March 16, 2006  Guidelines created by a joint task force help clarify
the diagnosis and management of true food allergies. They are
published in the March issue of the Annals of Allergy, Asthma and
Immunology.

"Food allergy, as defined for the purposes of this document, is a
condition caused by an IgE-mediated reaction to a food substance,"
write Jean A. Chapman, MD, and colleagues from the American Academy of
Allergy, Asthma and Immunology. "Adverse reactions to foods may also
occur due to non IgE-mediated immunologic and nonimmunologic
mechanisms.

The authors note that food allergy is an important subset of all
adverse food reactions that is often misunderstood. Because of
important new scientific findings, the evaluation and management of
food allergy have changed significantly in recent years. Potentially
fatal food allergy to peanuts and tree nuts is becoming more common or
at least more widely recognized.

"This has resulted in an increased awareness among the general public,
leading to policy changes in schools, eating establishments, and the
airline industry," the authors write. "At the same time, diagnostic
evaluation in patients suspected of having food allergy has become
both more sophisticated and more challenging."

The objectives of this practice parameter on food allergy include
improved understanding of food allergy by healthcare professionals,
medical and nursing students, interns, residents, fellows, managed
care executives, and administrators; establishing guidelines and
support for the practicing clinician; and improving the quality of
care for patients with food allergy. However, these guidelines are not
intended to replace clinical judgment or to establish a protocol for
all patients.

During their lifetime, about one quarter of the population will have
some sort of adverse reaction to food, especially during infancy and
early childhood. Based on the underlying pathophysiologic changes,
these adverse reactions are classified as food allergy, food
intolerance, pharmacologic reactions, food poisoning, and toxic
reactions. True food allergy is relatively uncommon, but individuals
with atopy are at greater risk, especially infants with moderate to
severe atopic dermatitis. Children who develop an IgE-mediated allergy
to one food are at increased risk of developing IgE-mediated reactions
to other foods and/or inhalants. Because the true prevalence of food
allergy is much lower than the number of adverse reactions to food,
healthcare professionals should not perpetuate false assumptions about
food allergy.

"If a patient is incorrectly diagnosed as having a reaction to a food,
unnecessary dietary restrictions may adversely affect quality of life,
nutritional status, and, in children, growth," the authors write.
"Severely restricted diets may lead to the development of eating
disorders, especially if they are used for prolonged periods, or may
make the patient susceptible to false claims of scientifically
unproven and often costly techniques that offer no actual benefit. In
addition, unintentional exposure to foods falsely thought to cause
adverse reactions can provoke unnecessary panic and use of medications
that have potentially potent adverse effects."

IgE-mediated food allergies may occur by sensitization through the
gastrointestinal tract, sensitization through the respiratory tract to
airborne proteins identical or homologous to those in particular
foods, or sensitization through epidermis with impaired barrier
function. Thenature and dose of antigen, host immaturity, genetic
susceptibility, rate of absorption of a dietary protein, and the
conditions of antigen processing may all affect mucosal adaptive
immunity in the gastrointestinal tract.

Molecular and immunologic techniques can help determine which
allergens or epitopes of an allergen in a particular food may be
responsible for specific clinical outcomes. Immune responses to a
particular allergen may differ based on the method of exposure and the
condition of the food.

Sensitivity to most food allergens, such as milk, wheat, and egg,
tends to resolve in late childhood, but allergies to peanut, tree
nuts, and seafood are likely to be lifelong. Peanut allergy, which
affects approximately 0.6% of the general population, is the most
common cause of fatalfood-induced anaphylaxis, especially in
adolescents with asthma. Allergies to fruits and vegetables are the
most common food allergies reported by adults, and these maydevelop
later in life because of shared homologous proteins with airborne
allergens such as pollens.

Risk factors for developing food allergy include a personal or family
history of atopy or food allergy, maternal consumption of major food
allergens during pregnancy or breast-feeding, atopic dermatitis, and
transdermal food exposure. For infants at increased risk,
breast-feeding and avoidance of highly sensitizing and/or solid foods
at a young age may help reduce this risk.

Symptoms of food allergy may be mild, develop gradually, and be
limited to the gastrointestinal tract, or they may be severe, rapidly
progressing, life-threatening anaphylactic reactions triggered by even
small amounts of food allergen. There is a strong temporal
relationship between the onset of the reaction and exposure to a
specific food or food additive, and symptoms may include skin
manifestations, gastrointestinal symptoms, respiratory symptoms,
hypotension, and laryngeal edema, occurring separately or together.
Anaphylaxis may occur in highly sensitive patients or when triggering
foods are ingested before or after exercise.

Evaluation of food allergy should begin with a detailed history
featuring a list of suspect foods, the quantity of food triggering a
reaction, the reproducibility of the reaction and its temporal
relationship to food ingestion, time elapsed between exposure and
reaction, clinical symptoms, resolution of symptoms when the suspect
food is eliminated, and duration of symptoms overall and after each
exposure. A written record of dietary intake may be helpful.

Physical examination should focus on suspected targeted organ systems
including the skin, lungs, and gastrointestinal tract, and it should
reveal or rule out alternative diagnoses to food allergy. Atopic
disorders including asthma, atopic dermatitis, and allergic rhinitis
increase the likelihood of food allergy.

Skin prick or puncture tests may be useful for screening. Commercial
food extracts from foods with stable proteins, such as peanut, milk,
egg, tree nuts, fish, and shellfish, reliably detect specific IgE
antibodies in most patients, but extracts from fruits, vegetables, and
other foods containing labile proteins are less reliable. In the
latter case, pricking the food and then the patient may be helpful.
However, skin or in vitro test results may remain positive even when
the patient's skin is no longer clinically sensitive.

Intracutaneous or intradermal skin tests are not recommended because
they are potentially dangerous, overly sensitive, and associated with
an unacceptable rate of false-positive reactions. A positive skin test
result has a positive predictive value of no greater than 50%, whereas
a negative skin test has a negative predictive value of 95% or
greater, virtually ruling out an IgE-mediated mechanism. Because
allergy to multiple foods is uncommon, skin testing should be
selective for suspected foods. Larger wheal-flare reactions on prick
or puncture tests and higher concentrations of food-specific IgE
measured by in vitro tests are correlated with a greater likelihood of
reaction.

In vitro tests to evaluate possible IgE-mediated reactions may be
especially valuable in patients with a history of a life-threatening
reaction to the suspected food; in those with medical conditions, such
as extensive atopic dermatitis or dermatographism that could hinder
interpretation of skin test results; in those with a nonreactive
histamine control; or in pregnant women. Patients with a history of
anaphylactic reaction and positive test results for specific IgE
antibodies usually require no further evaluation.

Other tests being investigated for their utility in diagnosing
IgE-mediated reactions to foods include atopy patch tests, hair
analysis, food specific IgG or immune complex assays, and newer
versions of the previously disproved cytotoxic tests. However,
provocation-neutralization is considered disproved as a diagnostic
method in allergy.

Challenge with a suspected food may help to determine if test results
were falsely negative or falsely positive, especially if done in a
double-blind, placebo-controlled fashion. Consultation with an
allergist-immunologist may benefit patients who have a history of
reactions to foods that could be IgE-mediated.

Managing food allergy relies primarily on avoiding exposure to foods
suspected or proven to be responsible for the patient's symptoms based
on history and appropriate tests. If this is not possible, patients
with chronic symptoms may benefit from an elimination diet. However,
patients have an increased risk of unintentional food allergen
exposure in special circumstances including schools and restaurants.
The patient and/or the patient's advocate should be educated to read
labels and to recognize that unfamiliar terms may indicate the
presence of a food allergen.

Avoiding the identified food allergen may improve the likelihood that
tolerance will develop with time, especially with cow's milk, egg, and
soy. There are currently no known oral or parenteral agents
consistently shown to prevent IgE-mediated reactions to food, and such
measures should not be relied upon. Immunotherapy to food proteins is
currently experimental. Injectable epinephrine is the treatment of
choice for an anaphylactic reaction of any cause.

"For this reason, patients who have experienced IgE-mediated reactions
to a food or their caregivers should be educated and provided with
injectable epinephrine to carry with them," the authors write.
"Because anaphylactic reactions may be prolonged or biphasic, it is
reasonable to instruct the patient to carry more than one epinephrine
injector, to seek immediate medical care after a reaction, and to be
monitored for an appropriate period."

Ann Allergy Asthma Immunol. 2006;96:S1-S68

Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
Describe the pattern, basis, and diagnosis of IgE-mediated and other
food allergies.
List management guidelines for IgE-mediated food allergies.
Clinical Context
According to the authors of the guidelines, the prevalence of
potentially life-threatening food allergy to peanuts and tree nuts is
increasing, leading to increased awareness and policy changes in
schools, restaurants, and the airline industry in the United States.
Adverse reactions to food affect some 25% of the population with the
highest prevalence during childhood and infancy. Such reactions may be
classified as food allergy, food intolerance, food poisoning,
pharmacologic reactions, and toxic reactions.

Diagnostic evaluation of food allergies has become more challenging
and sophisticated, according to the authors, and these guidelines
provide practitioners with an evidence-based approach to the diagnosis
and management of IgE-mediated allergic food reactions. Individuals
with atopy, or with pollen or latex sensitivity are more likely to
develop food allergies compared with the general population, with the
highest incidence in infants with moderate to severe atopic
dermatitis. IgE-mediated response to food represents only a small
percentage of all adverse reactions to foods; its prevalence ranges
from 2% to 5% and has definite ethnic variation.

These guidelines are based on a review of the medical literature and
expert consensus of the Joint Task Force on Practice Parameters, with
a goal toward improving understanding of food allergy, to guide
clinicians, and to improve quality of patient care.

Study Highlights

In children of parents with asthma, the rate of observed food allergy
may be 4 times higher than in the general population.
IgE-mediated food reactions may occur as a result of gastrointestinal
sensitization, respiratory tract sensitization, or sensitization
through the epidermis.
Immune responses include acute IgE-mediated, local inhalational,
systemic, and cell-mediated reactions (eg, atopic dermatitis and
celiac disease).
Sensitivity to most food allergens, such as milk, wheat, and egg, tend
to remit in late childhood.
Sensitivity to peanut, tree nuts (walnuts, cashew, Brazil nut,
pistachio), and seafood are likely to continue throughout life.
Allergies to fruits and vegetables tend to develop later in life as a
consequence of shared homologous proteins with airborne allergens (eg,
pollen).
Anaphylaxis after exposure to foods reflects reactions of respiratory,
dermatologic, cardiovascular, and other organ systems.
In children, anaphylaxis occurs most commonly after ingestion of
peanuts, other legumes, tree nuts, fish, shellfish, milk, and eggs.
Diagnosis requires a detailed history of exposures and targeted
physical examination.
Initial evaluation may include skin prick or puncture tests.
Commercial food extracts with stable proteins (eg, peanut, milk, egg,
tree nuts, fish, shellfish) are reliable to detect IgE antibodies in
most patients.
Extracts from foods with more labile proteins (eg, many fruits and
vegetables) are less reliable for diagnosis.
Intradermal skin tests are not recommended as they are dangerous.
A positive skin test has a positive predictive value (PPV) of less
than 50% (ie, not specific) but a negative skin test has a negative
predictive value (NPV) of more than 95% (ie, highly sensitive) and can
reliably rule out IgE-mediated food allergy.
Double-blind, placebo-controlled food challenge is most likely to
provide a high PPV in conjunction with a careful history.
In vitro serum tests are useful in patients with a history of
life-threatening reaction, with medical conditions, a nonreactive
histamine control, and in pregnant women.
If a patient has a history of anaphylactic reaction with a positive
test for IgE specific antibodies, no further evaluation is usually
required.
Provocation-neutralization is considered disproved as a diagnostic
method.
Hair analysis, food-specific IgG, cytotoxic tests, and immune complex
assays are considered experimental or unproven.
Adverse reactions to food additives (such as tartrazine) are rare.
Monosodium glutamate is a rare cause of angioedema, urticaria, or
bronchospasm in patients with asthma. Sulfites produce bronchospasm in
5% of the population with asthma.
Food allergy prevention strategies include breast-feeding, maternal
dietary restriction during breast-feeding, late introduction of solids
and allergenic foods, and the use of hypoallergenic infant formulas
although effectiveness of the strategies has not been established.
Avoidance of allergens is the key management strategy.
Because elimination diets may lead to malnutrition or other serious
adverse effects (eg, personality change), every effort should be made
to ensure that the dietary needs of the patient are met and that the
patient and/or caregiver(s) are fully educated in dietary management
measures to prevent inadvertent exposure to known or suspected
allergens.
Injectable epinephrine should be given to patients or caregivers of
patients with a history of IgE-mediated systemic reactions.
Delay in epinephrine administration is the most common cause of
fatalities, with peanuts and tree nuts accounting for most fatal and
near-fatal reactions.

Pearls for Practice

IgE-mediated food allergies may be diagnosed by careful history, skin
prick or puncture, and in vitro serum tests.
The main management strategies for IgE-mediated food allergy are
avoidance and use of injectable epinephrine in those with a history of
systemic reaction.