Introduction to Food Allergens

Robert A. Wood, MD
Professor of Pediatrics
Director, Pediatric Allergy and Immunology
Johns Hopkins University
 Food Allergy - Definition
• Must be differentiated from food intolerances
and other adverse food reactions
• Key components of food allergy:
• An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
• Exquisitely small amounts may cause a
reaction
• Reactions can be severe and even life-
threatening
Exposure

Genetic
Predisposition

Sensitization

Re-exposure

Symptoms
 Food Allergy - Prevalence

• 5 – 7% of young children
• 2 – 3% of adolescents and adults
• At least 11 million Americans are affected
• Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents / Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
 Food Allergy – Signs & Symptoms
• Range from chronic, low grade symptoms to
acute, life-threatening reactions
• Hives / angioedema
• Eczema
• Vomiting / diarrhea / poor growth
• Cough / congestion
• Wheezing / breathing difficulty
• Hypotension / shock
• Anaphylaxis – A systemic allergic reaction
 Food Allergy - Urticaria

• Rarely a cause of chronic urticaria

• More common in acute urticaria
• Peanuts, nuts, eggs, milk, fish, shellfish

most common
• Usually occurs within 2 hrs of ingestion
(history often diagnostic)
• May have angioedema and associated
GI / resp Sx
 Definition of Anaphylaxis

• Systemic allergic reaction

– Multiple organ systems may be involved
• Acute onset
• IgE mediated
• Manifestations vary from mild to fatal
• May be uniphasic, biphasic (30-40%), or prolonged
(rare)
 Atopic Dermatitis - Food Allergy

• 40-50% of patients with severe AD have food

allergy as a major trigger
• Food allergy in 20-25% with less severe AD
• Egg allergy is most common, followed by milk,
peanut, soy, wheat, and fish
• These 6 foods account for 80-90% of food
sensitivities in AD
• 36% react to one food, 26% to 2 foods, 18% to
3 foods, 10% to 4 foods, 10% to 5 or more
foods
 Gastrointestinal Food Hypersensitivity

IgE- Non-IgE-
Mediated Mediated

Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
 The Diagnosis of Food Allergy
• Detailed history
• Food(s) suspected
• Specific symptoms
• Timing of symptoms
• Reproducibility of reaction
• History may be diagnostic with some acute
reactions but overall will be verified only 30
– 40% of the time (especially in AD and GI
syndromes)
 The Diagnosis of Food Allergy

• High rate of false positive skin tests and

RASTs (poor positive predictive value)
• High negative predictive value (for IgE-
mediated syndromes)
• Must be carefully interpreted in the
context of the clinical picture
• Oral challenges are the only tests that
are more (but still not completely)
definitive
Diagnosis of Food Allergy: Oral Challenges

• May be open, single-blind, or double-blind

placebo-controlled
• Most accurate test for diagnosis of food
allergy
• Must be used if the history and lab results
do not provide clear diagnosis
• Also used to determine when an allergy has
been outgrown
• Must be done with considerable caution
Diagnosis of Food Allergy: Oral Challenges
• Open
• Greatest chance for bias, false positive
results
• Most efficient with regard to prep time and
need for just a single visit per food
• Single blind (patient blinded)
• Reduces patient bias
• Double-blind placebo-controlled
• Reduces patient and observer bias
• Gold standard – especially for research
purposes
 Risk of Oral Food Challenges
(Perry et al JACI 2004)

• 584 challenges in 382 patients, of whom

253 (43%) failed
• Data collected on
• demographics
• other atopic diseases
• symptoms during challenges
• treatment needed
• doses at which reactions occurred
 Risk of Food Challenges

Severity Categories

Mild = Skin and / or oral symptoms only

Moderate = Upper respiratory and / or

gastrointestinal symptoms only OR
Any 3 systems

Severe = Lower respiratory and / or cardio-

vascular symptoms OR Any 4 systems
 Failed challenges and system involvement (%)

Milk Egg Peanut Soy Wheat Total

N=90 N=56 N=71 N=21 N=15 N=253
Skin 75 75 77 76 100 78

Oral 26 21 38 14 7 26

Upper Resp 18 27 35 19 13 25

Lower Resp 27 34 21 19 33 36

GI 41 55 39 43 20 43

Cardiovasc 0 0 0 0 0 0

Perry et al JACI 2004

 Severity of failed food challenges (%)

Milk Egg Peanut Soy Wheat Total

N=90 N=56 N=71 N=21 N=15 N=253

Mild 37 32 39 43 67 39

Moderate 37 30 35 38 0 33

Severe 27 38 25 19 33 28

Perry et al JACI 2004

Median food-specific IgE (kUA/L) and reaction severity

Milk Egg Peanut * Soy Wheat

N=90 N=56 N=71 N=21 N=15

Mild 1.9 .84 1.3 10.1 15.8

Moderate 1.6 1.3 2.1 4.9 …

Severe 2.2 1.3 2.2 24 30.2

*P<0.05 for trend Perry et al JACI 2004

 Severity and % ingested

Milk Egg Peanut Soy Wheat Total

N=90 N=56 N=71 N=21 N=15 N=253

Mild 50 40 10 65 100 50

Moderate 25 50 75 45 … 45

Severe 15 30 45 63 40 30

Perry et al JACI 2004

 Food Challenge Decision Making

• Challenges based on history of reactions, skin

test and RAST results, and importance of food
to diet
• Suggested RASTs to perform challenge (in pts
with known allergy)
• Milk <2 KU/L
• Egg <2 KU/L
• Peanut <2 KU/L
• Cut-offs less clear for other foods (i.e.
consider challenges at much higher levels)
 Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated

Challenge or
Skin test or RAST Endoscopy
(+) (+) (-)
(-)
Stop Elimination Diet Stop
(-) (+)
Done
Food Challenge(s)
(+) (-) Stop
 Conclusions and Dilemmas
• Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
• Strict avoidance is essential to help prevent reactions
and possibly to help promote the outgrowing process
• Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
• However, challenges are limited in 2 ways:
• The most allergic patients must be included
• Determination of threshold doses for chronic food
allergic conditions, especially those that are not IgE
mediated, is likely impossible