Evidence Supporting Serology-based Pathway for Diagnosing Celiac Disease in Asymptomatic Children From High-risk Groups

Objective:The European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines for diagnosing celiac disease (CD) in children were modified in 2012. They recommend that in symptomatic children with anti-tissue transglutaminase antibody (anti-tTG) titer of >10 times upper limit of normal (>10x ULN) and who have positive anti-endomysial antibody and HLA-DQ2/DQ8 haplotype, the diagnosis of CD can be based on serology. The aim of this study is to establish whether serology-based pathway of the ESPGHAN guidelines could also be reliably applied to asymptomatic children from high-risk groups.Methods:From March 2007 to February 2017, prospective data on anti-tTG titer, age, sex, and reason for screening were collected at diagnostic endoscopy on all asymptomatic children being diagnosed as having CD. The relationship between modified Marsh-Oberhuber classification histological grading and contemporaneous anti-tTG titers was analyzed.Results:A total of 157 asymptomatic children were diagnosed as having CD. Eighty-four of 157 (53.5%) had antitTG >10x ULN (normal <10IU/mL) and 75 of 84 were from high-risk groups. All 75 had definitive histological evidence (Marsh-Oberhuber 3a-3c) of small bowel enteropathy. Fifty-three of 84 children had anti-tTG >200IU/mL and total villous atrophy was present in 29 of 53 (55%). Main reasons for serological screening were: type-1 diabetes mellitus (n=36) and first-degree relatives with CD (n=24). Mean age at diagnosis was 8.8 years. Serology-based diagnosis is cost-beneficial by around 1275 per child in the United Kingdom.Conclusions:All 75 asymptomatic children from high-risk groups with anti-tTG >10x ULN had histology-proven CD. This study provides further evidence that the guidelines for diagnosing CD by the serology-based pathway should be extended to these children.