Transnasal Endoscopy Acquires Esophageal Biopsies Adequate for Comprehensive Pathology Evaluation in Patients With Eosinophilic Esophagitis.

BACKGROUND: Transnasal endoscopy (TNE) does not require general anesthesia, an attractive characteristic for monitoring eosinophilic esophagitis (EoE). We evaluated the adequacy of TNE-obtained esophageal biopsies using the EoE Histology Scoring System (EoEHSS). METHODS: The Cincinnati Center for Eosinophilic Disorders database was searched for esophageal biopsies obtained by the same endoscopist, using either TNE or conventional endoscopy (CE). Whole-slide biopsy images were evaluated. The Mann-Whitney test was used for median (interquartile range) values and Fisher exact test for categorical variables. P ≤ .05 was considered significant. RESULTS: Median age (P = .82) or height (P = .83) did not differ between TNE (n = 17) and CE (n = 17) groups. Although median largest piece size (mm2) differed between the groups (TNE: 0.59 (0.45, 0.86), CE: 2.24 (1.09, 2.82), P < .001), all 8 EoEHSS features were evaluated in each group; only 1 feature (lamina propria fibrosis) was missing in both groups (TNE: 19/34, CE: 11/34, P = .09). The median peak eosinophil count/high-power field differed (TNE: 3 (0, 29), CE: 16 (1, 66), P = .03), but overall grade (TNE: 0.17 (0.10, 0.29), CE: 0.22 (0.14, 0.46), P = .12), stage (TNE: 0.14 (0.10, 0.24), CE: 0.20 (0.10, 0.43), P = .15), and non-eosinophil-related individual EoEHSS scores did not differ. CONCLUSIONS: TNE- and CE-obtained esophageal biopsies are similarly sufficient for evaluation of key pathological features in EoE.

Local type 2 immunity in eosinophilic gastritis.

BACKGROUND: Eosinophilic gastritis (EoG) associates with type 2 immunity. However, the type 2 cytokine cellular source, gastric T-cell composition, and gastric T-cell relationship (or relationships) with disease pathology remain understudied. OBJECTIVE: We defined gastric T-cell populations and their association with histologic and endoscopic EoG pathology. METHODS: Gastric biopsy samples (n = 6 EoG, n = 7 control) were subjected to histologic, endoscopic, and flow cytometry analyses. In a complementary cohort (n = 83 EoG), IL4, IL5, and IL13 mRNA levels were correlated with EoG pathologic parameters. RESULTS: Gastric biopsy samples contained CD3+ T cells that were mainly CD8+; the CD8/CD4 ratio was comparable in EoG and control biopsy samples (5.7 ± 3.0 and 4.3 ± 0.6, respectively; P = .28). Gastric regulatory T (CD3+CD4+FOXP3+) and TH2 (CD3+CD4+GATA3+) cell levels were increased in EoG versus controls (2-fold, P < .05 and 10-fold, P < .001, respectively) and correlated with gastric eosinophil levels (r = 0.63, P < .05 and r = 0.85, P < .001, respectively), endoscopic pathology (r = 0.56, P < .01; r = 0.84, P < .001, respectively), and histopathology (r = 0.72, P < .01; r = 0.82, P < .01, respectively). Cytokine-positive, most notably IL-4+, TH2 cell levels strongly correlated with histologic and endoscopic scores (r = 0.82, P < .0001 and r = 0.78, P < .0001, respectively). In an independent EoG cohort (n = 83), bulk gastric IL4, IL5, and IL13 mRNA levels correlated with histologic score (r = 0.22, P < .005; r = 0.54, P < .0001; and r = 0.36, P < .0001, respectively) and endoscopic score (r = 0.27, P < .001; r = 0.40, P < .0001; and r = 0.35, P < .0001, respectively). CONCLUSIONS: EoG is a TH2 cell-associated disease featuring increased gastric type 2 cytokine-producing CD3+CD4+GATA3+TH2 cells that strongly correlate with disease pathologies.

Role of mast cells in eosinophilic esophagitis.

PURPOSE OF REVIEW: This review will present what is known from recent research on the involvement of mast cells in eosinophilic esophagitis and identify questions requiring further investigation. RECENT FINDINGS: In the adults and children with eosinophilic esophagitis, there is increasing evidence that mastocytosis can persist, despite resolution of eosinophilia and is associated with persistent mucosal abnormalities and symptoms. Despite, treatment mast cells have an activated transcriptome. Mast cells likely contribute to epithelial barrier dysfunction, smooth muscle hypertrophy and contraction, and subepithelial fibrosis. It remains unclear whether targeting MCs alone has therapeutic efficacy to improve tissue damage. SUMMARY: Mast cells appear to play a key role in eosinophilic esophagitis and serve as a biomarker of mucosal healing in conjunction with eosinophils. Excessive mast cell activation likely contributes to tissue damage in eosinophilic esophagitis and need to be considered as a target of therapy along with eosinophils.

Defining the Patchy Landscape of Esophageal Eosinophilia in Children With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a patchy disease of the esophagus with significant variability in intraepithelial eosinophilia. Three biopsies each from distal and proximal esophagus are recommended for identification of active EoE. Recent work suggests 3 biopsy sites are more optimal. We sought to evaluate 2-site vs 3-site esophageal biopsy combinations for utility to identify active EoE. METHODS: We prospectively obtained 3-site esophageal biopsies based on rigorous endoscopic measurements of the proximal, mid, and distal esophagus and gastroesophageal junction. Biopsies were reviewed by a pathologist, and those with at least 15 eosinophils per high-power field were considered active EoE. The sensitivity of one or more sites to identify active EoE was determined, and endoscopic measurements were correlated to height and age. RESULTS: Five hundred ninety-six endoscopies were performed in 217 patients; of these, 304 endoscopies in 167 patients had active EoE. Among the initial esophagogastroduodenoscopies with active EoE, distal biopsies had greater than 80% sensitivity, whereas mid and proximal biopsies had sensitivity of 65% and 62%, respectively, and distal + proximal biopsies had the highest diagnostic sensitivity for a 2-site combination. Among the 304 endoscopies with active EoE, 9 had focal eosinophilia restricted to the mid esophagus, and 8 were restricted to the proximal esophagus. For patients with multiple endoscopies with active EoE, nearly one fourth had reduced sites with eosinophilia at the second time point. Endoscopic measurements strongly correlated with height and age. CONCLUSIONS: This study supports endoscopic measurement-guided 3-site biopsies for optimal disease assessment of active EoE in children.

Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis.

OBJECTIVES: Mast cells (MCs) are increased in eosinophilic esophagitis (EoE). Endoscopic abnormalities, symptoms, and epithelial changes can persist after treatment despite a reduction of esophageal eosinophilia. It is unknown whether this could be due to persistent MC infiltration. We aimed to determine whether patients with histologically inactive (HI) EoE (defined as <15 eosinophils per high-powered field) with persistent symptoms, endoscopic, or epithelial abnormalities after treatment have increased MCs. METHODS: Secondary analysis of prospective data from 93 children with EoE undergoing post-treatment endoscopy between 2011 and 2015. Thirty-five non-EoE controls were included. Immunohistochemistry for tryptase, an MC marker, was performed on mid and distal esophageal biopsies. Total and degranulated intraepithelial MCs per high-powered field (MC/hpf) were quantified. Symptoms and endoscopic findings were recorded at time of endoscopy. MC/hpf were compared between HI-EoE and control, and among HI-EoE based on endoscopic and histologic findings, and symptoms. Nine clinical remission (CR) patients were identified, with absence of endoscopic abnormalities and symptoms. RESULTS: MC/hpf were increased in HI-EoE compared with control (17 ± 11 vs 8 ± 6, P < 0.0). Patients with persistent endoscopic abnormalities had increased total (20 ± 12 vs 13 ± 10, P = 0.001) and degranulated (8 ± 6 vs 5 ± 4, P = 0.002) MC/hpf, with no difference in eosinophils. MC/hpf predicted furrowing (odds ratio = 1.06, P = 0.01) and rings (odds ratio = 1.05, P = 0.03) after controlling for treatment type, proton-pump inhibitor, eosinophils, and duration of therapy. Patients with persistent basal zone hyperplasia and dilated intercellular spaces had increased MC/hpf. Eosinophils were weakly correlated with MC/hpf in the mid (r = 0.30, P < 0.001) and distal (r = 0.29, P < 0.001) esophagus. Clinical remission patients had lower MC/hpf compared with patients with persistent symptoms and/or endoscopic abnormalities. DISCUSSION: MC density is increased in patients with endoscopic and epithelial abnormalities, as well as a few symptoms, despite resolution of esophageal eosinophilia after treatment. This association warrants further study to ascertain whether MCs play an eosinophil independent role in EoE.

Button battery and magnet ingestions in the pediatric patient.

PURPOSE OF REVIEW: Pediatric foreign body ingestion is a common occurrence that presents a challenge both to pediatric gastroenterologists and primary care providers. Increasing prevalence of smaller, more technologically advanced toys in the household has resulted in an increased exposure to higher voltage batteries and powerful magnets that carry a high incidence of morbidity and mortality. This review highlights the latest findings regarding the patients at risk for button battery and magnet ingestions, the symptoms of presentation, and complications of these objects in contributing to long-standing gastrointestinal injury. RECENT FINDINGS: Button batteries may lead to esophageal injury within a few hours. Batteries retained in the esophagus are larger in diameter on average and size is associated with esophageal impaction as well as higher grade esophageal injury. Magnet ingestions, when multiple or with another metallic object, are often initially asymptomatic but may have acute worsening, and therefore warrant close monitoring. SUMMARY: Button battery and magnet ingestions have increased in incidence over the past two decades. Recent literature demonstrates that higher voltage, larger lithium button batteries, and prevalence of high-powered magnets can lead to significant morbidity. High suspicion, early referral, and removal may lead to improved outcomes.