How to diagnose coeliac disease in 2026?

Coeliac disease (CD) is a chronic, immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals carrying HLA-DQ2 and/or -DQ8 alleles. Its diagnosis traditionally combines serology and confirmatory duodenal biopsy. IgA anti-tissue transglutaminase is the first-line test, supported by endomysial antibody. Duodenal histology remains the gold standard, though limitations include patchy involvement and variability in interpretation. Recent advances have proposed biopsy-sparing approaches, whereas applicability in adults remains debated. Moreover, CD is increasingly recognized in association with autoimmune conditions, including type 1 diabetes mellitus and autoimmune thyroid disease, underscoring the importance of proactive screening. However, distinguishing true CD from potential CD or false-positive serology requires careful clinical integration and, often, biopsy confirmation. Mass screening appears to demonstrate high yield and potential cost-effectiveness compared with case-finding. However, evidence is emerging and not yet definitive, and its implementation remains limited. For patients already on a gluten-free diet, gluten challenge protocols combined with HLA genotyping enhance diagnostic accuracy. Overall, while duodenal biopsy is still pivotal in most guidelines, evolving evidence supports a tailored, less invasive approach that integrates serology, genetics, histology, and novel diagnostics to improve early detection and management of CD.