The prevalence of food allergies continues to grow steadily, and due to certain difficulties in diagnosing allergies not associated with immunoglobulin E, some conditions are little known. Such diagnosis-challenging diseases include food protein-induced enterocolitis syndrome (FPIES), a relatively low-prevalence disease most commonly occurring in early childhood but, in some cases, affecting adults as well. The pathogenesis of FPIES has not been reliably studied. FPIES is associated with elevated serum tryptase and release of pro-inflammatory cytokines, including interleukin-17. A characteristic symptom of FPIES is uncontrollable vomiting, which is probably triggered by the serotonin secreted by enterochromaffin cells, which activates the vagus nerve and the vomiting reflex, determining a good response of vomiting relief with ondansetron, a serotonin receptor antagonist. Changes in gut microbiota composition were also reported in FPIES. FPIES can lead to severe complications such as hypovolemic shock due to the rapid progression of symptoms and rapid dehydration, which often requires hospitalization of patients with acute FPIES. The provoking factors usually include products from the "big nine" allergens: cow's milk, eggs, gluten, soy, nuts, peanuts, fish, seafood, and sesame. FPIES can be acute or chronic; the manifestations slightly differ depending on the disease form. Laboratory diagnosis is difficult due to the lack of reliable biomarkers, and the diagnosis is established clinically and confirmed with an oral provocation test. The key treatment for FPIES is to eliminate the trigger protein from the diet, and depending on the severity of the disease, some patients may be allowed to consume a heat-treated allergen. The prognosis of FPIES is favorable: tolerance to the trigger product in most cases is developed within two years. Further studies are required to clarify the pathogenesis, prevalence, and treatment methods, with prospective follow-up of patients with a history of FPIES and the analysis of concurrent and subsequent diseases, including allergic conditions. The article presents two clinical cases of children diagnosed with FPIES.
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