European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020

Abstract

Objectives: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated and expanded evidence-based guideline is presented. Methods: Literature databases and other sources of information were searched for studies that could inform on 10 formulated questions on symptoms, serology, human leukocyte antigen genetics, and histopathology. Eligible articles were assessed using QUADAS2. GRADE provided a basis for statements and recommendations. Results: Various symptoms are suggested for case finding, with limited contribution to diagnostic accuracy. If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations. We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing. Only if total IgA is low/undetectable, an IgG-based test is indicated. Patients with positive results should be referred to a paediatric gastroenterologist/specialist. If TGA-IgA is ≥10 times the upper limit of normal (10× ULN) and the family agrees, the no-biopsy diagnosis may be applied, provided endomysial antibodies (EMA-IgA) will test positive in a second blood sample. Human leukocyte antigen DQ2-/DQ8 determination and symptoms are not obligatory criteria. In children with positive TGA-IgA <10× ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken. Discordant results between TGA-IgA and histopathology may require re-evaluation of biopsies. Patients with no/mild histological changes (Marsh 0/I) but confirmed autoimmunity (TGA-IgA/EMA-IgA+) should be followed closely. Conclusions: CD diagnosis can be accurately established with or without duodenal biopsies if given recommendations are followed.

Efficacy Study of Anti-Endomysium Antibodies for Celiac Disease Diagnosis: A Retrospective Study in a Spanish Pediatric Population

“…According to our results, compared to anti-TG2, additional EMA evaluation increases the diagnostic sensitivity for CD diagnosis in asymptomatic children. Likewise, IDI and NRI values obtained in our study show that a combined use of both markers displays a higher statistically significant predictive capacity, thus supporting the use of EMA for CD diagnosis, according to the ESPGHAN 2012 and 2019 guidelines [1,4]. Moreover, our results are in line with the 2019 guidelines as HLA testing is of no additional value for a serology-based diagnosis without biopsy.…”

“…However, the majority of patients were included based on prior positive anti-TG2 tests, and because of the patient's preselection the specificity of EMA is lower (94%) than commonly described. Based mainly on these two studies, the 2019 ESPGHAN guidelines state that the non-biopsy approach is safe in children with anti-TG2 >10 × ULN and positive EMA without the need for HLA assessment [4].…”

Value of Biopsy in a Cohort of Children with High-Titer Celiac Serologies: Observation of Dynamic Policy Differences between Europe and North America

“…In one such study, the no-biopsy algorithm showed a positive predictive value of 0.988 and a negative predictive value of 0.958 [41]. This and similar recent observations [60,61] led to rea rmation and further extension of no-biopsy approach to include asymptomatic children as well [12].…”

“…The American Gastroenterological Association clinical update recently discussed both European and North American approach [11], but did not adopt a speci c position regarding the no-biopsy approach in any patient group. Since 2012, the European experts rea rmed and extended their position that pediatric CD can be diagnosed without biopsy in a selected group of children by following the recommended guidelines [12].…”

“…Positives are further divided into 3 categories: (i) >20-200 (<10x ULN), (ii) >200 (>10x ULN), and (iii) >2,000 Chem'U (>100x ULN). The cutoff of 200 represents ESPGHAN decision point [3,12] and 2,000 Chem'U is an arbitrary cutoff because the assay has a wide analytical range spanning more than two orders of magnitude above the upper limit of normal (Figure 1). We did not study patients with negative tTG any further.…”