Biopsy-Sparing Diagnosis of Coeliac Disease Based on Endomysial Antibody Testing and Clinical Risk Assessment

Background: Interest in a biopsy-sparing diagnosis of coeliac disease in adults is growing. Aims: To develop and prospectively validate a non-invasive diagnostic strategy for adults with suspected coeliac disease based on clinical features and endomysial antibodies (EmA). Methods: We retrospectively enrolled adults investigated for coeliac disease with EmA and duodenal biopsy between January 2000 and December 2021 in cohort 1 and stratified according to age at presentation (< 45 years; >= 45 years) and alarm symptoms. We evaluated diagnostic outcomes and accuracy of EmA. A prospective validation cohort was enrolled between Jan-2022 and Dec-2023 (cohort 2). Results: Cohort 1 included 972 patients (641 F, mean age 42 +/- 16); cohort 2 included 214 patients (145 F, 43 +/- 18). In cohort 1, 35.4% were diagnosed with coeliac disease and 1.5% with non-coeliac enteropathies. Of the coeliac disease diagnoses, 173 (50.3%) were in patients < 45 years old without alarm symptoms. No concomitant major organic disorders were diagnosed in patients with coeliac disease. EmA diagnostic accuracy was 99.1% (97.4% sensitivity; 100% specificity and PPV). Regarding non-coeliac enteropathies, 87% were diagnosed among the 139 patients aged >= 45 years old with alarm symptoms and negative EmA. No non-coeliac enteropathies were diagnosed in patients without alarm symptoms. Findings were confirmed in cohort 2. Conclusions: Low-risk adult patients could have been safely diagnosed with coeliac disease non-invasively based on EmA without endoscopy and duodenal biopsy. Older patients with alarm symptoms should undergo endoscopy with duodenal biopsy to avoid missing non-coeliac enteropathies. Further validation of our results is necessary.