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1. Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN

Author

Oliva, Salvatore, Dias, Jorge Amil, Rea, Francesca, Malamisura, Monica, Espinheira, Maria Céu, Papadopoulou, Alexandra, Koutri, Eleni, Rossetti, Danilo, Orel, Rok, Homan, Matjaž, Bauraind, Olivia, Auth, Marcus Karl-Heinz, Junquera, Carolina Gutierrez, Vande Velde, Saskia, Kori, Michal, Huysentruyt, Koen, Urbonas, Vaidotas, Roma, Eleftheria, Fernández, Sonia Fernández, Domínguez-Ortega, Gloria, Zifman, Eyal, Kafritsa, Panayota, Miele, Erasmo, Zevit, Noam, Oliva, Salvatore, Dias, Jorge Amil, Rea, Francesca, Malamisura, Monica, Espinheira, Maria Céu, Papadopoulou, Alexandra, Koutri, Eleni, Rossetti, Danilo, Orel, Rok, Homan, Matjaž, Bauraind, Olivia, Auth, Marcus Karl-Heinz, Junquera, Carolina Gutierrez, Vande Velde, Saskia, Kori, Michal, Huysentruyt, Koen, Urbonas, Vaidota, Roma, Eleftheria, Fernández, Sonia Fernández, Domínguez-Ortega, Gloria, Zifman, Eyal, Kafritsa, Panayota, Miele, Erasmo, Zevit, Noam, Clinical sciences, Growth and Development, and Pediatrics

Subjects
Proton Pump Inhibitors/therapeutic use, Male, Delayed Diagnosis, Adolescent, gastroenterology, Proton Pump Inhibitors, Eosinophilic Esophagitis, Endoscopy, Gastrointestinal, Enteritis, Eosinophilic Esophagitis/complications, Child, Preschool, Gastritis, Pediatrics, Perinatology and Child Health, Eosinophilia, Humans, Female, Deglutition Disorders/drug therapy, Pediatrics, Perinatology, and Child Health, Registries, Child, Deglutition Disorders, Food Hypersensitivity
Abstract

OBJECTIVES: Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. METHODS: pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. RESULTS: A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age

Published
2022

2. Pediatric Eosinophilic Esophagitis: Results of the European Retrospective Pediatric Eosinophilic Esophagitis Registry (RetroPEER)

Author

Michal Kori, Noam Zevit, Sonny K. F. Chong, Jorge Amil Dias, Carolina G Junquera, Alexandra Papadopoulou, Claudio Romano, Víctor Vila Miravet, Andrzej Załęski, Gloria Domínguez-Ortega, Luba Marderfeld, Salvatore Oliva, Vaidotas Urbonas, Frédéric Gottrand, Marcus Auth, Sebastian Otte, Johanna H. Oudshoorn, Assaf Hoofien, Monica Malamisura, Maria Jm Gomez, Francesca Rea, Rok Orel, Roger Garcia-Puig, Mark Furman, Saskia Vande Velde, Amir Ben Tov, Nicolas Kalach, Erasmo Miele, Eleftheria Roma, Danielle Nijenhuis-Hendriks, Hoofien, Assaf, Dias, Jorge A, Malamisura, Monica, Rea, MARTINA FRANCESCA, Chong, Sonny, Oudshoorn, Johanna, Nijenhuis-Hendriks, Danielle, Otte, Sebastian, Papadopoulou, Alexandra, Romano, Claudio, Gottrand, Frederic, Miravet, Victor V, Orel, Rok, Oliva, Salvatore, Junquera, Carolina G, Załęski, Andrzej, Urbonas, Vaidota, Garcia-Puig, Roger, Gomez, Maria J M, Dominguez-Ortega, Gloria, Auth, Marcus K-H, Kori, Michal, Ben Tov, Amir, Kalach, Nicola, Velde, Saskia V, Furman, Mark, Miele, Erasmo, Marderfeld, Luba, Roma, Eleftheria, and Zevit, Noam

Subjects
Male, medicine.medical_specialty, Adolescent, proton pump inhibitor, medicine.drug_class, MEDLINE, Proton-pump inhibitor, eosinophilic esophagitis, 03 medical and health sciences, 0302 clinical medicine, children, Food allergy, 030225 pediatrics, medicine, Humans, Registries, Child, Eosinophilic esophagitis, Retrospective Studies, allergen, Eosinophilic Oesophagitis, Children, business.industry, Gastroenterology, Retrospective cohort study, respiratory system, medicine.disease, Dermatology, Europe, Clinical Practice, Multicenter study, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, 030211 gastroenterology & hepatology, business
Abstract

OBJECTIVES: Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children. METHODS: Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were: Patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions. RESULTS: In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12 ± 33.5 months and age at diagnosis was 8.9 ± 4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines. CONCLUSIONS: In this "real world" pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal.

Published
2019
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3. Vaccinations and immunization status in pediatric inflammatory bowel disease: a multicenter study from the pediatric IBD Porto Group of the ESPGHAN

Author

Malgorzata Sladek, Gábor Veres, Marina Aloi, Massimo Martinelli, Tereza Lerchova, Iva Hojsak, Caterina Strisciuglio, Víctor Manuel Navas-López, Claudio Romano, Vaidotas Urbonas, F.P. Giugliano, Aleksandra Banaszkiewicz, Daniela Elena Serban, Ruta Kucinskiene, Erasmo Miele, Amit Assa, Graduate School, Tytgat Institute for Liver and Intestinal Research, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Martinelli, M., Giugliano, F. P., Strisciuglio, C., Urbonas, V., Serban, D. E., Banaszkiewicz, A., Assa, A., Hojsak, I., Lerchova, T., Navas-López, V. M., Romano, C., Sladek, M., Veres, G., Aloi, M., Kucinskiene, R., Miele, E., Martinelli, Massimo, Giugliano, Francesca Paola, Strisciuglio, Caterina, Urbonas, Vaidota, Serban, Daniela Elena, Banaszkiewicz, Aleksandra, Assa, Amit, Hojsak, Iva, Lerchova, Tereza, Navas-López, Víctor Manuel, Romano, Claudio, Sladek, Małgorzata, Veres, Gabor, Aloi, Marina, Kucinskiene, Ruta, and Miele, Erasmo

Subjects
Male, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Pediatrics, medicine.medical_specialty, pediatrics, Azathioprine, vaccinations, Opportunistic Infections, Measles, Rubella, Crohn Disease, Latent Tuberculosis, inflammatory bowel disease, Humans, Immunology and Allergy, Medicine, Child, Immunization Schedule, Retrospective Studies, Chickenpox, Latent tuberculosis, business.industry, Vaccination, Inflammatory bowel disease, pediatrics, vaccinations, Gastroenterology, Retrospective cohort study, Mycobacterium tuberculosis, Inflammatory Bowel Diseases, medicine.disease, pediatric, Immunization, Colitis, Ulcerative, Female, Guideline Adherence, business, Immunosuppressive Agents, medicine.drug
Abstract

BackgroundVaccine-preventable diseases and opportunistic infections in pediatric inflammatory bowel disease (IBD) are increasingly recognized issues. The aims of this study were to evaluate vaccinations, immunization status, and consequent therapeutic management in children with IBD and to analyze the differences among patients diagnosed before (Group 1) and after June 2012 (Group 2).MethodsThis was a multicenter, retrospective cohort investigation. Between July 2016 and July 2017, 430 children with IBD were enrolled in 13 centers. Diagnosis, therapeutic history, vaccinations, and immunization status screening at diagnosis and at immunosuppressant (IM)/biologic initiation and reasons for incomplete immunization were retrieved.ResultsVaccination rates at diagnosis were unsatisfactory for measles, mumps, and rubella (89.3%), Haemophilus influenzae (81.9%), meningococcus C (23.5%), chickenpox (18.4%), pneumococcus (18.6%), papillomavirus (5.9%), and rotavirus (1.9%). Complete immunization was recorded in 38/430 (8.8%) children, but specific vaccines were recommended in 79/430 patients (18.6%), without differences between the 2 groups. At IM start, 22% of children were tested for Epstein-Barr virus (EBV) status, with 96.2% of EBV-naïve patients starting azathioprine, without differences between Groups 1 and 2. Screening for latent tuberculosis (TB) before start of biologics was performed in 175/190 (92.1%), with up to 9 different screening strategies and numerous inconsistencies.ConclusionsWe demonstrated a poor immunization status at diagnosis in children with IBD, which was not followed by proper vaccination catch-up. EBV status before IM initiation and latent TB before biologics were not adequately assessed. Thus, the overall impact of the current guidelines seems unsatisfactory.

Published
2019

4. Diagnostic yield of next-generation sequencing in very early-onset inflammatory bowel diseases: A multicentre study

Author

Charbit-Henrion, Fabienne, Parlato, Marianna, Hanein, Sylvain, Duclaux-Loras, Remi, Nowak, Jan, Bègue, Bernadette, Rakotobe, Sabine, Bruneau, Julie, Fourrage, Cécile, Alibeu, Olivier, Rieux-Laucat, Frédéric, Lévy, Eva, Stolzenberg, Marie-Claude, Mazerolles, Fabienne, Latour, Sylvain, Lenoir, Christelle, Fischer, Alain, Picard, Capucine, Aloi, Marina, Amil Dias, Jorge, Ben Hariz, Mongi, Bourrier, Anne, Breuer, Christian, Breton, Anne, Bronski, Jiri, Buderus, Stephan, Cananzi, Mara, Coopman, Stéphanie, Crémilleux, Clara, Dabadie, Alain, Dumant-Forest, Clémentine, Egritas Gurkan, Odul, Fabre, Alexandre, Fischer, Aude, German Diaz, Marta, Gonzalez-Lama, Yago, Goulet, Olivier, Guariso, Graziella, Gurcan, Neslihan, Homan, Matjaz, Hugot, Jean-Pierre, Jeziorski, Eric, Karanika, Evi, Lachaux, Alain, Lewindon, Peter, Lima, Rosa, Magro, Fernando, Major, Janos, Malamut, Georgia, Mas, Emmanuel, Mattyus, Istvan, Mearin, Luisa, Melek, Jan, Navas-Lopez, Victor Manuel, Paerregaard, Anders, Pelatan, Cecile, Pigneur, Bénédicte, Pinto Pais, Isabel, Rebeuh, Julie, Romano, Claudio, Siala, Nadia, Strisciuglio, Caterina, Tempia-Caliera, Michela, Tounian, Patrick, Turner, Dan, Urbonas, Vaidotas, Willot, Stéphanie, Ruemmele, Frank, Cerf-Bensussan, Nadine, Charbit-Henrion, Fabienne, Parlato, Marianna, Hanein, Sylvain, Duclaux-Loras, Rémi, Nowak, Jan, Begue, Bernadette, Rakotobe, Sabine, Bruneau, Julie, Fourrage, Cécile, Alibeu, Olivier, Rieux-Laucat, Frédéric, Lévy, Eva, Stolzenberg, Marie-Claude, Mazerolles, Fabienne, Latour, Sylvain, Lenoir, Christelle, Fischer, Alain, Picard, Capucine, Aloi, Marina, Dias, Jorge Amil, Hariz, Mongi Ben, Bourrier, Anne, Breuer, Christian, Breton, Anne, Bronski, Jiri, Buderus, Stephan, Cananzi, Mara, Coopman, Stéphanie, Crémilleux, Clara, Dabadie, Alain, Dumant-Forest, Clémentine, Gurkan, Odul Egrita, Fabre, Alexandre, Fischer, Aude, Diaz, Marta German, Gonzalez-Lama, Yago, Goulet, Olivier, Guariso, Graziella, Gurcan, Neslihan, Homan, Matjaz, Hugot, Jean-Pierre, Jeziorski, Eric, Karanika, Evi, Lachaux, Alain, Lewindon, Peter, Lima, Rosa, Magro, Fernando, Major, Jano, Malamut, Georgia, Mas, Emmanuel, Mattyus, Istvan, Mearin, Luisa M, Melek, Jan, Navas-Lopez, Victor Manuel, Paerregaard, Ander, Pelatan, Cecile, Pigneur, Bénédicte, Pais, Isabel Pinto, Rebeuh, Julie, Romano, Claudio, Siala, Nadia, Strisciuglio, Caterina, Tempia-Caliera, Michela, Tounian, Patrick, Turner, Dan, Urbonas, Vaidota, Willot, Stéphanie, Ruemmele, Frank M., Cerf-Bensussan, Nadine, Laboratory of Intestinal Immunity (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), The Clinical Bioinformatics laboratory (Equipe Inserm U1163), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), GENIUS Group, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Pédiatrie, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Gastroentérologie-Hépatologie et Nutrition Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Hospital de São João [Porto], Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Le Mans (CH Le Mans), University of Messina, Department of Pediatrics, Centre Hospitalier Universitaire Mongi Slim [La Marsa], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Gastroentérologie, d'hépatologie et nutrition pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), CHU Le MAns, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, paediatric, VEO-IBD, Adolescent, monogenic disorder, Gastroenterology, High-Throughput Nucleotide Sequencing, Infant, Genetics and molecular epidemiology, Inflammatory Bowel Diseases, monogenic disorders, Corrigenda, Cohort Studies, paediatrics, Predictive Value of Tests, Child, Preschool, TNGS, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Age of Onset, Child, Genetics and molecular epidemiology, monogenic disorders, paediatrics, TNGS, VEO-IBD, Gastroenterology, AcademicSubjects/MED00260
Abstract

Background and Aims An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. Methods A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: Predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. Results Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. Conclusions Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.

Published
2018
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