Introduction to Food Allergens

Robert A. Wood, MD

Professor of Pediatrics

Director, Pediatric Allergy and Immunology

Johns Hopkins University

Food Allergy - DefinitionFood Allergy - Definition

• Must be differentiated from food intolerances Must be differentiated from food intolerances and other adverse food reactionsand other adverse food reactions

• Key components of food allergy:Key components of food allergy:

• An immunologic response to a food protein An immunologic response to a food protein (food intolerances usually related to (food intolerances usually related to carbohydrates)carbohydrates)

• Exquisitely small amounts may cause a Exquisitely small amounts may cause a reactionreaction

• Reactions can be severe and even life-Reactions can be severe and even life-threateningthreatening

Exposure

Sensitization

Symptoms

Genetic Predisposition

Re-exposureRe-exposure

Food Allergy - PrevalenceFood Allergy - Prevalence

• 5 – 7% of young children5 – 7% of young children

• 2 – 3% of adolescents and adults2 – 3% of adolescents and adults

• At least 11 million Americans are affectedAt least 11 million Americans are affected

• Prevalence appears to be rising (sharply)Prevalence appears to be rising (sharply)

Common Food Allergens

ChildrenChildren Adolescents / AdultsAdolescents / Adults

MilkMilk PeanutsPeanuts

EggEgg Tree NutsTree Nuts

PeanutPeanut FishFish

SoySoy ShellfishShellfish

WheatWheat

Tree nutsTree nuts

Food Allergy – Signs & SymptomsFood Allergy – Signs & Symptoms

• Range from chronic, low grade symptoms to Range from chronic, low grade symptoms to acute, life-threatening reactionsacute, life-threatening reactions

• Hives / angioedemaHives / angioedema

• EczemaEczema

• Vomiting / diarrhea / poor growthVomiting / diarrhea / poor growth

• Cough / congestionCough / congestion

• Wheezing / breathing difficultyWheezing / breathing difficulty

• Hypotension / shockHypotension / shock

• Anaphylaxis – A systemic allergic reactionAnaphylaxis – A systemic allergic reaction

Food Allergy - UrticariaFood 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 AllergyAtopic 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- Mediated

Non-IgE- 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 AllergyThe Diagnosis of Food Allergy

• Detailed historyDetailed history

• Food(s) suspectedFood(s) suspected

• Specific symptomsSpecific symptoms

• Timing of symptomsTiming of symptoms

• Reproducibility of reactionReproducibility of reaction

• History may be diagnostic with some acute History may be diagnostic with some acute reactions but overall will be verified only 30 reactions but overall will be verified only 30 – 40% of the time (especially in AD and GI – 40% of the time (especially in AD and GI syndromes)syndromes)

The Diagnosis of Food AllergyThe Diagnosis of Food Allergy

• High rate of false positive skin tests and High rate of false positive skin tests and RASTs (poor positive predictive value)RASTs (poor positive predictive value)

• High negative predictive value (for IgE-High negative predictive value (for IgE-mediated syndromes)mediated syndromes)

• Must be carefully interpreted in the Must be carefully interpreted in the context of the clinical picturecontext of the clinical picture

• Oral challenges are the only tests that Oral challenges are the only tests that are more (but still not completely) are more (but still not completely) definitivedefinitive

Diagnosis of Food Allergy: Oral ChallengesDiagnosis of Food Allergy: Oral Challenges

• May be open, single-blind, or double-blind May be open, single-blind, or double-blind placebo-controlledplacebo-controlled

• Most accurate test for diagnosis of food Most accurate test for diagnosis of food allergyallergy

• Must be used if the history and lab results Must be used if the history and lab results do not provide clear diagnosisdo not provide clear diagnosis

• Also used to determine when an allergy has Also used to determine when an allergy has been outgrownbeen outgrown

• Must be done with considerable cautionMust be done with considerable caution

Diagnosis of Food Allergy: Oral Challenges

• OpenOpen

• Greatest chance for bias, false positive Greatest chance for bias, false positive resultsresults

• Most efficient with regard to prep time and Most efficient with regard to prep time and need for just a single visit per foodneed for just a single visit per food

• Single blind (patient blinded)Single blind (patient blinded)

• Reduces patient biasReduces patient bias

• Double-blind placebo-controlledDouble-blind placebo-controlled

• Reduces patient and observer biasReduces patient and observer bias

• Gold standard – especially for research Gold standard – especially for research purposespurposes

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 ORAny 3 systems

Severe = Lower respiratory and / or cardio- vascular symptoms OR Any 4 systems

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 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 2004Perry et al JACI 2004

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 39

Moderate 37 30 35 38 0 33

Severe 27 38 25 19 33 28

Perry et al JACI 2004Perry et al JACI 2004

Milk

N=90

Egg

N=56Peanut*

N=71

Soy

N=21

Wheat

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

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

*P<0.05 for trend Perry et al JACI 2004Perry et al JACI 2004

Milk

N=90

Egg

N=56

Peanut

N=71

Soy

N=21

Wheat

N=15

Total

N=253

Mild 50 40 10 65 100 50

Moderate 25 50 75 45 … 45

Severe 15 30 45 63 40 30

Severity and % ingested

Perry et al JACI 2004Perry et al JACI 2004

• Challenges based on history of reactions, skin Challenges based on history of reactions, skin test and RAST results, and importance of food test and RAST results, and importance of food to dietto diet

• Suggested RASTs to perform challenge (in pts Suggested RASTs to perform challenge (in pts with known allergy)with known allergy)

• Milk <2 KU/LMilk <2 KU/L

• Egg <2 KU/LEgg <2 KU/L

• Peanut <2 KU/LPeanut <2 KU/L

• Cut-offs less clear for other foods (i.e. Cut-offs less clear for other foods (i.e. consider challenges at much higher levels)consider challenges at much higher levels)

Food Challenge Decision Making Food Challenge Decision Making

Food Allergy - Diagnosis

Detailed HistoryDetailed History

IgE-mediated Non-IgE-mediatedIgE-mediated Non-IgE-mediated

Challenge orChallenge or Skin test or RAST EndoscopySkin test or RAST Endoscopy (+) (+) (-)(+) (+) (-) (-) (-) Stop Elimination Diet StopStop Elimination Diet Stop (-) (-) (+)(+)

Done Done

Food Challenge(s) Food Challenge(s)

(+)(+) (-) Stop (-) Stop

Specific elimination dietSpecific elimination diet

Conclusions and DilemmasConclusions and Dilemmas

• Food allergy is common and potentially deadly and Food allergy is common and potentially deadly and avoidance is currently the only treatment option avoidance is currently the only treatment option

• Strict avoidance is essential to help prevent reactions Strict avoidance is essential to help prevent reactions and possibly to help promote the outgrowing processand possibly to help promote the outgrowing process

• Food challenges are a useful means to diagnose food Food challenges are a useful means to diagnose food allergy (and determine threshold doses)allergy (and determine threshold doses)

• However, challenges are limited in 2 ways:However, challenges are limited in 2 ways:

• The most allergic patients must be includedThe most allergic patients must be included

• Determination of threshold doses for chronic food Determination of threshold doses for chronic food allergic conditions, especially those that are not IgE allergic conditions, especially those that are not IgE mediated, is likely impossible mediated, is likely impossible