Plasminogen Activator Inhibitor-1 as a Marker of Esophageal Functional Changes in Pediatric Eosinophilic Esophagitis.

BACKGROUND & AIMS: Esophageal remodeling in eosinophilic esophagitis (EoE) can lead to esophageal rigidity with eventual luminal compromise and stenoses. Gauging esophageal functional alterations in EoE is challenging. An epithelial marker of functional remodeling would impact EoE management. METHODS: Esophageal biopsy specimens from children with and without EoE and primary human esophageal epithelial cells were used for PAI-1 immunohistochemistry, and cell proliferation experiments. PAI-1 immunostaining and basal cell hyperplasia were assessed in the context of concurrently obtained esophageal compliance measures on endoscopic functional lumen imaging probe (EndoFLIP). RESULTS: EndoFLIPs were performed in 45 children (32 with and 13 without EoE). Epithelial PAI-1 was increased in patients with active EoE versus inactive or control patients (P < .01). Esophageal compliance was lower in EoE patients versus controls, particularly in the proximal esophagus (P < .001). Proximal compliance was the strongest predictor of EoE (AUROC 0.88, 95% CI 0.77, 0.98) with esophageal compliance of less than 2.6%mL/mmHg demonstrating 82% sensitivity and 84% specificity for EoE. PAI-1 inhibition significantly diminished esophageal epithelial cell proliferation, suggesting PAI-1 could trigger basal cell hyperplasia. A composite mid-esophageal BZH + PAI-1 score was the strongest predictor of altered compliance (P = .02, AUROC 0.89 (95% CI 0.80, 0.99). CONCLUSIONS: PAI-1 is significantly elevated in pediatric EoE and distinguishes altered compliance in children. PAI-1 may be a novel disease marker and therapeutic target.

Allergies and Eosinophilic Esophagitis-Current Updates for the Pediatric Gastroenterologist.

PURPOSE OF REVIEW: The purpose of this article is to review recent developments demonstrating the role of allergies, the utility of allergy testing, and the role of the allergist in eosinophilic esophagitis (EoE) management. RECENT FINDINGS: The majority of patients with EoE have concurrent atopic disorders including food anaphylaxis, asthma, allergic rhinitis, and eczema. An atopic population likely is at greater risk for EoE. Delayed type hypersensitivity to food antigens is the most common pathogenic mechanism. Aeroallergens and pollen-food cross-reactivity also can trigger EoE. Th2 cell-mediated adaptive and innate immunity in response to epithelial damage occurs via IL-13- and IL-4-producing T cells and innate lymphoid cells. While IgE testing for foods is insufficient to build an elimination diet, IgE-mediated allergy may play a role in EoE severity and clinical course. There is strong evidence that Th2 immunity drives EoE. Optimal EoE management should include elucidating and managing EoE triggers and concurrent atopic diatheses.