In children and young adults suffering from eosinophilic esophagitis (EoE), proton-pump inhibitor (PPI)-responsiveness may be predicted by eosinophil-derived neurotoxin (EDN) measured in esophageal epithelial samples obtained by brushing during endoscopy.

• In this prospective cross-sectional study, EDN was compared between PPI-responsive and PPI-nonresponsive EoE individuals from 2018 through 2020; patients with active EoE were treated with high-dose PPI and had repeat endoscopy.

• Of 36 patients with EoE, 15 patients (age range 2–18 years, 73.3% male) were PPI-responsive and 21 (age range 2–19 years, 95.2% male) were PPI-nonresponsive.

• In the PPI-nonresponsive group, a significantly higher EDN concentration was identified, vs the PPI-responsive group (219.1 ± 229 mcg/mL vs 75.7 ± 60 mcg/mL, respectively).

• No difference was found between the two groups in EREFS (endoscopic reference score) or peak eosinophilic count.