Introduction
Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE cell-mediated allergy characterized by repetitive vomiting and diarrhea after ingestion of offending food. Symptoms are often severe and can result in acute dehydration and lethargy.1 Although FPIES cases are currently increasing, little is known about the pathophysiology of this disease. In the absence of specific laboratory tests, diagnosis predominantly relies on clinical responses to elimination diets with a resolution of symptoms, oral food challenges with reappearance of symptoms following ingestion of the offending food, results of endoscopic and biotic exams, and exclusion of causes such as infection, inflammatory bowel disease, ischemia, and metabolic disorders.2
Previous studies have suggested that several cytokines are involved in the pathogenesis of FPIES.3-5 The serum levels of interleukin (IL)-2 and IL-10 were found to be elevated in patients with FPIES after oral food challenge (OFC) tests.4,5Kimura et al.4reported that the increase in T cell-produced serum IL-2, detected in OFC-positive patients, is associated with FPIES pathophysiology. Caubet et al.5 suggested that, in patients with acute FPIES, T cells have a reduced capacity to secrete IL-10, and other cell populations, such as monocytes, may produce compensatory IL-10 in response to antigen exposure. The increased serum level of IL-8 and the elevation of neutrophils after OFC suggest that neutrophils play an important role in acute-phase FPIES.
This disease is classified as acute or chronic FPIES and each timing and duration of symptoms is different. Recent international consensus guidelines define acute FPIES by the following criteria: 1) it occurs after intermittent food exposure, 2) emesis usually starts within 1–4 hours and is accompanied by lethargy and pallor, 3) diarrhea can follow within 24 hours (usual onset after 5–10 hours), and 4) symptoms usually resolve within 24 hours after elimination of the food from the diet.6 However, due to the absence of predictive biomarkers, these criteria are mainly based on clinical symptoms.
Since the main symptom of acute FPIES is vomiting, analytical tools capable of distinguishing FPIES from mimicking diseases that also cause vomiting, such as infectious enterocolitis, are strongly required. Lee et al.7examined the clinical and laboratory characteristics of patients referred to emergency departments for symptoms suggestive of acute FPIES, such as lethargy, floppiness, pallor, and normal C-reactive protein (CRP), and compared these features with those of gastroenteritis and bacterial sepsis. However, their retrospective study had substantial limitations because the diagnoses were not made by allergists, and comprehensive data, including FPIES-related cytokines, were not evaluated.
Therefore, we aimed to identify biomarkers capable of differentiating acute FPIES from infectious enterocolitis or IgE-mediated anaphylaxis. In order to identify changes specific to acute FPIES, we compared the serum levels of different cytokines in patients with acute FPIES, infectious enterocolitis, and IgE-mediated anaphylaxis. Our results revealed new potential biomarkers for the differential diagnosis of acute FPIES.