food allergy 2013
TRANSCRIPT
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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