Challenges in the Pediatric Celiac Disease Diagnosis: An Up-to-Date Review

Celiac disease (CD) is an autoimmune disorder that affects genetically susceptible individuals, characterized by specific serological and histological features, and is triggered by the consumption of gluten. The current diagnosis is based on the demonstration of intestinal damage in small bowel biopsies, as well as the serological presence of CD-specific antibodies (usually IgA) against tissue transglutaminase (tTG), deamidated gliadin peptides (DGP), and endomysium (EMA). The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), in the 2020 updated guidelines, states that the diagnosis of CD in children and adolescents can be established without a biopsy if they have IgA tTG2 >10 ULN confirmed by positive IgA endomysial antibodies on two separate blood tests. Challenges, though, arise in serological and clinical diagnosis: in several cases false-positive results are observed. False-negative serological tests may also occur in children < 2 years of age, in patients adhering to a gluten-free diet, in individuals on immunosuppressive therapy, in cases of selective IgA deficiency, and finally due to potential laboratory errors. CD has a wide range of clinical manifestations, either gastrointestinal or extraintestinal. However, CD may be clinically silent and diagnosed through screening. Delayed diagnosis and treatment can lead to serious complications. Therefore, understanding and awareness of these challenges is imperative. Hence, the aim of this review is to highlight the diagnostic challenges of celiac disease in children and adolescents and stress the importance of prompt recognition in order to ensure appropriate management and prevention of complications.