Diagnostic outcomes after gluten challenge in adult patients with unconfirmed coeliac disease already on a gluten-free diet: A 20-year retrospective cohort study.

Background: In uncertain cases of coeliac disease (CD), gluten challenge (GC) may be necessary to confirm or exclude the diagnosis. However, data on diagnostic outcomes after GC are limited.

Aims: We aimed to evaluate outcomes after GC in patients with unconfirmed CD who had already started a gluten-free diet (GFD), and identify predictors of a confirmed diagnosis.

Methods: Patients with unconfirmed CD already on a GFD, who underwent GC and subsequent testing with endomysial antibodies (EmA) and duodenal biopsy between 06/2000-06/2021 were included. Clinical data, prior test results, and final diagnoses were retrospectively collected and analysed.

Results: 158 patients underwent GC (median duration 3 months, IQR 3-6) and CD was confirmed in 47/158 (29.7 %) (41 conventional CD, 1 CD + IgAdeficiency, 5 potential CD), non-coeliac enteropathies (NCEs) were diagnosed in 3 patients, and enteropathy was ruled out in 108. Prior positive serology strongly predicted CD diagnosis after GC (OR 36.8, 95 %CI 13.8-100.0, p < 0.001), whereas prior reported villous atrophy did not (p = 0.83), as this was frequently (35 %) due to incorrect sampling/interpretation of poorly oriented specimens. Duration of GC was also not associated with diagnostic outcomes (p = 0.37).

Conclusion: Prior positive serology strongly predicted CD diagnosis after GC, while histological results without positive serology should be interpreted cautiously. Clinicians should consider NCEs in older patients with severe symptoms.