Inflammatory events during food protein‐induced enterocolitis syndrome reactions

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Food protein‐induced enterocolitis syndrome (FPIES) is increasingly diagnosed among infants,1 despite the problematic differential diagnosis2 and the limited awareness among pediatricians.3 This food‐allergic disorder is characterized by profuse, repetitive emesis, lethargy, and pallor accompanied or followed by watery/bloody diarrhea after the ingestion of specific foods. In severe cases, hypothermia, acidemia, and hypotension/hypovolemic shock may ensue, showing several similarities to a septic state. Although triggered by a specific food, in FPIES, food‐specific IgE could be rarely found. No cutaneous or respiratory involvement is described.
The immune mechanism remains elusive. FPIES may shift to IgE‐mediated food allergy (FA) and vice versa.4 Eosinophils do not seem to play a central role in this disease, so the involvement of T cells, in particular Th1, has been investigated.5 Indeed, white blood counts with neutrophilia, thrombocytosis, metabolic acidosis, and methemoglobinemia characterize a severe acute FPIES reaction.6 TNF‐α increases and higher expression of HLA‐DR in dendritic cells have been observed.7 A comprehensive analysis of T‐cell cytokine responses in children with non‐IgE‐mediated gastrointestinal allergies to milk (FPIES, enteropathy, and proctocolitis) found an increased expression of inflammatory (TNF‐α), monocyte (IL‐10), eosinophil (IL‐5), T cells (IL‐2, IL‐6), and Th2 (IL‐13) cytokines. In FPIES triggered by cow's milk, CD4+ T‐cell‐proliferative response and Th2 cytokines production after casein stimulation were found to be similar to those of control subjects, while after positive oral food challenges (OFCs), higher levels of IL‐10 and of IL‐8 have been recently reported.8 A profound activation of cells of the innate immune system after food challenge, including NK cells, has been found.9 We investigated inflammatory markers in a series of well‐characterized acute FPIES reactions, hypothesizing that FPIES may be associated with features typical of acute inflammatory reactions.
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