Eosinophil ETosis in severe non-IgE-mediated gastrointestinal food allergy, a neonatal necrotizing enterocolitis: A case report

Non-IgE-mediated gastrointestinal food allergy is a hypersensitivity disorder that affects the gastrointestinal tract, operating independently of IgE. While eosinophilic inflammation has been implicated in the literature, its precise role in the pathophysiology of non-IgE-mediated gastrointestinal food allergy remains poorly understood. We report the first documented case of severe non-IgE-mediated gastrointestinal food allergy in which eosinophil infiltration, eosinophil extracellular traps, and Charcot-Lyden crystals were observed in the tissue. A 1-month-old female infant presented with fever, watery diarrhea, and poor weight gain associated with the ingestion of cow's milk-based formula. Despite transitioning to an extensively hydrolyzed formula, she developed necrotizing enterocolitis. Following a switch to an amino-acid-based infant formula, her abdominal symptoms resolved, and her weight gain normalized. However, 1 month later, bile-like vomiting led to the diagnosis of jejunal atresia, which was attributed to scarring from necrotizing enterocolitis. Surgical resection revealed histopathological findings of eosinophil infiltration, cytolytic eosinophil cell death (ETosis), extracellular traps, and Charcot-Lyden crystals. The necrotizing enterocolitis was ultimately diagnosed as a severe manifestation of non-IgE-mediated gastrointestinal food allergy triggered by cow's milk protein. After surgery, the patient resumed feeding with an amino-acid-based infant formula. During regular follow-up, she continued to gain weight well without any clinical symptoms while being fed an amino-acid-based infant formula. To our knowledge, this is the first report to identify a histopathological link between severe non-IgE-mediated gastrointestinal food allergy-related inflammation and eosinophil ETosis. This suggests a potential role of ETosis in the pathogenesis and its complications.