March 2025
Eosinophils at the Table: Is a Milk-Only Diet Effective for Pediatric Eosinophilic Esophagitis?
Article: One-food versus 4-food elimination diet for pediatric eosinophilic esophagitis: a multisite randomized trial.
Kliewer KL, Abonia JP, Aceves SS, et al.
J Allergy Clin Immunol. 2025
Reviewed by Nicholas Genovese, Jefferson Einstein Philadelphia Hospital, Pennsylvania, United States
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated condition in which eosinophils accumulate in the esophagus, leading to tissue damage and swallowing difficulties. While dietary elimination is a common therapeutic strategy, highly restrictive regimens can be challenging for pediatric patients. Read more
In this randomized, multicenter trial, 63 children with EoE were assigned to either a milk-only elimination diet or a four-food elimination diet (excluding milk, egg, wheat, and soy) for 12 weeks. Clinical symptoms, esophageal eosinophil counts, inflammatory gene expression, and dietary adherence were monitored, alongside dropout rates.
Both diets achieved histologic remission in approximately 40% of participants, reflecting significant reductions in eosinophil density. Parents reported slightly greater symptom relief with the four-food regimen, while children’s self-reports demonstrated similar improvements across both arms. Transcriptomic analyses revealed that responders in each group exhibited broad downregulation of type 2 inflammatory markers such as IL-13 and periostin; non-responders retained persistently high levels of immune signaling. Dietary adherence was lower in the four-food group, resulting in a dropout rate of 32% compared to 11% in the milk-only cohort.
Methodologically, randomization and a multisite design bolstered external validity and minimized selection bias. Standardized histologic endpoints strengthened outcome measurement. However, the small sample size and relatively short 12-week follow-up may limit the detection of subtle differences and longer-term outcomes. The open-label design could also introduce subjective bias in symptom reporting, and differential dropout rates could hamper generalizability.
Longer studies are needed to determine whether these diets induce sustained immune tolerance or only transiently suppress inflammation. Incorporating genomic, microbiome, and immunologic data may support more personalized dietary strategies. Additional research into mast cells, fibroblasts, and other inflammatory pathways may further elucidate EoE pathophysiology.
Overall, this study underscores the pivotal role of diet in EoE and illustrates how dietary triggers can modulate disease severity. Emerging molecular evidence suggests a complex interplay among immune pathways, genetics, and epithelial dysfunction in EoE. Thus, combining dietary approaches with targeted molecular therapies may yield more durable, patient-centered treatments.
Nicholas Paul Genovese is a dedicated pediatric resident at Jefferson Einstein Philadelphia Hospital, deeply committed to pursuing a fellowship in allergy and immunology upon completing his residency. His passion for allergy and immunology was ignited by his early research in evolutionary ecology, where he studied plant defense mechanisms and later their implications for allergenicity at Fordham University. This foundation was further solidified through his investigation of maternal and environmental factors contributing to severe atopic dermatitis within a NICU cohort. Nicholas has worked with Dr. Kathleen Sullivan on a congenital athymia case report, highlighting his dedication to complex case management. He is an active member of the International Eosinophil Society, mentored by Dr. Praveen Akuthota. Nicholas's commitment to advancing knowledge in this field is evidenced by his participation in the 2024 AAAAI Chrysalis Program and his active research on atopic dermatitis and primary immunodeficiencies. Prior to medical school, as a Jumpstart AmeriCorps member, he served as a preschool teacher in the South Bronx and is passionate about education in anaphylaxis among schools. His involvement in the "A Shot to Live" project, supported by a CATCH grant from the American Academy of Pediatrics, allows him to work with schools and community leaders, building strong relationships in the community and raising awareness.