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Eosinophilic esophagitis (EoE) is a chronic allergen-mediated disease of the esophagus. Pharmacologic treatment has largely relied on repurposing corticosteroids. Ciclesonide (CIC) is a corticosteroid for the treatment of asthma with biochemical properties that improve topical potency.To determine whether CIC decreased clinicopathological features of EoE.We performed a retrospective cohort study of patients with EoE treated with CIC at a pediatric hospital from 2010 to 2019. Data were extracted from the electronic health record. Patients who were prescribed CIC with pre- and post-CIC endoscopic and histological data available were included for analysis.A total of 281 patients were treated with CIC and 81 met criteria for inclusion. Use of CIC was associated with reduced symptoms including dysphagia (P.001), abdominal pain (P.001), vomiting (P = .01), heartburn (P = .02), and behavior changes (P = .02). Average composite endoscopic reference scores decreased from 2.54 to 1.37 (P.001), with improvement in exudates, edema, and furrows (all P.001). Peak eosinophil counts decreased from 48 to 23 eosinophils/hpf (P.001). Forty-three patients (53%) achieved remission (15 eosinophils/hpf). Esophageal Candida was reported in 1 patient. Fasting morning cortisol concentrations were low in 10 of 31 patients tested. Six of these 10 patients had abnormal adrenocorticotropic hormone stimulation testing, 5 of 6 diagnosed with adrenal insufficiency before transition to CIC and 3 of 6 with subsequent normalization of adrenal function on CIC therapy.Patients with EoE treated with CIC experienced significant reductions in clinicopathological features of EoE. CIC can be considered an alternative therapy in patients with known adrenal insufficiency or at risk of developing adrenal insufficiency.

Background: Eosinophilic esophagitis (EoE) is a chronic antigen‐mediated clinicopathologic disease of the esophagus characterized by an eosinophil‐predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis, and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting granulocyte‐macrophage colony‐stimulating factor (GM‐CSF; an agonist cytokine linked with eosinophil survival and activation) would be protective in a preclinical model of EoE. Methods: Eosinophilic esophagitis‐like esophageal inflammation was induced in the L2‐IL5OXA EoE mouse model, and GM‐CSF production was assessed by mRNA and protein analyses. Granulocyte‐macrophage colony‐stimulating factor‐receptor‐alpha expression patterns were examined by flow cytometric and immunofluorescence analysis. L2‐IL5OXA EoE mice were treated with anti‐GM‐CSF neutralizing antibody or isotype control and assessed for histopathological indices of eosinophilia, epithelial hyperplasia, and angiogenesis by immunohistochemistry and RT‐PCR. Results: Significantly increased levels of esophageal GM‐CSF expression was detected in the L2‐IL5OXA mouse EoE model during active inflammation. Granulocyte‐macrophage colony‐stimulating factor‐receptor‐alpha was predominantly expressed on esophageal eosinophils during EoE, in addition to select cells within the lamina propria. Anti‐GM‐CSF neutralization in L2‐IL5OXA EoE mice resulted in a significant diminution of epithelial eosinophilia in addition to basal cell hyperplasia and vascular remodeling. This treatment response was independent of effects on esophageal eosinophil maturation or activation. Conclusion: Granulocyte‐macrophage colony‐stimulating factor is a potential therapeutic target to reduce esophageal eosinophilia and remodeling.