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To The Editor,
Food protein-induced enterocolitis syndrome (FPIES) is a non
IgE-mediated food allergy that predominantly affects infants and is
characterized by repetitive vomiting 1-4 hours after causative food
ingestion which often leads to diarrhea, lethargy, and pallor. Although
the involvement of cellular immunity is suggested, comprehensive
mechanisms of the disorder have been poorly understood. Diagnosis is
often hampered by delayed onset of non-specific symptoms after allergen
exposure and lack of awareness of FPIES. In addition, reliable specific
biomarkers are absent, although acute FPIES attack is accompanied by
neutrophilia, thrombocytosis, methemoglobinemia, and metabolic
acidosis.1
Thymus and activation-regulated chemokine (TARC), a member of the CC
chemokine family, recruits CC chemokine receptor 4+Th2-polarized memory/effector T cells into inflamed tissues. A serum
TARC level serves as a reliable biomarker of AD disease severity in
clinical practice.2 Although high levels of serum TARC
discriminate FPIES from vomiting associated with infectious
gastroenteritis,4 TARC levels are influenced by
several factors such as age and presence of eczema, which make it
difficult to evaluate FPIES by a single measurement of TARC level. A
recent report has demonstrated that serum levels of TARC elevate after
oral food challenge (OFC) in two patients with FPIES, suggesting that
serum TARC levels are potential biomarker of the
disease.3 To validate the utility of TARC in the
diagnosis of FPIES, we examined TARC ratio in a larger number of
patients with FPIES.
The present study enrolled patients with solid FPIES diagnosed by
positive OFC results in our hospital between April 2018 and April 2021.
The open OFC was performed by ingestion at a single or three-divided
doses with 30-minute intervals. OFC was considered positive for FPIES by
delayed abdominal reactions without immediate skin or respiratory
reactions. Tolerance acquisition was defined by both (1) negative OFC
and (2) ability to repeatedly consume daily intakes without FPIES
symptoms for three months at home. Serum TARC levels and C-reactive
protein (CRP) were measured before (pre-OFC) and 24 hours after OFC
(post-OFC). TARC ratio was defined as the ratio of post-OFC to pre-OFC
TARC levels. In the present study, we excluded OFC which missed the data
of TARC ratio. We compared TARC ratio and post-OFC serum CRP levels
between the negative and positive OFC groups. We also collected data of
sex, causative food, age of onset and diagnosis, the number of previous
episodes before diagnosis, specific immunoglobulin E (sIgE) to causative
foods by ImmunoCAP test, and current eczema. A sIgE values higher than
0.35 UA/ml were defined as positive. Statistical
analyses were performed using GraphPad Prism8. Mann-Whitney U test was
used for continuous data between two groups. A correlation of TARC ratio
and serum CRP after OFC was evaluated by using the Spearman correlation
coefficient. A P value of < 0.05 was considered statistically
significant. This study was approved by the institutional review board
of KKR Sapporo Medical Center (2020-54).
Of total 57 OFCs in 25 patients, seven OFC were excluded because of
missing data of TARC ratio. As a result, TARC ratio was analyzed in 50
OFC of 23 patients which consisted of 22 OFC for diagnoses and 28 OFC
for evaluations of tolerance. Characteristics of patients were shown in
Table 1. Tested foods for OFC were 36 for egg yolk (EY), 10 for wheat, 3
for scallop, and 1 for soy. Forty-two (84.0%) of all OFC were positive.
Eight negative OFC (eight patients) were all confirmed acquisition of
tolerance later.
As shown in Figure 1, the median TARC ratio was significantly higher in
the positive OFC group than in the negative OFC group (3.85 vs 1.15,
p=0.018). The pre-OFC CRP levels were all negative (n=50, median 0.02
mg/dL, IQR 0.01-0.03 mg/dL). The median of post-OFC CRP levels in the
negative and the positive OFC groups were 0.02 mg/dL (n=8, IQR 0.01-0.05
mg/dL) and 0.51 mg/dL (n=42, IQR 0.23-1.70 mg/dL), respectively
(p=0.027). Additionally, there was a weak positive correlation between
TARC ratio and post-OFC CRP levels (r2=0.699, p <0.0001).