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

Abstract

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.

Keywords: coeliac disease; duodenal biopsy; endoscopy; gluten; gluten‐free diet; serology; villous atrophy.

FIGURE 1

Flowchart showing patients included and excluded from the study cohort and reasons for exclusion. EmA, endomysial antibodies; GFD, gluten‐free diet.

FIGURE 2

Comparison of diagnostic outcomes in patients investigated for suspected enteropathy with endomysial antibodies and upper endoscopy with duodenal biopsies according to age at presentation and presence of alarm symptoms. CD, coeliac disease; NCE, non‐coeliac enteropathy.

FIGURE 3

Proposed diagnostic strategy for future research on non‐invasive evaluation of adult patients with suspected coeliac disease incorporating EmA based on our results and the available literature data. CD, coeliac disease; CVID, common variable immune deficiency; EmA, endomysial antibodies; IgA, immunoglobulin A; OGD, oesophagogastroduodenoscopy; TTA, tissue transglutaminase antibodies; ULN, upper limit of normality. *If non‐coeliac enteropathies or seronegative coeliac disease are strongly suspected due to severe malabsorption or other clinical clues, consider upper endoscopy with duodenal biopsy. Otherwise, consider testing for alternative causes of symptoms besides enteropathy in this group of patients. †For centres lacking access to EmA, we propose diagnosing coeliac disease without duodenal biopsy only in patients with positive TTA > 10× upper limit of normal and performing duodenal biopsy in patients with positive TTA < 10× upper limit of normal.