FOOD ALLERGY

AND HYPERSENSITIVITY

Sitti Hajar , dermatologist

Medical Faculty
Syiah Kuala University
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FOOD ALLERGY
AND HYPERSENSITIVITY

INTRODUCTION

HISTORY OF FOOD ALLERGY

REVIEW OF BASIC IMMUNOLOGY OF ALLERGY

TYPES OF ADVERSE REACTIONS TO FOOD

DIAGNOSTIC FOR FOOD ALLERGY

TREATMENT OF FOOD ALLERGY

CONCLUSION
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INTRODUCTION

Alergy :
antigens immune responses tissue
inflammation and organ dysfunction.

Food allergy :
food immune mediated symptoms.

US: 25-30%, in children (cow milk 2.5%,

peanuts 0.5-0.7%).

Internationally: 2.5% of infants, 1.4-1.8% of adults.

eggs 2%,

HISTORY OF FOOD ALLERGY

China (3000 B.c) :

cutaneous reactions caused by food
Hippocrates :
milk gastric distress and urticaria
Von Pirquet (1906) :
introduced the concept of allergy
skin tests detect food allergies
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HISTORY OF FOOD ALLERGY

Rinkel (1934) :
developed the oral food challenge
Schloss, Rowe, and Coca :
delayed food sensitivity
Dr. Carleton Lee (1958) :
serial endpoint skin testing
singlefood antigens

responses

to

HISTORY OF FOOD ALLERGY

1963 :
provocation techniques
neutralization techniques
dietary management

treatment of food allergies

BASIC IMMUNOLOGY OF
ALLERGY

Immune System

Made up : cells (in the circulation & the body

tissues) chemical substances interacting and
affecting foreign molecules.
An antigen
The nonspecific immune response :
reacts to broad categories of antigens
The specific immune response :
develops differently in every individual

Immune System
The specific immune response :
antigen activates specific lymphocytes

lymphocytes coordinate an immune response

eliminates the antigen

The immune response : humoral & cellular.
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Lymphocytes

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Lymphocytes

20% of total leukocytes

T cells :
cell mediated immunity and cytotoxicity
regulate the immune system

B cells :
differentiates and secrete immunoglobulin
presence of specific surface ab receptors antigen
Natural killer cells : large granular lymphocytes

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Lymphocytes

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Lymphocyt B NK Cell

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NK Cell

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Lymphocytes

T helper cells :
interacts and stimulates B cells
T suppressor cells :
antigen specific suppressor role
inhibit B-cell functions
T cytotoxic cells :
the destruction of infected or malignant cells
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Immunoglobulins

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Immunoglobulins

the primary effectors of the humoral immune

response
basic structure :
the heavy chain :
determines the ability of an antibody to bind to
cells
confers immunoglobulin class

the light chains :

determine the specific antigen binding site
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Immunoglobulins
Immunoglobulin E :
responsible for hypersensitivity reactions
bind to basophils and mast cells
Immunoglobulin M (10%) :
activates the classic complement pathway
assists IgA in defending external surfaces
Immunoglobulin A :
major immune barrier to antigen penetration
Immunoglobulin G (70-75 %) :
Protective, and forms blocking antibodies

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Antigen Processing Cells

Antigens enters the body phagocytes engulf and destroy

smaller fragments presenting these antigen fragments to
lymphocytes lymphocyte T or B cell is activated

B cells produces and secretes antibody specific to the

antigen, producing the sensitization.

T cell become a helper, suppressor, or cytotoxic cell.

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Antigen-Processing Cells

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Mediator Cells

Antigen antibody complexes mediator cells release

molecules :
histamine
chemotactic factors :
attract other leukocytes affect local tissues
leukotrienes :
control the development and duration of immune
reactions

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Mediator Cells

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Mediator Cells

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Complement

The complement system :

classic and alternative pathways.
Complement :
Amplification and regulation of immune
inflammation.
Enhances uptake and removal of immune
complexes by phagocytosis.

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Complement

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Hypersensitivity Reaction

Allergy is a malfunction of the immune system that

involve any immune effector cells.

Hypersensitivity reactions immune responses acting

inappropriately cause inflammatory reactions and
tissue damage.

Hypersensitivity usually appears on subsequent contact.

Gell and Coombs classified into four classes of immune

reactions.

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Type I
Immediate Hypersensitivity

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Type I
Immediate Hypersensitivity

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Type I
Immediate Hypersensitivity
Prevalence approximately a 5%.
Each exposure to the offending food produces
an immediate symptom response.
Often severe and can be life threatening.
Can result : urticaria, rhinitis, angioedema, and
asthma, and anaphylaxis
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Type ll
Cytotoxic Reactions

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Type ll
Cytotoxic Reactions
Antibody binds antigen leads to :
phagocytosis
killer cell activity
complement mediated lysis
Clinical :
hemolytic anemia, transfusion reactions, and
rare cases of food reactions.

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Type III
Immune Complex Reactions

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Type III
Immune Complex Reactions
Formation of antigen antibody complexes with
subsequent tissue damage.
IgG + circulating antigens macromolecular
complexes precipitate in capillary beds,
binding and activating complement to produce
tissue inflammation.
Delayed in onset and prolonged in symptom
production.
Most common causing food hypersensitivity.
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Type IV
Delayed Type Hypersensitivity

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Type IV
T-cell mediated .
Delayed Type Hypersensitivity

Response occurring 24-48 hours after contact.

Sensitization the cell activated by a new
contact with the antigen T cells release a
variety of cytokines mobilize other
inflammatory cells produce a direct effect on
the target organ.

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Mixed Type Reactions

Mixtures of Gel and Coombs reaction types :

Circulating complexes.
Immunoglobulin (particularly IgE and IgG).
Complement activation.

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THEORY OF ACTION OF
NEUTRALIZATION TREATMENT
Jerne :
immune system negative feedback regulation.
This network turns on or turns off :
antibody formation and the activities of T
cells.
Low doses of antigen regulatory system is
shifted toward shutting off Ab 1 to the original
immunogen.

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THEORY OF ACTION OF NEUTRALIZATION

TREATMENT

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THEORY OF ACTION OF
NEUTRALIZATION TREATMENT
Direct effect of antigen on T cells :
Low
dose
antigen

T-cell
regulatory
mechanism favors the suppression of antibody
production.
The nonimmunologic mechanism involves
prostaglandin production : cytoprotective effects
of prostaglandin (Robert et al).
Low dose antigen desensitization of basophils
for histamine release.
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THEORY OF ACTION OF
NEUTRALIZATION TREATMENT
Low dose antigen therapy :
Downregulating
both
B
cell
production and T-cell function.
Increasing intracellular
monophosphate levels.

cyclic

antibody

adenosine

Decreasing cell metabolism.

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TYPES OF ADVERSE
REACTIONS TO FOODS

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Food Intolerance

Nonimmunologic Reactions.

Anaphylactoid reactions :
Due to the nonimmune release of chemical mediators
contained in foods .

Idiosyncratic reactions :
Due to abnormal responses genetically predisposed
patients.
Asthmatic patient reacting to salicylates.

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Food Intolerance

Digestive enzyme deficiencies :

Lactase deficiency gastrointestinal symptoms.

Toxic reactions :
Food components or additives and toxins released by
microbes in food.

Pharmacologic reactions :
Chemicals in foods produce drug like effects.

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Food Hypersensitivity

Penetration of antigen crossing the gut

triggering the formation of specific antibodies .
Factors influencing food allergies :
The permeability of the gut mucosa.
Crossreactivity between a food and
inhalant allergen.

an

Clinically : fixed food allergy and cyclic types.

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ADVERSE REACTIONS TO FOODS

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Fixed Food Allergy

IgE mediated responses.

Immediate
allergen.

reaction

after

contact

with

the

Sensitivity to the food usually persists for years.

Symptom doesnt depend on the quantity of
food eaten.
Present in various ways.
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Atopic Dermatitis

37% of children with moderate to severe atopic

dermatitis have type I food allergy.
Most common : cow's milk, fish, and eggs .
Mechanism unrelated to IgE mediated histamine
release also can trigger mast cell degranulation
after the ingestion : alcohol, spicy foods, or
additives.

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Asthma

Inhalation of airborne food antigens, steam from

cooking food or also can be triggered by
ingestion of the offending food
Symptoms may include rhinoconjunctivitis,
urticaria, laryngeal edema, and shock.
Foods : eggs, flour, cocoa, peanut, soy, garlic,
tea, fish.

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Urticaria

Urticaria is a wheal and flare cutaneous reaction.

Contact urticaria :
cutaneous contact with prolonged handling of raw food,
and occur around the mouth in children.

Angioedema (45% of the cases ):

nonpruritic swelling, sometimes
suddenly and no more than 3 days.

painful,

developing

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Oral Allergy Syndrome

Local IgE mediated mast cell activation

swelling of the lips, tingling of the tongue and
throat, and blistering of the oral mucosa.
Associated with the ingestion of food crossreact
with their specific allergic inhalant (40% ).

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Oral Allergy Syndrome

Major cross-reactions include:

Birch with apple, carrot, celery, hazelnut, kiwi, peach,
pear, and potato.
Dust mites with shrimp and snail.
Grass with kiwi, melon, tomato, watermelon, wheat,
and other grains.
Latex with avocado, banana, chestnut, kiwi, and rose
family fruits such as cherry and peach.
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The Gastrointestinal Syndrome

Accompanied allergic manifestations in other

target organs.
Symptoms :
abdominal cramps, nausea,
watery diarrhea, hypotension.

vomiting,

and

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Anaphylaxis

Death : respiratory or cardiac failure.

Clinicaly :
Early stages : urticaria, angioedema, bronchospasm,
laryngeal edema.
Gastrointestinal tract : nausea, vomiting, diarrhea.
Cardiovascular : hypotension, dysrhythmia, collapse.

Factors associated severe reaction :

Asthma.
History of previous severe reactions.
Failure to initiate therapy expeditiously.
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Cyclic Food Allergy

IgG mediated, type III immune complex disease (6O% to

80% of food sensitivity).

Dose and frequency related.

antigens immune complexes
frequency sensitivity
More often IgG forms immune complex
formation.
Omission of the food
antibody levels and
immune complexes symptoms.
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Stage of Cyclic Food Allergy

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DIAGNOSTIC
FOR FOOD ALLERGY

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HISTORY

Diagnosis depends on a patient's history.

Actual diet habits, time of ingestion.

Time of any symptoms observed.

Record any improvement of symptoms.

Analyzes :
production.

Most people tend to be habit eaters, the hidden foods are

an universal problem.

frequently

eaten

foods

and

symptom

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HISTORY

Problem : hidden food, allergic crossreactions

between closely related foods .

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Signs and Symptoms

Depend on : fixed or cyclic.

Fixed allergy :
Obvious signs and symptoms.
Symptoms are secondary to release of histamine,
preformed mediators, and the late phase reaction.
Patients can not identify what food is causing :
mixture of foods
chronic allergy conditions
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Signs and Symptoms

Cyclic food allergy :
More complex and difficult to recognize.
Secondary to the slow accumulation of
immune complexes in the capillary beds of
target organs.
Symptoms depends on frequency and the
amount of antigen consumed.
There are many common symptoms and
signs .
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Neurologic Symptoms

Neurologic symptoms :
headaches
learning disabilities
forgetfulness
short attention
insomnia
even seizures can be food triggered

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Ophthalmologic Symptoms

Mild symptoms :
pruritus, stinging, (conjunctival, eyelid,
periorbital, lid) edema with itching, scaling,
and erythema.
Severe symptoms :
tearing, burning, discharge, photophobia,
rough tarsal mucosa, blurred vision, the
cornea should not be inflamed, or eroded.

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Otologic Symptoms

External : chronic otitis externa, narrowed ear

canals, red auricles, scaling.
Middle ear : pressure sensation, lancinating
pains, otitis media with effusion, persistent
otorrhea.
Inner ear : dizziness, disequilibrium, tinnitus,
and dull ear pain.

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Nasal Symptoms

Nasal obstruction
Voice change, Snoring
Sleep disturbance
Edema of the turbinates
Rhinorrhea
Thick postnasal discharge
Crusting
Pruritus, Sneezing
Decreased olfaction

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Oral Symptoms

Pruritus oral, perioral, and palatal.

Dry mouth.
Halitosis.
Geographic tongue.
Angioedema of the lips and oral mucosa.
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Pharyngeal and Laryngeal

Symptoms

chronic sore throat

pharyngitis
chronic throat clearing
perception of a lump in throat
enlarged lateral pharyngeal bands and posterior
pharyngeal lymphoid islands (due to postnasal
drip)
laryngeal edema with intermittent hoarseness

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Pulmonary Symptoms

chronic cough
shortness of breath
chest tightness
chest pain with breathing
Wheezing
thick-tenacious-colorless sputum
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Gastrointestinal Symptoms

intermittent abdominal pain

vomiting
diarrhea
abdominal distention
constipation
pruritus ani
perirectal inflammation ("burned butt")
acute cramps

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Genitourinary Symptoms

Enuresis
Pruritic
Vaginitis
Food or inhalant induced allergic nephrotic
syndrome

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Musculoskeletal Symptoms

Arthralgias
Myalgias
Stiffness
Erythema or edema over joints

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The Skin Symptoms

Atopic dermatitis and eczema.

Urticaria.
Angioedema.
The Id reaction.

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DIAGNOSTIC TECHNIQUES
FIXED FOOD ALLERGY

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Specific Immunoglobulin E Testing

History : serious reaction, significant asthma.

Low sensitivity results :
Commonly are seen without history food
allergic.
High sensitivity results :
Significant symptoms will be produced if that
food is ingested.
Those foods should be permanently avoided.
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Prick Tests

Lewis and Grant (1926), and Pepys (1970s).

Specific, easily, and infrequently cause systemic allergic

reactions.

Variations : precisely reproducing the depth of

penetration, amount of force used, and the amount of
skin lifting.

Correlations : 85% to 90% (in vivo tests), 81% to 89%

(intradermal skin endpoint titration tests).

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Patch Tests
Detect delayed allergic reactions.
Allergens are applied to the intact skin
occlusive dressing allowed to react.
Variations of patch testing :
skin preparation technique
antigen dose
method of antigen solubilization
the type of occlusion
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DIAGNOSTIC TECHNIQUES
CYCLIC FOOD ALLERGY

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In Vitro Food Tests

Cytotoxic test .
IgG and IgG4 in vitro assays.
The antigen leukocyte antibody test.
The ELISA activated cell test.
Basophil histamine release tests.
Positive results should be corroborated by oral
food challenge.
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Oral Challenge Test

The oral challenge test :

Dietary analysis.
Elimination of a specific food for 4 to 5 days.
Ingestion of that food in large amounts.

Difficulty : only one food can be tested at a time.

Easier to perform and more closely mimics normal food

the open, unblinded oral challenge.

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Rechallenge
Initial avoidance period of 2 or more months
rechallenge produce no symptoms rotated
food.
Positive food should be avoided for several
months another challenge no reaction, or
until 2 years of avoidance.
Positif after 2 years fixed food allergen
lifelong avoidance.
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Food Skin Testing Safety Guidelines

Never test : food fixed allergy.

Test only for foods on a regular basis.
Carefully for a history of any past serious
allergic reaction.
All foods to be tested must have been eaten
within 24 hours of testing.
Consider IgE in vitro testing.
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TREATMENT OF FOOD ALLERGY

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TREATMENT OF FOOD ALLERGY

Medical Care.
Education.
Consultations.
Elimination of food allergen.
Neutralization.
Avoid high-risk situations.
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Education
Education is of paramount importance.
Resource information by contacting the
Food Allergy and Anaphylaxis Network (toll-free phone
number is 800-929-4040)
International Food Information Council (phone number
is
202-296-6540
and
email
address
is
foodinfo@ific.org).

Remember that appropriate restriction of the relevant

food allergen(s) is the only current effective therapy.

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Medication

Medication : accidental may occur.

For patients with mild reaction :
treatment may be limited to an oral antihistamine.
For patient with significant systemic symptoms :
the treatment of choice is epinephrine injection.
Medical therapy of food allergen induced allergic reactions
:
the use of antianaphylactic agents, antihistamines,
bronchodilators, and corticosteroids is suggested.
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COMBINING
DIETS AND NEUTRALIZATION

The best treatment is elimination of the food :

Fixed food allergy : eliminated indefinitely.
Cyclic food allergy : eliminated for several months
reintroduction (a rotary, diversified diet).

Neutralization immunotherapy + the best possible diet :

Allergies to ubiquitous foods.
Cannot eliminate those foods from the diet.
Difficult to rotate in the diet or to eliminate.
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CONCLUSION

True food allergies are those reactions that occur because

of the activity of the immune system when exposed to
sensitizing foods.

Clinically, true food allergies occur in two very different

types: immediate, fixed reactions, and delayed, cyclic
reactions.

Fixed food allergies develop rapidly after food exposure,

and therefore usually are easy to diagnose.

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CONCLUSION

Conversely, cyclic food allergies often develop slowly and

vary with both the quantity and frequency with which
allergenic foods' are eaten.

It is important to learn about cyclic food allergies because

they represent most of the clinically observed food
allergies, and are a very important cause of treatable
chronic allergy symptoms.

Understanding the clinical behavior of cyclic food allergies

allows the physician and patient to cooperate for both
diagnosis and successful intervention..

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THANK YOU

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