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 Sensitization Symptoms 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)

Children Adolescents / Adults 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 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

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 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

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

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

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

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 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

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