1. Introduction to Food Allergens
Robert A. Wood, MD
Professor of Pediatrics
Director, Pediatric Allergy and Immunology
Johns Hopkins University

2. 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

3. Exposure Sensitization Symptoms
Genetic Predisposition
Sensitization
Re-exposure
Symptoms

4. 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)

5. Children Adolescents / Adults
Common Food Allergens
Children Adolescents / Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts

6. 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

9. 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

13. 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)

15. 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

16. Gastrointestinal Food Hypersensitivity
Non-IgE- Mediated
IgE- Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease

17. 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)

18. 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

19. 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

20. 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

21. 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

22. 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

23. Failed challenges and system involvement (%)
Milk
N=90
Egg
N=56
Peanut
N=71
Soy
N=21
Wheat
N=15
Total
N=253
Skin 75 77 76
100 78
Oral 26 21 38 14 7
Upper Resp 18 27 35 19 13 25
Lower Resp 34 33 36 GI 41 55 39 43 20
Cardiovasc
Perry et al JACI 2004

24. Severity of failed food challenges (%)
Milk
N=90
Egg
N=56
Peanut
N=71
Soy
N=21
Wheat
N=15
Total
N=253
Mild 37 32 39 43 67
Moderate 30 35 38 33
Severe 27 25 19 28
Perry et al JACI 2004

25. Median food-specific IgE (kUA/L) and reaction severity
Milk
N=90
Egg
N=56
Peanut*
N=71
Soy
N=21
Wheat
N=15
Mild
1.9
.84
1.3
10.1
15.8
Moderate
1.6
2.1
4.9 …
Severe
2.2 24
30.2
*P<0.05 for trend
Perry et al JACI 2004

26. Severity and % ingested
Milk
N=90
Egg
N=56
Peanut
N=71
Soy
N=21
Wheat
N=15
Total
N=253
Mild 50 40 10 65
100
Moderate 25 75 45 …
Severe 15 30 63
Perry et al JACI 2004

27. 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)

28. Food Allergy - Diagnosis IgE-mediated Non-IgE-mediated
Detailed History
IgE-mediated Non-IgE-mediated
Challenge or
Skin test or RAST Endoscopy
(+) (+) (-)
(-)
Stop Elimination Diet Stop
(-) (+)
Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet

29. 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