iv. Main text:
To the Editor,
Hen’s egg (HE) is consumed worldwide and is one of the most frequent
causes of food allergy.1,2 In Japan, HE is consumed
most frequently among avian eggs, followed by quail’s egg (QE). Quails
(Coturnix japonica ) belong to the same Galliformes
Phasianidae family as chicken (Gallus gallus domesticus );
therefore, cross-reactivity may occur between HE and QE. Consequently,
HE allergic patients are generally advised to avoid QE consumption.
However, there has been only one report on the serological
cross-reactivity of HE and QE3 and one case report on
clinical cross-reactivity.4 Moreover, whether all HE
allergic patients need to avoid QE consumption remains unclear. This
study, therefore, aimed to evaluate
the clinical cross-reactivity
between HE and QE by performing oral food challenge (OFC) tests.
We conducted a prospective study to determine whether HE allergic
patients show cross-reactivity to QE. We performed QE-OFC in patients
with HE allergy between January 2018 and October 2019. HE allergy was
diagnosed through OFCs, which were performed stepwise, starting from a
low-dose HE-OFC (containing 1/25 of a heated HE). Patients with negative
results proceeded to a medium-dose HE-OFC (containing 1/8 of a heated
HE). Patients with positive low-dose or medium-dose HE-OFC were included
in this study. Patients with missing clinical data were excluded. QE-OFC
was performed using one heated QE. All OFCs were performed in a
single-dose or two-dose administration. In the two-dose OFCs, the
challenged food was distributed at 60-min intervals. Symptom severity
during OFCs was assessed according to the Japanese guidelines for food
allergy.2 Serum levels of total immunoglobulin E (IgE)
and specific IgE to HE white (HEw-sIgE), HE ovomucoid (OVM-sIgE), and QE
white (QEw-sIgE) (ImmunoCAPTM; Thermo Fisher
Scientific/Phadia, Uppsala, Sweden) were measured within four months of
conducting QE-OFC, and skin prick test (SPT) was performed during
QE-OFC. The SPT procedure is described in Supplemental Methods. This
study was approved by the ethics committee of Sagamihara National
Hospital (approval number: 2017-021), and was registered at the
University Hospital Medical Information Network Clinical Trials Registry
(no: UMIN000034820). The written informed consent was obtained from the
guardians of all patients.
Among 870 patients who underwent HE-OFC, 183 failed in the low-dose or
medium-dose HE-OFC, 22 of whom underwent a QE-OFC. Two patients were
excluded because of missing clinical data, and the remaining 20 were
enrolled (Figure 1). Median patient age was 2.9 (range, 1.0–16.4)
years, and nine (45%) patients had a history of anaphylaxis to HE. The
median HEw-sIgE, OVM-sIgE, and QEw-sIgE levels were 9.95 (2.67–365),
8.66 (<0.10–191), and 4.15 (0.73–>100)
kUA/L, respectively (Table 1). There was a correlation
between HEw-sIgE and QEw-sIgE levels (Supplemental Figure 1). SPT was
performed in 13 patients, and 12 (92%) were found to be sensitized to
QE. The median SPT wheal diameters for HEw and QEw were 15 (3–32) and
12 (0–25) mm, respectively.
Among the 20 patients, four reacted to the low-dose HE-OFC (threshold
dose, 1/25 of a heated HE or lower), and 16 passed the low-dose HE-OFC
but reacted to the medium-dose HE-OFC (threshold dose,
>1/25–1/8 of a heated HE). Of the 20 patients, 9 (45%)
failed in the QE-OFC. The median interval between QE-OFC and HE-OFC was
2.8 months. The rate of positive QE-OFC results was significantly higher
in patients with a threshold dose of ≤1/25 of a heated HE than in those
with a threshold dose of >1/25–1/8 of a heated HE (100%
[4/4] vs. 31% [5/16], p = 0.026; Figure 2). Patients’
symptoms, severity, and treatment during the QE-OFC are described in
Supplemental Table 1. Three patients presented with symptoms in multiple
organs; however, their symptoms improved after treatment with
antihistamine and steroid or inhalation of β 2stimulants. The HEw-sIgE, OVM-sIgE, and QEw-sIgE levels were
significantly higher in patients with a positive QE-OFC result than in
those with a negative QE-OFC result. There was no significant difference
in the SPT wheal diameter to HEw and QEw between patients who reacted to
QE-OFC and those who did not (Table 1).
To our knowledge, this is the
first prospective study to evaluate the clinical cross-reactivity
between HE and QE through OFC tests. In this study, clinical
cross-reactivity to QE was observed in almost half of the patients who
were allergic to HE.
In a previous case report, a patient with HE allergy showed
cross-reactivity to QE.4 Furthermore, approximately
70% of HE allergic children had a positive SPT result to
QEw5; however, whether they showed clinical
cross-reactivity to QE was not confirmed. In our study, 92% of the HE
allergic patients had a positive SPT result to QEw, and 45% reacted to
one QE.
The mean weight of HE and QE is 58g and 11.3g,
respectively.6 Because the ratio of egg white and egg
yolk mass in HE is almost equivalent to that of QE6,7and the percentage of protein in HEw is also equivalent to that of
QEw,6 the amount of protein in the egg white of one QE
would be equivalent to approximately 1/5 of that in one HE. Since the
main antigen of immediate-type egg allergy is egg white, if the
antigenicity of HEw and QEw is deemed to be identical, all HE allergic
patients with a threshold dose of ≤1/8 of a heated HE would be expected
to fail a QE-OFC. However, in this study, while all the patients with a
threshold dose of ≤1/25 of a heated HE failed the QE-OFC, only 31%
patients with a threshold dose of >1/25–1/8 of a heated HE
failed. Therefore, QEw antigenicity seemed to be lower than that of HEw
when comparing in terms of the same amount of protein, and whether HE
allergic patients reacted to one QE appeared to depend on their
threshold of HE.
This study has some limitations. First, OFCs were not double-blind and
placebo-controlled. However, as most patients exhibited objective
symptoms during OFCs, the number of false-positive OFC results would be
low. Second, some patients may have achieved tolerance during the
interval between the OFCs. However, the interval between QE-OFC and
HE-OFC was relatively short, with a median of 2.8 months. Moreover, the
median age of the subjects in this study was 2.9 years, and since it has
been reported that only 30% of Japanese HE allergic patients achieve
tolerance between 3 and 6 years old,8 the influence of
the interval between the OFCs is considered minimal. Third, we did not
evaluate whether patients with negative QE-OFC results were reactive to
amounts larger than one QE. Therefore, our study may have underestimated
the rate of patients who had true clinical cross-reactivity to QE.
Further studies with a larger number of patients, including those with a
higher HE threshold, are necessary.
In conclusion, this study showed that some HE allergic patients are
clinically cross-reactive to QE. Furthermore, patients with a lower
threshold of HE were more likely to react to QE. Therefore, HE allergic
patients, especially those with a low threshold, should consider
avoiding QE consumption.
Masatoshi Mitomori, MDa, Noriyuki Yanagida,
MDa, Mari Takei, MDb, Kinji Tada,
MDb, Makoto Nishino, MDa, c, Sakura
Sato, MDb, Motohiro Ebisawa, MD,
PhDb
aDepartment of Pediatrics, National Hospital
Organization, Sagamihara National Hospital, Kanagawa, Japan
bClinical Research Center for Allergy and
Rheumatology, National Hospital Organization, Sagamihara National
Hospital, Kanagawa, Japan
cCourse of Allergy and Clinical Immunology, Juntendo
University Graduate School of Medicine, Tokyo, Japan.