Margreet Wessels1, Anouk Velthuis2, Ellen van Lochem3, Eline Duijndam2, Gera Hoorweg-Nijman4, Ineke de Kruijff4, Victorien Wolters5, Eveline Berghout6, Jos Meijer7, Jan Alle Bokma8, Dick Mul9, Janielle van der Velden10, Lian Roovers11, M Luisa Mearin12, Petra van Setten2. 1. Department of Pediatrics, Rijnstate Hospital, Arnhem, The Netherlands; Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. 2. Department of Pediatrics, Rijnstate Hospital, Arnhem, The Netherlands. 3. Department of Medical Microbiology and Immunology, Rijnstate Hospital, Arnhem, The Netherlands. 4. Department of Pediatrics, St Antonius Hospital, Utrecht, The Netherlands. 5. Department of Pediatric Gastroenterology, University Medical Center Utrecht-Wilhelmina Children's Hospital, Utrecht, The Netherlands. 6. Department of Pediatrics, Deventer Hospital, Deventer, The Netherlands. 7. Department of Pathology, Rijnstate Hospital, Arnhem, The Netherlands. 8. Department of Pediatrics, Spaarne Hospital, Hoofddorp, The Netherlands. 9. Department of Pediatrics, Haga Hospital (Juliana Children's Hospital), The Hague, The Netherlands. 10. Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. 11. Clinical Research Department, Rijnstate Hospital, Arnhem, The Netherlands. 12. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
OBJECTIVE: To study the optimal cut-off value for anti-tissue transglutaminase type 2 IgA antibodies (TG2A) in serum to select for diagnostic small bowel biopsies for celiac disease in children with type 1 diabetes mellitus. STUDY DESIGN: Children with type 1 diabetes mellitus with elevated TG2A titers and duodenal biopsies performed during the course of their diabetes treatment were included. Anti-endomysial antibodies were recorded if present. The optimal TG2A cut-off value, expressed as the ratio between obtained value and upper limit of normal (ULN), was determined using receiver operating characteristic curve analysis and compared with the cut-off value used in the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines in terms of sensitivity, specificity, positive and negative predictive value. RESULTS: We included 63 children. The optimal cut-off value for performing biopsies is demonstrated to be 11 times the ULN. Raising the cut-off value from 3 times the ULN to 11 times the ULN changed sensitivity from 96% to 87% and increased specificity from 36% to 73%, increased the positive predictive value from 88% to 94% and lowered negative predictive value from 67% to 53%. The percentage of normal histology was decreased from 12% to 6%. CONCLUSIONS: Increasing the TG2A cut-off value for performing duodenal biopsies in children with type 1 diabetes mellitus and suspected celiac disease leads to a substantial reduction of unnecessary biopsies. We advocate to adapt the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2012 guidelines for this group of children, including monitoring patients with TG2A levels of less than 11 times the ULN over time.
OBJECTIVE: To study the optimal cut-off value for anti-tissue transglutaminase type 2 IgA antibodies (TG2A) in serum to select for diagnostic small bowel biopsies for celiac disease in children with type 1 diabetes mellitus. STUDY DESIGN: Children with type 1 diabetes mellitus with elevated TG2A titers and duodenal biopsies performed during the course of their diabetes treatment were included. Anti-endomysial antibodies were recorded if present. The optimal TG2A cut-off value, expressed as the ratio between obtained value and upper limit of normal (ULN), was determined using receiver operating characteristic curve analysis and compared with the cut-off value used in the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines in terms of sensitivity, specificity, positive and negative predictive value. RESULTS: We included 63 children. The optimal cut-off value for performing biopsies is demonstrated to be 11 times the ULN. Raising the cut-off value from 3 times the ULN to 11 times the ULN changed sensitivity from 96% to 87% and increased specificity from 36% to 73%, increased the positive predictive value from 88% to 94% and lowered negative predictive value from 67% to 53%. The percentage of normal histology was decreased from 12% to 6%. CONCLUSIONS: Increasing the TG2A cut-off value for performing duodenal biopsies in children with type 1 diabetes mellitus and suspected celiac disease leads to a substantial reduction of unnecessary biopsies. We advocate to adapt the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2012 guidelines for this group of children, including monitoring patients with TG2A levels of less than 11 times the ULN over time.
Authors: Mara Cerqueiro Bybrant; Elin Udén; Filippa Frederiksen; Anna L Gustafsson; Carl-Göran Arvidsson; Anna-Lena Fureman; Gun Forsander; Helena Elding Larsson; Sten A Ivarsson; Marie Lindgren; Johnny Ludvigsson; Claude Marcus; Auste Pundziute Lyckå; Martina Persson; Ulf Samuelsson; Stefan Särnblad; Karin Åkesson; Eva Örtqvist; Annelie Carlsson Journal: Pediatr Diabetes Date: 2020-12-12 Impact factor: 4.866