Putting It Together: NIAID- Sponsored 2010 Guidelines for Managing Food Allergy

American Academy of Allergy, Asthma and Immunology FIT Symposium # 1011 Putting It Together: NIAID- Sponsored 2010 Guidelines for Managing Food Allergy February 22, 2013 11:45 AM Scott H. Sicherer, MD Mount Sinai School of Medicine Jaffe Food Allergy Institute Pediatric Allergy & Immunology New York, NY

Putting Together Diagnosis and Putting Together Management Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAIDsponsored expert panel. J Allergy Clin Immunol 2010; 126(6 Suppl):S1-58.

Major Points for Successful Diagnosis Pathophysiology Epidemiology Careful history Understanding utility of tests

Step 1: Pathophysiology Adverse reactions (not hypersensitivity) Bacterial food poisoning Scombroid fish poisoning Non-Allergic Lactase deficiency Galactosemia Allergy (Immune-mediated) IgE-Mediated IgE? Non-IgE mediated Anaphylaxis Expect Urticaria Positive Skin Test Atopic Dermatitis Eosinophilic gastroenteritis Isolated Accept gastrointestinal Negative reactions Skin Test Skin rashes

Step 2: Epidemiology Of foods Common in Adults -peanut -tree nuts -seafood -(fruits/vegetables) Of disorders Common in Children -egg -peanut -milk -tree nuts -soy -seafood -wheat Not usually associated with food -chronic asthma Often associated with food -chronic allergic rhinitis -anaphylaxis -chronic urticaria -urticaria (acute) -atopic dermatitis (~35%) -syndromes of gastrointestinal allergy

Step 3: Careful History Symptoms Food(s) ingested Frequency of ingestion (ever tolerated?) Timing of symptoms Co-ingestion of ASA, alcohol Association with exercise Diet records Labels

Step 4: Incorporation of Tests IgE-mediated acute symptoms Tests positive eliminate Tests negative reintroduce (possibly as oral challenge) IgE-Mediated chronic symptoms (Atopic dermatitis, eosinophilic gastroenteropathies) Screening tests by history and a priori, elimination diet, if resolved do oral challenges Non-IgE (enterocolitis, enteropathies) Elimination diet and oral challenges

Probability of a reaction (%) 100 90 80 70 60 50 40 30 20 10 0 Food-Specific IgE Antibody Concentrations Correlate with Risk of Clinical Reactivity Food-specific IgE Antibody Concentration Negative test does not guarantee no reaction! Curve varies by: Food Disease Age Other ~95% Predictive Values (CAP-System): Egg-7 kiu/l Milk-15 kiu/l Peanut-14 kiu/l

Food Diagnostic Decision Points (Food-specific IgE in ku/l) Mean age 5 years ~50% react Mean age 5 yrs ~95% react Age <2 yrs ~95% react Egg 2 > 7 > 2 Milk 2 > 15 > 5 Peanut 2-5 > 14 -- Sicherer & Sampson JACI Primer 2006 (based mostly on US studies)

Component Resolved Diagnosis Pollen crossreactive components* LTP Pollen non-cross-reactive components** Peanut Ara h 8 Ara h 9 Ara h 1; Ara h 2; Ara h 3 Ara h 5 Arah 4; Ara h 6; Ara h 7 Hazelnut Cor a 1 Cor a 8 Cor a 9 Cor a 2 Cor a 11 Soybean Gly m 4 Gly m 1 Gly m 5 Gly m 3 Gly m 6 Wheat Tri a 12 Tri a 14 Tri a 19 (ω-5 gliadin) Tri a 21 - alfa gliadin Tri a 26 - HMW glutenin Tri a 28 - AAI dimer 0.19 PRP-10 Profilin *Birch tree pollen, Timothy grass pollen for wheat ** Storage seed proteins, albumins and globulins

Prior Probability and Likelihood Ratios LR(+)=sens/(1-spec) Must estimate pretest probability (history, prior tests) Use simple, additional tests with (hopefully) strong predictive accuracy Decide upon further testing that may be definitive but more costly/risky/invasive

From Sicherer SH, Wood RA. Advances in diagnosing peanut allergy. J Allergy Clin Immunol: In Practice. 2013;1:1-13

CASE PRESENTATIONS Tests: Diagnosis: OFC?: Risk Modality Location Prep Monitor Dose Post care

6 week old, breast fed Mucousy bloody stools No vomit Good growth Mother on regular diet Tests: Diagnosis: OFC?: Risk Modality Location Prep Monitor Dose Post care

6 week old, breast fed Mucousy bloody stools No vomit Good growth Mother on regular diet Tests: not relevant Diagnosis: proctocolits OFC?:not yet Risk Monitor Modality Dose Location Post care Prep

6 week old, breast fed Mucousy bloody stools No vomit Good growth Mother on regular diet Mother off milk-all better Returns age 11 months still off milk Tests: Diagnosis: OFC?: Risk Modality Location Prep Monitor Dose Post care

6 week old, breast fed Mucousy bloody stools No vomit Good growth Mother on regular diet Mother off milk-all better Interval Hx: No atopic disease Regular diet except no milk Returns age 11 months still off milk Tests: Diagnosis: OFC?: Risk Modality Location Prep Monitor Dose Post care

6 week old, breast fed Mucousy bloody stools No vomit Good growth Mother on regular diet Mother off milk-all better Interval Hx: No atopic disease Regular diet except no milk Returns age 11 months still off milk Tests: maybe Diagnosis: proctocolitis OFC?:yes Risk low Monitor Modality opendose Location homepost care Prep

37 year old with ragweed AR Banana ingestion, within minutes Itchy throat Numb hands Generalized urticaria Took diphenhydramine Trouble breathing, LOC awoke and went to ER, stable Tests: Diagnosis: OFC?: Risk Modality Location Prep Monitor Dose Post care

37 year old with ragweed AR Banana ingestion, within minutes Itchy throat Numb hands Generalized urticaria Took diphenhydramine Trouble breathing, LOC awoke and went to ER, stable Tests: Banana extr SPT neg sige-neg RW-PST 9mm Diagnosis: OFC?: Risk Modality Location Prep Monitor Dose Post care

37 year old with ragweed AR Banana ingestion, within minutes Itchy throat Numb hands Generalized urticaria Took diphenhydramine Trouble breathing, LOC awoke and went to ER, stable Tests: Banana extr PST neg sige-neg RW-PST 9mm Diagnosis: Banana Ana? OAS-panic? OFC?: Risk Modality Location Prep Monitor Dose Post care

37 year old with ragweed AR Banana ingestion, within minutes Itchy throat Numb hands Generalized urticaria Took diphenhydramine Trouble breathing, LOC awoke and went to ER, stable Tests: RAW Banana PST 13 mm Diagnosis: Banana Ana? OAS-panic? OFC?: Risk Modality Location Prep Monitor Dose Post care

3 years old Tried scrambled egg at age 11 months Generalized urticaria, vomit, cough Age 2, accident with mayonnaise, small amount, facial urticaria Tests: PST 8 mm sige 10 kiu/l Diagnosis: Current vs. Resolved egg allergy OFC?: Risk Modality Location Prep Monitor Dose Post care

3 years old Tried scrambled egg at age 11 months Generalized urticaria, vomit, cough Age 2, accident with mayonnaise, small amount, facial urticaria Tests: PST 8 mm sige 10 kiu/l Diagnosis: Current vs. Resolved egg allergy OFC?: NO Risk Modality Location Prep Monitor Dose Post care

3 years old Tried scrambled egg at age 11 months Generalized urticaria, vomit, cough Age 2, accident with mayonnaise, small amount, facial urticaria RETURNS age 4, mild asthma No interval reactions, tolerated baked egg Tests: PST 3 mm sige 1.5 kiu/l Diagnosis: Current vs. Resolved egg allergy OFC?: Risk Modality Location Prep Monitor Dose Post care

3 years old Tried scrambled egg at age 11 months Generalized urticaria, vomit, cough Age 2, accident with mayonnaise, small amount, facial urticaria RETURNS age 4, mild asthma No interval reactions, tolerated baked egg Tests: PST 3 mm sige 1.5 kiu/l Diagnosis: Current vs. Resolved egg allergy OFC?: needed if.. Risk Mod Monitor Modality open Dose slow Location? Post care Prep?no IV

10 year old ate cashew anaphylaxis Tolerates peanut, walnut and almond but stopped eating them after this reaction 3 weeks ago Mild atopic history (resolved AD, mild SAR) Tests: Diagnosis: OFC?: Risk Modality Location Prep Monitor Dose Post care

10 year old ate cashew anaphylaxis Tolerates peanut, walnut and almond but stopped eating them after this reaction 3 weeks ago Mild atopic history (resolved AD, mild SAR) Family would be interested in adding peanut/ allowed nuts Tests (IgE): Cashew-11.7 Peanut-1.4 Almond-3.4 Walnut < 0.35 Diagnosis: TNA-but what to instruct? OFC?: Risk Modality Location Prep Monitor Dose Post care

3 year old, asthma, anaphylaxis X 5 Severe reactions to egg, milk, peanut and high IgE to these Diet restricted to turkey, soy, 3 fruits, rice, oat, 3 vegetables (no other beans) and amino acid formula Tests: Diagnosis: OFC?: Risk Modality Location Prep Monitor Dose Post care

3 year old, asthma, anaphylaxis X 5 Severe reactions to egg, milk, peanut and high IgE to these Diet restricted to turkey, soy, 3 fruits, rice, oat, 3 vegetables (no other beans) and amino acid formula Tests serum/skin): Beef-3.7/ 4 mm Pea-2.8/ 2 mm String bean-4.3/0 mm Soy-19.9/ 6 mm Wheat-15.4/ 5 mm Pork-5.5/ 5 mm Diagnosis: MFA OFC?: Risk Modality Location Prep Monitor Dose Post care

Atopic Dermatitis Referral 18 month old with severe atopic dermatitis Pediatrician sent tests, many positives Left on a very limited diet Skin care maximized, environmental controls, rash is moderate, still waxes/wanes not happy! You have the pre-determined tests You can take a history

The tests! Eating PST (MM) IgE (kiu/l) plum 3 0.47 peach 2 0.70 chicken 4 2.3 beef 5 44 spelt Suspected soy 3 8 wheat 7 >100 apple 3 <0.35 rice 3 2.0 pea 3 4.18 corn 2 3.12 barley 0 <0.35 banana 0 1.14 sweet potato 0 <0.35 Acute reaction-eliminated milk 8 >100 egg 4 7.15 Lets vote: Eat Restrict Challenge Never tried: Peanut-67 kiu/l Codfish-47 kiu/l

Avoidance advice Management Home, restaurants, school, vacation, cross-contact, label reading, interpersonal, anxiety, nutritional assessment, agerelated issues. Treatment advice When and how to use self-injectable epinephrine, medical identification, dosing, written materials, age-related issues

Written Action Plan and Medical Jewelry Resource: www.foodallergy.org/actionplan.pdf Consider cetirizine

Treatment: Dietary Elimination Cross contact Restaurants/Hidden ingredients Labeling laws/advisory labeling Law covers milk, egg, wheat, soy, peanut, nuts, fish, shellfish Advisory labeling is voluntary (may contain)

Pediatrics. 2012;130(1):e25-32 Followed for ~ 3 years Register all reactions real time

Half of reactions: food not from the parent Lesson- educate all caregivers and watch siblings

Purposeful Exposures in 11% Reasoning- Uncertain (suspect misdiagnosis, small amount) Lesson- Education and anticipatory guidance

Severity of Reactions 11% were severe Lesson: Emphasize avoidance of ingestion

Under-treatment with Epinephrine Overall, 30% of severe reactions were treated with epinephrine Severe=lower respiratory, cardiovascular, or combination of skin/oral/upper respiratory and GI. Among 65 reactions when not given but caregiver admitted should have - reaction not recognized (48%), medicine not on hand (23%), afraid (12%), waiting to worsen (6%). Lesson: emphasize safety of epinephrine, indications and technique of administration

Summary Diagnosis: Synthesis of a priori (epidemiology, pathophysiology, history) and tests. Management: Education Resources: See Guidelines Page S58. Includes: www.aaaai.org, www.cofargroup.org, www.niaid.nih.gov and others