Eosinophilic Esophagitis and Neurodevelopmental Disorders: a potential association requiring further investigations

Introduction: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease characterised by eosinophilic inflammation. A potential association with Autism Spectrum Disorder (ASD) or other neurodevelopmental disorders (NDDs), such as intellectual disability (ID), has been reported in literature. Shared pathways have been hypothesized, with a potentially pathogenetic role of type 2 allergic inflammation. Our aim was to assess the prevalence of ASD/NDDs in our paediatric EoE population. Methods: We retrospectively analysed (01/2017-01/2024) a single-centre cohort of EoE paediatric patients concomitantly diagnosed with ASD/NDDs. Data collection included baseline demographics, EoE diagnosis and related symptomatology, ASD/NDDs diagnosis and related clinical features. Results: In a cohort of 33 patients with EoE, 5 (15%) were diagnosed with ASD/NDDs (3 with ASD - 9% and 2 with other NDDs - 6%). All were male; the median age at EoE diagnosis was 9 years (IQR: 2.3-11.4 ). Among the 3 patients with ASD, 2 had high-functioning ASD and presented with classic EoE symptoms (food obstruction/dysphagia). The third child had more severe ASD features with limited verbal abilities; EoE symptoms at diagnosis were reduced appetite with necessity of water intake to help food swallowing. Regarding the 2 patients with other NDDs, one had a 14q32.2 microdeletion with macrocephaly and clinical features of psychomotor and speech delay. EoE symptomatology at the diagnosis was dysphagia, with exclusive preference for a soft diet. The second child had a 9q34.11 microdeletion with features of psychomotor and speech delay accompanied by ataxia and muscular hypotonia. EoE symptoms were prolonged chewing and frequent vomiting after swallowing with meal refusal and food aversion. Conclusions: Overall, our single-center analysis reveals an increased prevalence of NDDs in paediatric EoE patients compared to general paediatric population (ASD: 9 % in our cohort vs 0,4-1,3% in general population; other NDDs; 6 % vs 0,63-1,2%). Multicentric studies are needed to further investigate this potential association. If confirmed an EoE diagnosis should be considered in children with ASD/NDDs when presenting with feeding disorders or suspicious EoE symptomatology, maintaining a low threshold for investigations in those ASD/NDDs patients with a substantial compromise in verbal communication to avoid under-recognition.