학술논문
Non-responsive celiac disease in children on a gluten free diet.
Document Type
Academic Journal
Author
Veeraraghavan G; Division of Gastro-enterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States.; Therrien A; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States.; Degroote M; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States.; McKeown A; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States.; Mitchell PD; Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA 02115, United States.; Silvester JA; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States.; Leffler DA; The Celiac Center, Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States.; Leichtner AM; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States.; Kelly CP; The Celiac Center, Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States.; Weir DC; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States. dascha.weir@childrens.harvard.edu.
Source
Publisher: Baishideng Publishing Group Country of Publication: United States NLM ID: 100883448 Publication Model: Print Cited Medium: Internet ISSN: 2219-2840 (Electronic) Linking ISSN: 10079327 NLM ISO Abbreviation: World J Gastroenterol Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Non-responsive celiac disease (NRCD) is defined as the persistence of symptoms in individuals with celiac disease (CeD) despite being on a gluten-free diet (GFD). There is scant literature about NRCD in the pediatric population.
Aim: To determine the incidence, clinical characteristics and underlying causes of NRCD in children.
Methods: Retrospective cohort study performed at Boston Children's Hospital (BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh III histology between 2008 and 2012 were identified in the BCH's Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo (responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.
Results: Six hundred and sixteen children were included. Ninety-one (15%) met criteria for NRCD. Most were female (77%). Abdominal pain [odds ratio (OR) 1.8 95% confidence interval (CI) 1.1-2.9], constipation (OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension (OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure (30%) and constipation (20%) being the most common causes. Other causes for NRCD included lactose intolerance (9%), gastroesophageal reflux (8%), functional abdominal pain (7%), irritable bowel syndrome (3%), depression/anxiety (3%), eosinophilic esophagitis (2%), food allergy (1%), eating disorder (1%), gastric ulcer with Helicobacter pylori (1%), lymphocytic colitis (1%), aerophagia (1%) and undetermined (13%). 64% of children with NRCD improved on follow-up.
Conclusion: NRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.
Competing Interests: Conflict-of-interest statement: Leffler DA is employed by Takeda Pharmaceuticals International Co. Kelly CP has acted as a scientific advisor to companies attempting to develop new diagnostic and management approaches for Celiac disease including Cour Pharma, Glutenostics, Innovate, Immunogenx and Takeda. He also acts as Principal Investigator on a research grant on Celiac disease supported by Aptalis. Silvester JA has served on an advisory board for Takeda Pharmaceuticals and has received research funding from Biomedal S.L., Cour Pharma and Glutenostics.
(©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)
Aim: To determine the incidence, clinical characteristics and underlying causes of NRCD in children.
Methods: Retrospective cohort study performed at Boston Children's Hospital (BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh III histology between 2008 and 2012 were identified in the BCH's Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo (responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.
Results: Six hundred and sixteen children were included. Ninety-one (15%) met criteria for NRCD. Most were female (77%). Abdominal pain [odds ratio (OR) 1.8 95% confidence interval (CI) 1.1-2.9], constipation (OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension (OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure (30%) and constipation (20%) being the most common causes. Other causes for NRCD included lactose intolerance (9%), gastroesophageal reflux (8%), functional abdominal pain (7%), irritable bowel syndrome (3%), depression/anxiety (3%), eosinophilic esophagitis (2%), food allergy (1%), eating disorder (1%), gastric ulcer with Helicobacter pylori (1%), lymphocytic colitis (1%), aerophagia (1%) and undetermined (13%). 64% of children with NRCD improved on follow-up.
Conclusion: NRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.
Competing Interests: Conflict-of-interest statement: Leffler DA is employed by Takeda Pharmaceuticals International Co. Kelly CP has acted as a scientific advisor to companies attempting to develop new diagnostic and management approaches for Celiac disease including Cour Pharma, Glutenostics, Innovate, Immunogenx and Takeda. He also acts as Principal Investigator on a research grant on Celiac disease supported by Aptalis. Silvester JA has served on an advisory board for Takeda Pharmaceuticals and has received research funding from Biomedal S.L., Cour Pharma and Glutenostics.
(©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)