Implementing Precision Medicine in Pediatric Eosinophilic Gastrointestinal Disorders

Eosinophilic gastrointestinal diseases (EGIDs), particularly eosinophilic esophagitis (EoE), are emerging, heterogeneous, and chronic disorders affecting adults and children equally. Although several efforts have been made in the last decade, many unmet needs remain unsolved. We investigated some of these aspects, achieving several notable findings. We find that the epidemiology of non-EoE EGIDs in symptomatic patients is higher than that reported in observational studies or surveys, highlighting that these disorders are common and should be included in the differential diagnostic process of inflammatory gastrointestinal diseases. We collected data on patients with EGIDs followed at our Pediatric Hospital for five years, and we found that 1) the epidemiology of these conditions is increased; thus, EGIDs are not rare diseases; 2) EGIDs affect patients with atopic comorbidities and children with non-atopic diseases, suggesting different potential phenotypes; 3) symptoms are unspecific and depend on the site of intestinal inflammation. Subsequently, we first identified three potential phenotypes of pediatric EGIDs using a cluster analysis approach. Notably, we confirmed and characterized two subgroups of EoE patients, an atopic and non-atopic phenotype, with a relevant impact on clinical practice and potential significance in prognosis and response to therapy. The clinical heterogeneity of EGIDs and the absence of specific noninvasive biomarkers are probably the main limitations to a prompt diagnosis and a shorter diagnostic process, especially in non-esophageal EGID cases. We identified that the diagnostic time is significantly associated with impaired child growth in children with EGIDs, highlighting that raising awareness among family pediatricians on EGIDs and promptly referring suspicious cases to specialized pediatric centers is fundamental. On the other hand, allergists and gastroenterologists should promptly consider GI endoscopy in all those children with refractory GI symptoms, especially if complicated by atopy, peripheral eosinophilia, failure to thrive, or feeding issues. EoE significantly impacts the quality of life of affected children, primarily because of the absence of noninvasive biomarkers and the need to periodically monitor treatment response with esophagogastroduodenoscopy. Consequently, identifying noninvasive biomarkers is an urgent need in pediatric EoE management. The last part of Ph.D. research aimed to identify potential noninvasive biomarkers for EoE diagnosis and monitoring, assessing disease activity with the new proposed set of outcome measures for improving the data quality of trials and observational studies (COREOS). We identified three promising noninvasive biomarkers for EoE diagnosis and surveillance using a panel of inflammatory, tissue, vascular, and eosinophil-derived markers. We found that interleukin (IL)-17 values predicted clinically, endoscopically, and histologically active disease. As reported in the asthma model, high expression of IL-17 might define a potential “Th-2 low" endotype, which might correspond to a severe and difficult-to-treat EoE phenotype. In the case-control comparison, galectin (GAL)-10 and transforming growth factor (TGF)-β values were significantly increased in EoE patients compared to healthy, non-allergic children. The results of this explorative prospective study are promising and open new scenarios in EoE diagnosis and surveillance that should be investigated with further and more extensive studies.