Eosinophilic esophagitis in children: doubts and future perspectives

Abstract

Background Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder and represents the leading cause of food impaction. The pathogenesis of EoE is the result of an interplay between genetic, environmental and host immune system factors. New therapeutic approaches for EoE have been proposed. In this manuscript we review the current evidence regarding EoE management in pediatric age, with a particular focus on new findings related to the efficacy and safety of monoclonal antibodies. Main body Conventional therapies have failed in treating some patients with EoE, which then requires aggressive procedures such as esophageal dilatation. The most effective available medical therapy for EoE is swallowed topic corticosteroids (fluticasone propionate and budesonide), which have two main drawbacks: they are related to well-known adverse effects (especially in the paediatric population), and there are not enough long-term data to confirm that they are able to reverse the remodelling process of the esophageal mucosa, which is the major cause of EoE symptoms (including dysphagia, abdominal pain, nausea, obstruction, perforation and vomiting). The monoclonal antibodies appear to be an interesting therapeutic approach. However, the studies conducted until now have shown substantial histological improvement not coupled with significant clinical improvements and no significant relationship between a decreasing number of eosinophils and clinical symptoms, highlighting the importance in the pathogenesis of EoE of cells such as T-helper cells, mast cells, B cells, epithelial cells and natural killer cells. Conclusions Monoclonal antibodies targeting a signal involved in the pathogenesis of EoE may not break the complex self-propagating inflammatory activation responsible for perpetuation of the inflammatory response and the development of symptoms and complications. We speculate that combined biological therapies targeting more than one molecule or cell may provide better results, with conventional therapies potentially enhancing the effects of antibodies. However, further studies should aim to find the best therapeutic approach to target the cells involved in the remodelling process and to reverse the histological changes in this complex clinical condition.

Clinical Features of Eosinophilic Esophagitis: A Single Center Experience in Ecuador

“…EoE can occur at any age in children. The mean age at the time of diagnosis ranges from 5.4 to 9.6 years [ 5 ]. The presentation age in our study was 9.4±4.5 years (range, 1–18 years), which is similar to that of other studies.…”

“…In our study, the most common endoscopic features were furrowing (82.9%), edema (74.3%), rings (47.5%), and exudates (22.9%). Normal endoscopic findings of the esophageal mucosa have been reported in approximately 32% of the children diagnosed with EoE [ 5 ]. In contrast, in the present study, visually normal esophageal mucosa was observed in only one patient.…”

“…EoE is a chronic, progressive disease and therapeutic strategies aim to resolve clinical symptoms and esophageal inflammation to avoid long-term complications related to fibrosis and deterioration of health-related quality of life [ 5 ]. Therapeutic options currently available for EoE include elimination diets, PPIs, and steroids.…”

EoE behaves as a unique Th2 disease: a narrative review

“…The initial conceptualization for the presented review was derived from review articles describing the consistently disappointing results of published EoE studies that (I) attempted to identify EoE serum markers (3,4) and (II) attempted to treat EoE with parenteral biological therapies (5)(6)(7). To examine more closely if other Th2 diseases faced the same problems, four comprehensive literature searches were then conducted through January 2022, to compare EoE and three other representative Th2 diseases (asthma, AD, and CRS).…”

Eosinophilic esophagitis: Immune mechanisms and therapeutic targets

“…The most characteristic histopathologic feature of EoE is esophageal intraepithelial eosinophilia (≥15 eosinophils/HPF). Eosinophil numbers can be significant with micro‐abscesses and esophageal eosinophilia correlates with histopathologic features (including DIS and BZH) and disease severity 111,112 . In a registry of EoE patients, O'shea et al compared patients with high‐grade esophageal eosinophilia (>350 eosinophils per hpf) to patients with low‐grade eosinophilia (15–24 eosinophils per hpf) and found statistically significant differences in histologic severity, endoscopic severity and gene expression but not symptoms 113 …”