Food Allergy in Children

Food Allergy in Children Elizabeth F. Jaffe, M.D., Ph.D. Timberlane Allergy and Asthma Associates, S. Burlington,VT Clinical Associate Professor, UVM Department of Pediatrics

Overview Definition Signs and symptoms Prevalence Misconceptions Diagnosis Treatments Management in schools

What is Food Allergy? Abnormal or exaggerated immunological response to specific food proteins Differentiate from metabolic, toxic, intolerance reactions

Case Studies CASE 1: 9 year old girl develops tongue itchiness, hives, shortness of breath 15 minutes after eating egg rolls, and shrimp lo mein at a Chinese restaurant. She had a Shirley Temple to drink. She has mild intermittent asthma and cat allergy, but has never had a reaction to food before. CASE 2: 15 year old boy has itchy lips and throat when eating fresh apples, but not apple pie. He has itchy eyes, sneezing, runny nose each Spring.

Case Studies (cont) CASE 3: 16 year old athlete developed hives and fainted on two separate occasions, while running, 2 hours after lunch. She had a tuna salad sandwich with celery. She has eaten this same sandwich since without symptoms but not within 6 hours of running CASE 4: 9 yo boy with 4 mo history of vomiting, abdominal pain, weight loss, difficulty swallowing food. Endoscopy reveals eosinophilic infiltration of esophageal mucosa and strictures.

Food Allergy is not Food Intolerance Food intolerance-any non-immunological adverse reaction to food Pharmacological (MSG: headaches, flushing, wheezing) Metabolic (lactose intolerance, gluten intolerance) Toxic (scromboid: flushing, nausea, vomiting with contaminated fish)

Symptoms of Food Allergy Results in one or more of the following: Hives and/or facial swelling/itchiness Itchy, watery eyes/nose/throat/lips or tongue Breathing problems Vomiting, nausea, diarrhea Dizziness, fainting Anaphylaxis (involvement of several organ systems)

Foods Involved More than 170 foods reported to cause IgEmediated reactions 90% of food allergy in children from milk, egg, peanut, soy, wheat 85% of food allergy in adults from peanut, tree nuts, fish, shellfish Incidence varies by country, depends on exposure, genetics, and mode of food preparation

Oral Allergy Syndrome Oral allergy syndrome: Also IgE-mediated, but little anaphylactic potential Itchiness of tongue, throat Fresh fruits and vegetables. OK if cooked. Caused by cross-reactivity between pollens and foods Birch : apple, pear, peach, hazelnut, almond, carrot, kiwi, peapods Ragweed/mugwort : melon, banana Grass pollen : celery, tomato, citrus, peanut Helped by allergy shots to pollens

Prevalence CDC study reported 3 million school-aged children in U.S. have food allergies (2007) Affects 1/25 school-aged children Approx 1/5 children with known food allergy have reaction in school

Prevalence/Natural History of Food Allergy Affects 4-8% of children younger than 3 years 85% with egg, milk, soy, wheat allergy will generally outgrow by teen years. Except for egg, generally by age 6 Baked egg, milk tolerated in up to 80% who are allergic to egg and milk in uncooked form Introducing in baked from may accelerate development of tolerance, but not advised if had anaphylaxis, strong positive skin test or high level specific IgE (RAST)

Prevalence/Natural Hx (cont) Shellfish, fish, peanut, tree nut usually persist 20% chance outgrow PN 9% TN Rarely fish/shellfish (case reports) may reacquire Eat weekly if outgrown, carry epi pen for a year Food allergy affects 1-2% of adolescents and adults One-third of adults believe they have some food allergy

Prevalence Has Increased 3-fold increase in prevalence of peanut allergy in UK between 1994 and 2000 Asthma, eczema, allergic rhinitis prevalence have increased as well Cleaner living conditions, fewer infections (sanitation hypothesis)? BAD physician advice about food avoidance?

Increased Incidence from Bad Prevention Advice? Immunological tolerance develops with early exposure Advice to delay foods may have increased allergy (AW Burks. AAAAI, 2008, 123, 424-425). Israeli infants 8-14 mo eat ave 7g peanut protein (equivalent 15 PN)/mo vs. 0g in UK. Incidence PN allergy 10-fold higher in UK. Maternal avoidance of highly allergenic foods during pregnancy and lactation does not decrease risk. German study that delaying solids beyond 4-6 mo of age associated with more food allergy by age 6.

Sanitation Hypothesis bacteria, viruses T H 1 IFN-gamma, IL-12 Macrophage Ingest bacteria, infected cells T H 0 FH atopy IgE IL-4, IL-13 T H 2 B cell HISTAMINE Mast cell

IgE-Dependent release of inflammatory mediators. IgE binds to high- and low-affinity receptors (FcRI or FcRII) on effector cells. The inflammatory cascade is initiated when a critical mass of IgE antibodies bound to effector cells is cross-linked by allergen. This results in the degranulation of effector cells and the release of a comprehensive array of mediators that are causally linked to the pathophysiology of allergic disease.

Epidemiological Evidence for Sanitation Hypothesis In W. Africa, negative correlation between measles and development of atopy, and decreased risk of atopy if pigs in living space. 4 years after reunification of E. and W. Germany in 1990, hayfever incidence doubled in East, despite improvement in air quality. Children with 2 or more older sibs, and children in daycare during 1st 6 months of life, less likely to have asthma after 6 years of age (TM Ball et al., NEJM, 2000, 343, 538-543).

Misconceptions Food intolerance can be confused with food allergy Food allergy blamed for the wrong symptoms Food allergy does not cause fatigue, lethargy, behavioral problems, autism Sugar is not an allergen, food dyes rarely a problem Food allergy is not due to combinations of foods

Genetics May inherit predisposition to make IgE antibodies to food Food allergy more common if other atopic diseases present affects 30% of children with moderate or severe eczema 4-10% with asthma

Genetics (cont.) Peanut allergy twin study (Sicherer et al, JACI 2000. 106;53-56) 58 pairs of twins: 14 identical, 44 fraternal 64% of identical twin pairs both had peanut allergy 7% of fraternal twins pairs both had peanut allergy

Diagnosis History Very important, but positive history only validated by food challenge in 30-40% of cases Timing and nature of reaction Generally within two hours of eating Symptoms need to fit Has the same food been eaten since without a problem?

Diagnosis (cont.) Laboratory studies Skin prick test False positive rate 50% compared to food challenges False negatives 5% with good quality food extracts Few missed, but may have antibody and have no clinical reaction when eaten

Laboratory Studies (cont) RAST IgE Measures level of IgE antibody to specific foods Class 3 or 4, similar to positive skin prick test For peanut, milk, egg there are established IgE levels that predict a good chance of passing an oral challenge. Size of skin test and original reaction also factored into decision to perform oral challenge RAST IgG4 levels completely unreliable

Diagnosis-Gold Standard Gold standard is double-blind placebo-controlled food challenges (powder in capsules) Open food challenge (directly feeding food) more practical in office setting Food challenge generally only done if diagnosis unclear If tolerate one egg white, one 4oz glass of milk, 1T peanut butter, food allergy very unlikely

Current therapy Avoidance, read labels, no snack sharing. Carry epi pen (change from jr at 40-50lbs) Administer epinephrine in case of accidental ingestion, with more than skin symptoms, history of anaphylaxis, and go to ER Have written emergency action plan at school, daycare

Vaccine Advice In egg allergic patients: OK to give flu vaccine without prior testing for most patients. Often given as divided dose (1/10th, then rest 30 min later) Yellow fever and rabies vaccine contraindicated without testing first. Rabies (Imovax) OK- no egg Can have MMR or MMRV without special precautions

How well does current therapy work? Repeated exposure and undertreatment of food allergies are common Foods most common cause of anaphylaxis treated in ERs Few fatalities with prompt use of epinephrine

Food allergy phone survey 45% with peanut or tree nut allergy reported more than 5 lifetime reactions Only 53% evaluated by physician Only 24% of those that saw physician were prescribed an epi-pen (though 90% had respiratory or multiorgan symptoms) Only 50% who were prescribed epi-pens had one available at the time of the interview

Risk factors for severe reactions 100 fatal cases of food-induced anaphylaxis each year in U.S. Risk factors are asthma, delayed use of epi pen, and exposure away from home ( Fatal and near fatal anaphylactic reactions to food in children and adolescents. Sampson et al, NEJM,'92, 327,380-384. 13 deaths/near deaths in Colorado all had asthma none had epinephrine with them only three were ever prescribed epinephrine, but all were known to have food allergies Mean delay of 75 minutes until epi, none sooner than 22 min

Risk factors (cont) Not all individuals are equally sensitive In one study dosage of peanut to cause reaction varies 250-fold between different individuals (Oppenheimer et al, JACI 1992, 256-2620) 1/100-2 peanuts to cause a reaction in double-blind placebo-controlled food challenge Size of skin test or level of RAST test does not predict severity of reaction

Labeling Laws FALCPA-1/1/06 (Food Allergy Consumer Protection Act) Clear labeling contains milk, egg, peanut, tree nut, shellfish, fish, wheat, soy, even if in color, flavor, or spice Similar laws in Europe and Canada (sesame, mustard, sulfites also included) Exceptions highly refined oils

Tension in the Peanut Gallery

Rxn with Casual Contact Simonte et al. 2003;112:180-182 Study of 30 children with very high specific peanut-ige levels, with hx of anaphylaxis or reported inhalation-contact reaction Had peanut butter pressed flat on back for 10 min, inhalation 12 in. from face for 10 min None had respiratory or systemic symptoms reaction 34% had erythma or pruritis with skin contact At least 90% of peanut-allergic individuals would not have a significant reaction by casual contact Inhalation reactions to peanut have been from self-report; ingestion not excluded

Table/Hand Cleaning Penaut protein effectively cleaned off hands with bar soap, liquid soap, commercial hand wipes, but not alcohol based hand sanitizer Table surface effectively cleaned by soaps and commerical cleansers, but not duishwashing liquid

Kissing Can Transfer Significant Allergen Up to 88mcg peanut protein in a kiss May be a way that infants become sensitized Waiting several hours and peanut-free meal need to significantly decrease exposure

Classroom Precautions More reactions occur in classroom than the cafeteria, generally from crafts using peanuts or tree nuts or parties No PN/TN crafts. Wash hands before and after snack Consideration of PN/TN free classrooms depending upon age

How Close By Should Epi Be? Review of 123 cases of anaphylaxis seen in ER Ave time from exposure to to anaphylaxis 10 min, ave time to receive epi 40 min Access to epi should be within minutes Locked location is not acceptable Rxns can occur in a variety of school locations Almost all states have laws permitting students to carry and potentially self-administer epi

Managing Life-Threatening Allergic Conditions at School No snack sharing No crafts utilizing these allergens Non-food rewards in class Peanut or other allergen- free tables Reporting relevant bullying related events No eating on school buses Training food service, teacher, nurse, bus drivers in recognition and management

Document utilization Uva, JL et al, 2010 10 question survey sent to all school nurses 2 years after document available 104/372 VT schools sent responses 63% aware of document, 42% using it Majority did not change policy after reading Majority state training course primarily for teachers, but lack of training for nurses, bus drivers, coaches, school vounteers

Food Allergy Management Plans Study 100 randomly selected patients from PN/TN registry Plan at school 33% of time Plan followed only 73% of time Deficiencies in recognition and treatment of anaphylaxis Epi pen training suboptimal Plan should clearly state when epi is needed Use if more than skin sx occur If hx of very severe rxn use before symptoms occur, with witnessed ingestion ER if epi used

What else can be done? Immunotherapy: Well-established treatment for inhalant and venom allergens Changes the immune response, more IgG and less IgE antibody, development of T supressor cells Increasing amounts of allergen until maintenance dose reached Injected immunotherapy for foods dangerous Oral immunotherapy is a possible future treatment

Immunotherapy for Food Allergy: Treatment of anaphylactic sensitivity by immunotherapy with injections of aqueous peanut extract, (Nelson et al., JACI 97, 99, #6, 744-751) -Six peanut allergic adults given increasing amounts of peanut extract, with 1 year maintenance injections -Increased tolerance to peanut maintained in three subjects who tolerated full maintenance dose -Maintenance IT gave a higher rate of systemic reactions (39%) than build-up phase (23%).

Life-threatening fish allergy successfully treated with immunotherapy Casimir et al. Ped All Imm 97, 8(2), 103-105 39 month-old with severe breathing problems after fish inhalation, one requiring intubation -Highest attained dose (100 mcg cod extract) repeated once a week for 6 weeks -Subjected to fish odor in hospital without reaction -At home accidentally ate a piece of cod without reaction

Food Allergy in Children: Results of a Standardized Protocol for Oral Desensitization Patriarca et al. 1998, Hepato-Gastroenterology 45, 52-58 -Fourteen cases of children with food allergies (milk, egg, fish) confirmed by skin tests and food challenges -3-5 months to maintenance; side effects of IT generally less than original sx -Maintenance, eating food twice /week -All who finished were symptom free, even with three to six year follow-up

Peanut Oral Immunotherapy (Varshney et al. 2011 JACI: 127, 654-660) 28 children, ages 1-16 enrolled. Divided into peanut flour or placebo 3 withdrew because allergic side effects. Remaining 16 peanut treated patients able to tolerate equivalent of 20 peanuts Initial day-starting dose 0.1mg peanut protein (1/2400 th of a peanut), doubled every 30 min until 6mg or symptoms Escalation-Every 2 weeks for 44 weeks, dose increased 50-100% Maintenance-eat daily Unknown if tolerance maintained if ingestion is stopped Fever, food on empty stomach can cause rxns

Future Therapies Anti-IgE antibodies Xolair used for severe allergic asthma Binds IgE antibody 84 people in study (2 years to recruit) (DYM Leung et al. 2003, NEJM. 348:986-993) Randomly assigned to subq injections 4 times every 4 weeks of placebo or anti-ige antibody Double-blind oral food challenge before and at end of treatment At highest treatment dose (450mg) average threshold of sensitivity increased from less than one peanut to almost nine peanuts Very expensive and does not provide protection when stopped

Future Therapies (continued) Chinese herbal remedy given twice daily for 7 weeks in peanut sensitized murine model blocked anaphylaxis after PN challenge vs. severe anaphylaxis in every sham treated mouse (Srivastava etal. 2005 AAAAI. 115, 171-178) Studies ongoing with human subjects currently

Policy Development Policies should be based on food allergy avoidance Avoid food sharing, and cross contamination with shared utensils Recommendations should be based on published literature Anaphylaxis almost exclusively from ingestion, not from inhalation or skin contact Routine hand washing/table cleaning to remove food allergens Follow food allergy action plans Resources: Food Allergy and Anaphylaxis Network www.foodallergy.org Vermont Dept of Health- Managing Life-threatening Allergic Cinditions at school http://education.vermont.gov/new/pdfdoc/pgm_health_ser vices/food_allergies_manual_0608.pdf