Food Allergy Cases David R. Naimi, DO Clinical Assistant Professor of Pediatrics University of Washington School of Medicine Northwest Asthma & Allergy

Food Allergy Cases David R. Naimi, DO Clinical Assistant Professor of Pediatrics University of Washington School of Medicine Northwest Asthma & Allergy Center Washington State NAPNAP 2013 Spring Conference March 11, 2013

Introduction Undergraduate Go Dawgs! Medical School (Pomona, CA) Pediatric Residency Case Western - Rainbow Babies & Childrens Allergy/Immunology Fellowship CHOP & U Penn

Seattle Redmond Red Ridge Issaquah Renton Everett Mt. Vernon Yakima Richland

Learning Objectives Understand the clinical manifestations of food allergic disorders Appreciate the utility of tests used to diagnose food allergy Understand when to refer to an allergist and how to follow patients with food allergy Appreciate and respond to the educational needs of patients diagnosed with food allergy in regard to avoidance and treatment

Cases Infant w/mucousy/blood streaked stools Teenager with oral itching to certain foods Infant with eczema Sarah and the Cashew Cookie Stephanie vs the Bagel 15yo w/fatigue, h/a, occasional abd pain and loose stools 12yo w/salmon allergy 3yo w/hives after peanut ingestion Crustacean allergy 2yo w/facial rash after food ingestion 17yo who couldnt swallow his pill Infant w/delayed vomiting after solid food introduction

Food Allergy Definitions Adverse food reactions any untoward reaction to food or food additive Food allergy/hypersensitivity adverse food reaction due to an immunologic mechanism Example: Peanut allergy Food intolerance adverse reaction due to a physiologic or non-immunologic mechanism Lactose intolerance Caffeine

Differences between IgE & Non-IgE food reactions IgE mediated allergyNon-IgE mediated Symptoms Skin, respiratory tract, GI tract, Cardiovascular GI tract and/or skin, other Timing of symptoms Rapid (seconds to minutes). Rarely past 2hrs. Reproducible. Subacute, chronic (>2hrs to days) ExamplesPeanut anaphylaxis -Celiac disease -Milk-protein induced proctocolitis -FPIES (Food Protein Induced Enterocolitis Syndrome) Mixed IgE/non-IgE: Eosinophilic Esophagitis & Atopic Dermatitis

IgE-Mediated Mixed Non-IgE-Mediated Skin UrticariaAtopic Dermatitis Angioedema Dermatitis herpetiformis Respiratory (isolated symptoms rare) Asthma Rhinitis Gastrointestinal GI AnaphylaxisEosinophilic Celiac disease Oral AllergygastrointestinalInfant syndromedisorders(EoE)gastrointestinal Systemicdisorders -Anaphylaxis -Food-associated or exercise-induced anaphylaxis Spectrum of Immune mediated Food Allergy - - - - - - - - - - Histamine related symptoms???

The infant with mucousy or blood streaked stools 2mo exclusively breastfed infant Mucousy stools w/occasional streaks of blood noted recently Clinical history NOT consistent w/constipation. Normal growth & feeding pattern. Normal exam (no rectal fissures).

Questions to ask yourself Diagnoses? Food protein induced proctocolitis. Major cause of colitis 50% of infants usually exclusively breastfed IgE or non-IgE mediated? Non-IgE Risk of anaphylaxis? No What is the most common cause? Cows Milk, often Soy Skin or blood testing needed? No What to advise parent? Mother to trial off of Cows milk/dairy +/- Soy Is this going to improve? Yes. Usually resolves by 9-12mo

What if this patient were bottle fed? Change to hydrolyzed formula (Alimentum, Neutramigen, etc) Consider elemental formula (Elecare, Neocate) but NOT likely needed Consider Soy formula (however, high likelihood of problems with soy) Consider soy as an alternative nutrient AFTER age 6mo per European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Recommendations

12yo with oral itching with almond, fresh fruits & veggies Began 1-2 yrs ago Occurs w/fresh apple, pitted fruits, melons, & fresh carrot Same symptoms w/almond No problems w/cooked fruits & veggies No other symptoms (no hives, respiratory symptoms, etc).

Oral Allergy Syndrome (aka Pollen Food syndrome) Oral itching w/certain foods (mild lip angioedema possible) Contact reaction in oropharyngeal mucosa IgE mediated Onset

Oral Allergy Syndrome (aka Pollen Food syndrome) Cross-reactive allergens BIRCH: apple, peach, apricot, cherry, and plum, pear, almond, hazelnut, carrot, celery, parsley, caraway, fennel, coriander, aniseed, GRASS: Melon, Tomato, Orange, Lettuce, peanut *RAGWEED: cantaloupe, honeydew, watermelon, zucchini, cucumber, banana *There is NO RAGWEED in the Pacific NW

How to alleviate oral allergy syndrome Cook/heat food (20sec in microwave) Avoid ripe fruits Peel & wash PO antihistamine few hrs before ingestion Allergy immunotherapy (allergy shots)

Food Allergens TypeClass IClass II DescriptionWater soluble glycoproteinsPlant-derived ExamplesWheat, Egg, Milk, PeanutApple, Carrot, Celery CharacteristicsResistant to heat, acid, and proteases Highly heat labile. Cooking reduces allergenicity. Susceptible to digestion SensitizationGI tractRespiratory tract w/cross- reactive pollens Clinical reactionAnaphylaxis, eczemaOral allergy syndrome

The infant w/eczema 4mo infant w/eczema - present since he was weeks old involving most areas of body. Birth & developmental hx normal. Growing & feeding well w/out history of recurrent infections or chronic diarrhea. Exclusively breastfed mother asking if FOOD ALLERGIES are playing a role in eczema - certain foods she ingests possibly flares his skin (? dairy)

The infant w/eczema Eczema only partially improved w/1% hydrocortisone regularly Physical exam: significant for scattered dry & minimally erythematous patches few excoriations on cheeks, trunk, & extremities.

What is the relationship between eczema and food allergy? They CAN be associated extent of this association is controversial Potential causes of eczema Young children (2-3hrs) and not immediate">

15yo w/fatigue, h/a, occasional abd pain and loose stools Questionable cause Workup & labs normal thus far Dairy and wheat might be the cause, but unclear If this is food related, seems delayed (>2-3hrs) and not immediate

So is this most likely an Intolerance or Allergy ?

my neighbor recommended a food allergy/sensitivity panel Obtained blood test at local allergy lab. (+) to various foods: grains, dairy, egg, blueberry, etc Blood test report = IgG testing

IgG to foods Proposed to identify non- IgE-mediated hypersensitivity to foods: IBS, migraine headaches, myalgia, fatigue, etc Assays may measure total IgG, IgG subclasses (i.e. IgG4), or IgG/IgE combined testing. www.usbiotek.com

IgG to Foods: Availability Large scale screening for hundreds of food items by ELISA-type and RAST-type assays USA & several European countries, mainstream allergy diagnostic labs now offer IgG assays to foods Direct-to-consumer advertising for panels of IgG Direct marketing by some companies to PCPs May not be covered by a patients medical insurance

What I tell my patients Food intolerance vs True allergy Food intolerance is a TRUE entity, but there is NOT an accurate way to actually test for this IgG testing is controversial and is/should be used for research purposes.

What I tell my patients (cont..) IgG is elevated to many foods in healthy individuals & is often (+) to what is common in our diet: (Wheat/Gluten, Dairy, and Egg). Patients who note improvement w/avoidance of IgG (+) foods often DRASTICALLY change their dietary habits If food intolerance/sensitivity is suspected: Best way to diagnose this is avoidance of above foods/food groups for a certain duration (few/several weeks) followed by re-introduction Consultation with dietitian if continued avoidance of foods is done

(2004) - UK (2005) - UK (2006) - USA (2007) - China IgG4 antibodies to milk, eggs, wheat, beef, pork and lamb were elevated. Significant improvement reported in pain severity (pB/0.001), pain frequency (p/0.034), bloating severity (p/0.001), satisfaction with bowel habits (p/0.004) and effect of IBS on life in general (p/0.008) at 3mo & 6mo. Rectal compliance was significantly increased (p/0.011) at 6mo. Zar et al 25 IBS IgG 4 (2005) UK (13 IBS-D, 10 IBS-C, 6mo elimination 2 alternating)

(2004) - UK (2005) - UK (2006) - USA (2007) - China Zar et al 25 IBS IgG 4 (2005) UK (13 IBS-D, 10 IBS-C, 6mo elimination 2 alternating) IgG4 antibodies to milk, eggs, wheat, beef, pork and lamb were elevated. Significant improvement reported in pain severity (pB/0.001), pain frequency (p/0.034), bloating severity (p/0.001), satisfaction with bowel habits (p/0.004) and effect of IBS on life in general (p/0.008) at 3mo & 6mo. Rectal compliance was significantly increased (p/0.011) at 6mo. Critiques No placebo diet group (thus, difficult to further interpret these data, b/c potential for placebo effect). Data at 6mo only available on 15 patients. Patients eliminated average of 8 foods (most common being foods common in a Western diet) including milk, eggs, beef, pork, wheat & tomatoes To be discussed No placebo group. Probiotics were also given. Potential for placebo effect was huge. Authors discuss the detection of serum IgG antigen-ab complexes, so what was actually measured is not clear. No significant correlation between symptom severity and elevated serum food antigen-specific IgG Abs. (Chinese). No Placebo diet group. Considerable overlap observed in IgG titers for certain foods between IBS and controls. IBS pts: elevated IgG4 abs to ave of 8 foods. Controls: 5 foods. No correlation seen between pattern of elevated IgG4 ab titers & patients symptoms.

Results of studies of IgG antibody elimination diets for migraine headaches AuthorSubjec ts TrialResults Alpay K, et al Cephalalgia 2010 Turkey 30 migraine Double blinded randomized controlled cross-over trial 6wk elimination Average count of reactions with abnormally high titer was 2411 against 266 foods. Compared to baseline, there was statistically significant reduction in # of headache days (from 10.54.4 to 7.53.7; P

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Food Allergy Cases David R. Naimi, DO Clinical Assistant Professor of Pediatrics University of Washington School of Medicine Northwest Asthma & Allergy