A Gene Expression Profile Test (EoGenius) Can Predict Subsequent Development of Histologic Eosinophilic Esophagitis in Patients with Non-diagnostic Index Biopsies

Abstract

Introduction: The AGA consensus on eosinophilic esophagitis (EoE) requires a minimum of 15 eosinophils per high-power field (eos/HPF) to be counted in the squamous epithelium. Some patients with typical clinical signs and symptoms of EoE have low, non-diagnostic eosinophil counts in their esophageal biopsies, and above-threshold infiltrates become evident only at subsequent biopsies. A recently developed RNA gene expression profile test (EoGenius) has been shown to distinguish EoE from other conditions independently of the numbers of intraepithelial eosinophils (Dellon et al., 2016). Methods: Here we report 4 patients in whom EoE was clinically suspected, in spite of equivocal presentations. Their initial biopsies were reviewed and determined to be either non-diagnostic or at-threshold for histologic EoE. Within 3 to 6 months of the first biopsy, the patients had a follow-up endoscopy with esophageal biopsies that were diagnostic of EoE. We retrospectively performed the EoGenius test on the specimens from the first (negative) biopsy specimens to determine whether EoGenius could predict the subsequent development of histologic EoE. Results: Demographic and clinical data are summarized in Figure 1. T1 indicates the first biopsy on which EoGenius was performed. T2 indicated the follow-up biopsy. In patients A and B the biopsies were unequivocally negative for EoE (zero eos/HPF). In patient C the eosinophil count reached 15 eos/HPF, but sampling was exclusively from the distal esophagus at the gastroesophageal junction (GEJ), and there was neither eosinophilic degranulation nor microabscesses, making the diagnosis of EoE difficult to ascertain. Patient D had a diagnosis of EoE at the first biopsy based on the presence of 16 eos/HPF in the upper esophagus. However, there were neither eosinophilic degranulation nor microabscesses, and no samples from other parts of the esophagus were available, leaving the diagnosis tentative at best. In all patients the EoGenius test on the T1 biopsy specimens was positive.Figure 1Conclusions: If these results are confirmed by a large study, currently underway, then the results of EoGenius performed on non-diagnostic or equivocal esophageal biopsy specimens could be used to make informed management decisions. In a numbers of cases, the performance of a second EGD with biopsies within a short interval from the first one could be avoided, resulting in both risk reduction and financial advantages for patients and payers.