THE PHYSICIAN’S PERSPECTIVE ON FOOD ALLERGY NUTRITION EXCHANGE June 2, 2011

1. THE PHYSICIAN’S PERSPECTIVE ON FOOD ALLERGYNUTRITION EXCHANGEJune 2, 2011 Antony Ham Pong MBBS Consultant in Allergy, Asthma & Immunology Clinical lecturer, Pediatrics, Univ of Ottawa; Consultant, Chest Clinic, CHEO Co-Chair, Infection/Immunology/Allergy Block, U of Ottawa School of Medicine

2. OBJECTIVES • Define allergic and atopic disorders • The Allergic March & the Allergy Epidemic • What is a food allergy? • How to diagnose food allergies

3. ATOPY & ALLERGY • ATOPY is the genetic predisposition to produce IgE on allergen exposure, resulting from an imbalance between TH1 and TH2 helper lymphocytes • Specific IgE produced attaches to the surface of mast cells • Subsequent allergen exposure causes mast cell inflammatory mediator release • ALLERGY is the clinical hypersensitivity which occurs as a manifestation of atopy

9. Childhood asthma : Blame your parents • Both parents asthmatic : 75% risk • One parent asthmatic : 30% risk • One parent & one sibling : 40% risk • No one with asthma : 5–10% risk

10. The Allergy Epidemic • Atopic Eczema 10-20% • Hay Fever 10-20% • Asthma 12-20% • Peanut allergy 1.62%

11. The Allergic March • Atopic eczema onset age 0 - 2 yrs • Food allergy onset age 0 - 2 yrs • Asthma onset age 2 - 5 yrs • Allergic rhinitis onset age > 5 yrs

12. The Allergy Epidemic • The Hygiene Theory proposes that the major increase in allergies, which is seen only in well-developed countries, is due to excess cleanliness. Our immune system does not have enough work to do, therefore it begins to react to harmless things in our environment, causing allergies. • This may explain in part why 70% of allergic children have no family history of atopic disease

16. Microbial exposures associated with less allergy and asthma: Clinical studies • Older siblings / large family size • Early day care • Less antibiotic use • Lactobacillus ingestion • Infections • Respiratory tract: measles, tuberculosis, tuberculin positivity • Gastrointestinal : Hep A, H. pylori, • Being brought up on a farm • Animal exposure / Stables exposure • Drinking unpasteurized milk ( higher endotoxin levels) • Endotoxin levels higher • Keeping a dog/cat ( unless one is allergic to it!) • Home environment contaminated with endotoxin

17. Timing is everything Genetics ,timing and degree of exposure to irritants, microbes and allergens will determine whether allergic sensitization or tolerance will develop

18. What is food allergy? ____________________________________________ Sicherer and Sampson JACI 2006; Food Allergy, available at www.worldallergy.org

19. Features of IgE-mediated food induced allergic reactions • Onset within 30 mins, rarely up to 4 hrs • Duration < 4-6 hours • Reactions recur reliably with re-exposure • Threshold dose (usually small amount) • Anaphylaxis can occur with a small amount of a potent allergen or a larger amount of a ‘milder’ allergen

24. ANAPHYLAXIS: OVERVIEW • Anaphylaxis is a severe, potentially fatal systemic allergic reaction that occurs suddenly (minutes to hours) after contact with an allergy-causing substance • Death can occur in minutes, usually due to closure of airways • Allergic reaction affects many body systems : rash & swelling, breathing difficulties, vomiting & diarrhoea, heart failure & low blood pressure  ANAPHYLACTIC SHOCK

25. Common Allergenic Foods and their Labeling in Canada – A Review (Zarkadas M., Scott F, Salminen J, Ham Pong AJ. Can J Allergy Clin Immunol 1999, 4: 118-141) ANAPHYLAXIS Common Less common Peanut Soy Tree Nuts Wheat Fish * Mustard Shellfish: Crustaceans Shellfish: Mollusks Cow’s Milk Sulfites Egg Sesame

26. Factors Affecting Food Allergy Early Dietary Exposure & Food Allergy Prevalence Peanut North America Rice E. Asia esp. Japan Fish Scandinavia Sesame Israel Chickpea India Wheat America, Europe Edible Bird’s Nest Singapore (dried cave swallow saliva)

27. How much is too much? • MILK – fatality from 2.5ml ( ½ tsp) • EGG – anaphylaxis from 10mg (1/3,000 oz) • FISH - anaphylaxis from 1 gm (1/30 0z) • SHRIMP – anaphylaxis from 1 gm (1/4 shrimp)

28. Threshold Doses:How much peanut is too much? • Dose of peanut causing a subjective reaction eg itchy mouth = 10 ug or 1/50,000 peanut • Objective reaction in challenge studies = 0.25 to 2mg ( 1/2,000 to 1/250 peanut ) • Usual starting dose in challenge studies = 100mg peanut flour ( 1/5 peanut )

29. Can the smell or touch of peanut cause anaphylaxis? • Possibility that high level peanut dust can provoke anaphylaxis in airplanes ( Sicherer 1999) • Smell of peanut butter does not cause allergic reactions– reactions to this are most likely due to intense dislike of the smell ( the smell is due to volatile organic molecules and not allergenic proteins), or inadvertent ingestion • Anaphylaxis has been induced inhalation of steam carrying food particles eg shrimp, fish, milk

30. FOOD ALLERGY : ROUTE OF EXPOSURE • Ingestion – directly or indirectly (eg maternal dietary proteins via breast mlk) • Inhalation eg boiling foods (eg shrimp, milk), food dust (eg peanut, egg, wheat, psyllium), ?milk contaminated lactose in asthma dry powder inhalers • Musosal contact : eye (eg shrimp), rectal (eg milk enema) • Skin : abraded skin eg milk containing ointment or lactobacillus capsules; egg lecithin containing creams • Parenteral : drug & intralipid formulations

31. Diagnosis of Food Allergy Positive Allergy Skin Prick Test (SPT) or blood test (CAP IgE) Indicates presence of IgE antibody NOT clinical reactivity Must be interpreted in the context of clinical history Negative SPT and CAP IgE Essentially excludes IgE antibody (>95%) __________________________________________ Sampson et al. JACI 2003

32. Allergy Skin tests • Prick/puncture – most common technique, introduces allergen into the very superficial skin (epicutaneous layer) usually flexor surface of forearm, sometimes on back; is more specific but not as sensitive as intradermal • Intradermal – introduces a larger quantity of allergen into a deeper layer of skin of upper forearm; more sensitive but less specific than prick • Scratch – old technique, not used now as too variable

35. ALLERGY PRICK SKIN TEST “SIZE DOES MATTER” Peanut PST > 6mm : ½ will be allergic Peanut PST > 8mm : Most likely allergic Cow’s Milk PST > 8mm : “ “ Egg PST > 7mm : “ “

36. Probability Curve for Peanut

37. Food Challenge • Reasons to challenge: • Confirm reactivity • Confirm non-reactivity • Follow for tolerance • Oral challenge testing (MD supervised, ER meds available) • Open • Single-blind • Double-blind, placebo-controlled (DBPCFC) • Sensitivity, Specificity, PPV, NPV ~ 100% • Limitations: • Risk to patient • Dose • Duration of challenge • Success of blinding __________________________________________ Saleh Al-Muhsen et al CMAJ 2003

38. Food allergyIgE non-IgE .

39. Food allergyIgE non-IgE .

40. FOOD ALLERGY PROGNOSIS • Onset before age 3 years esp cow’s milk (age 2-3), egg(age 5-7), soy & wheat (age 2-3) : usu outgrown • Onset after age 3 years : usu lifelong • Peanut allergy : up to 20% reported to be outgrown ( probably optimistic) • Usually lifelong : Peanut, tree nuts, fish, shellfish, seeds

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42. ACTIONS OF HISTAMINE • Peripheral vasodilation • Increased vascular permeability • Altered cardiac conduction • Bronchial/intestinal smooth muscle contraction • Nerve stimulation-Cutaneous pruritus/pain • Increased glandular mucus secretions

43. Signs and Symptoms: IgE vs Non-IgE IgE Non-IgE Skin Urticaria Angioedema Atopic dermatitis Respiratory Throat tightness Rhinitis Asthma Gut Vomit Diarrhea Pain Anaphylaxis ____________________________________________ Sicherer and Sampson JACI 2006; Sampson JACI 2003