The 2012 ESPGHAN coeliac disease (CD) diagnostic guidelines seek to aid physicians in properly identifying CD and to allow for the absence of duodenal biopsies in certain patients. An evidence-based guideline that has been revised and enhanced is offered here. Studies on symptoms, serology, human leukocyte antigen genetics, and histology were sought using literature databases and other sources of information. QUADAS2 was used to evaluate eligible publications, while GRADE served as the foundation for assertions and recommendations. Several symptoms are recommended for case detection, although their contribution to diagnostic accuracy is minimal. If CD is suspected, total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) measurements outperform other combinations. For initial testing, we advise against using deamidated gliadin peptide antibodies (DGP-IgG/IgA). An IgG-based test is advised only if total IgA is low or undetectable. If TGA-IgA is 10 times higher than the upper limit of normal and the family agrees, the no-biopsy diagnosis may be used, providing endomysial antibodies (EMA-IgA) test positive in a second blood sample. The presence of symptoms and the identification of human leukocyte antigen DQ2-/DQ8 are not required requirements. At least four biopsies from the distal duodenum and one from the bulb should be obtained in children with positive TGA-IgA 10 ULN. Discordant TGA-IgA and histology findings may need re-evaluation of biopsies. Patients who have no/mild histological alterations (Marsh 0/I) but have autoimmunity (TGA-IgA/EMA-IgA+) should be continuously monitored.

If the guidelines are followed, a CD diagnosis can be made with or without duodenal biopsies.