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Proton-pump inhibitor-responsive esophageal eosinophilia is a newly recognized entity with an unclear prevalence in children, as only retrospective data are available. The aim of this study was to determine the prevalence and clinical features of proton-pump inhibitor-responsive esophageal eosinophilia in children.This prospective study enrolled patients with esophageal symptoms and esophageal eosinophilic counts as 15 or more than 15 eos/hpf (eosinophils per high-power field). Children received treatment with esomeprazole 1 mg · kg−1 per dose twice daily for 8 weeks and the endoscopy was repeated. Complete response to proton-pump inhibitor (PPI) was defined as 5 or less than 5 eos/hpf, and a partial response as >5 and <15 eos/hpf in post-treatment biopsies.Fifty-one children (74.5% boys) were included. Histological response was observed in 35 children (68.6%): 24 children (47%) had a complete response and 11 children (21.6%) had a partial response. Only 16 children (31.4%) were diagnosed with eosinophilic esophagitis (EoE). There were no differences in history of atopy, allergy tests, pH study results, and endoscopic scores. Clinical symptoms were similar, with the exception of food impaction, which was more frequent in children with EoE (56.2% vs 20%, P = 0.01). The mean pretreatment peak eosinophil count was higher in patients with EoE (74.8 ± 36.2 vs 46.3 ± 30.7, P = 0.007). Eleven of the 14 patients (78.6%) on a lower PPI treatment maintenance dose remained in clinicopathologic remission at 1-year follow-up.A significant proportion of children with esophageal eosinophilia responded to high dose PPI treatment. Clinical, endoscopic, and pH study results were similar, with exception of patients with EoE, who were more likely to experience food impaction and have higher esophageal eosinophil counts.