Clinical Management Review

Clinical Management of Food Allergy

J. Andrew Bird, MDa, Gideon Lack, MD, FRCPCHb,c, and Tamara T. Perry, MDd,e Dallas, Tex; London, United Kingdom; and
Little Rock, Ark

INFORMATION FOR CATEGORY 1 CME CREDIT

Activity Objectives

Credit can now be obtained, free for a limited time, by reading the
review articles in this issue. Please note the following instructions.

1. To use tests for food allergy appropriately.

Method of Physician Participation in Learning Process: The core

material for these activities can be read in this issue of the Journal or
online at the JACI: In Practice Web site: www.jaci-inpractice.org/. The
accompanying tests may only be submitted online at www.jaciinpractice.org/. Fax or other copies will not be accepted.
Date of Original Release: January 2015. Credit may be obtained for
these courses until February 28, 2016.

3. To recognize and appropriately treat a food-induced allergic

reaction.
4. To provide appropriate guidance for a child with food allergy who is
attending school.

Copyright Statement: Copyright 2014-2016. All rights reserved.

Recognition of Commercial Support: This CME has not received

external commercial support.

Overall Purpose/Goal: To provide excellent reviews on key aspects of

allergic disease to those who research, treat, or manage allergic disease.

Disclosure of Signicant Relationships with Relevant Commercial

Target Audience: Physicians and researchers within the eld of

allergic disease.
Accreditation/Provider Statements and Credit Designation: The
American Academy of Allergy, Asthma & Immunology (AAAAI) is
accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates these educational activities for a maximum
of 1 AMA PRA Category 1 Credit. Physicians should only claim credit
commensurate with the extent of their participation in the activity.
List of Design Committee Members: J. Andrew Bird, MD, Gideon
Lack, MD, FRCPCH, and Tamara T. Perry, MD

Food allergies are commonly seen by the practitioner, and

managing these patients is often challenging. Recent
epidemiologic studies report that as many as 1 in 13 children in
the United States may have a food allergy, which makes this an
important disease process to appropriately diagnose and manage
for primary care physicians and specialists alike. Having a
understanding of the basic immunologic processes that underlie
varying presentations of food-induced allergic diseases will guide
a

2. To instruct patients and families on recommendations for food

allergen avoidance, including label reading, potential cross-contact, and
eating away from home.

Division of Allergy and Immunology, Department of Pediatrics, University of

Texas Southwestern Medical Center, Dallas, Tex
b
Division of Asthma, Allergy and Lung Biology, MRC and Asthma UK Centre in
Allergic Mechanisms of Asthma, Kings College London, London, United Kingdom
c
Childrens Allergy Unit, Guys and St Thomas NHS Foundation Trust, London,
United Kingdom
d
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Ark
e
Department of Allergy and Immunology, Arkansas Childrens Hospital, Little
Rock, Ark
No funding was received for this work.
Conicts of interest: J. A. Bird has received research support from DBV Technologies,
Allergen Research Corporation, and the Foundation of the American College of
Asthma, Allergy and Immunology; and has received lecture fees from Nutricia North
America. G. Lack has received research support from the Immune Tolerance

Companies/Organizations: J. A. Bird has received research support

from DBV Technologies, Allergen Research Corporation, and the
Foundation of the American College of Asthma, Allergy and Immunology; and has received lecture fees from Nutricia North America.
G. Lack has received research support from the Immune Tolerance
Network/National Institute of Allergy and Infectious Diseases, Food
Allergy Initiative, National Peanut Board, Food Allergy Anaphylaxis
Network, the MRC Asthma UK Centre, Department of Health/National
Institute for Health Research, and Food Allergy Research and Education; and has stock in DBV Technologies. T. T. Perry has received
research support from the National Institutes of Health.

the clinician in the initial workup. This review will cover the
basic approach to understanding the immune response of an
individual with food allergy after ingestion and will guide the
clinician in applying appropriate testing modalities when needed
by conducting food challenges if indicated and by educating the
patient and his or her guardian to minimize the risk of accidental
ingestion. 2015 American Academy of Allergy, Asthma &
Immunology (J Allergy Clin Immunol Pract 2015;3:1-11)

Network/National Institute of Allergy and Infectious Diseases, Food Allergy Initiative, National Peanut Board, Food Allergy and Anaphylaxis Network, the MRC
Asthma UK Centre, Department of Health/National Institute for Health Research, and
Food Allergy Research and Education; and has stock in DBV Technologies. T. T.
Perry has received research support from the National Institutes of Health.
Received for publication April 7, 2014; revised June 9, 2014; accepted for publication June 11, 2014.
Corresponding author: J. Andrew Bird, MD, Division of Allergy and Immunology,
Department of Pediatrics, University of Texas Southwestern Medical Center, 5323
Harry Hines Blvd, Dallas, TX 75390-9063. E-mail: drew.bird@utsouthwestern.edu.
2213-2198
2015 American Academy of Allergy, Asthma & Immunology
http://dx.doi.org/10.1016/j.jaip.2014.06.008

BIRD ET AL

Abbreviations used
AD- Atopic dermatitis
DBPCFC- Double-blind, placebo-controlled food challenge
FA- Food allergy
FALCPA- Food Allergy Labeling and Consumer Protection Act
FPIES- Food proteineinduced enterocolitis syndrome
OFC- Oral food challenge
PA- Peanut allergy
SPT- Skin prick test

Key words: Food allergy; Anaphylaxis; Skin prick test; Oral food
challenge; Label reading; Travel; Cross-contact; Autoinjectable
epinephrine

IgE-mediated food allergies (FA) may be life-threatening,1

negatively impact the quality of life for affected individuals and
their families,2-5 and require coordinated efforts among affected
individuals and their caregivers to minimize the risk of accidental
ingestion. The most recent epidemiologic studies show that
approximately 1 in 13 US children has an FA,6 which makes FA
an important disease process to be recognized, properly diagnosed, and effectively managed. This review primarily focuses on
diagnosis and management of IgE-mediated FAs, with practical
advice regarding avoidance and care of individuals with FA.

CLINICAL SPECTRUM
Specific food-induced allergic conditions
IgE-mediated FA occurs by cross linking of IgE on mast cells
and basophils by allergenic proteins, which leads to the release of
histamine and other mediators, and is the mechanism that underlies immediate hypersensitivity. Symptoms of IgE-mediated
FA disease include urticaria, angioedema, vomiting, diarrhea,
bronchospasm, and multisystem allergy that can result in
anaphylaxis. A mild form of allergic disease, pollen-food syndrome, also referred to as oral allergy syndrome, occurs due to
IgE cross-reactivity to PR10 proteins in fruits and nuts in patients with pollen allergies (Table I).7,8 These foods usually are
tolerated in cooked or processed forms, and anaphylaxis is rarely
seen in this condition. In more recent years, delayed foodinduced anaphylaxis to meats has been described,9-11 which appears to be mediated via IgE specic for an oligosaccharide in red
meat, galactose-alpha-1,3-galactose, and sensitization is associated with Lone Star tick exposure. The reason for the appearance
of delayed symptoms is unclear.
A summary of the spectrum of food-induced allergic disease is
provided in Table II. There are a number of noneIgE-mediated
FA diseases. Perhaps with the exception of celiac disease, there is
little mechanistic understanding of the pathologic processes that
underpin such diseases. Food proteineinduced enterocolitis
syndrome (FPIES) specically presents with acute recurrent
vomiting and diarrhea that starts between 2 and 8 hours of
ingestion of food, most commonly milk or soy.12 Although patients with FPIES are not at risk of anaphylaxis, they are at risk of
developing shock and acidosis due to dehydration. Other none
IgE-mediated diseases of the gastrointestinal tract are typically
characterized by eosinophilic inammation of different segments
of the gastrointestinal tract. Eosinophilic esophagitis may appear

J ALLERGY CLIN IMMUNOL PRACT

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at any age, and symptoms vary by age of presentation. Younger

children may present with failure to thrive and frequent vomiting; whereas older children and adults may have symptoms
including food impaction, dysphagia, and heartburn. tends to in
older children and adults, with symptoms of food impaction,
dysphagia, and heartburn. Eosinophilic proctocolitis presents
with blood and mucous in the stools of young infants who are
often exclusively breast fed but exposed to cows milk or soy
proteins in maternal milk.
Mixed IgE FA diseases can occur, for example, in eosinophilic
esophagitis or atopic dermatitis (AD), in which FA can be
demonstrated by elimination and reintroduction diets, but IgE to
the food may only be present a portion of the time. Some people
refer to these conditions as IgE-associated conditions because it is
unclear whether the IgE (when detected) plays a pathologic role.
It may be that IgE is acting through antigen-presenting cells and
driving facilitated antigen presentation to T cells, which drive
Th2 responses and recruitment of eosinophils to the affected
tissue. Frequently, eosinophilic gastrointestinal diseases may occur
together with AD and that, indeed, individuals can be affected by
both IgE-mediated FA and mixed or non-IgE allergic conditions.

EPIDEMIOLOGY
There are both study limitations and methodologic problems
that inuence our estimation of the incidence and prevalence of
FAs. The majority of studies that document the prevalence of egg
allergy, milk allergy, and peanut allergy (PA) occur in Western
countries, and, to our knowledge, there are no published studies
that examined FA at a global level. There is very little knowledge
about FA in the developing world, although it seems to be reported far less frequently. There are methodologic differences
that explain different results that have been obtained in different
surveys. Whereas double-blind, placebo-controlled food challenges (DBPCFC) are the criterion standard, these are performed
in few studies.13 Other surveys use FA questionnaires (generally
unvalidated), skin prick test (SPT) responses, or IgE sensitization
as markers of FA. However, neither correlates with FA, and it is
remarkable that, in countries such as Ghana, for example, where
the prevalence of PA is much lower, IgE positivity to peanut is
extremely high compared with Western countries. This appears
to be due to cross-reactive low-afnity antibodies to carbohydrate
determinants.14
In the United States, FAs are thought to occur in approximately 6% to 8% of infants and preschool children. Egg and
milk allergies are the most common FAs in most countries and
cultures. However, a meta-analysis of 51 articles from different
countries showed that the self-reported prevalence of allergy
varied from 0.2% to 7% for egg and from 1.2% to 17% for
milk.15 Allergy determined by challenges was estimated to be
much lower, which ranged from 0% to 1.7% for egg, and 0% to
3% for milk. The prevalence and rise of PA has been greatest in
Western countries. PA is much less common in certain countries,
for example, Israel, where sesame seed allergy is more common.16
Mustard allergy is more commonly reported in France,17 whereas
buckwheat and wheat allergies are most commonly reported in
Japan. Generally, the most common allergens in childhood
include egg, milk, peanut, tree nuts, wheat, soy, sh, shellsh,
and sesame. Fish and shellsh allergies do occur in childhood but
are more prevalent in adolescents and adults. If pollen-food
syndrome is included, in which IgE to pollens such as birch cross

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TABLE I. Pollen and plant allergens with the cross-reactive foods in pollen-food syndrome*
Plant

Allergen

Cross-reacting protein family

Fruits and vegetables

Birch

Bet v 1

PR-10

Apple, apricot, carrot, celery, cherry, hazelnut, jackfruit,

peanut, pear, soy, strawberry

Ragweed
Timothy grass
Mugwort

Bet v 2
Amb a 8
Phl p 12
Art v 4

Prolin
Prolin
Prolin
Prolin

Almond, apple, banana, bell pepper, carrot, celery, hazelnut,

kiwi, melon, peach, pineapple, soy, strawberry, tomato

Art v 3

Lipid transfer protein

Hev b 2

PR-2 (b-1,3-glucanase)

Asparagus, apple, apricot, cherry, grape, hazelnut, lettuce, corn,

peach, strawberry, tomato, walnut
Banana

Hev b 8

Prolin

Hev b 11

PR-3 (class I chitinases)

Latex

Almond, apple, banana, bell pepper, carrot, celery, hazelnut, kiwi,

melon, peach, pineapple, soy, strawberry, tomato
Avocado, banana, chestnut, kiwi, mango, papaya, passion fruit, tomato

*From Refs 7 and 8.

TABLE II. Spectrum of food-induced allergic diseases

IgE mediated
Acute urticaria, acute angioedema, pollen-food syndrome, gastrointestinal anaphylaxis, generalized anaphylaxis,
food-dependent exercise-induced anaphylaxis, acute bronchospasm (wheezing), delayed food-induced
anaphylaxis to meats
Non-IgE mediated
Celiac disease, dermatitis herpetiformis, food-induced pulmonary hemosiderosis (Heiner syndrome), food
proteineinduced enteropathy, food proteineinduced proctocolitis, FPIES, allergic contact dermatitis
Mixed IgE or non-IgE
Eosinophilic esophagitis, eosinophilic gastroenteritis, AD

react with food allergens, then the prevalence of FA is considerably higher. A recent study showed that between 1.8% and
4.1% of adults in the United Kingdom may have pollen-food
syndrome18 and that as many as 50% to 90% of those with birch
pollen allergy may be affected.19,20
In general, the majority of children outgrow their milk, egg,
soy, or wheat allergies, whereas peanut and tree nut allergies are
typically more persistent.21 The age at which a child will outgrow
a milk, egg, soy, or wheat allergy varies from study to study based
on the phenotypes of the patients studied. For example, in tertiary care centers where children were seen with a more-severe
phenotype of egg and milk allergies accompanied by much
higher IgE titers, a much lower rate of cows milk and egg allergies resolution was seen, with substantial allergy that persisted
into adolescence.22

PREVENTION
Prevention of FA remains a controversial topic. Prolonged
exclusive breast feeding has long been supported as a measure to
prevent FAs, although there is little evidence that this strategy is
effective. Given that careful elimination diets have failed to
prevent the development of FAs in children, the strategy of
exposing young infants to food allergens is now receiving
attention.16,23 An ecological study that compared the prevalence
of PA in Jewish children in the United Kingdom and Israel
found a 10-fold increase in FA in the UK primary school children compared with the Israeli children. The study also found
that UK infants were generally avoiding peanuts completely in
the rst year of life, whereas Israeli infants were consuming
peanut snacks on a regular basis as of 4 to 6 months of age.13
Studies are now focusing on the early introduction of an allergen
into the infants diet to induce oral tolerance and to prevent the
development of FAs. The Learning Early About Peanut Allergy

study is of 640 infants, ages 4 to 11 months, at high risk who are

randomized to complete avoidance of or to high-level exposure to
peanut protein until the age of 5 years to see which is the better
strategy to prevent PA.24,25 The Enquiring About Tolerance
study is randomizing infants who are both at normal risk and at
high risk of developing FAs at 3 months of age into either
continued exclusive breast feeding or continued breast feeding,
together with the early introduction of complementary foods,
including food allergens.26

DIAGNOSIS OF FA
A detailed medical history is critical to the evaluation of the
patient with suspected FA. The medical history can aid the
proper identication of suspected food allergen(s) and limit the
diagnostic evaluation to the allergen(s) most likely associated
with symptoms. Foods that consistently elicit symptoms of FA
should be the focus of diagnostic evaluations27 because foods that
have been historically tolerated and have been eaten on multiple
occasions are less likely to be causal foods. However, clinicians
should also consider ingestion of hidden or unidentied food
allergens as factors that may obscure the dietary history. Other
historical factors, including patient characteristics such as underlying comorbid conditions (eg, asthma), activities proximate
to ingestion of the causative food (eg, exercise), dose, and/or
preparation of the causative food, may play a role in the clinical
presentation and severity of reactions to foods.
Diagnosis of IgE-mediated reactions
IgE-mediated allergic reactions may involve 1 or multiple organ
systems and typically occur immediately to a few minutes or hours
after ingestion of the causative food.28 The majority of IgEmediated food reactions involve skin manifestations, such as urticaria, erythema, or angioedema.27,29 Laboratory allergy testing,

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TABLE III. Predictive value of ImmunoCAP specific IgE testing in positive or negative OFCs*
>95% Positive predictive value
Food

Serum specific IgE (kU/L)

Egg white
Cows milk
Peanut
Fish

7;
2 if <2 y old

15;
5 if <1 y old

14

20

Approximate 50% negative predictive value

SPT wheal (mm)

Serum specific IgE (kU/L)

SPT wheal (mm)

7

8

8

2
2
2 if history of prior reaction; 5 if no history of prior reaction

3
3

*From Refs 30-33, 35-37, 58.

Serum specic IgE measurements are based on the ImmunoCAP platform.

including SPT and/or serum IgE testing, should be used to aid the
accurate diagnosis of IgE-mediated FA; however, the clinician
should be aware that a positive test does not equate to clinical
reactivity.30,31 Also, the majority of IgE-mediated food reactions
are caused by a limited number of foods; therefore, panel testing to
a large number of allergens is not recommended.27 In an effort to
reduce the risks of overdiagnosis and unnecessary dietary eliminations, allergy testing should be limited to specic foods that
have been temporally related to acute symptoms or to foods that
are suspected to exacerbate chronic symptoms (eg, AD). However,
it has been recommended that infants who present with severe-tomoderate AD and a single FA (eg, milk, egg, peanut) should be
tested for the other commonly associated food allergens32 because
of the high coreactivity of milk, egg, peanut, and nut allergies in
such infants.32

SPTs. SPTs can be performed in the ofce setting and are a

safe, effective method of detecting specic IgE antibodies.31,33 A
positive SPT only reects the presence of specic IgE bound to
the surface of cutaneous mast cells, not clinical reactivity or
disease severity. If positive, the wheal size may aid in medical
decision making because a larger wheal size may be more likely to
be clinically relevant. The mean diameter wheal size can help the
clinician establish the probability of clinical reactivity versus oral
tolerance and determine the need for further testing (eg, oral
food challenge [OFC]) or dietary manipulations (Table III).34-41
A negative SPT can be particularly useful to rule out suspected
food allergens due to the relatively high negative predictive value
of SPT.30 However, the clinician should note that a negative
SPT result does not guarantee clinical tolerance, and, when there
is a high degree of clinical suspicion, further diagnostic procedures should be used.
Serum-specific IgE tests. Serum specic IgE testing is
another important diagnostic tool that can aid in accurate
identication of causal food allergens.42-47 Serum specic IgE
testing is particularly useful for patients who cannot discontinue
antihistamine therapy or for those with extensive skin disease or
dermatographism.27 Although specic IgE results can neither
denitively rule out nor rule in clinical FA, predictive values for a
limited number of foods have been established (Table III).
Generally, higher specic IgE levels are more likely to be associated with clinical reactivity, but the predictive value of specic
IgE levels varies across patient populations and may be related to
other factors, such as the patients age, race and/or ethnicity, and
time since last ingestion of the suspected allergen.43,46-50 The
history of clinical reactivity, along with results of other diagnostic
tests are useful adjunctive tools when specic IgE testing is
negative or below the established positive predictive value

thresholds (Table III).21 It is important to note that the predictive curves have been established by using the ImmunoCAP
platform (Phadia, Uppsala, Sweden) and that investigators have
shown a discordance among specic IgE measurements when
using other technologies.51

Component-resolved diagnostic testing. Componentresolved diagnostic testing uses allergenic proteins derived from
recombinant DNA technology or purication from natural
sources to identify the patients specic IgE reactivity to recombinant allergenic proteins rather than whole allergens.52 Investigations of component-resolved diagnostic testing for a few
allergens, such as peanut and hazelnut, have shown promising
results.53-57 However, it is not routinely recommended for the
diagnosis of FA. Analysis of results of recent investigations suggests that component-resolved diagnostic tests could potentially
enhance diagnostic accuracy and provide insight regarding
severity risks; however, studies have been limited to a few foods,
and results have varied, depending on geographic region and
population age.58-61 Whole blood basophil activation testing has
recently been shown to enhance diagnostic accuracy for PA,
which may substantially reduce the need for OFC.62
OFCs. The types of OFCs include open (unmasked), single
blind, with or without placebo, and DBPCFC. The DBPCFC is
the criterion standard and is the most rigorous type of challenge.
However, an open OFC is the criterion standard for establishing
tolerance and should follow a negative DBPCFC.63 Although
DBPCFCs reliably predict clinical reactivity, they are labor- and
time-intensive procedures. Single-blind and open OFCs are
frequently for clinical use. For a diagnosis of IgE-mediated FA
graded dosing during OFC is recommended regardless of the
type of challenge conducted. Graded dosing minimizes the risks
of severe allergic reaction and identies the lowest provoking
dose (dose threshold). Example protocols for OFCs can be found
in a recently published workgroup report and the PRACTicing
ALLergology (PRACTALL) consensus report.63,64
During the diagnostic evaluation, the decision to conduct an
OFC should be determined by both the patients history of
clinical reactivity and specic IgE testing.63-65 In many cases,
OFC is not prudent or necessary if the patient has an unequivocal, convincing history of clinical reactivity to a known food
allergen and positive specic IgE testing (SPT or serum specic
IgE). Furthermore, the patients history may take priority over
laboratory ndings because results of specic IgE testing should
not be interpreted as absolute indications or contraindications for
conducting an OFC. OFCs can be used to determine clinical
reactivity when the history is uncertain and results of specic IgE
testing (SPT or serum specic IgE) are negative or when specic

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BIRD ET AL

FIGURE 1. An interactive Food Allergy Card, which may be completed individually; download from the Food Allergy Research and
Education Web site at www.foodallergy.org/managing-food-allergies-at/dining-out/at-the-restaurant.

IgE test results are positive but below established positive predictive cutoffs for the suspected food (Table II). OFCs also can
be effective in determining the development of oral tolerance
during the follow-up of patients with established FA.
A discussion regarding the risks-benets of food challenge and
informed consent should be obtained before OFCs.63 The risk of
allergic reaction, including anaphylaxis, should factor into the
decision making and the benets of conducting OFC, such as
the possibility of expanding the patients diet if the OFC is
negative. Due to the risk of life-threatening symptoms or
anaphylaxis, OFC should always be conducted under the supervision of trained medical staff in a health care facility equipped to treat anaphylaxis.27,63,64,66

MANAGEMENT OF FA
Dietary management and allergen avoidance
Strict avoidance of the allergenic food is the cornerstone of
management for individuals with FA.27 Although this is a
seemingly straight-forward recommendation, adhering to strict
avoidance may be challenging. In a 2-year period, accidental
ingestion of peanut has been reported in as many as 50% of
children with PA,67 and in up to 75% within 10 years.68 Children younger than 5 years old may be at particular risk of having
a reaction, with a recent study that showed that 72% of participants in a prospective study who had received avoidance education experienced reactions during a 3-year period.69 Keeping
an individual with food allergy safe depends on frequent label
reading, preventing cross-contact, providing anticipatory guidance to caregivers regarding reaction severity and treatment of
reactions, and communicating with restaurant staff when eating
outside of the home.
Label reading
Label reading requires constant vigilance secondary to changing
manufacturing practices over time. The Food Allergy Labeling
and Consumer Protection Act of 2004 (FALCPA) (www.fda.gov/
Food/FoodSafety/FoodAllergens) requires all packaged foods
(except meat, poultry, certain egg products, and alcoholic beverages) sold in the United States to list the name of the most
common allergens (milk, egg, peanut, tree nuts, wheat, soy, sh,
and crustacean shellsh) in plain English on the ingredient label.
For tree nuts, sh, and shellsh, the specic food must be listed
(eg, almond, tuna, or shrimp). The law applies to all food items

manufactured in the United States or packaged food imported for

sale and subject to the US Food and Drug Administration regulation. The ingredient must be listed in either a Contains
statement or the common name must be embedded in the ingredients label. FALCPA does not apply to may contain labeling, which is voluntary. Additional information regarding label
reading may be found on the Food Allergy Research and Education Web site at www.foodallergy.org/food-labels.
Individuals allergic to foods outside of the 8 most common
allergens may have more difculty with ingredient label interpretation. Certain foods, for example, sesame seed, may not be
listed directly on the ingredient label. Spices or natural avors may include a multitude of foods or food products not
included in FALCPA. It is especially important for individuals
allergic to foods outside of those covered under FALCPA to
contact manufacturers for clarication on products when listing
is not certain.

Traveling
Traveling may also present a particular challenge. With individual differences in labeling laws and regulatory oversight
around the world, it is important for individuals with FA to take
special precautions when traveling abroad. It is recommended
that patients and families learn the names of the food allergens in
the foreign language, have a written statement, which is shown to
the hotel and restaurant staff, that states that the individual
cannot eat the named food(s) and that the food(s) can cause a
severe reaction. Many embassies will provide this translation
service.
Air travel also is a particular challenge for the patient with FA
and creates signicant anxiety for many individuals with FA and
their families. Sicherer et al70 were the rst to report on foodinduced allergic reactions during commercial ight and presented
self-reported data from participants in a national peanut and tree
nut allergy registry. More recent surveys have further characterized reactions on airlines and identied areas of concern that may
help in educating patients with FA who are planning to y on
commercial airlines.71-73 Consistent among the surveys is that
individuals who experienced reactions did not commonly inform
the ight crew that they were having a reaction and that
epinephrine was underadministered. Therefore, it is of primary
importance to review signs and symptoms of anaphylaxis and
appropriate use of epinephrine with all individuals with FA who

BIRD ET AL

are planning to travel and remind them to inform the ight crew
in case of concern for an allergic reaction. Greenhawt et al73
reported that signicantly fewer persons who had reactions on
ights had the following characteristics: (1) had a personal source
of epinephrine, (2) had made a specic request of the airline, and
(3) had performed personal risk-mitigating behaviors.
Although the risk-mitigating behaviors have not been proven
to effectively minimize allergen exposure, the investigators suggest that these measures are likely to minimize passenger anxiety.73 The 8 risk-mitigating behaviors are (1) making any
request of the airline, (2) requesting a buffer zone, (3) requesting
an announcement that passengers not eat peanut and/or tree nutcontaining foods, (4) requesting a peanut- and/or tree nut-free
meal, (5) wiping their tray table, (6) bringing their own food
from home, (7) avoiding use of an airline-provided pillow, and
(8) avoiding use of an airline-provided blanket. Patients with PA
who are traveling with an airline should be reassured that peanut
is unlikely to aerosolize.

Cross-contact. Cross-contact may occur during meal preparation or food packaging, and refers to inadvertent transfer from
a food that contains an allergen to a food that does not contain
the allergen. Fleischer et al69 reported that 15.1% of reactions in
their cohort of children younger that age 5 years occurred secondary to cross contact. Challenges for individuals with FA and
their families include interpreting may contain statements,
preparing safe foods at home, and eating food prepared by others
(eg, school cafeteria, restaurant, relatives house). The most
common phrasing states may contain [allergen], manufactured on shared equipment with [allergen], and manufactured
in the same facility with [allergen].74 Rather than informing the
consumer that the ingredient is within the product, this labeling
is often interpreted to mean that the food may or may not have
inadvertently entered into the food product in question, which
creates ambiguity and anxiety for some. One study showed that
17% of manufactured items in the United States contained
precautionary labels75 and that 65% of products in Australia may
carry such warnings.76 It has been reported that the labeling is
often ignored,77,78 and there are results of studies that indicate
that the type of wording used inuences whether or not the
product is avoided. Within the population with FA, adolescents
and young adults may be least likely to avoid foods with such
labeling, with 42% of participants stating that they purposefully
ingest foods with a label that states may contain.79
The signicance of small amounts of cross-contact and the need
for avoidance of foods with precautionary labeling rely on knowledge of threshold levels of reactivity for individual allergens.
Reference doses for threshold levels of reactivity have been suggested,80 but standards have not been adopted by the US Food and
Drug Administration. Investigators have tested products with may
contain labeling for milk, egg, and peanut, and found that 5.3% of
products with advisory labeling contained detectable amounts of
these allergens.81 Products purchased from small companies versus
large companies were more likely to have contaminated products
(5.1% vs 0.75%). Given that individual threshold doses vary widely
for consumers with allergy, the consensus expert recommendation
is to avoid products with may contain labeling.27
Eating outside of the home. Minimization of cross-contact
at restaurants requires communication and vigilance on behalf of
the individual with FA or his or her guardian. Cross-contact may

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be more common at a buffet, ice cream parlor, bakery, Asian

restaurant (which commonly uses peanut and tree nut products),
and seafood restaurant, and with deep-fried foods (oil may be
reused for different foods, which leads to contamination).82 It is
recommended to talk with the manager and the waiter, present a
chef card (Figure 1), order simple foods (ie, few ingredients),
and avoid fried foods. Preparing children and adolescents for FA
management away from home starts with initiating supervised
self-management techniques when developmentally appropriate.

Dietary supplementation. Avoidance and appropriate

nutritional supplementation often require the coordinated efforts
of a medical team, including a physician, nurse, and registered
dietitian. Examples of overly restrictive diets that led to nutritional deciency have been reported in the literature,83-85 which
emphasizes the importance of appropriate use of currently
available diagnostic tests and food challenges when needed to
ensure appropriate diagnosis. Even in the absence of unnecessary
avoidance, children with FA may be smaller than their peers
without FA. Flammarion et al86 followed children who received
dietary education and appropriate supplementation, and found
that, despite these interventions, children with FA were smaller
for their age than were controls.86 There is no clear explanation
for this difference, although the investigators hypothesize that
intestinal absorption may differ based on ongoing allergic
inammation or higher protein and energy needs of children
with moderate-to-severe AD, which is supported by ndings
from other investigators.87
Although growth deciency may be seen in any child with FA,
children with cows milk allergy are particularly at high risk
secondary to loss of a vital nutrient source for growth and
development. Christie et al88 reported that children with a cows
milk allergy or with 2 or more FAs were statistically shorter than
their peers without FA and were at a greater risk of having
inadequate calcium intake. Children allergic to cows milk also
are at a higher risk for osteoporosis,89 are at risk for malnutrition
without adequate supplementation,90 and are at higher risk of
developing rickets.91,92 For these reasons, it is recommended that
children with FAs have nutritional counseling and regular growth
assessments,27 and evaluation and counseling by a registered
dietitian should especially be considered for children with milk
allergy or with 2 or more FAs.88
Heated milk and heated egg. Exceptions to the rule for
complete allergen avoidance have begun to take hold for foods
such as milk and egg. There is evidence that ingestion of tolerated forms of allergenic food proteins might be benecial and
safe for some FAs. As outlined within this issue of The Journal of
Allergy and Clinical Immunology: In Practice,93 ingestion of baked
and extensively heated forms of milk and egg may hasten the
development of tolerance to lesser cooked or raw forms of milk
and egg for some individuals with allergy. Allergenicity appears to
be affected by alterations in protein conformation94 and effects
on gastrointestinal absorption.95 Controlled trials are lacking,
and there is no universal agreement regarding the appropriate
amount of protein to be ingested or frequency of ingestion
required to make a noticeable difference in acquisition of tolerance. Regardless of these limitations, the introduction of extensively heated and baked milk and egg products for those able to
tolerate them appears to be safe and intuitively may improve the

J ALLERGY CLIN IMMUNOL PRACT

VOLUME 3, NUMBER 1

quality of life for the majority of children with egg and milk
allergy.

Treatment of acute FA reactions

Food-induced anaphylaxis is a rapidly progressive, multiorgan
allergic reaction that can result in death. Prompt recognition of
signs and symptoms of an allergic reaction is essential for
appropriate management. Symptoms may be uniphasic, biphasic,
or protracted, and may involve all organ systems.27,96,97 Foodinduced fatalities are most commonly reported from exposure to
peanuts and tree nuts, but severe and fatal reactions may occur
with any culprit food allergen. Fatalities are often associated with
a lack of, or delayed, treatment with epinephrine. Other risk
factors associated with increased mortality include teen and
young adult age groups, pre-existing and/or poorly controlled
asthma, concomitant use of b-blocker medications, and a previously diagnosed FA. Other factors include an absence of skin
symptoms, patients denial of symptoms, concomitant alcohol
consumption, or reliance on oral antihistamines in place of
epinephrine to manage symptoms.27,98-100
Intramuscular epinephrine is the rst-line treatment in all
cases of anaphylaxis in both inpatient and outpatient situations,
and repeated epinephrine dosing should be used when symptoms
progress or response is suboptimal.27,96,97 Self-injectable
epinephrine must be readily available to patients with IgEmediated FA, and patients must be instructed on the importance
of its use and self-administration. Patients also must be educated
on how and when to use an autoinjectable epinephrine device
and when to seek immediate medical attention.
Adjunctive therapy for acute IgE-mediated allergic reactions
includes bronchodilators and antihistamines (H1 blockers) in
both inpatient and outpatient settings. Oxygen supplementation,
volume replacement, pressors, corticosteroids, and H2 blockers
also may be administered in inpatient or emergency department
settings.21,96 It is particularly important to note that bronchodilators should be prescribed and readily available to patients
with concomitant asthma, regardless of severity because acute
IgE-mediated allergic reactions may result in signicant respiratory symptoms. Volume replacement is the recommended
treatment for acute management of patients with FPIES, a
medical emergency with up to a 15% risk of hypovolemic shock.
Vigorous intravenous hydration with rapid normal saline solution boluses should be used. Epinephrine may be used in cases of
severe hypotension but is not helpful as a rst-line treatment.101
A single dose of intravenous methylprednisolone 1 to 2 mg/kg
may be used for some patients with protracted symptoms,
although efcacy has not been established. In milder reactions,
oral rehydration may be possible.102 In proctocolitis and enteropathy, symptoms are usually chronic, and there is low risk for
acute reactions.
Written emergency action plans and medical alert
jewelry. All patients with FA should have a written emergency
treatment plan.27,103 Treatment protocols should be designed
to prevent delays in recognition and treatment of symptoms.
These plans should be simple so that symptoms can be recognized
and treated quickly and appropriately. Commonly used action
plans are available at http://www.foodallergy.org/document.doc?
id234 and http://www.aaaai.org/Aaaai/media/MediaLibrary/
PDF%20Documents/Libraries/Anaphylaxis-Emergency-ActionPlan.pdf. FPIES is underrecognized and frequently mismanaged;

BIRD ET AL

TABLE IV. Web-based resources

FA resources
Food Allergy Research and Education: www.foodallergy.org
Consortium on Food Allergy Research: www.cofargroup.org
Asthma and Allergy Foundation of America: www.aafa.org
American Academy of Allergy, Asthma and Immunology: www.aaaai.org
American College of Allergy, Asthma and Immunology: www.acaai.org
Kids with Food Allergies: www.kidswithfoodallergies.org
AllergyReady.com
Centers for Disease Control and Prevention: www.cdc.gov/
healthyyouth/foodallergies
National Institute of Allergy and Infectious Diseases: www.niaid.nih.
gov/topics/foodallergy
University of Nebraska-Lincoln Food Allergy Research and Resource
Program: farrp.unl.edu/
Allergy Home: www.allergyhome.org
Food Allergy Management and Education: www.stlouischildrens.org
Eosinophilic esophagitis
American Partnership for Eosinophilic Disorders: apfed.org
The Childrens Hospital of Philadelphia Center for Pediatric
Eosinophilic Disorders: www.chop.edu/service/center-for-pediatriceosinophilic-disorders
Cincinnati Center for Eosinophilic Disorders: http://www.
cincinnatichildrens.org/service/c/eosinophilic-disorders/
North American Society for Pediatric Gastroenterology, Hepatology
and Nutrition: www.naspghan.org
FPIES
The FPIES Foundation: fpiesfoundation.org
International Foundation for Food Protein Enterocolitis: www.iaffpe.org
Celiac disease
Celiac Disease Awareness Campaign: celiac.nih.gov
Celiac Disease Foundation: celiac.org

therefore, a letter that describes manifestations of FPIES and

management of acute reactions should be provided to patients.
Patients should be instructed to present this letter to medical
personnel on arrival to the medical facility. A template of an FPIES
emergency letter may be found in an article by Sicherer et al.101
Medical alert jewelry should be considered for patients at risk for
severe allergic reactions and for certain populations, such as children or other individuals who may not be able to verbalize that they
are experiencing an allergic reaction. Also, medical alert jewelry can
potentially prompt rst responders to initiate appropriate emergency medical treatment if the patient is found unconscious or
unable to communicate.

Care at school. Caring for the child with FA includes having

a familiarity with national and state laws regarding FA preparedness at school. In October of 2013, the Centers for Disease
Control and Prevention published the rst national comprehensive guidelines for school FA management. The voluntary national guidelines were developed to provide practical information
for parents, district administrators, school administrators and
staff, and early childhood education program administrators and
staff to develop or strengthen plans for food allergy management
and prevention.104 A link to the guidelines may be accessed at
www.cdc.gov/healthyyouth/foodallergies/. Many states have
adopted guidelines for the care of children with FAs. A list of
these states may be accessed at the Food Allergy Research and

BIRD ET AL

J ALLERGY CLIN IMMUNOL PRACT

JANUARY/FEBRUARY 2015

FIGURE 2. Food Allergy Patient and/or Provider Checklist. Recommended items to review with new and follow-up patients with FA.

Education Web site (http://www.foodallergy.org/laws-andregulations/guidelines-for-schools). Typical advice within the

guidelines includes instructions on recognition of the signs and
symptoms of anaphylaxis, safe and easy access to autoinjectable
epinephrine, recommendations for minimizing food in the
classroom, and proper cleaning techniques in the lunchroom to
minimize inadvertent allergen contact. Schools should be
encouraged to maintain usual cleaning techniques with a standard
cleanser, and children should wash hands with either hand wipes
or soap and water. Perry et al105 showed that household cleaners
and commercial wipes effectively remove peanut allergen, whereas
tables washed with dishwashing liquid left residual low concentrations of peanut allergen. The same study showed that commercial wipes, liquid soap, and bar soap removed all traces of
peanut protein from hands, whereas water alone or antibacterial
hand sanitizer alone left detectable peanut residue.105
Results of 2 studies showed that life-threatening reactions
occur after ingestion rather than inhalation or contact in the
overwhelming majority of cases.106,107 Therefore, attention
should focus on minimization of ingestion. Foods such as peanut
butter are not aerosolized, rather the odor results from airborne
volatile organic compounds that are not allergenic.82 Aerosolization of food proteins may result with cooking or processing,
which may lead to respiratory reactions and skin symptoms,107-109
which may more commonly occur with foods such as shellsh,
nned sh, and milk.

The School Access to Emergency Epinephrine Act was signed

into law on November 13, 2013. The law encourages schools to
stock autoinjectable epinephrine at school that is not specically
labeled for 1 child. As many as 25% of food-induced allergic reactions at school may occur with children not previously diagnosed with an FA,110 and 16% to 18% of school-age children with
FA experienced a reaction in the school setting,2,111 which underscores the importance of educating school personnel on the
recognition of a life-threatening allergic reaction and having stock
autoinjectable epinephrine at schools to use if needed.
Allowing children to self-carry autoinjectable epinephrine is
typically left to the discretion of the guardian and the health care
provider. There are no established guidelines that dene when a
child should be allowed to carry his or her own autoinjectable
epinephrine, but, at a bare minimum, the child with an FA should
verbalize understanding to the health care provider the following,
without prompting, (1) symptoms of an allergic reaction and (2)
symptoms that would require use of autoinjectable epinephrine;
and should demonstrate (3) appropriate use of an autoinjectable
epinephrine trainer. Managing FAs in college creates a new
challenge and may be particularly anxiety provoking for the
adolescent with FA who is preparing to leave home. Food Allergy
Research and Education recommends communicating directly
with the food services director, providing emergency treatment
plans, discussing signs and symptoms of anaphylaxis with roommates, and consulting the campus health clinic. A list of numerous

J ALLERGY CLIN IMMUNOL PRACT

VOLUME 3, NUMBER 1

Web-based resources is given in Table IV; a comprehensive

checklist of topics to be covered in a yearly visit for a child with FA
is covered in Figure 2.

CONCLUSIONS
Although we are currently making advances in nding a cure
for FA, safe and effective management relies on proper diagnosis
and avoidance of food allergens that may trigger a reaction.
Diagnosis is reliant on taking a complete and thorough history of
the reaction of concern and ordering directed testing, led by
clinical suspicion. OFCs are helpful in establishing the diagnosis
of FA and should be performed when test results are inconclusive
and/or it is believed that tolerance has developed. Providing
comprehensive care to children with FA includes being knowledgeable about labeling laws, appropriate environmental control
measures, and federal and state guidelines established for keeping
children safe with FA in environments outside of the home. In
addition, it is imperative that patients and guardians are educated
regarding recognition of an allergic reaction and that they understand how to treat a reaction should accidental ingestion occur.
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