food allergy 2013

7/30/2019 Food Allergy 2013

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Food Allergy

Timothy J. Sullivan, M.D.

Mechanisms of Food Allergy

Clinical Manifestations

Diagnosis

Clinical assessment

Diagnostic tests

Management

May 16, 2013


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Food Allergy

Timothy J. Sullivan, M.D.

Disclosures

Novartis/Genentec - Xolair

No other potential conflict of interest withany organization or company that isinvolved in food allergy diagnosis,

treatment, or tolerance induction


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Allergy

An immunologically specific

Reaction to an exogenous antigen

That results in a pathologic effect


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Immune Exclusion Immune surveilance of GI contents has at

least two purposes

Identify and respond to pathogens

Identify and respond to digestionresistant proteins that reach the intestinal

wall in significant amounts

IgA and IgG responses are common


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B cell

IgE synthesis

IL-4 germlinetranscription T cells

Isotype switchingand expression of

mature transcripts

Signal 1

Signal 2

IgE antibody responses


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IgE-Dependent Release ofInflammatory Mediators

Immediate ReleaseGranule contents:Histamine, TNF-,Proteases, Heparin

Minutes to HoursCytokine production:

Including IL-4, IL-5, TNF-,IL-13, Chemokines

IgE MediatorsFcRI

FcRIbinding site

Within MinutesLipid mediators:ProstaglandinsLeukotrienes


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Mast Cells, Eosinophils, Parasites, and

Protective Immunity


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Clinical Manifestations of Food Allergy IgE antibody-mediated

Anaphylaxis

Urticaria and angioedema

Gastrointestinal symptoms

Rhinoconjunctivitis and asthma

Mixed IgE and Cell-Mediated Atopic dermatitis

Eosinophilic esophagitis and enteritis


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Clinical Manifestations of Food Allergy Cell-Mediated

Contact dermatitis

Dermatitis herpetiformis

Food protein-induced enteropathy syndromes

Celiac disease

Food-induced pulmonary hemosiderosis(Heiners syndrome)


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Prevalence of Food Allergy Based on questionnaire studies, 20% to 25% of

Americans think they have a food allergy

Based on studies of patients, ~6% of childrenand 2% to 4% of adults in the US have, orhave had, food allergy

Peanut allergy has increased in prevalence 2-fold in the US and UK over the past decade


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The Big 8 Milk

Egg

Soy

Wheat

Tree nuts

Peanuts

Shellfish

Fish


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Assessment of Acute Reactions to FoodsA 6 year old boy ate dinner at a Chineserestaurant. He ate egg drop soup and then

a stir-fry containing shrimp, fish, tofu, and apeanut sauce. Within 25 minutes hedeveloped generalized pruritus, urticaria,angioedema of his lips, tongue, and larynx,

wheezing and shortness of breath, and lostconsciousness.


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Assessment of Acute Reactions to Foods

In the ER vital signs were BP 60/0, P 126,R 22

Responded to IM epinephrine, IV saline, 1mg/kg diphenhydramine IV, 4 mg/kgcimetidine IV, and was given 125 mgmethylprednisolone IV

Serum tryptase was 58 ng/mL,2.3 ng/mL on follow-up 2 months later


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Analysis of Cause Epicutaneous skin tests

Positive with shrimp wheal 15 mm/flare 38 mm

Negative with egg, wheat, peanut, soybean, several fish antigens

ImmunoCap Assays for Specific IgE Positive with shrimp 25 kU/L

Negative with egg, wheat, peanut, soybean, several fish antigens

< 0.35 kU/L

Avoid shrimp, crab, lobster, crayfish


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Exercise & Food Induced Anaphylaxis Maulitz RM, Pratt DS, Schocket AL. Exercise-

induced anaphylaxic reaction to shellfish. J Allergy& Clinical Immunology. 63(6):433-4, 1979.

Within a short time dozens of case reportspublished

Two variations recognized

Subclinical specific food allergy + Exercise

Eating any meal within 2 hours + Exercise


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In Vitro assays for specific IgE Williams PB, Barnes JH, Szeinbach SL, Sullivan TJ. Analytical

precision and accuracy of commercial immunoassays forspecific IgE: Establishing a standard. J Allergy Clin Immunol

2000;105:1221-1230.

Szeinbach SL, Barnes JH, Sullivan TJ, Williams PB. Precisionand accuracy of commercial laboratories ability to classify

positive and/or negative allergen-specific IgE results. AnnAllergy Asthma Immunol 2001;86:373-381.


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In Vitro assays for specific IgE 17 serum samples with varying levels of

specific IgE to aeroallergens sent to 6 labs

using 5 different assays 3 times, a monthapart.

Some strongly positive samples were seriallydiluted with negative sera and sent to theselabs to see if their assays were linear withantibody concentration.


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In Vitro Assays for Specific IgE Accessible to any physician

ImmunoCap assays preferred

Sensitivity less than with skin tests

Provide quantitative data that are useful in

detecting remission of clinical food allergy


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Skin Tests for Specific IgE Sensitive

May detect IgE that does not lead to allergic

reactions when food is ingested

Antigens for some foods may be degradedby the time tests are done

Can use fresh food, especially fruit, todetect IgE to labile antigens


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Patient EducationFood Allergy Research & Education (FARE)

http://www.foodallergy.org/

Food Allergy Action Plan

http://www.foodallergy.org/document.doc?id=

125Food allergen free products

http://www.ener-g.com/
http://www.foodallergy.org/http://www.foodallergy.org/document.doc?id=125http://www.foodallergy.org/document.doc?id=125http://www.ener-g.com/http://www.ener-g.com/http://www.ener-g.com/http://www.ener-g.com/http://www.foodallergy.org/document.doc?id=125http://www.foodallergy.org/document.doc?id=125http://www.foodallergy.org/


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Indications for Epinephrine Glossal angioedema threatening the airway

Laryngeal edema threatening the airway

Acute SOB, chest tightness, wheezing

Lethargy or any other suggestion of

hypotension


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Epinephrine Administration Small Children: Place the child on the

ground face up. Administer the medication

to the upper outer thigh. Older Children: Stand behind the child. Hold

the child with one hand across the chest.Administer the medication to the upperouter thigh.

Independent Patients


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Anaphylaxis Action Plan


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EpiPens 0.3 mg and 0.15 mg(1 mg/kg up to 30 kg)

EpiPen (epinephrine) Auto-Injector

First, remove the EpiPen Auto-Injector from the plastic carrying

case

Pull off the blue safety release cap

Hold orange tip near outer thigh (alwaysapply to thigh)

Swing and firmly push orange tip againstouter thigh. Hold on thigh for approximately 10 seconds.

Remove Auto-Injector and massage the area for 10 more seconds.


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Auvi-Q 0.3 mg and 0.15 mg

Auvi-Q TM (epinephrine injection, USP)

Remove the outer case of Auvi-Q. This willautomatically activate the voiceinstructions.

Pull off RED safety guard.Place black end against outer thigh, then

press firmly and hold for 5 seconds.


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Food Allergy in Children Cows milk allergy most common food

allergy in young children

Chicken egg allergy most common foodallergy in children

Peanut allergy most common food allergy

beyond age 4 years


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How do you know food allergy has remitted?

Tests for specific IgE every 6 months

1+ or 2+ positive skin tests

Low levels of serum specific IgE

Oral challenges in the office

Avoidance is difficult. If the allergy hasresolved, quality of life is improved whenverified


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IgE-Dependent Release ofInflammatory Mediators

Immediate ReleaseGranule contents:

Histamine, TNF-,Proteases, Heparin

Minutes to HoursCytokine production:Including IL-4, IL-5, IL-13

IgE MediatorsFcRI

FcRIbinding site

Over MinutesLipid mediators:ProstaglandinsLeukotrienes

Eosinophil recruitment& activation


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Eosinophilic Esophagitis (EoE) Active in ~4/10,000 children

Active in up to 4.8% of adults

Food allergy, allergic rhinitis, asthma, oreczema present in 42% to 93% of childrenand 28% to 86% of adults with EoE

Blood eosinophils increased in 40% to 50%

Serum IgE elevated in 50% to 60%


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Eosinophilic Esophagitis

More than 15 eosinophils/hpf Full thickness of esophagus involved

Endoscopy and multiple esophagealbiopsies essential to diagnose EoE


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Symptoms of EoE Infants & toddlers:Feeding difficulties

School age:Vomiting and pain

Adolescents: Dysphagia

Adults:

Dysphagia, chest pain, food impaction, upperabdominal pain

33% to 54% develop food impaction


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Eliminate Causes of EoE Elemental diet:

Up to 97% have clinical and biopsy improvement. Up to84% can then identify foods to avoid

Limited food exclusion:

Avoid milk, corn, peanut, wheat, beef, soy, and eggs

Specific food exclusion:

Avoid foods to which the patient expresses IgE

Remission in up to 80% of EoE patients

Aeroallergen immunotherapy


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Treatment of EoE Fluticasone MDI 2 puffs into mouth and

swallowed twice a day

Viscous suspension of budesonide can beswallowed once a day

Acid suppression if GERD is present

Esophageal dilation may be needed


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Oral Allergy SyndromeBuccal, palatal, pharyngeal, laryngeal pruritus

Without systemic symptoms of allergy

Birch Mugwort Ragweed


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Latex Allergy and Food Allergy

Defense proteins in many foods cross-react


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Oral Allergy SyndromeAllergy Trigger

Ragweed Pollen

Cross Reactors

BananaCantaloupe

Cucumber

Zucchini

Honeydew

Watermelon

Chamomile tea


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Type I and Type II Food Antigens Type I food antigens elicit immune responses via

the gastrointestinal route

Heat stable, acid stable, resistant to digestive enzymes

More common in children

Type II food antigens cross-react with antigens inaeroallergens that have provoked an immune

response by inhalation Heat labile, acid labile, susceptible to digestive enzymes

More common in adults


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How can fruit and vegetable antigens

cross-react with pollen antigens? Pathogenesis related proteins (PRP)

Lipid transport proteins (LPT)

Chitinases

Seed storage proteins

Levels vary according to conditions duringgrowth, conservation, and processing


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What May The Future Hold? Desensitization and tolerance induction by

oral administration of specific foods

Normalization of Vitamin D levels

Monoclonal antibody neutralization of IgE


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Oral immunotherapy Sublingual immunotherapy for peanut allergy: a randomized, double-

blind, placebo-controlled multicenter trial. DM Fleischer et al. JACI

2013. 131:119-127. No serious reactions. Most patients

had a modest level of desensitization. Safety and predictors of adverse events during oral immunotherapy

for milk allergy: severity of reaction at oral challenge, specific IgEand prick test. M Vasquez-Ortiz et al. Clin Exp Allergy 2012. 43:92-

102. Tolerance of 200 mL of cows milk in 86% of

81 children. 25% had frequent, fairly severe, andunpredictable reactions during and after reachingmaintenance doses. High serum specific IgE andstrong positive skin tests predicted strong reactions


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Anti-IgE Neutralization of specific IgE an attractive

idea

One published trial with anti-IgE indicatedsignificant protection in peanut allergicsubjects.

No indication for this use and no clinicaltrials underway.


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Vitamin D and Food Allergy Season of birth, latitude of residence data

Vitamin D levels and food and environmental allergies in theUnited States: results from the NHANES 2005-2006 survey. SSharief et al. JACI 2011. 127:1195-202.

Normal 25 OH Vitamin D levels 30-100 ng/mL

Children and adolescents studied

Compared those >30 ng/mL to those less than 15 ng/mL.

Peanut allergy Odds Ratio 2.39; 95% CI 1.20-2.80

Oak allergy Odds Ratio 4.75; 95% CI 1.53-4.94


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Food Allergy 2013 History consistent with food allergy

Tests for specific IgE can be very helpful

Written action plans important

Resources available to help educate patientsand families about food allergy

Physicians much better able to recognizeand manage food allergy

food allergy 2013

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