differences in pediatric IBD compared with adult disease, particularly in its impact on growth and its potential to delay puberty. Current opinion regarding the cause of IBD favors the hypothesis that IBD results from an interaction between immunologic, genetic, and environmental factors. A natural model for UC has been described in the cotton top tamarin. Although no natural animal CD model exists, a large number of biologic (e.g., peptidoglycan polysaccharide), chemically induced (e.g., TNBS), and genetically derived (e.g., IL-I0 knockout mice) animal models of CD have been developed. These models offer insights into the immunologic basis of IBD, which in turn have led to advances in the study of human disease. It appears that it some cases CD and UC can be differentiated immunologically on the basis of serologic findings (e.g., pANCA in UC, ASCA in CD) and cytokine profiles. CD typically is characterized by a T lymphocyte helper 1 (Thl) cytokine pattern, in which ILl, IL2, TNF and interferon-y are predominant. UC tends to be characterized by more of a T lymphocyte helper 2 (Th2) pattern. Although these models have advanced our understanding of the immunology of IBD, the cause of the human disease remains elusive. The role of pathogens as inducers of disease, such as mycobacteria or measles, remains controversial. Genetic factors play an important role, with about 15% of affected individuals having firstdegree relatives with disease. However, IBD appears to be a complex, polygenic disorder that cannot be explained by a simple Mendelian model. Current therapeutic goals in children and adolescents seek to induce and maintain clinical and histologic remission and allow children to achieve their full potential for growth, social interaction, and educational attainment. Treatment modalities and clinical responses are similar to those seen in adult patients, although there are important differences in the treatment of pediatric patients. In particular , therapies for children must be designed to promote rather than interfere with growth, sexual development, and bone mineral accretion. These therapeutic requirements have resulted in a number of The input of Maraci Rodriguez into this report is gratefully acknowledged. Journal of Pediatric Gastroenterology and Nutrition 35:S151–S158

Diagnostic utility of modified gliadin peptide antibody assays in New Zealand children.

Objective: The aim of the present study was to evaluate a panel of different antibody assays, including second-generation antigliadin kits, in a local paediatric population thought to be at risk for coeliac disease (CD). Methods: Seventy-nine children, who tested positive for immunoglobulin A (IgA) antibodies to tissue transglutaminase (TG), underwent duodenal biopsy. At endoscopy, serum was collected from all of the patients, and 9 different coeliac antibody assays were performed, both as isolated assays and in combination. These included immunoglobulin A (IgA) anti-tissue transglutaminase (TGA), and IgA plus IgG anti-deamidated gliadin peptide (DGPAG). A diagnosis of CD was made if the biopsies showed Marsh grade 3 lesions. Results: Twenty-four of 79 children had CD confirmed histologically. Only 39 of 79 were positive for Inova TGA, and 35 of 79 were positive for Inova DGPAG. Twenty-four of 39 who were TGA positive and 24 of 35 who were DGPAG positive had confirmed CD on biopsy. There was good correlation between TGA and DGPAG-positive predictive values. None of the modified gliadin tests produced false-negative results, and neither did the TGA. Conclusions: The Inova DGPAG and TGA assays have similar use in predicting CD in a selected paediatric population; however, in children who are positive for TGA when screened for CD, more than half have negative TGA serology when repeat testing is done at the time of biopsy. Those with persistent TGA positivity have only a 61.5% probability of having histologic CD, compared with 68.6% of those children positive for DGPAG.

Hodgkin disease relapse discovered at the time of liver transplant for acute liver failure

Hope BC, Chau KY, Evans HM, Mouat S, Munn S, Yeong ML, Chin SE. Hodgkin disease relapse discovered at the time of liver transplant for acute liver failure. 
Pediatr Transplantation 2012: 16: E10–E14.

Fatal hyperammonemia associated with disseminated Serratia marcescens infection in a pediatric liver transplant recipient

Hyperammonemia is a rare and important complication post‐liver transplantation. We review a case of a 5‐month‐old boy with biliary atresia who received a split liver transplant following a variceal bleed. The transplant was complicated by recurrent portal vein thrombosis. Colonized with Serratia marcescens pretransplant, he developed disseminated infection associated with very high levels of ammonia that led to his death. It is important to be aware of serum ammonia levels in patients with portal vein thrombosis, particularly in the setting of gastrointestinal bleeding and sepsis.

Point Prevalence of Pediatric Inflammatory Bowel Disease in New Zealand in 2015: Initial Results from the PINZ Study

Background: The incidence of pediatric inflammatory bowel disease (IBD) around the world is increasing. However, there is a scarcity of data on the epidemiology of pediatric IBD in the Southern Hemisphere. This study aimed to document the point prevalence of pediatric IBD in New Zealand on June 30, 2015. Methods: All patients in New Zealand, under 16 years of age, with a diagnosis of IBD on June 30, 2015 were identified. Demographic and disease phenotypic details were collected and entered into a secure database. Age-specific population data for New Zealand were obtained and national and regional prevalence rates were calculated. Results: The point prevalence of pediatric IBD, Crohns disease, ulcerative colitis, and inflammatory bowel disease unclassified in New Zealand on June 30, 2015 was (95% confidence intervals) 21.7 (18.9–24.8), 16.5 (14.0–19.2), 3.3 (2.2–4.6), and 1.9 (1.2–3.0) per 100,000 children, respectively. There was a striking disparity between the prevalence rates in the North and South Islands. Conclusions: The point prevalence of pediatric IBD in New Zealand represents the first-ever national, population-based prevalence rates of pediatric IBD published. Results from the Paediatric IBD in New Zealand (PINZ) study are also the first to show markedly higher prevalence rates of IBD in the southern part of a country compared with its northern counterpart. Ongoing prospective ascertainment of the incidence of pediatric IBD is required.