Food Allergy

H
Dr. Mohamed Elmaghraby
Assistant Lecturer of Pediatrics
Al Hussein University Hospital
Al Azhar University
TERMINOLOGY
 The term "food allergy" refers to an abnormal immunologic reaction to a
food that results in the development of symptoms on exposure to that
food. This clinical reactivity is assessed by history or challenge.

 Such reactions can be mediated by IgE molecules directed against

specific food proteins that activate mast cells and basophils or can arise
from other cellular processes involving eosinophils or T cells.

 The term "sensitization" is used to denote the presence of IgE directed

against a specific antigen (a "positive" test), as detected by in vivo (skin
prick testing [SPT]) or in vitro (fluorescent enzyme immunoassay
[FEIA]) testing. However, a patient who is sensitized to a particular food
may not be clinically reactive upon exposure to the food. Less
commonly, a patient may have a clear history of food-allergic reactions
with low or undetectable levels of food-specific IgE.
PATHOGENESIS
 Food allergy is predominantly caused by IgE-mediated and cell-mediated
immune mechanisms.

 In susceptible individuals exposed to certain allergens, food-specific IgE

antibodies are formed that bind to receptors on mast cells, basophils,
macrophages, and dendritic cells. When food allergens penetrate
mucosal barriers and reach cell-bound IgE antibodies, mediators are
released that induce vasodilation, smooth muscle contraction, and mucus
secretion, which result in symptoms of immediate hypersensitivity
(allergy).
 Activated mast cells and macrophages may release several cytokines
that attract and activate other cells, such as eosinophils and lymphocytes,
leading to prolonged inflammation.

 In non-IgE food allergies, lymphocytes, primarily food allergen–specific T

cells, secrete excessive amounts of various cytokines that lead to a
“delayed,” more chronic inflammatory process.
PREVALENCE OF CHILDHOOD FOOD
ALLERGY
 Up to one-third of parents report adverse food reactions in their young
children, although the rates of verifiable food allergy are much lower.
Nonimmunologic adverse reactions account for the bulk of adverse food
reactions. Food sensitization and/or allergy occur in approximately 5 to
10 percent of young children, with peak prevalence at approximately
one year of age. However, studies that measure sensitization to food
allergens can overestimate the prevalence of true allergic reactions to
foods because not all sensitized children will develop symptoms upon
ingestion.

 Most food allergy is acquired in the first or second year of life. The peak
prevalence of food allergy is approximately 6 to 8 percent at one year of
age. Prevalence then falls progressively until late childhood, after which
it remains stable at approximately 3 to 4 percent. Some studies have
suggested that the prevalence of food allergy has increased over time.
Clinical manifestations of food allergy:
An overview
 Adverse food reactions can be divided into food allergies, which are
immunologically mediated, and all other reactions, which are
nonimmunologic.

 Adverse food reactions are common and often assumed by patients to be

allergic in nature. However, nonimmunologic reactions to food are more
common than true food allergies.

 Food allergies are broadly categorized into either immunoglobulin E

(IgE)-mediated or non-IgE-mediated processes. Some disorders, such as
atopic dermatitis or the eosinophilic gastrointestinal disorders (EGIDs),
have characteristics of both mechanisms.
IgE-MEDIATED REACTIONS
 IgE-mediated food allergic reactions are rapid in onset, typically
beginning within minutes to two hours from the time of ingestion.

 Signs and symptoms can involve the skin, respiratory, gastrointestinal

tracts, and cardiovascular system and are believed to be caused by
mediator release from tissue mast cells and circulating basophils.

Clinical features
Dermatologic - Pruritus, flushing, urticaria/angioedema, diaphoresis
Eyes - Conjunctival injection, lacrimation, periorbital edema, pruritus

Respiratory tract - Nose/oropharynx (sneezing, rhinorrhea, nasal congestion, oral pruritus,

metallic taste), upper airway (hoarseness, stridor, sense of choking, laryngeal edema), lower
airway (dyspnea, tachypnea, wheezing, cough, cyanosis)

Cardiovascular - Conduction disturbances, tachycardia, bradycardia (if severe), arrhythmias,

hypotension, cardiac arrest

Gastrointestinal - Nausea/vomiting, abdominal cramping, bloating, diarrhea

Neurologic - Sense of impending doom, syncope, dizziness, seizures
Urticaria and angioedema
 Acute urticaria and angioedema are probably the most common
cutaneous manifestations of allergic reactions to food, generally
appearing within minutes of ingestion of the food allergen. Food allergy
may account for 20 percent of cases of acute urticaria.

 By comparison, food allergies are an uncommon underlying cause of

chronic urticaria and angioedema.

 Food can also cause acute contact urticaria. In this condition, urticaria
develops only on skin that was in direct contact with the food. In addition
to the common allergens, raw meats, seafood, raw vegetables and fruits,
mustard, rice, and beer are among the foods that have been implicated in
this form of reaction.
Respiratory tract symptoms

 Asthma and environmental allergies (allergic rhinitis and conjunctivitis)

are more common in children with food allergy.

 In addition, conjunctival, nasal, and lower respiratory tract symptoms are

common components of systemic food allergic reactions (ie,
anaphylaxis).

 However, isolated allergic rhinoconjunctivitis or asthma in response to

foods is rare.
Gastrointestinal symptoms
 IgE-mediated gastrointestinal symptoms, including nausea, abdominal
pain, abdominal cramping, vomiting, and/or diarrhea, are more prominent
features in anaphylaxis due to ingestion of a food allergen.

 The term "gastrointestinal anaphylaxis" is used when gastrointestinal

symptoms occur in isolation. However, gastrointestinal symptoms are
rarely the sole manifestations of a food-allergic reaction. More commonly,
gastrointestinal symptoms occur in conjunction with involvement of other
target organs.

 The onset of upper gastrointestinal symptoms (nausea, vomiting,

abdominal pain) is generally minutes to two hours after ingestion of the
offending food, but lower gastrointestinal symptoms, such as diarrhea,
can begin two to six hours after ingestion.
Anaphylaxis
 Anaphylaxis is defined as a serious allergic reaction that is rapid in onset
and may cause death.

 Patients may develop a combination of symptoms and signs related to

the cutaneous, respiratory, gastrointestinal, and/or cardiovascular
systems that constitute anaphylaxis.

 Anaphylactic reactions may culminate in hypotension, vascular collapse,

cardiac dysrhythmias, or death.

 Cofactors may increase the risk that a food allergen will elicit
anaphylaxis rather than a mild reaction, including menstruation,
nonsteroidal antiinflammatory drugs (NSAIDs), alcohol, elevated body
temperature, acute infections, and antacids
NON-IgE-MEDIATED REACTIONS

 Non-IgE-mediated food allergies present as more subacute and/or

chronic symptoms that are typically isolated to the gastrointestinal tract
and/or skin. Affected patients commonly present with a characteristic
constellation of clinical and demographic features that are consistent
with well-described disorders.

 The exclusive non-IgE-mediated food allergy disorders principally

include:

● Food protein-induced enterocolitis syndrome (FPIES; entire

gastrointestinal tract)
● Food protein-induced enteropathy (small bowel)
● Food protein-induced allergic proctocolitis (FPIAP; rectum and colon)
● Food-induced pulmonary hemosiderosis (Heiner syndrome)
Gastrointestinal manifestations
 The type of gastrointestinal signs and symptoms may vary in some
disorders, depending upon whether the food is consumed regularly or
infrequently.

 In addition, certain disorders are associated with systemic manifestations.

 Chronic vomiting and diarrhea, particularly if accompanied by failure to

thrive, suggests disorders such as food protein-induced enteropathy,
celiac disease, FPIES, or an eosinophilic gastrointestinal disorder
(EGID).

 EGIDs are mixed IgE and non-IgE-mediated reactions.

Food protein-induced allergic proctocolitis
(FPIAP)
 Passage of blood-tinged stools and mucus in an otherwise healthy
infant without an anal fissure is suggestive of food protein-induced
allergic proctocolitis.

 The most common trigger is cow's milk in the mother's diet, although it
can also occur in formula-fed infants.

 This disorder typically presents between two and eight weeks of age
and resolves in a few days with complete elimination of the offending
protein.
Food protein-induced enterocolitis syndrome
(FPIES)
 Infants with FPIES are generally sicker in appearance than those with
other non-IgE-mediated allergic gastrointestinal disorders, with lethargy
and pallor.

 The stools are typically watery, with occasional mucus, although grossly
bloody diarrhea (melena) is possible.

 The vomiting is intermittent in the chronic setting but can be severe and
can lead to dehydration. Patients may also have malabsorption.

 Poor weight gain/failure to thrive is common.

 Laboratory abnormalities include hypoalbuminemia, anemia, and

leukocytosis
 Symptoms of FPIES resolve upon elimination of the causative food,
although it may take several weeks to a month to start to see an
improvement.

 The acute manifestations of FPIES can be clinically identical to IgE-

mediated gastrointestinal anaphylaxis; therefore, testing is usually
necessary to determine if food-specific IgE is present.

 FPIES in older children and adults is rare and typically presents a

milder syndrome of nausea, protracted vomiting, and cramping
several hours after ingestion.

 FPIES is uncommon in exclusively breastfed infants.

 Cow's milk and soy are the most common triggers in infants and
children, although many other food protein triggers have been
reported.
Protein-induced enteropathy
 Infants with food protein-induced enteropathy can present with
findings similar to patients with FPIES who are regularly ingesting a
causative food (eg, chronic vomiting and diarrhea, failure to thrive).

Celiac disease
 Celiac disease is not classically considered a food allergy, but it is
caused by a non-IgE-mediated immune reaction to a food protein
(gluten).

 Also known as gluten-sensitive enteropathy, is an immunemediated

inflammatory disease.

 Flatulence and steatorrhea are suggestive of celiac disease rather

than other forms of food-protein-induced enteropathy or FPIES.
Pulmonary manifestations

 Food-induced pulmonary hemosiderosis (Heiner syndrome) is a

rare syndrome in infants that consists of recurrent pneumonia with
pulmonary infiltrates, hemosiderosis, iron deficiency anemia, and
failure to thrive.

 Cow's milk is the most common causative food, with pork and egg
also being reported.

 Elimination of the offending food results in resolution.

MIXED IgE AND NON-IgE-MEDIATED REACTIONS
 Some food allergy disorders can have both IgE and non-IgE-mediated
components.

 Similar to the exclusively non-IgE-mediated food allergies, the mixed

disorders are typically isolated to the gastrointestinal tract and/or skin.

 The mixed disorders primarily include:

● Atopic dermatitis.
● Eosinophilic esophagitis (EoE).
● Eosinophilic gastroenteritis.
Atopic dermatitis (eczema)
 Occurs within minutes to a few hours if the reaction is IgE
mediated but may take hours to days if the reaction is non-IgE
mediated.

 The following features characterize the relationship between atopic

dermatitis and food:

● The elimination of suspected food allergens frequently improves

symptoms of atopic dermatitis within a few weeks.

● Repeated exposure to suspect foods commonly exacerbates skin

symptoms.

● Eliminating foods to which an infant has demonstrable allergy can

partially improve skin symptoms.
Eosinophilic gastrointestinal disorders
 The eosinophilic gastrointestinal disorders (EGIDs) are characterized by
symptoms of postprandial gastrointestinal dysfunction accompanied by
eosinophilic infiltration of various segments of the intestinal tract on
biopsy.

 Chronic symptoms are typical if the food trigger is consumed regularly.

 Symptoms are intermittent but can be delayed by hours to days if the

food trigger is eaten infrequently.

 The pathophysiology of the EGIDs is poorly understood. Many patients

have evidence of allergic sensitivities to food and/or environmental
allergens, but the causal role of these sensitivities is unclear.
Eosinophilic esophagitis

 EoE should be suspected in patients of any age presenting with esophageal

symptoms.

 Infants and young children may present with feeding disorders and failure to
thrive, whereas older children and adults typically present with dysphagia,
vomiting, and abdominal pain.

 A history of food impaction is common, particularly in adolescents and adults.

 Failure to respond to antacids and antireflux therapies is an important aspect

of the history.

 The most commonly implicated foods in children are cow's milk, egg, soy,
corn, wheat, and beef, and most patients with evidence of food sensitivity
tested positive for multiple foods.

 Elimination or elemental diets result in clinical and histologic improvement in

most.
Eosinophilic gastroenteritis

 Eosinophilic gastroenteritis can present at any age with abdominal pain,

nausea, diarrhea, malabsorption, and weight loss.

 In infants, it may present as outlet obstruction with postprandial projectile

vomiting that can mimic pyloric stenosis.

 Symptoms vary depending on the layer and portion of the gastrointestinal

tract that is involved.

 Approximately one-half of patients have allergic disease, such as defined

food sensitivities, asthma, eczema, or rhinitis.

 An empiric elimination diet or elemental diet may improve symptoms and

histologic findings in up to half of patients.
Diagnostic evaluation of IgE-mediated food
allergy

 The evaluation of a patient with possible immunoglobulin E (IgE) mediated

food allergy includes some combination of the following diagnostic tools,
although not all of these elements are necessary in every patient.

● History and physical examination.

● Prick/puncture skin testing.
● In vitro testing.
● Food challenges.
HISTORY AND PHYSICAL EXAM

 Every evaluation begins with a detailed history and physical

examination.

 The clinical history is critical in the diagnosis of food allergy

since it is used to determine subsequent testing and interpretation of
results.
 ROLE OF ALLERGY TESTS IN DIAGNOSIS
 Allergy testing, in the form of skin testing or in vitro tests, must always
be selected and interpreted in the context of the patient's specific
clinical history because a "positive" test (ie, sensitization, or formation of
IgE to a specific substance) does not always indicate clinical allergy.

 The details of the history are used to generate an estimate of the

patient's pretest probability of having allergic disease.

 Testing is not required for diagnosis in a patient with a clear IgE-

mediated reaction such as anaphylaxis to a single food, but a baseline
value is helpful for monitoring over time.

 Testing should be avoided in most patients without a history consistent

with an IgE-mediated reaction, unless it is felt that a negative test will
encourage reintroduction of the food into the diet.
 If a patient is tolerating a food without immediate symptoms, the food
should not be eliminated from the diet solely because of a "positive" IgE
test.
 Approach to determining when to test for IgE-mediated food
allergies based upon clinical history
 This algorithm summarizes our approach to determining whether
testing for IgE-mediated food allergies is warranted based upon the
clinical history.

 Several factors determine whether a history is consistent with an IgE-

mediated reaction, including the signs and symptoms of the reaction
(common findings include urticaria, nausea/vomiting, wheezing),
timing in relation to food ingestion (usually within minutes), and the
food trigger suspected (eg, a common allergen such as peanut).

* Testing is generally indicated when there is ambiguity in the clinical

history (eg, unclear if an IgE-mediated reaction, unclear food trigger,
possible cross-contact with other allergens, etc) and/or multiple food
allergies are suspected.

¶ Testing for IgE-mediated allergy is generally avoided because false-

positive tests can lead to unnecessary dietary restrictions. However, for
patients/caregivers who are reluctant to reintroduce the avoided food, a
negative test may be helpful.
APPROACH TO TESTING
 This algorithm summarizes our approach to interpreting results of
allergy testing in patients with a convincing or suggestive history of
IgE-mediated food allergy and to determining the need for additional
testing.

 Critical pieces of the history include the suspected food(s), the type
and timing of signs and symptoms, any contributing factors, and
response to treatment.

 The choice of testing depends upon a several factors including

availability of testing, patient/caregiver and clinician preferences, and
technical limitations and accuracy of the tests.

 Options include skin prick testing (SPT) with food extracts or fresh
foods and immunoassays to whole foods.
SKIN TESTING
 Skin prick testing (SPT) is best used to investigate the possibility of an
IgE-mediated reaction to a specific food in a patient with a suggestive
clinical history (ie, a high pretest probability) of allergy.

 It is also highly effective for excluding IgE-mediated allergy, particularly

in a patient with a low pretest probability, because of its high sensitivity.

 Because of the low specificity of SPT, it should not be used to screen

patients for allergy by testing with broad panels of food allergens
without regard for clinical history, since this is likely to yield false-
positive (clinically irrelevant) results.

 Prick/puncture skin tests are highly reproducible and less costly to

perform than in vitro testing. SPT causes minimal patient discomfort
and yields results within 15 minutes. This type of testing can be safely
performed in patients of any age.
Precautions and preparations
 Allergy skin testing is considered a safe procedure. However, it
occasionally causes systemic reactions in very sensitive patients.

 Thus, it is recommended that this type of testing be performed by allergy

specialists trained in the treatment of anaphylaxis and in a setting where
full emergency equipment and medications are available.

 The following factors should be considered in the decision to perform skin

testing:
* SPT should be performed with caution in patients who, by history, are at
high risk for a systemic reaction, such as patients with moderate or severe
asthma who have experienced anaphylaxis previously.
* Certain medications, such as antihistamines, can interfere with SPT and
must be stopped beforehand.
* SPT is not usually performed for several weeks after an episode of
anaphylaxis, because it has been observed that anaphylaxis can render the
skin temporarily nonreactive.
IN VITRO TESTING (Immunoassays)
 Immunoassays are in vitro assays used to identify food-specific IgE
(sIgE) antibodies in the serum.

 Immunoassays are more costly than skin testing, and the results are
not as immediately available.

 However, immunoassays for sIgE have several useful features. In vitro

tests are:

● Widely available
● Unaffected by the presence of antihistamines or other medications
●Useful in patients with severe anaphylaxis in whom skin testing may
carry an unacceptable degree of risk.
● Useful in patients with dermatologic conditions that may preclude skin
testing.
 Higher concentrations of sIgE correlate to an increased likelihood of
a reaction upon ingestion, an individual patient with a significant
food allergy can have a high, medium, low, or even negative in vitro
test using these systems.

 Importantly, as with skin testing, the sIgE level does not correlate
well with the severity of a reaction.

 It is also true that a patient can have a positive sIgE for a food to
which they are tolerant.

 Thus, the patient's clinical history is critical to both determining the

tests to perform and confirming the diagnosis.
FOOD CHALLENGES
 Oral Food Challenges are structured protocols in which the patient
ingests a suspect food under clinician supervision.

 Food challenges should only be performed by allergy specialists familiar

with food-allergic reactions and in settings equipped with the necessary
medications, equipment, and staff to treat anaphylaxis.

 The OFC serves two roles in managing food allergies:

* To confirm diagnosis of a specific food allergy.
* To determine if an identified allergy persists or has resolved.

• Elimination diets followed by oral food challenges are the only way to
establish the diagnosis.

• Before a food challenge is initiated, the suspected food should be

eliminated from the diet for 10-14 days for IgE-mediated food allergy and
up to 8 wk for some cell-mediated disorders, such as EoE.
Management of food allergy:
Avoidance
 The primary therapeutic strategy in the management of food allergy is
avoidance.

 Complete avoidance is typically prescribed for immunoglobulin E (IgE)-

mediated food allergies as well as food-protein enterocolitis in infants.

 Important observations about avoidance include the following:

* Studies indicate that less than a milligram of milk, egg, or peanut can
induce symptoms in some highly sensitive individuals, while others may
not experience a reaction until more than 10 grams have been ingested.

* Clinical experience and observational studies show that some individuals

with egg or milk allergy tolerate these foods in low amounts and as minor
ingredients baked into products, such as cakes or cookies.
Maternal dietary avoidance of allergens
for infants with proven food allergy
 Food allergens ingested by the mother can be detected in breast milk,
with individual variability.

 There are case reports and case series indicating that allergic reactions,
including anaphylaxis, can occur in the infant from transfer of maternally
ingested allergen through breast milk.

 There is also evidence that infants may have chronic atopic dermatitis or
gastrointestinal symptoms (vomiting, diarrhea, failure to thrive,
proctocolitis) triggered by food allergens in breast milk.

 When a breastfed infant is diagnosed with an allergy to a specific food,

the infant must avoid direct ingestion of the allergen.
 Options regarding the maternal diet include strict avoidance, reduced
ingestion, no avoidance, or, for milk and egg, ingestion of only
extensively heated forms (eg, bakery goods) that appear to have
reduced allergenicity.

 An alternative option is the cessation of breastfeeding.

 There are no controlled trials upon which to base recommendations

about maternal avoidance, and strict avoidance could be recommended
in all circumstances.

 We generally recommend strict maternal dietary avoidance if the infant

had an acute reaction to an allergen in breast milk, a severe
anaphylactic reaction to an allergen the infant ingested directly, chronic
symptoms attributable to the food despite a low maternal intake of the
trigger, or a reaction to a food that often triggers severe reactions and is
generally eaten by the mother in larger quantities during meals (eg,
peanut, nuts, fish, shellfish).
New treatment of Food Allergy
 Sublingual immunotherapy (SLIT).

 Epicutaneous immunotherapy.

 Oral immunotherapy (OIT).

* Combining oral immunotherapy with anti-IgE treatment may improve

safety compared to oral immunotherapy alone.
PREVENTION
 It was once thought that avoidance of allergenic foods and delayed
introduction to the diet would prevent allergy, but the opposite is probably
true; delayed introduction of these foods may increase the risk of allergy,
especially in children with atopic dermatitis.

 Exclusive breastfeeding for the 1st 4-6 mo of life may reduce allergic
disorders in the 1st few yr of life in infants at high risk for development of
allergic disease.

 Potentially allergenic foods (eggs, milk, wheat, soy, peanut/tree nut

products, fish) should be introduced after this period of exclusive
breastfeeding and may prevent the development of allergies later in life.

 Do not avoid allergenic foods during pregnancy or nursing.

 Soy-based formulas do not prevent allergic disease

SUMMARY
 The peak prevalence of food allergy is approximately 6 to 8 percent at one
year of age and then falls progressively. By late childhood, the prevalence
is 3 to 4 percent and remains stable thereafter. Children with food allergy
are at high risk for developing later allergic rhinitis and asthma.

 Food allergies arise from abnormal immunologic reactions, usually to food

proteins. Food allergies are broadly categorized into either immunoglobulin
E (IgE) mediated or non-IgEmediated processes. Some disorders have
characteristics of both mechanisms.

 IgE-mediated food allergy typically develops rapidly after food ingestion (ie,
usually within minutes). Symptoms can affect one or more organ systems.

 Non-IgE-mediated food allergies present as more subacute and/or chronic

symptoms, which are typically isolated to the gastrointestinal tract.
 Both IgE and non-IgE-mediated mechanisms can be involved in atopic
dermatitis and eosinophilic gastrointestinal disorders (EGIDs).

 The first step in the evaluation of food allergy is the history and physical
exam. This is typically followed by skin testing, in vitro testing, and/or food
challenges.

 The history is critical in the diagnosis of food allergy and is the first step in
discerning the type of food allergy present (immunoglobulin E [IgE]
mediated or not), whether there is an alternative explanation for the
patient's symptoms (eg, viral rash, food intolerance, etc) that should not be
evaluated with allergy tests, and the suspected causative food.

 Skin testing for food-specific immunoglobulin E (sIgE) is used only in the

diagnosis of IgE mediated food allergies. Skin testing is more sensitive than
in vitro testing in some cases. It should be performed by an allergy
specialist because of both the risk of anaphylaxis and the skill required for
proper interpretation. Skin testing is contraindicated or unreliable in certain
subsets of patients.
 A positive skin test to a particular food only indicates the possibility that
the patient has true allergy to that food because of lower specificity of
the test, which varies from 50 to 95 percent depending upon the food in
question and the size of the skin test reaction. Further tests or
challenges may be needed to confirm that the patient is truly reactive to
the food upon ingestion, depending upon the patient's pretest
probability of having allergy.

 In contrast and importantly, a negative skin test result has a high

sensitivity and indicates the absence of an IgE-mediated allergy.
Further testing or challenge is sometimes indicated.

 IgE immunoassays are in vitro assays used to identify sIgE in the

serum. These tests are widely available and are unaffected by the
presence of medications. Their sensitivity varies among different foods.
 Supervised food challenges are sometimes required for the
definitive diagnosis of food allergy. Foods are selected for testing
based upon the history and the results of skin and/or in vitro testing.
Food challenges should only be performed by allergy specialists
familiar with food-allergic reactions and equipped with the necessary
medications, equipment, and personnel to treat anaphylaxis and
shock.

 Once a diagnosis of food allergy is made, education of patients (and

families) about avoidance is a crucial therapeutic intervention. Strict
avoidance is simple in theory and difficult in practice.

 The vast majority of serious allergic reactions follow ingestion of

food. Skin contact may cause local cutaneous symptoms, and
inhalation may cause rhinitis and asthmatic symptoms. Simply
smelling food is not associated with allergic reactions.
To not over Diagnose Food Allergy

 Follow the algorithm.

 Exclude other diagnoses.

 Do challenge test after elimination.

 Do not forget the value of investigations.

 Refer to consultant.
Thank You