iii. Main text
To the Editor,
Generally, hen’s egg is recommended to be introduced in
infancy.1 However, infants who have food allergies
(FA) other than egg allergy (EA) or eczema are sometimes found to be
sensitized to egg before introduction of egg, and these infants are
often advised to completely avoid egg consumption. Since some infants do
not have true EA, evaluating whether these patients can ingest eggs is
crucial. To date, no method has been established for initiating egg
consumption in sensitized infants. Oral food challenge (OFC) is the gold
standard for the diagnosis of FA and is also critical for patient
management.2 The 2020 Japanese guidelines for food
allergy recommend stepwise OFCs for the diagnosis and management of
FA.3 We have previously reported that stepwise OFCs
are useful and safe for patients suspected with EA.4,5However, most patients in the study had a history of immediate reaction
to eggs and were aged > 1 year. There have been no reports
regarding stepwise OFCs in infants without a history of previous
consumption of egg who were instructed to completely avoid egg
consumption owing to sensitization (egg-sensitized infants). This study
aimed to evaluate the usefulness of stepwise OFCs in egg-sensitized
infants for introducing egg in order to determine the threshold and safe
ingestion dose of egg.
We retrospectively examined infants who were found to be sensitized to
egg after blood tests performed to assess eczema or FA other than EA who
underwent stepwise OFCs between May 2016 and December 2018. Stepwise
OFCs were performed starting with a low dose (containing 1/25 of a
heated whole egg [HE], 250 mg of egg protein). After the low-dose
OFC, we performed an OFC containing 1/8 of a HE (775–769 mg of egg
protein, medium-dose OFC) and later 1/2 of a HE (3076–3100 mg of egg
protein, high-dose OFC) if the results of each previous OFC were
negative. Patients who passed the high-dose OFC received an OFC with
scrambled egg containing a whole egg (6591.5 mg of egg protein,
full-dose OFC) or were instructed to increase egg consumption up to one
HE at home. If the result of the low-dose OFC was positive, the patients
were advised to completely avoid egg consumption. The patients who
failed medium-, high-, or full-dose OFCs were advised to consume the
amount of egg that they could safely ingest (e.g., a seasoned powder,
bread or processed meat, and a donut or slice of cake for positive
medium-, high-, and full-dose OFC patients, respectively, Figure S1).
The challenge foods used in this study are shown in Table S1. Serum
specific immunoglobulin E to egg white (EW-sIgE) and ovomucoid
(OVM-sIgE) levels were measured within 3 months of the low-dose OFC.
Sensitization to egg was defined as an EW-sIgE level > 0.10
kUA/L.
Of the 148 egg-sensitized infants who underwent low-dose OFC, 61 were
excluded because they did not meet the eligibility criteria (Figure 1).
The median OVM-sIgE level of the patients included in this study was
significantly higher than that of those who were excluded (Table S2).
The median age was 9.9 (interquartile range, 8.9–10.9) months, and the
median EW-sIgE and OVM-sIgE levels were 18.0 and 0.99
kUA/L, respectively.
Among 87 egg-sensitized infants, 12 failed the low-dose OFC and 9 and 8
failed medium- and high-dose OFC, respectively. Of the 58 patients who
passed the high-dose OFC, 32 underwent full-dose OFC and 26 were
instructed to increase egg consumption at home. Two patients failed the
full-dose OFC and 56 were able to ingest a full dose (Figure 1). Thus,
64% (56/87) of egg-sensitized infants did not have an allergic reaction
to egg. Of the 31 patients allergic to egg, the threshold dose was ≤1/25
of a HE for 39% (12/31), >1/25–1/8 for 29% (9/31),
>1/8–1/2 for 26% (8/31), and >1/2–1 for 6%
(2/31) (Figure 2). Therefore, 14% (12/87) of egg-sensitized infants
needed to continue to completely avoid egg consumption. The median time
between the low- and full-dose OFC was 10.8 months. The median time
between the low-dose OFC and the date when the patients were able to
ingest a full dose was 16.1 months. Probability curves based on the
results of these OFCs are shown in Figure 3. The probability curves show
that >50% of egg-sensitized infants would pass a low-dose
OFC even if their EW-sIgE or OVM-sIgE levels exceeded 100
kUA/L. The symptoms and treatment during OFCs are
described in Table S3. There were no severe symptoms in the medium- and
full-dose OFCs. However, one patient received intramuscular adrenaline
during the low-dose OFC because of vomiting and appearance of a pale
face. In the high-dose OFC, one patient developed a severe reaction
(barking cough).
This study revealed that the rate of positive reactions to stepwise OFCs
for egg-sensitized infants was not high, and stepwise OFCs clarified the
threshold and safe ingestion dose of eggs in these infants. Since the
rate of positive reactions to low-dose and medium-dose OFCs was lower in
egg-sensitized infants than in patients with a history of immediate
reactions to egg4 (14% vs. 21% and 12% vs. 14%,
respectively), stepwise OFCs seem to be safer in egg-sensitized infants
than in those with immediate reactions to egg. In addition,
>50% of egg-sensitized infants passed low-dose OFCs even
if their EW-sIgE or OVM-sIgE levels exceeded 100 kUA/L.
Therefore, even if infants have relatively high levels of EW-sIgE or
OVM-sIgE, performing OFCs from a low initial dose may be considered.
Regarding the threshold dose in egg-sensitized infants, a previous study
reported that 33% reacted to a boiled egg white OFC equivalent to one
half of an egg.6 In our study, the proportion of
egg-sensitized infants who reacted to ≤1/2 of a HE was similar (33%,
29/87). However, by performing stepwise OFCs, 59% (17/29) could ingest
≤1/8 of a HE. For patients with EA, avoiding complete elimination of
eggs may improve their prognosis7,8 and quality of
life (QOL).9 Therefore, stepwise OFCs appear to be
beneficial for egg-sensitized infants.
This study had some limitations. First, OFCs were not double-blind
placebo-controlled. However, since most symptoms induced during OFCs
were objective, the number of false-positive OFCs was considered to be
low. Second, a few patients may have achieved tolerance during intervals
between OFCs. However, since only 30% of Japanese EA patients achieve
tolerance by 3 years of age,10 the influence of
intervals between OFCs is likely minimal. Third, approximately 40% of
the egg-sensitized infants were excluded because of not undergoing
stepwise OFCs, and the median OVM-sIgE level of these patients was
significantly lower than that of those who were included. Therefore, our
study may have overestimated the rate of positive reactions to stepwise
OFCs for egg-sensitized infants.
In conclusion, stepwise OFCs appeared to be relatively safe for the
introduction of egg in egg-sensitized infants. We found that only a
small number of these infants required complete avoidance of eggs and
that the majority of them were able to ingest a whole egg in the form of
scrambled egg. We expect that stepwise OFCs will help improve the
management of egg-sensitized infants who have completely avoided egg
consumption.