Distinguishing gastroesophageal reflux disease and eosinophilic esophagitis in adults: The role of esophageal mucosal immunoglobulin G4

Abstract Background and Aim Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) can be difficult to distinguish as many of their clinical and histological features overlap. Preliminary data suggest a potential association between EoE and immunoglobulin G4 (IgG4) but not GERD. This study aimed to examine the role of esophageal mucosal IgG4 staining when differentiating EoE from GERD. Methods Esophageal biopsy specimens from patients with proven EoE and GERD were evaluated, and immunohistochemical staining for IgG4 was performed by an experienced gastrointestinal pathologist blinded to the clinical and endoscopic data. The results on IgG4 staining were then correlated with clinical, endoscopic, and histological features. Results Sixty patients were included in the study, with 30 EoE (38.8 ± 12.8 years, 23 M:7 F) and 30 GERD (50.7 ± 14.3 years, 14 M:16 F) patients. The prevalence of a positive intercellular IgG4 stain was significantly higher in the EoE patients than those with GERD (23/29 vs 2/30; P < 0.0001). Positive IgG4 stain had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 77%, 93%, 92%, and 80% for predicting the diagnosis of EoE, respectively. In both EoE and GERD patients, correlation was found between positive IgG4 staining and food bolus obstruction, dysphagia to solids, reflux, fixed rings, Barrett's esophagus, hiatus hernia, and esophagitis. In EoE patients, positive IgG4 staining was not correlated with the type of symptoms, endoscopic findings, histological findings, proton pump inhibitor therapy, or history of allergy/atopy. Conclusion Given the high specificity and PPV of positive IgG4 staining in esophageal biopsies for EoE, this can be a useful marker to distinguish the disease from GERD.