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.