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Food Allergy Update

Food Allergy Update. Wanda Phipatanakul, MD, MS Associate Professor of Pediatrics Division of Allergy and Immunology Children’s Hospital, Boston Harvard Medical School. Disclosures. Funding from Astra Zeneca NIH ACAAI Advisory Board- MedImmune. Objectives.

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Food Allergy Update

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  1. Food Allergy Update Wanda Phipatanakul, MD, MS Associate Professor of Pediatrics Division of Allergy and Immunology Children’s Hospital, Boston Harvard Medical School

  2. Disclosures • Funding from • Astra Zeneca • NIH • ACAAI • Advisory Board- MedImmune

  3. Objectives • Understand the epidemiology and clinical manifestations of food allergy. • Understand the diagnosis and management of food allergies based on the current guidelines • Identify new therapies in development of food allergies in the future

  4. 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

  5. Pathophysiology Burks AW. Lancet 2008;371,9623:1538-1546

  6. Background: Food Allergy Prevalence: 3 million school age children (3.9%) 18% increase since 1997 Branum 2009 Pediatrics. 124:1549-55 7 most common food allergens in U.S. Milk, egg, peanut, tree nuts, shellfish, soy, wheat Peanut allergy Prevalence ~1% Most common cause of anaphylaxis in children presenting to the ED Most common cause of fatal food anaphylaxis Standard of care Avoidance of only foods appropriately diagnosed Self-injectable epinephrine/antihistamines Vander Leek, J Peds 2000 Bock, J Allergy Clin Immunol 2007

  7. Maternal Consumption of Peanut during Pregnancy is Associated with Peanut Sensitization in Atopic Infants 500 infants Sicherer SH, et al JACI 2010; 126: 1191-1197

  8. Peanut/Tree Nut/Sesame/CoconutCross-Reactivity Stutius L, Phipatanakul, W Ped Allergy, Immunology 2010; 21: 1114-8

  9. Clinical Manifestations

  10. Adverse Food Reactions Immunologic • Systemic (Anaphylaxis) • Oral Allergy Syndrome • Immediate gastrointestinal allergy • Asthma/rhinitis • Urticaria • Morbilliform rashes and flushing • Contact urticaria IgE-Mediated (most common) Non-IgE Mediated Cell-Mediated • Protein-Induced Enterocolitis • Protein-Induced Enteropathy • Eosinophilic proctitis • Dermatitis herpetiformis • Contact dermatitis • Eosinophilic esophagitis • Eosinophilic gastritis • Eosinophilic gastroenteritis • Atopic dermatitis Sampson H. J Allergy Clin Immunol 2004;113:805-9, Chapman J et al. Ann Allergy Asthma & Immunol 2006;96:S51-68.

  11. The Reaction 2-3 minutes 3-10 minutes 30 seconds No rash in 10-20% 30 minutes 25 minutes 20 minutes

  12. Cutaneous Manifestations of Food Allergy

  13. Atopic Dermatitis

  14. Eosinophilic Gastrointestinal Disorders: eosinophilic esophagitis/gastritis/gastroenteritis Symptoms of Reflux/ Dysphagia/Difficulty swallowing Diagnosis Biopsy: eos infiltration (mucosa  serosa): >20/HPF Presence of eos doesn’t necessarily invoke food allergy May affect esophagus to rectum Response to specific food elimination found in a subset of patients (especially eosinophilic esophagitis): can screen for food allergy with prick/in vitro IgE, patch testing with food may help in those with negative skin tests and suggestive history

  15. Allergic Eosinophilic Esophagitis

  16. Evaluation

  17. Food Allergy Algorhithm Detailed history IgE-mediation suspected Non-IgE-mediation suspected Skin testing Patch Test Endoscopy Positive Positive Negative Negative Open oral challenge Positive Negative Blinded oral challenge Positive Counseling on allergen avoidance, anaphylaxis risk and prospects for specific therapy Negative Self-injectable epinephrine

  18. ImmunoCAP-IgE for >90% Probability Food Allergy Diagnosis Sampson H. J Allergy Clin Immunol 2004;113:805-19 Garcia-Ara C, et al. J Allergy Clin Immunol 2001;107(1);185-90, Permaul/Phipatanakul Allergy Asth Pro 2009; 30: 643-648 Overall <2 yrs Challenge level Milk 15 5 2 Egg 7 2 2 Peanut 14 5 2 Tree nuts 10-15 2-5, 7 (Sesame) Soy 60 10-20 Wheat 80 10-30

  19. Predicting Outcomes of Baked Egg Challenges based on SPT/RAST/Ovomucoid Arveiller C, Sheehan WJ, Phipatanakul, AAAAI 2011

  20. Management of Food Allergy Complete avoidance of specific food trigger Ensure nutritional needs are being met Education Anaphylaxis Emergency Action Plan if applicable Epi/911, Medic Alert most accidental exposures occur away from home This frozen dessert could have peanut, tree nut, cow’s milk, egg, wheat

  21. Development of Treatment Options • Allergen non-specific • Anti-IgE (milk/peanut pilot open labels at CHB) • Chinese herbal medicine, Promising in peanut induced anaphylaxis in mice • Allergen-specific • Engineered recombinant protein • Oral immunotherapy (OIT) • Sublingual immunotherapy (SLIT) • Skripak Current Opinion In Immunology 2008,20:690-696

  22. Immunotherapy for Food Allergy - Future OIT/SLIT – still investigational Studies needed to understand possible clinical benefit and mechanism randomized, blinded controlled trials – in process now optimizing pharmacokinetics targeting appropriate population(s) Determine mechanism of action of OIT/SLIT Basophils/mast cells, humoral, cellular Determine if food IT induces Desensitization without/and clinical tolerance Is desensitization only worthwhile?

  23. Methods of Immunotherapy Oral IT (OIT) swallowed with food Sublingual IT (SLIT) sublingually then swallowed Differences amount of protein, route?, digestion?, possibility of causing tolerance? OIT SLIT

  24. Sublingual Immunotherapy for Hazelnut Allergy (Enrique et al, JACI 116:1073, 2005) • 23 patients with varying degree of hazelnut allergy divided into active and placebo groups • “Rush” desensitization with 22/23 reaching the planned maximum dose at 4 days P=0.02 P<0.05 50% could tolerate the entire 20 g challenge

  25. Milk Dose Threshold Active (n=18) Placebo (n=7) P = 0.0003 Milk dose (mg) Skripak et al. J Allergy Clin Immunol 2008

  26. Oral immunotherapy for cow’s milk allergy witha weekly up-dosing regimen: a randomizedsingle-blind controlled study N = 30 Aged 4-10 18 week Pajno, et al Annals Allergy 2010; 105: 376-381.

  27. Individualized IgE-based dosing of egg oral IT and tolerance6 Children age 3-13 daily doses of egg based on Skin Test Size Vickery BP, et al Annals Allergy 2010; 105;444-450

  28. Serum Levels of Peanut-Specific IgE and IgG4 Change with Treatment Jones et al. -AAAAI 2010 ImmunoCAP-FEIA (Phadia)

  29. Adverse Reactions in Open Label Follow-Up • >2000 cumulative doses • 407 local reactions (21% of doses, range 2-105 per child) • 74 gastrointestinal (3.8%) • 20 respiratory (1%) • Treatment: diphenhydramine for 68 (3.5%) reactions, albuterol in 12 (0.6%), epinephrine 6 (0.3%) • Reactions were largely unpredictable but have become less and less common over time

  30. “Engineered” Recombinant Proteins Identified the peanut allergens Ara h 1-3 (Arachis hypogaea) and with the gene produced peanut proteins in the laboratory Identify IgE-binding epitopes on Ara h 1 – 3 Substitute single amino acid within epitope e.g. Ara h 2 – a.a. 27- 36 - DRRCQSQLER eliminates or markedly reduced IgE binding T cell response unchanged Utilized the “engineered” peanut protein in a mouse model of peanut allergy – the “new” proteins worked to help prevent anaphylaxis in the peanut-allergic mice Initial safety studies through CoFAR started in 2009 and are continuing now

  31. Summary and Conclusions • Food allergy is on the rise for unclear reasons but likely host of genetic and environmental factors with no current cure • IgE & non-IgE-mediated conditions exist • The history and physical are paramount • Elimination diets, skin testing, in vitro assays, and food challenges also have roles in diagnosis • Avoidance, education, and preparation for emergencies are the pillars of current management • Periodic re-challenge to monitor tolerance as indicated by history, allergen, and level of food- specific IgE is an important part of ongoing follow-up, given that many do outgrow food allergy • Food Allergy Treatment utilizing immunomodulatory techniques given orally/or by injection is on the Horizon

  32. CASE: Crustacean Allergy: IgE Towards Protein in the Food, NOT Iodine 79 year old man had anaphylaxis to shrimp at age 20, 25 Doctors told him he was allergic to iodine in seafood Avoided seafood, iodized salt for years Age 70: retirement dinner, hostess picked shrimp out of his portion and gave it to him --- ER visit for anaphylaxis At age 79, specific IgE measurement extremely high to shrimp: >100 kU/L On follow-up after education on avoidance, happily consuming foods with iodized salt because he didn’t have to screen salt source any more

  33. CASE: Owen 7 year old with asthma ordered a shrimp dinner off the adult menu. Within 30 minutes he developed profuse vomiting, nasal congestion, and itchy skin. You tell the patient he had a reaction to shrimp and prescribe self-injectable epinephrine. Three weeks later he has a similar reaction after eating pasta with pesto.

  34. You would • Refer to an allergist for testing (and wish you had done so after the first reaction!) • Get a list of the items in the meals • Reinstruct on the use of epinephrine • All of the above (turns out it was pine nut allergy, not shrimp)

  35. CASE: Robby 8 year old with peanut allergy since age 2. At age 2 he developed hives around the mouth and swelling after eating peanut candy. Four years later at age 6 he had a generalized rash and some difficulty breathing after eating a few bites of a peanut candy. His most recent reaction (age 8) included an itchy mouth and lower lip swelling after eating a piece of chocolate candy (not known to contain peanut) which resolved by itself without any treatment

  36. What would your prescribed Anaphylaxis Emergency Action Plan be for Robby? Liquid diphenhydramine at start of next reaction, watch for 20 minutes, if worsens, call 911 Use self-injectable epinephrine at the start of the next reaction, even if only mild symptoms, and call 911 Do nothing, the reaction will go away by itself Drive to the ER but have the self-injectable epinephrine ready for use in case things get worse

  37. Key Point: Diphenhydramine will not block anaphylaxis • Unfortunately, reaction severity CANNOT be predicted to again be mild with the next episode • In a United Kingdom series of anaphylaxis fatalities, 1/3 of food allergy deaths were in patients with such mild reactions to foods (mainly peanuts/tree nuts) that they had not been prescribed self-injectable epinephrine* • Consider self-injectable epinephrine for all at risk of anaphylaxis *Pumphrey RS. Clin Exp Allergy. 2000 Aug;30(8):1144-50.

  38. MYTH: Prior Episodes Predict Future Reactions • No predictable pattern • Severity depends on: • Sensitivity of the individual • Dose of the allergen • Other factors (e.g., food matrix effects, exercise, concurrent medications, airway hyperresponsiveness) • Must always be prepared for an emergency .

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