Updates in Food Allergy

Updates in Food Allergy Ebrahim Shakir MD Disclosures None 1

OUTLINE ADVERSE REACTIONS TO FOODS? Conflation of terms What is food allergy? ALLERGY Sensitization Gel/Coombs Type I IgE mediated Immediate hypersensitivity reaction to foods INTOLERANCE Sensitivity Everything else Non-IgE mediated Lactose intolerance Fructokinase deficiency Bacterial overgrowth syndromes Irritable bowel syndrome GERD FPIES Food protein proctocolitis Food protein enteropathy 2

OUTLINE ADVERSE REACTIONS TO FOODS IgE Non -IgE Type 1 hypersensitivity Pollen food allergy syndrome Atopic dermatitis Eosinophilic gastrointestinal diseases Allergic proctocolitis FPIES Food protein enteropathy OUTLINE ADVERSE REACTIONS TO FOODS IgE Non -IgE Type 1 hypersensitivity Pollen food allergy syndrome Atopic dermatitis Eosinophilic gastrointestinal diseases Allergic proctocolitis FPIES Food protein enteropathy 3

TYPE 1 HYPERSENSITIVITY Prevalence 64% Cows milk 5% 5% 31% Peanut Egg Adverse reaction None reported Verified CASE 1 First time exposure to cashews No other food allergies or atopic history 4

TYPE 1 HYPERSENSITIVITY IgE - mediated Urticaria Angioedema Respiratory insufficiency Nausea/emesis Hypotension Immediate reactions Anaphylaxis TYPE 1 HYPERSENSITIVITY Anaphylaxis Exposure to known allergen + -Cutaneous -Respiratory -GI -BP drop by 30 % >2 Rapid, within minutes of exposure (in most cases) Multiple systems involved 5

CASE 1 First time exposure to cashews No other food allergies or atopic history TYPE 1 HYPERSENSITIVITY Skin-test? Bloodwork? 6

Mast cell IgE Allergens Fc RI Immediate Release Granule contents: Histamine, Proteases (Tryptase), Heparin, TNF- Sneezing, Itchy and watery eyes, Nasal itching, hives Over Minutes Lipid mediators: Prostaglandins (PGD 2, Tx), Leukotrienes (LTC 4 ) Wheezing, Bronchoconstriction, Runny nose, Nasal congestion Over Hours Cytokine production: Specifically IL-4, IL-13 Mucus production Eosinophil recruitment Animation by Mitchell Grayson, MD Allergic sensitization Damage to surrounding tissue; further cellular recruitment Th2 ~4 weeks Production of specific IgE IL-4 IL-6 B cell Th2 Th2 Th2 Th2 Mast Cell Presentation of Proliferation of allergen APC antigen APC specific Th2 cells 15 mins. 4-6 hours + Allergen crosslinking IgE Mediators released: Release: MBP/ECP/EDN Leukotrienes Eosinophil Cells recruited Histamine Tryptase Leukotrienes PGD 2 IL-4 & other cytokines Th2 Basophil Specific allergen Animation by Mitchell Grayson, MD 7

TYPE 1 HYPERSENSITIVITY Skin-test? Bloodwork? Percutaneous testing 8

Percutaneous testing Immunoassays 9

Allergy testing Skin prick test Immediate results Cost-effective Sensitivity >85% Specifity > 85% No antihistamines Higher false positives in certain patients Immunoassay Takes 4-7 days Typically 4-fold cost over SPT Sensitivity 60-95% Specificity 60-95% Can be on antihistamines Can use in all patients TYPE 1 HYPERSENSITIVITY skin test +ve to cashew cashew-specific IgE IgG testing NOT helpful Positive skin test and increased specific IgE level confirm sensitization BUT may not indicate actual allergy Level of sensitization does not predict type, or severity, of future reactions 10

OUTLINE ADVERSE REACTIONS TO FOODS IgE Non -IgE Type 1 hypersensitivity Pollen food allergy syndrome Atopic dermatitis Eosinophilic gastrointestinal diseases Allergic proctocolitis FPIES Food protein enteropathy Case 2 7 y/o female with itchy, burning mouth and throat to fresh carrots and apples, and other fresh fruits, but also peanuts 11

Skin testing Positive to birch pollen Negative to all foods Panallergens and their impact on the allergic patient. Hauser, et al Allergy, Asthma & Clinical Immunology20106:1 12

Pollen food allergy syndrome Treatment of underlying seasonal allergy will help Can pretreat with antihistamines before eating fresh fruit No risk for anaphylaxis 13

OUTLINE ADVERSE REACTIONS TO FOODS IgE Non -IgE Type 1 hypersensitivity Pollen food allergy syndrome Atopic dermatitis Eosinophilic gastrointestinal diseases Allergic proctocolitis FPIES Food protein enteropathy Case 3 14

Atopic dermatitis Rates of sensitization to food antigens is higher in atopic dermatitis patients but does not confirm allergy. Case 3 Large positive skin-test to egg white Small positive to peanut, milk Negative to all others Removed egg from maternal diet Some resolution of rash Not worse after reintroduction 15

Case 3 Child is now 10 months Egg and milk have been reintroduced What about peanut? Component testing HIGH RISK FOR ANAPHYLAXIS HIGH RISK FOR ANAPHYLAXIS 16

Case 4 Severely elevated IgE Milk Egg Peanut Treenuts Beef Chicken Soy Wheat Rice Image 1: Fitzpatrick TB, Johnson RA, Wolff K, et al (Eds). Color Atlas and Synopsis of Clinical Dermatology, 3rd ed, McGraw-Hill, New York, 1997. Copyright McGraw-Hill. Eczema action plan 17

Case 4 Open oral challenges Serial increasing doses of food antigen Vitals every 15 minutes Epinephrine at bedside Image 1: Fitzpatrick TB, Johnson RA, Wolff K, et al (Eds). Color Atlas and Synopsis of Clinical Dermatology, 3rd ed, McGraw-Hill, New York, 1997. Copyright McGraw-Hill. Case 4b 18

Severe atopic dermatitis Consider expanding the differential MRSA colonization Superimposed contact dermatitis Superimposed urticaria Histiocytosis, immune deficiency Genetic mutations FLG SPINK5 KIF3A OVOL1 ADAMTS Case 4b Allergic contact dermatitis Construction work Allergy to epoxy resins 19

OUTLINE ADVERSE REACTIONS TO FOODS IgE Non -IgE Type 1 hypersensitivity Pollen food allergy syndrome Atopic dermatitis Eosinophilic gastrointestinal diseases Allergic proctocolitis FPIES Food protein enteropathy Case 5 9 y/o male with recurrent episodes of random emesis 20

Case 5 Diagnosed with viral gastroenteritis Diagnosed with nervous stomach Picky eater Slow eater Growth curves plateau Images courtesy of Dr. Sharrad Kunnath, Boystown Department of Gastroenterology 21

Eosinophilic Esophagitis (EoE) Symptoms related to esophageal dysfunction Eosinophils on biopsy (>15/hpf) Mucosal eosinophilia persists despite 8 weeks of PPI Secondary causes for eosinophilia excluded Responds to standard treatment EoE Treatment Testingdirected elimination Empiric elimination Elemental +/- Medications 22

EoE Treatment TIGERS data Swallowed steroid Fluticasone Budesonide PPI Systemic steroid Esophageal dilation Images courtesy of Dr. Sharrad Kunnath, Boystown Department of Gastroenterology 23

OUTLINE ADVERSE REACTIONS TO FOODS IgE Non -IgE Type 1 hypersensitivity Pollen food allergy syndrome Atopic dermatitis Eosinophilic gastrointestinal diseases Allergic proctocolitis FPIES Food protein enteropathy Case 6 My child does this after I feed him Is this food allergy? Figure 3b, from Harland Winter, MD Dev Med Child Neurol 1980; 22(3): 374-378 24

Food protein induced enterocolitis syndrome Non-IgE-mediated No urticaria, angioedema No respiratory insufficiency No available confirmatory testing No established diagnostic criteria FPIES Innate immune activation First few weeks/months of life Symptoms isolated to gastrointestinal tract Profuse protracted emesis Ashen grey skin Hypothermia 25

FPIES Cowsmilk Soy Grains (Rice, oats, barley, corn) Meat Poultry Seafood Eggs Vegetables Fruit My child does this after I feed him Avoid offending food for at least 12-18 months before oral challenge Rule out other etiologies anatomic, infectious, allergic, metabolic Harland Winter, MD Dev Med Child Neurol 1980; 22(3): 374-378 26

OUTLINE ADVERSE REACTIONS TO FOODS IgE Non -IgE Type 1 hypersensitivity Pollen food allergy syndrome Atopic dermatitis Eosinophilic gastrointestinal diseases Allergic proctocolitis FPIES Food protein enteropathy CASE 1b 27

Pleistocene epoch 1997 2000 2003 2005 2008 2011 2014 2015 2017 AAP workgroup on Breastfeeding and the use of human milk Emergence of Homo sapiens AAP nutrition guidelines WHO/UNICEF Global strategy AAP Breastfeeding revision statement AAP Policy statement on early life nutrition LEAP study and ABM Revised Position statement NIAID Addendum guidelines AAP Breastfeeding revision statement USBC Best Practices guide for implementing Newborn Exclusive Breastfeeding in Electronic Health Records 2008 AAP Recommendations High Risk Infants (1 first degree relative) Role of breastfeeding in either preventing or delaying the onset of specific food allergies is inconclusive Greer, F. R. et al. Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Timing of Introduction of Complementary Foods, and Hydrolyzed Formulas, AAP Committee on Nutrition. Pediatrics. 2008;121(1)183-191 28

2014 Clinical Review Evidence is inadequate to advise women to avoid specific foods during pregnancy or breastfeeding to protect their children from allergic diseases Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Volume 9, Issue 2, June 2014.Pages 447 483 Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med 372: 803-813, 2015 29

Learning Early About Peanut Allergy (LEAP) Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med 372: 803-813, 2015 Learning Early About Peanut Allergy (LEAP) 1.9% 13.7% 10.6% 35.3% Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med 372: 803-813, 2015 30

2016 NIAID Addendum guidelines What about egg, milk, and the other top 8? 6 months 12 months 4 6 months 31

CASE 1b My recommendations 32

My recommendations And if the child has severe eczema, take precautions with early introduction and seek expert guidance Hot of the press Pitt, TJ et al. Reduced risk of peanut sensitization following exposure through breast-feeding and early peanut introduction. J Allergy Clin Immunol 2018; 141: 620-25 33

OUTLINE ADVERSE REACTIONS TO FOODS IgE Non -IgE Type 1 hypersensitivity Pollen food allergy syndrome Atopic dermatitis Eosinophilic gastrointestinal diseases Allergic proctocolitis FPIES Food protein enteropathy Desensitization therapies Established guideline based approaches Allergic rhinitis Allergic asthma Drug hypersensitivity (Type 1) Food allergy? New frontier 34

Oral immunotherapy (OIT) What is it? It is NOT standard of care One decade of trials Milk, egg, peanut most extensively studied Daily ingestion of allergenic food Goal Desensitization or sustained unresponsiveness (SU) Definitions 35

Standard OIT regimen Wood, RA. Food allergen immunotherapy: current status and prospects for the future. J Allerg Clin Immunol 2016:137;973-82 Allergen sensitization Damage to surrounding tissue; further cellular recruitment Th2 ~4 weeks Production of specific IgE IL-4 IL-6 B cell Th2 Th2 Th2 Th2 Mast Cell Presentation of Proliferation of allergen APC antigen APC specific Th2 cells 15 mins. 4-6 hours + Allergen crosslinking IgE Mediators released: Release: MBP/ECP/EDN Leukotrienes Eosinophil Cells recruited Histamine Tryptase Leukotrienes PGD 2 IL-4 & other cytokines Th2 Basophil Specific allergen Animation by Mitchell Grayson, MD 36

Allergen desensitization Damage to surrounding tissue; further cellular recruitment ~4 weeks Production of specific IgE Th2 APC B cell IL-2 TGF-beta Th2 Th2 Th2 Th2 APC Mast Cell Presentation of allergen 15 mins. 4-6 hours + Allergen crosslinking IgE Mediators released: Release: MBP/ECP/EDN Leukotrienes Eosinophil Cells recruited Histamine Tryptase Leukotrienes PGD 2 IL-4 & other cytokines Th2 Basophil Animation by Mitchell Grayson, MD 37

Desensitization future therapies Adjuvant OIT Anti-IgE therapy with OIT Sublingual (SLIT) Epicutaneous (EPIT) Recombinant peanut vaccines OUTLINE ADVERSE REACTIONS TO FOODS IgE Non -IgE Type 1 hypersensitivity Pollen food allergy syndrome Atopic dermatitis Eosinophilic gastrointestinal diseases Allergic proctocolitis FPIES Food protein enteropathy 38

ADVERSE REACTIONS TO FOODS? shakire@mwaac.com 402 397 7400 16945 Frances St. Omaha, NE 68130 39