Optimal Biopsy Protocol to Evaluate Histological Effectiveness of Proton Pump Inhibitor Therapy in Patients with Eosinophilic Esophagitis

Abstract

Objective: Recent guidelines propose that both proton pump inhibitor (PPI) responders and nonresponders are included in eosinophilic esophagitis (EoE). Although multiple biopsies should be required to diagnose EoE because of patchy distribution of esophageal eosinophils, it is unclear whether multiple biopsies are required to evaluate histological effectiveness of PPI therapy. This study aimed to determine the optimal biopsy protocol after PPI therapy in patients with EoE. Methods: Of 110 EoE patients, 22 PPI nonresponders were enrolled. Intraepithelial eosinophils were counted in areas of high density in multiple biopsy specimens after PPI therapy. The prevalence of esophageal eosinophilia and peak eosinophil counts after PPI therapy was analyzed according to the biopsy sites and endoscopic findings. Positive predictive value (PPV) was calculated according to the number of biopsies. Results: Of 124 biopsies, 59 (47.6%) specimens showed esophageal eosinophilia (≥15 per high-power field). Eosinophil counts were significantly higher in specimens from the lower esophagus than in those from the upper esophagus but not in those from the middle esophagus. Prevalence of esophageal eosinophilia was 76.2, 40.9, and 24.3% in the lower, middle, and upper esophagus respectively. PPI nonresponders were diagnosed in all cases with 4 biopsy specimens obtained from the lower and middle esophagus, showing that PPV for non-effectiveness of PPI therapy was 0.910 (95% CI 0.773–1.000). The prevalence of esophageal eosinophilia and peak eosinophil counts was higher in cases with white plaques and linear furrows. Conclusion: Multiple biopsies should be required to evaluate histological effectiveness of PPI therapy in patients with EoE. Four biopsies from the lower and middle esophagus may be sufficient.

Eosinophilic esophagitis and asymptomatic esophageal eosinophilia display similar immunohistological profiles

“…Because the study was done in a medical health check-up setting, there was a limitation on taking multiple biopsy specimens, even though multiple biopsies (at least four biopsies) should be required to evaluate the histological state. (3) Of course, we obtained specimens from areas with the most abnormal endoscopic findings, which were compatible with EE, and sufficient eosinophilic infiltration were observed in all evaluated specimens. Third, we did not evaluate cytokines, such as IL-4 and IL-13, directly.…”

“…Introduction E osinophilic esophagitis (EoE) is a chronic immune-related disease characterized by clinical symptoms because of esophageal dysfunction and intraepithelial infiltration of ³15 eosinophils per high power field (HPF) with multiple biopsies. (1)(2)(3) Inflammation and fibrosis of the lamina propria and muscularis propria results in esophageal dysfunction and stricture formation. (4) The prevalence of EoE is higher in Western countries than Asian countries, including Japan.…”

Symptom-based diagnostic approach for eosinophilic esophagitis

“…Moreover, the American College of Gastroenterology guidelines strongly recommends that 2-4 biopsies should be obtained from both the proximal and distal esophagus [1]. In our previous study [64], two biopsies each from the lower and middle esophagus revealed a high diagnostic accuracy rate. Therefore, multiple biopsies (4-6) should be recommended in patients with typical symptoms.…”

Clinical Features of Esophageal Eosinophilia According to Endoscopic Phenotypes

“…Second, most of the patients with localized EE underwent only one biopsy in which samples were taken from normal-appearing mucosa for the histological confirmation of nonsignificant eosinophilic infiltration. The number of biopsies might have been insufficient for the judgement of localized EE because the distribution of infiltrating eosinophils in EoE is reported to be considerably heterogeneous (35). However, this issue would not be resolved completely even if multiple biopsies was performed.…”