Diagnostic delay and its implications in pediatric eosinophilic gastrointestinal disorders

Backgrounds and aims: Primary eosinophilic gastrointestinal disorders (EGIDs) are a rare and heterogeneous group of diseases characterized by eosinophilic inflammation of different segments of the gastrointestinal tract. To date, few studies have been realized worldwide assessing the diagnostic delay of EGIDs in the pediatric population. Materials and methods: We performed a retrospective cross-sectional analysis of pediatric patients followed at the Center for Pediatric Eosinophilic GI Disorders (CPED) in Pavia. We assessed demographic, clinical, endoscopic features, and associated comorbidities. We estimated the diagnostic delay as the time lapse between the onset of symptoms indicative of EoE or non-esophageal EGIDs and the final diagnosis. Results: We enrolled 68 EGID patients, 43 (63%) of which with eosinophilic esophagitis (EoE) and 25 (37%) with non-esophageal EGIDs. Most of the patients were males (72%) and Caucasians (84%). The most encountered symptom overall was abdominal pain (47%). However, symptoms depended on the site of GI inflammation: dysphagia, GERD-like symptoms, feeding issues, and reduced appetite were almost only present in EoE affected patients (respectively p 0.02, p 0.0005, p 0.04); diarrhea, on the other hand, was much more prevalent in non-esophageal forms (p 0.0001). Moreover, symptoms of EoE also varied according to patients’ age, with a prevalence of nausea and vomiting (50%) and failure to thrive (50%) in infants (0-1 years old); GERD-like symptoms (70%) in toddlers and pre-school children (1-6 years old); abdominal pain (63%) in school-aged children (6-12 years old) and symptoms of GER (71%), dysphagia (58%) and food impaction (43%) among adolescents (>12 years old). Such clinical variability was not observed in non-esophageal EGIDs patients. More than half of enrolled patients (60%) had an atopic phenotype, which significantly prevailed in children with EoE than non-esophageal EGIDs (70% vs. 48%). At diagnosis, the mean age was 9.0 years old for EoE and 9.2 years old for non-esophageal EGIDs. The overall mean diagnostic delay was estimated to be 15.7 months, and was significantly higher in the non-esophageal forms compared to the esophageal one (25.6 months vs. 9.9 months, p 0.0005), overall particularly among toddlers and pre-school children (1-6 years old) and when they were comorbid with allergic diseases. The most significant diagnostic delay was observed in non-esophageal forms presenting with an atopic phenotype. Symptoms of EoE associated with the longest diagnostic delay were failure to thrive (23.7 months), feeding issues, and reduced appetite (19.3 months). Similarly, the longest diagnostic delay in non-esophageal EGIDs was mainly associated with failure to thrive (55.0 months) and weight loss (38.3 months). The association between diagnostic delay and impaired child growth was never studied before. The diagnostic delay in EoE was associated with a fibrotic endoscopic presentation (20%), when it was longer than 24 months. On the other hand, the endoscopic phenotypes were less variable in the non-esophageal forms. Conclusions: We quantified the diagnostic delay of EGIDs children and adolescents, followed by the CPED in Pavia. We examined demographic and clinical features and comorbidities associated with a significant diagnostic delay. Finally, we studied the consequences of such a delay, in terms of clinical presentation and endoscopic findings. Notably, the diagnostic delay had an impact on child growth by causing failure to thrive. A timely diagnosis is needed to prevent such complication and improve patients’ outcomes and quality of life. Validated questionnaires, specific biomarkers, and reliable scores could be valuable tools to shorten the diagnostic delay. Family pediatricians should be aware of these diseases, the importance of a multidisciplinary assessment, and the inclusion of EGIDs in the differential diagnosis of failure to thrive in children.