Letter: oesophageal histological abnormalities and GERD - an underestimated relationship requiring more attention

Dear Sirs, we read with great interest the manuscript by Vakil et al (1) regarding a post-hoc analysis of the Diamond study, a single-blind, single-arm investigation evaluating the accuracy of the diagnosis of gastro-oesophageal reflux disease (GORD) by the Reflux Disease Questionnaire (RDQ), family practitioners, gastroenterologists and a test of esomeprazole therapy. The Authors analyzed distal oesophageal biopsies from 127 (55%) of the 231 included patients who were diagnosed with GERD based on endoscopic and functional investigations and found that adding epithelial hyperplasia (>430 µm) at histological assessment, as a diagnostic criterion, increased the number of patients diagnosed with GERD on investigation by 28 [12%; number needed to diagnose (NND): 8] to 155 (67%). We appreciated the efforts made by the Authors in order to confirm the role of histology in defining a GERD diagnosis in case of negative endoscopy, normal acid exposure time and negative symptom-reflux association. To note, the value of histology in this particular setting (i.e. endoscopy negative patients with negative or borderline reflux testing) has been recently emphasized by an international consensus of experts (2). Indeed, relevant recent studies underlined the potential increasing diagnostic yield of diagnosing GERD by adding esophageal histological assessment (3,4). In particular, using current state of the art method for reflux monitoring, that is impedance-pH, we observed that a diagnosis of microscopic esophagitis, based on the presence of dilatation of intercellular spaces, papillary elongation, basal cell hyperplasia and inflammatory cells, was able to differentiate patients with non-erosive reflux disease from those with functional heartburn and healthy volunteers with an accuracy of 79%, a sensitivity of 74%, and a specificity of 86%, similar to what has been demonstrated by Kandulski et al (3,4). On the other hand, Vakil et al. showed that epithelial thickness >430 µm on esophageal biopsies performed 2 cm above the Z line had a specificity of only 76% and a sensitivity of 48%. For this reason, we strongly argue that whether we want to consider histology as additional tool for GERD diagnosis, the inclusion of the whole histological lesions associated to GERD should be considered and evaluated, in order to maximize the value of the information we can obtain from the esophageal mucosal status. Furthermore, we would like also to say that, in contrast to what has been reported by Roman et al. (5), histological assessment has low cost and, in general, is increasing suggested by different guidelines underling the need of biopsies due to the raising incidence of eosinophilic esophagitis in the general population. In conclusion, given the increased diagnostic yield of histology in case of GERD suspicion, we believe that histological evaluation should be performed when clinical suspicion is high and endoscopy or reflux monitoring are negative or provided inconclusive results.