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REVIEW
Optimizing Patient Care in Egg Allergy Diagnosis
and Treatment
Aikaterini Anagnostou
1,2
1
Baylor College of Medicine, Section of
Pediatric Immunology, Allergy and
Retrovirology, Houston, TX, USA;
2
Texas
Children’s Hospital, Department of
Pediatrics, Section of Immunology,
Allergy and Retrovirology, Houston,
TX, USA
Abstract: Egg allergy occurs frequently in childhood with a reported prevalence of
1.3–1.6%. Providing optimal care to egg-allergic patients requires knowledge of the
most up-to-date developments in both diagnosis and management, as well as effective
communication skills, which will engage the patient in the shared decision-making
process. This review aims to provide up-to-date information on egg allergy and also
serve as a concise guide on optimal patient diagnosis and management. The eld of food
allergy has seen multiple advances in recent years, including use of component resolved
diagnostics, early egg introduction into the infant diet as a way of preventing egg allergy,
baked egg introduction and oral immunotherapy as a form of active therapy. Faced with
a variety of options and treatment paths, it is important to ensure that patients and
families taking part in the decision-making process have fully understood the potential
outcomes and trade-offs and can undertake a detailed discussion of all options that are
available to them. Shared decision-making remains the cornerstone of optimal patient
care.
Keywords: food allergy, children, egg, components, prevention, food challenge, food allergy
action plan, management, oral immunotherapy, desensitization, shared decision-making
Introduction
Food allergies are common, affecting 6–8% of the children
1,2
and affect the
quality of life of children and their caregivers.
3
Food-allergic patients often
worry about unintentional exposures and their consequences, especially anaphy-
laxis and life-threatening events. Patients face multiple dietary and psychosocial
restrictions (such as exclusion from peer social activities and bullying).
4–7
Optimal care for food allergy should place the best interests of the patient in its
core and include the ability to adhere to evidence-based clinical guidelines, support
patient needs, have an established referral system within a dened provider network
and implement shared decision-making. Providing optimal care to egg-allergic
patients requires knowledge of the most up-to-date developments in both diagnosis
and management, as well as effective communication skills, which will engage the
patient and their family in the shared decision-making process.
We live in an era when patients have access to a multitude of medical informa-
tion sources, are encouraged to make their own decisions about their care and opt
for the options that best t their needs. This review aims to provide up-to-date
information on egg allergy and also serve as a concise guide on optimal patient
diagnosis and management.
Correspondence: Aikaterini Anagnostou
Baylor College of Medicine, Section of
Pediatric Immunology, Allergy and
Retrovirology, 1102 Bates Avenue Ste
330, Houston, TX, 77030, USA
Tel +1 832-824-1319
Fax +1 832-825-1260
Email Aikaterini.Anagnostou@bcm.edu
Journal of Asthma and Allergy 2021:14 621–628 621
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Epidemiology and Natural History
Egg allergy is one of the most frequent childhood food
allergies with a reported prevalence of 1.3–1.6%.
8,9
In
a US-based study, using data from the National Health
and Nutrition Examination Survey, prevalence estimates
for sensitization to egg were 3.4% for children 6 years old
and over, and 14.2% for children below the age of 6
years.
10
The clinical egg allergy prevalence was overesti-
mated, but the study provided some insight into prevalence
rates.
10
In a recent Australian study, egg allergy was
reported as affecting 8.9% of 1-year old infants
11
all of
whom underwent an oral food challenge for conrmation
of the diagnosis.
Egg allergy usually develops in the rst year of life
12
and
is outgrown by the majority of patients. Knowing the natural
history of egg allergy is important for the physician, in order
to plan next steps in management, such as avoidance of egg
or consideration of baked egg introduction (less allergenic
form than cooked or raw egg) or even reintroduction of egg
in all forms into the diet if the allergy has resolved. Research
studies have examined the natural history of egg allergy
13–16
showing that although most children will outgrow it, resolu-
tion occurs gradually, over many years. A UK prospective
study in 95 egg-allergic children reported that nearly one-
third had outgrown their allergy to well-cooked egg at 3 years
of age and two-thirds at 6 years.
15
Generally, allergy to well-
cooked egg was shown to resolve twice as quickly as allergy
to the uncooked form.
15
In 881patients with egg allergy in the
United States, it was shown that 4% outgrew their allergy by
age 4 years, 12% by age 6 years, 37% by age 10 years, and
68% by age 16 years.
13
Another study examining egg allergy
resolution in 213 egg-allergic children recruited from pri-
mary care, the median age of resolution was 6 years with
50% of children outgrowing their allergy by this time.
16
These studies highlight geographical differences as well as
population differences in the observed natural history of egg
allergy. High egg-white specic IgE levels and sensitization
to the stable egg-white allergen component Gal d 1 have also
been associated with persistent egg allergy.
17
It is important to inform patients and families of these
resolution rates, in order to address any misconceptions
(some families may believe egg allergy is lifelong, for
instance) and manage expectations.
Diagnosis
The gold standard diagnostic tool for egg allergy remains
an oral food challenge under medical supervision. In daily
practice, a clinical history of an allergic reaction occurring
after ingestion of egg, together with positive testing (egg
skin prick test or egg-specic IgE) is usually used for
diagnosis.
18
Sampson et al reported on the 95% egg-
specic IgE-positive predictive value for diagnosis as 6
kUA/L, assisting clinicians in the diagnostic process.
19
Their retrospective analysis included 100 with atopic der-
matitis and food allergy, between 3 months and 14 years of
age.
19
Using the above cut-offs, physicians may also plan
oral food challenges to egg accordingly.
As mentioned above, egg allergy is naturally outgrown
over time by the majority of children.
13
Monitoring egg-
specic IgE antibodies regularly may help to decide when
an egg challenge can be repeated.
20,21
Both the patient and
their family stand to benet from re-introducing egg into
the diet, in terms of nutrition and a wider variety of food
product choices.
22,23
In addition to diagnostic cut-offs,
studies have examined cut-offs for recommending an egg
challenge to evaluate allergy resolution. When the chance
of passing a challenge is 50% or more, most allergists
would recommend an oral challenge.
24
Matsui et al pro-
posed a cutoff level for egg-specic IgE of 2 kUA/L;
almost two-thirds of patients at less than this level were
able to pass their challenge.
24
However, It is important to
note that even when levels of egg-specic IgE are unde-
tectable, it is still possible for patients to fail an egg
challenge.
24
Therefore, the decision to undertake
a challenge should be made jointly by physician and
patient, as part of the shared decision-making process
and discussions.
There are currently no universally accepted cut-offs for
either skin prick test or specic IgE that may predict which
children will be able to tolerate the baked form of egg.
However, component resolved diagnostics (CRDs) have
emerged as a novel diagnostic tool, with improved speci-
city compared to traditional specic IgE testing, as well
as the potential to differentiate clinical allergy from
sensitization.
25
In egg-allergic children, two components
are used to help physicians differentiate between transient
and persistent egg allergy.
26–29
First, Gal d 1 (ovomucoid),
a dominant allergen, which is stable against heat and
digestion has been associated with persistent egg allergy
and a decreased probability of cooked/heated egg
tolerance.
26–28
Second, Gal d 2 (ovalbumin), representing
55% of the total egg white protein, has been associated
with transient egg allergy and an increased probability of
cooked/heated egg tolerance.
17,28,29
Identifying different
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patient phenotypes of egg allergy is an important contribu-
tion of component resolved diagnostics.
In a hypothetical scenario of an egg-allergic patient
requesting diagnostic conrmation or further management
options (such as baked egg introduction), CRDs and oral
food challenges have a role to play in optimizing both
diagnosis and care and the patient should be informed of
these options, if available to them.
Prevention with Early Introduction
of Egg
The timing of food allergen introduction to infants likely
plays a role in the development of food allergy later in life.
For many years, patients were advised to delay the intro-
duction of allergenic foods, including egg, but this advice
was reversed in recent guidelines, which strongly encou-
rage early introduction of all common food allergens into
the infant diet from 6 months of age.
30
This recommenda-
tion came as a result of multiple research studies support-
ing the notion that early introduction of allergenic foods
into an infant’s diet may prevent the development of
a food allergy.
31–34
Specically for egg, in the EAT study, there was
a signicant decrease in egg allergy for infants introducing
egg at age 3 months compared with infants that were
exclusively breast fed when per protocol analysis was
applied (1.4 vs 5.5%, p = 0.009).
35
In an Australian
study of high-risk infants with moderate to severe eczema,
approximately a third of infants in the early introduction
group (from 4 months of age) developed egg allergy,
compared with half the infants in the late egg introduction
group (from 8 months of age), p=0.11; the assessment was
performed at 1 year of age. Interestingly, even as early as 4
months of age, over one-third of the included infants
already had detectable egg-specic IgE levels, despite
not having any oral egg exposure. This nding suggests
that sensitization to egg occurs early in life, before 4
months.
36
In a larger cohort of healthy high-risk infants
randomized to either raw egg or placebo from 4 to 6
months of age results were similar between the groups.
Egg allergy developed in 7% of infants receiving raw egg
compared with 10.3% of infants in the placebo arm (p =
0.20).
37
A different RCT reported a signicant difference
in the proportion of infants sensitized to egg at 12 months –
20% versus 11% in infants randomized to placebo and
egg, respectively (p = 0.03).
38
A more recent two-center Japanese study (the ‘PETIT’
study)
39
found that the introduction of heated egg in small,
gradual dose increases was both safe and effective in the
prevention of egg allergy (p = 0.0001). A total of 147 infants
were randomly assigned to early introduction of egg or
placebo. Egg allergy was diagnosed in only 8% of the
infants receiving 50 mg of heated egg powder daily from 6
to 9 months of age and 250 mg daily thereafter until 12
months of age. In the placebo group, egg allergy was diag-
nosed in 38% (p=0.0001). Finally, in a cross-sectional study
by Koplin et al, which included 2589 infants, a lower rate of
egg allergy was noted for participants who received cooked
egg at 4–6 months than those who received cooked egg after
that age.
40
Older age of introducing egg increased the risk of
developing egg allergy in both low-risk infants and high-risk
infants (those with eczema, history of reactions to foods, or
a family history of food allergy) with reported p=0.22 and
p < 0.001, respectively.
40
In addition to the above research studies, a recent sys-
tematic review and meta-analysis, which included six RCTs
and a total of 3032 participants, reported a protective effect
with early egg introduction with 37 fewer cases of egg
allergy per 1000 people (assuming a 9.3% incidence of
egg allergy in the studied population).
41
Recent Australian data show a complete change in the
behavior of new parents with earlier introduction of egg in
their infants’ diet following publication and dissemination
of the new guidelines supporting early introduction.
42
The
majority of parents fed their infants cooked (rather than
baked) egg in an effort to limit the amount of sugar in the
diet. It is reported that the majority of Australian parents
are following the new recommendations from the govern-
ment and medical societies and are successfully feeding
their infants egg by 1 year of age, which is much earlier
than what was seen previously.
42
Management
The optimal management of egg allergy includes various
components, such as medical interventions, dietetic input
and active treatment approaches, such as introduction of
baked egg and oral immunotherapy. These components are
explored in more detail below.
Medical Management
A comprehensive management plan or “Food allergy Action
plan” is essential and should include advice on identication
and treatment of allergic reactions as well as education on
the use of epinephrine auto-injectors.
43,44
The management
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plan needs to include not only immediate family members
but also members of the wider environment of the child,
such as nannies, grandparents and school personnel.
Reactions to accidental exposures may occur, but education
on how to quickly identify the relevant signs and symptoms
and how to promptly administer the appropriate treatment
are key to mitigate negative outcomes.
44,45
Provision of emergency medication is another key ele-
ment of medical management. Epinephrine is the rst-line
treatment for anaphylaxis, and long-acting oral antihista-
mines may be used for mild reactions.
44,46
Finally, patient follow-up by a qualied allergist is
important. The allergist may provide ongoing education
on preventing and managing future reactions as well as
perform allergy tests periodically to assess for natural
resolution. Additionally, for patients who are avoiding all
forms of egg, regular assessments should be made to
evaluate for baked egg challenges and introduction.
Dietary Management
All patients require clear information on egg avoidance.
47
Dietitians play a key role in educating patients and
families in this area.
48
Education should include discus-
sions on food labelling (both ingredients list and “may
contain” statements) and patients should be advised to
read both the ingredients list and the precautionary aller-
gen labelling (PAL) on the foods they buy, every time, as
recipes may change over time.
49
Patients often nd PAL
statements difcult to interpret without dietetic input.
When eating outside the home patients need to be edu-
cated on certain risks. Miscommunication is a common
problem, so patients should liaise directly with staff in
restaurants and other food establishments to avoid egg
“contamination” (also known as “cross contact”) in their
meal.
50
Clear communication (such as alerting the restau-
rant in ahead of time of the food allergy, involving senior
staff or the chef in the order, and ensuring the table sur-
face is adequately cleaned) is key in minimizing risk.
51
Cross-contact is common in buffets where food is shared
and cleaning tends not to be thorough. Parents should be
advised that simple dishes with ingredients that are
clearly stated are often a better option than complex
dishes with multiple different ingredients and complicated
recipes.
50
Role of Baked Egg Introduction
Different forms of egg display different allergenicity, with
raw egg being the most allergenic and baked egg the least.
Generally, heating appears to reduce allergenicity.
52
Studies suggest that up to 70% of egg-allergic children
are able to tolerate egg that is baked.
53
This provides some
benets such as a more inclusive diet, better nutrition, less
social restrictions and, as a result, better quality of life.
The role of baked egg introduction in the resolution of
egg allergy is more controversial, with a recent systematic
review suggesting that more evidence is needed in this
area, especially in the form of randomized trials of baked
egg consumption versus baked egg avoidance in baked-
tolerant participants.
54
However, multiple observational
research studies report a benecial effect with regular
baked egg consumption.
55,56
Children who react to baked
egg in their initial exposure appear to have a more severe
phenotype and lower rates of natural resolution. In con-
trast, children with negative or low sensitization to Gal d 1
are more likely to tolerate baked/heated egg.
26,27
This
information may be helpful to the clinician when consider-
ing an oral challenge and introduction of baked egg.
Peters et al examined 140 infants with challenge-
conrmed egg allergy at age 1 year and reported egg
allergy resolution in 47%, 12 months later (at age 2).
55
Those infants who had reacted to baked egg at baseline,
showed lower rates of resolution. Additionally, infants
that consumed baked egg more than 5 times per month
had better odds in developing tolerance.
55
A similar
study, which included 70 participants who regularly ate
baked egg, evaluated the role of baked egg in the devel-
opment of tolerance to regular egg.
56
A reported 53% of
the above participants were able to tolerate regular egg
after an approximately 3-year study period, compared
with only 28% of the participants in the comparison
group (who all adhered to strict avoidance).
Additionally, regular baked egg consumers were 14
times more likely to develop tolerance compared with
the strict avoidance group and tolerance was achieved
much earlier (50 months versus 78.7 months in the avoid-
ance group).
56
As part of optimal care, the role of baked egg intro-
duction should be discussed with patients, including ben-
ets (nutritional, social) and risks (allergic reactions
during the challenge), as this simple intervention has the
potential to change the daily life of the egg-allergic child
and potentially speed up their allergy resolution.
Egg Oral Immunotherapy
Food oral immunotherapy (OIT) is a new form of active
therapy for food allergies. The administration of small but
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increasing doses of the allergenic food allows patients to
gradually increase their ability to consume small to medium
amounts of their allergen without reactions.
57
Food oral
immunotherapy studies have been conducted for most of
the common childhood food allergens, including egg.
58–61
In a seminal randomized oral immunotherapy study of
55 children, with egg allergy, a 55% rate of desensitization
was noted in the active arm after 10 months of therapy
compared with 0% in the placebo arm. An additional year
of egg OIT increased the desensitization rate to 75%
supporting the notion that longer treatment periods likely
result in higher desensitization rates
59
. A 4-year follow-up
of the above subjects has reinforced the above statement
showing that longer duration of therapy increases the like-
lihood of tolerating regular egg.
58
A recent trial evaluated 50 participants aged 3–16 years,
which were reactive to unbaked egg and were assigned to 2
years of treatment with either baked egg or egg OIT.
62
A comparison group of baked egg-reactive children were
also included and received egg OIT. Following 2 years of
treatment, therapy was discontinued for 8–10 weeks to
examine sustained unresponsiveness.
62
A total of 11.1% of
children consuming baked egg compared with 43.5% of
children receiving egg OIT achieved the desired outcome
(sustained unresponsiveness, P = 0.009).
62
In the baked egg-
reactive group, 17.9% achieved sustained unresponsiveness.
Children receiving egg OIT were much more likely to reach
the desired outcome compared with those consuming baked
egg alone (without OIT).
62
Finally, a systematic review investigating efcacy and
safety of egg OIT included 10 RCTs and a total of 439
participants between 1 and 18 years.
63
The majority of
children receiving egg OIT were able to consume
a partial serving of egg (1–7.5 g) compared to only 10%
in the avoidance group. A full portion of egg was success-
fully consumed by almost 50% in the OIT group compared
to 10% of the avoidance group.
63
The authors reported that
OIT induces tolerance in almost 50% of the subjects
compared with only 1 in 10 subjects who follow egg
avoidance.
63
However, adverse events are much more
frequent in the treatment arm and some children (reported
as 1 in 12 study participants) may suffer severe allergic
reactions requiring epinephrine.
63
It appears that oral immunotherapy for egg allergy is
effective, but this is not without risk. The risk–benet ratio
should be clearly outlined and discussed in detail with
patients and families, so they can make the decision that
best ts their expectations and preferences.
Shared Decision-Making
Shared decision-making is important for any disease with
long-term management, such as egg allergy.
64,65
As there are
multiple different management and therapy options available
to patients currently, each with its own benets and risks,
shared decision-making presents signicant value.
66
The landscape of egg allergy has evolved in both
diagnostics and treatment over recent years, with
a variety of novel interventions such as component
resolved diagnostics, oral immunotherapy, and early intro-
duction with the aim to prevent egg allergy development.
This rapid advancement can be challenging to patients as
they try to understand potential outcomes and trade-offs of
different available options, and decide which aspects of
management matter to them the most, so they can reach
a decision on how to proceed.
66,67
See Figure 1.
The role of young children in decision-making discus-
sions should also be emphasized and youngsters should be
encouraged to participate in decisions about their care, if
they wish, from an appropriate age. Both parents and
healthcare providers have a duty to support children as
they navigate the – often confusing – landscape of their
disease and learn to make decisions on their own. The
young patient’s concerns may be addressed during the
Figure 1 Optimizing patient care in egg allergy.
Abbreviations: CRDs, component resolved diagnostics; OIT, oral immunitherapy.
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clinic visit by the allergist, their opinions should be sought
and their preferences for care should be investigated and
discussed. Children may sometimes not reveal their lack of
understanding of complex concepts, so a jargon-free lan-
guage would be useful to assist them in this area.
68
Parents
may also engage their children separately in decision-
making and ensure they are ready to transition to indepen-
dence during adolescent and adult years.
68
A relationship of trust and respect between patients,
families and clinicians in combination with a safe,
unrushed environment where different opinions may be
heard and analyzed, and validated decision aids may be
incorporated into patient care will provide the patient with
a valuable and optimal care experience.
69
Conclusions
It is clear that optimizing the care of the egg-allergic
patient includes multiple elements, both in terms of diag-
nosis and management. These need to be addressed by the
physician looking after the patient so that jointly, patients/
families and physicians may discuss available options and
treatment pathways and make appropriate decisions. It is
important to note that shared decision-making remains the
cornerstone of optimal patient care and should be applied
in all relevant interactions in the allergy clinic.
Abbreviations
OIT, oral immunotherapy; PAL, precautionary allergen
labelling; QoL, quality of life; RCT, randomized con-
trolled trials.
Funding
There is no funding to report.
Disclosure
None directly relevant to this work.
Dr Aikaterini Anagnostou is the principal investigator
for Aimmune Therapeutics research peanut oral immu-
notherapy trials and receives Institutional grant funding,
and serves as an advisory board member for DBV
Technologies.
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