Objectives. 1 st half: 2 nd half:

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1 Ask the Allergist Edmond S. Chan, MD, FRCPC Clinical Associate Professor, UBC Division of Allergy & Immunology June 14, 2014 Metro Vancouver Anaphylaxis Group Burnaby

2 Objectives 1 st half: Discuss: How to diagnose food allergies Examine: How to manage non-acute food allergies Review: Update on the prevention of food allergy 2 nd half: Ask the Allergist

3 Case: 4 year old girl Older brother with confirmed, multiple IgE mediated food allergy and eczema Girl has mild eczema, parents afraid to introduce allergenic foods Mom paid for IgG blood tests via alternative health practitioner 2 yrs ago: egg specific IgG blood test negative mom gave egg at home & girl had anaphylaxis Currently: egg specific IgE negative Approach?

4 What does food allergy really mean? ADVERSE REACTION to food=any abnormal reaction, due to: I) TOXIC Bacterial enterotoxins Other food poisonings II) NON-TOXIC 1. Food Allergy = Immune mediated 2. Food Intolerance = Non-immune Johansson S, EAACI, Allergy 2001; 56:813-24

5 Definitions, cont d 1. Food Allergy IgE mediated (e.g. anaphylaxis, oral allergy syndrome) Mixed IgE/non-IgE (e.g. eosinophilic esophagitis) Non-IgE (e.g. Protein induced enterocolitis) 2. Food Intolerance Enzyme deficiency (e.g. lactase deficiency) Pharmacologic sensitivity (e.g. caffeine) Psychologic (e.g. food aversion) Johansson S, EAACI, Allergy 2001; 56:813-24

6 IgE mediated Food Allergy: Suspected foods Majority of IgE mediated reactions due to these foods: Cow s milk* Egg* Peanut* & Tree nuts Sesame seed Fish & Shellfish (Soy) (Wheat)

7 Predictive values for skin tests Positive predictive value low unless recent and clear history Asymptomatic sensitization Negative predictive value high i.e.) negative results more useful than positive ones Guidelines for the Diagnosis and Management of Food Allergy in the U.S. J Allergy Clin Immunol 2010; 126:S1-S58

8 Predictive values for serum specific IgE Positive predictive value low unless recent and clear history Asymptomatic sensitization Negative predictive value high i.e.) negative results more useful than positive ones Guidelines for the Diagnosis and Management of Food Allergy in the U.S. J Allergy Clin Immunol 2010; 126:S1-S58

9 PREDICTIVE VALUES FOR COMMON FOODS, Specific IgE blood tests Sampson HA, J Allerg Clin Immunol, 2004;113:805-19

10 Oral Food Challenges The gold standard in the allergist s evidence based approach For ruling out food allergy For the follow-up of food allergy (?outgrowing) Generally done when specific IgE levels fall to a level at which ~50% tolerate the food Sicherer SH & Bock SA. J Allergy Clin Immunol 2006;117:

11 positive test results for food-specific IgG are to be expected in normal, healthy adults and children The CSACI strongly discourages the practice of food specific IgG testing for the purposes of identifying or predicting adverse reactions to food

12 Objectives 1 st half: Discuss: How to diagnose food allergies Examine: How to manage non-acute food allergies Review: Update on the prevention of food allergy 2 nd half: Ask the Allergist

13 Management of allergic conditions Allergen avoidance Medical management Immunotherapy (where indicated)

14 Egg allergy: eat baked goods regularly? 1. May result in outgrowing egg allergy earlier Via tolerance induction 2. Possible improved quality of life 3. Often, children are already eating occasionally, and message is then to increase to daily ingestion

15 Dietary baked egg accelerates resolution of egg allergy in children Prospective, 79 subjects, baked oral challenges, 37.8 month F-up, usual recipe, control Egg tolerance median 50.0 vs 78.7 mo (p<.0001) IgE, IgG 4 Leonard SA, Sampson, Sicherer et al. JACI 2012

16 Egg allergic children not currently eating baked goods Recent evidence suggests 70-80% of children with egg allergy tolerate baked goods Difficult to predict the 20-30% who will react if not currently eating already History, skin tests, and specific IgE blood tests do not reliably correlate with chance of reacting if not currently eating Decision to offer oral challenge individualized 2013 Bartnikas L, Schneider L et al, JACI IP

17 Intramuscular flu vaccine can be safely given to those with egg allergy Canadian multi-centre study: 367 patients recruited (132 severe egg allergy) Analyzed with other studies, total 4172 patients (513 severe egg allergy) None had anaphylaxis Des Roches A et al. J Allergy Clin Immunol Nov;130(5):

18 Case: 6 year old boy History of peanut and tree nut allergy Has been carrying an Epipen Junior since 2 yrs of age Child is now 21 kg MD writes prescription for Epipen Regular 0.3mg Pharmacist faxes back with message that monograph for Epipen says to use 0.3mg only for 30kg or more What to do next?

19 Only 2 doses of epinephrine autoinjectors Balance of efficacy & safety 0.3mg (Epipen or Allerject) 25kg children 20kg children at higher risk (asthma) 0.15mg ( Junior ) 10-25kg children Often prescribed for less than 10kg due to lack of alternatives Sicherer SH and Simons FER. Pediatrics 2007;199(3),

20 FOOD IMMUNOTHERAPY MECHANISMS Jones SM et al. J Allergy Clin Immunol 2014;133:318

21 Randomized, controlled crossover trial Primary outcome of desensitization at 6 months (passed oral challenge) 62% in active group, 0% in control group 84% of the active group tolerated 800mg peanut protein daily (~ 5 peanuts) Side effects mild in majority

22 Long term follow-up: cow s milk oral immunotherapy 16 subjects Hopkins: 8 wks build-up, 3 mo maintenance follow-up median 4.5 yrs 16 subjects Duke: 30 wks build-up, 15 mo maintenance follow-up median 3.2 yrs No more than 31% tolerating at least full servings of CM with minimal or no symptoms Higher doses, longer maintenance needed Possibly less ability to eat regularly if peanut? Keet CA et al. J Allergy Clin Immunol 2013;132:737-9

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24 Oral food immunotherapy not ready for clinical use yet Safety: anaphylaxis risk variable in studies,?eosinophilic esophagitis risk Efficacy: short term desensitization versus long term tolerance? No standard protocol Some data for return of cow s milk allergy after therapy Cost effectiveness? More studies needed Greenhawt MJ. Lancet 2014;383:1272-4

25 Objectives 1 st half: Discuss: How to diagnose food allergies Examine: How to manage non-acute food allergies Review: Update on the prevention of food allergy 2 nd half: Ask the Allergist

26 Case: 3 month old boy History of atopic dermatitis 5 yo brother with severe anaphylaxis to peanut, atopic dermatitis, severe asthma Mom asks you Should I introduce peanut to Billy? If yes, then Why? When? Where? How? He could get anaphylaxis the first time Am I putting Mike in danger?

27 Delayed introduction of particular solids for High Risk infants 2000 AAP recommendations (AAP Committee on Nutrition, Pediatrics 2000;106:346-9) Pregnancy: possibly avoid peanuts Lactation: avoid peanuts/tree nuts Newborns: Delay of Solids until 6 months Dairy until 12 months Egg until 2 years Peanuts, nuts, fish (+ shellfish) until 3 years

28 AAP Clinical Report 2008 Greer FR, Sicherer SH, Burks AW et al. Pediatrics 2008;121: Replaced the 2000 report Recommendations pertain to high risk infants No current convincing evidence for delaying solids beyond 6 months Including dairy (e.g. yogurt), egg, peanut, fish Insufficient data for any dietary intervention beyond 4 to 6 months

29 Lack G. J Allergy Clin Immunol 2012; 129:

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32 Why did AAP 2008 have seemingly Flip flop/confusion? little impact? Poor dissemination of message to primary care and general public? Afraid of anaphylaxis on 1 st ingestion? Media question Irony Burden of food allergy

33 CPS Position Statement Dec 2, 2013 Chan ES, Cummings C. Dietary exposures and allergy prevention in high-risk infants. Paediatr Child Health 2013;18(10): Joint statement of the CPS and the CSACI (Canadian Society of Allergy & Clinical Immunology)

34 Canadian Family Physician, April 2014 issue

35 Defining risk An infant at high risk for developing allergy usually has a first degree relative (at least one parent or sibling) with an allergic condition such as atopic dermatitis, food allergy, asthma, or allergic rhinitis While recommendations are intended for high-risk infants, some of the studies cited included infants from the general population not considered high risk

36 CPS Position Statement Recommendations 1. Do not restrict maternal diet during pregnancy or lactation 2. Breastfeed exclusively for the first six months of life 3. Choose a hydrolyzed cow s milk based formula for mothers who cannot or choose not to breastfeed Extensively hydrolyzed casein likely more effective than partially hydrolyzed whey

37 CPS Position Statement Recommendations 4. Do not delay the introduction of any specific solid food beyond six months of age Includes non-choking forms of peanut, egg, fish, etc Delay does not prevent and may increase risk of food allergy 5. More research is needed on inducing tolerance via early introduction between 4 to 6 months of age

38 CPS Position Statement Recommendations 6. Once introduced, regularly ingest the food (e.g. several times/week) to maintain tolerance Routine skin or specific IgE blood testing before a first ingestion is discouraged due to the high risk of potentially confusing false-positive results

39 Summary #1 DIAGNOSIS History is the most important test Skin prick or specific IgE testing is susceptible to false positive results unless history of recent immediate reaction Food-specific IgG testing to diagnose a food allergy is inappropriate, not evidence based, & strongly discouraged

40 Summary #2 NON-ACUTE MANAGEMENT Eating baked goods with egg may help with outgrowing egg allergy faster Intramuscular flu vaccine is safe for egg allergy Switch from the 0.15mg ( Junior ) epinephrine auto-injector dose to the 0.3mg ( Adult ) dose when a child reaches 20-25kg weight Oral immunotherapy to food is not ready for clinical use

41 Summary #3 PREVENTION Do not delay introduction of any solid food beyond 6 months of age Once introduced, eat regularly (e.g. several times/week)

42 Food allergy research Edmond Chan

43 Food allergy research, E Chan Epidemiology (multi-centre CIHR, McGill, UBC, Calgary) Peanut allergy Seafood allergy Prevention Survey of family physicians and parents re: food introduction Very early oral introduction (?)

44 Food allergy research, E Chan Diagnosis Role of peanut Arah2 component testing Quality of life Oral food challenges Waiting lists Parent/patient confidence with using epinephrine auto-injector Bullying

45 Food allergy research, E Chan Treatment Cow s milk oral immunotherapy (multi-centre, CIHR) 6 to 20 years old 16 week build-up, maintenance up to 52 weeks Peanut epicutaneous immunotherapy (?) Eosinophilic esophagitis Patient registry Medical management

46 Research team Trainees S. Leo, T. Wong, A. Haynes, B. Torabi, B. Chin, V. Cook McGill B. Mazer, M. Ben-Shoshan University of Calgary A. Clarke Eosinophilic esophagitis V. Avinashi, P. Vekaria, C. Koo, T. Teoh

47 7 to 17 years old*

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49 Ask the Allergist Questions & Answers