Update on Food Allergies: 2011
William Parker, MD
Head, Division of Allergy and Immunology
Dayton Children’s
Objectives
 Definitions and statistics
 Know the current recommendations regarding
immunizations in children with egg allergy
 Food allergies in the school setting
 Be familiar with the latest information regarding prevention
and treatment of food allergy
 Key issues in the latest practice parameters for management
of food allergy
Food-induced allergic disorders
IgE dependent
Disorder
Key features
Typical age
Common
foods
Natural course
Urticaria and
angioedema
Ingestion/skin
contact, acute
20%, chronic 2%
Children > adults
Primarily major
allergens
Depends on food
Oral allergy
syndrome
Pruritus, mild
edema of oral
cavity
Adults/older
children>young
Raw fruits and
vegetables, cooked
tolerated
Varied, may
fluctuate with
pollen season
Rhinitis and asthma
Rarely isolated or
sole symptom
unless inhaled
Infant /child >
adult unless
occupational
Major allergens ;
Depends on food
wheat, egg and
seafood occupation
Anaphylaxis
Rapidly
progressive,
multiple organ
systems
Any
Any but peanut,
tree nuts, shrimp
fish, milk, egg
Depends on food
Food-associated
exercise-induced
anaphylaxis
Triggered only if
food followed by
exercise
Older children and
adults
Wheat, shellfish
and celery most
described
Presumed
persistent
Food-induced allergic disorders
IgE associated/cell-mediated
Disorder
Key
features
Pathology
Typical age
Common
foods
Natural
course
Atopic
Dermatitis
Associated
with food in
35% of
children with
moderate to
severe rash
Might relate to
homing of
foodresponsive T
cells to the
skin
Infant > child
> adult
Major
allergens,
especially egg
and milk
Typically
resolves
Eosinophilic
esophagitis,
enteropathy
Symptoms
vary with
site/degree of
eosinophilic
inflammation
Esophageal:
dysphagia and
pain
Eotaxin and
IL-5
Any
Multiple
Likely
persistent
Food-induced allergic disorders
Cell-mediated
Disorder
Key
features
Pathology
Typical age
Common
foods
Natural
course
Dietary
protein
enterocolitis
Chronic :
emesis,
diarrhea, poor
growth,
lethargy
Re-exposure:
emesis,
diarrhea,
hypotension
(15%) 2 hrs
later
Increased
TNF-alpha
response,
decreased
response to
TGF-beta
Infants
Milk, soy,
rice, oat,
wheat
Usually
resolves
Dietary
protein
proctitis
Mucus-laden,
bloody stools
Eosinophilic
inflammation
Infants
Milk,
including
through
breast
feeding
Usually
resolves
Average hospital discharges per year of
children with any diagnosis related to
food allergy
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
1998-2000
2001-2003
2004-2006
Diagnosing food allergy
History
 What symptoms
 Quantity and how prepared
 Time between ingestion and symptoms
 Similar instances or tolerance in past
 Other factors necessary (e.g., exercise)
 How long since the last reaction
 What food
 A few foods account for about 90% of reactions
Prevalence of Food Allergy
Food
Milk
Egg
Peanut
Tree nuts
Wheat/soy
Fish
Shellfish
Sesame
Overall
infant/child
2.5%
1.5%
1%
0.5%
0.4%
0.1%
0.1%
0.1%
5%
adult
0.3%
0.2%
0.6%
0.6%
0.3%
0.4%
2%
0.1%
3% to 4%
Food allergens-Cow’s milk
 Most common food allergy in young children
 Casein fraction 80% of proteins
 Whey fraction 20%
 Lactoglobulins, bovine Ig’s and albumin
 Casein proteins are most immunogenic
 Lactoglobulins and BSA in whey also important
 >90% will react to goat/sheep milk
 About 10% react to beef
Food allergens-chicken egg
 Most common IgE-mediated food allergy
 Egg white contains 23 different proteins
 ovomucoid, ovalbumin, ovotransferin
 Ovomucoid is responsible for most reactions and has a unique
structure
 70% of egg allergic children can tolerate extensively
heated/baked products
 Bread, cakes, cookies
Vaccines in egg-allergic children
Vaccine
ACIP
Red Book
PI
MMR/MMRV
May be used
May be used
Use with caution,
cites AAP
Influenza
Consult a physician
Contraindicated
Contraindicated
Rabies
Use with caution
No recommendation
Use with caution
Yellow fever
Contraindicated
Contraindicated
Protocols given
Vaccines in egg-allergic children
 FluMist has a very low ovalbumin content
 No pediatric data and effect of respiratory route unclear
 Fluarix and Fluvirin have low ovalbumin content
 No data on FluLaval or Agriflu
 Affluria very low
 Not indicated below age 9
 Fluzone has the highest
 Only product approved for ages 6-23 months
 Amount still relatively low
Vaccines in egg-allergic children
 Skin testing not universally recognized as helpful
 Prospective and retrospective studies-reactions rare
 Rabies vaccine Imovax not made in chick embryro
 2-dose approach becoming popular
 10% of dose followed by 30 minute observation, then 90%
 Recent EP recommendation stated ‘insufficient evidence’ to
make broad recommendations, but felt that current ACIP,
AAP Red Book, and PI recommendations ‘may be too
conservative’
How should you vaccinate the eggallergic child?
 Skip the immunization
 Use the 2 dose method
 Give 10% of dose
 Wait 30 minutes, give the remainder of vaccine
 Use the same brand product for booster if possible
 Same lot is not necessary
 You should be prepared for anaphylaxis – unlikley
• Or
 Refer to an allergist
Food allergens-peanut
Which of the following foods should be avoided by patients
allergic to peanut?
a. Mike-Sells potato chips
b. Penn Station french fries
c. Chick-fil-A products
d. all of the above
e. none of the above
Food allergens-peanut
 Most common pediatric food allergy above age 4
 Peanut butter patented in 1865, hydrogenated oils added in
1922, first brand – Skippy
 At room temp has no vapor phase containing protein
 Refined/commercial peanut oil safe, pressed oils retain some
allergenicity
 Cross-reactivity to other beans – 5%
Food AllergensTree nuts
Walnuts
34%
Cashew
20%
Almond
15%
Pecan
9%
Pistachio
7%
Hazelnut
Brazil nut
<5%
Pine nut
Macademia nut
Cross-reactivity 35%
higher for cashew-pistachio
almond-hazel, walnut-pecan
Food allergens-shellfish
 2% or more of adult population
 Crustacea-lobster, crab, shrimp, crawfish
 Extensive cross-reactivity within group, little to mollusks or
radiocontrast media
 Mollusks-oysters, scallops, clams, squid, snails, mussels
 Raw vs cooked makes little difference
Food allergens-fish
 Several hundred species in class Osteichthyes
 Extensive cross reactivity on testing, modest but clinically
relevant on challenges
 Most patients allergic to fresh cooked tuna or salmon can
tolerate canned product
 Reactions to airborne allergen emitted during cooking not
uncommon
Food allergens-wheat
 Several important proteins
 Globulins and glutenins in IgE mediated disease
 Gliadins in celiac disease
 Albumin in Baker’s asthma
 Extensive cross reactivity between wheat, rye, and barley on
testing, 20% on challenges
 Similarities to grass proteins may account for clinically
irrelevant positive tests to wheat and other grains
Diagnosing food allergy
Skin prick testing (SPT)
 Positive tests suggest, negative tests essentially confirm
(>90% NPV)
 Increasing SPT wheal size is correlated with increasing
likelihood of allergy, not severity
 Testing with fresh food preparation helpful for fruits and
vegetables
Diagnosing food allergies
Food-specific IgE antibodies
 Several available assays
 Increasingly higher values correlate with likelihood of
reaction but not severity
 Exceedingly high values at diagnosis may reflect poor prognosis
for outgrowing allergy
 Mean level for 5 yo at which 50% react (kUa/L)
 Milk 2
 Egg 2
 Peanut 5
Diagnosing food allergies
Food-specific IgE antibodies
Positive Predictive Values
Negative Predictive Value
Food
kUa/L
PPV
kUa/L
NPV
Egg
infants<2
7
2
95%
90%
.6
90%
Milk
infants<1
15
5
95%
95%
.8
1.0
95%
90%
Peanut
14
99%
.35
85%
Fish
20
99%
.9
95%
Soy
30
73%
2
95%
Wheat
26
74%
5
95%
A 5 year old child presents with atopic dermatitis for
evaluation of food allergy. Results of the diagnostic
evaluation are listed below. Which of the following foods
would be most likely to induce a clinical reaction on a
DBPCFC?
egg
milk
soy
wheat
Prick skin test
wheal
8mm
3mm
5mm
10mm
Specific IgE
kU/L
7
0.35
5
15
Treatment options
Natural history
 80% of milk allergic children and 66% of egg allergic




children are tolerant by age 5
30% of wheat allergy outgrown by age 4, 60% by age 8
25% of soy allergy gone by age 4, 45% by 6, 69% by 10
Only 20% of peanut allergic children become tolerant
Recurrence of allergy after tolerance reached is rare
 4% of patients who do not eat peanuts regularly suffer
recurrence
Treatment options
Active therapy
 Standard subcutaneous immunotherapy
 Modified protein vaccine
 Anti-IgE antibodies
 Probiotics, Chinese herbal FAHF-2
 Oral immunotherapy
 Promising studies in milk, egg, and peanut
 Some epi doses required in all studies
 Desensitization but not tolerance, continued regular ingestion
of food required
Effects of Infant Feeding on
Development of Atopic disease
 In high-risk infants, exclusive breast-feeding for 4 months has
been shown to decrease the risk of:
 A) asthma
 B) atopic dermatitis
 C) food allergies
 D) all of the above
 E) none of the above
Effect of Introduction of Solid Foods
 Past AAP recommendations were to delay:
 Solid foods until 4-6 mos
 cow’s milk until 12 mos
 In at risk infants delay egg until age 2 and peanuts, tree nuts and
fish until age 3
 More recent prospective studies are conflicting, raising
“serious questions about the benefit of delaying solid foods”
past 4-6 mos, including highly allergenic foods
Is Early Introduction of Peanut
Protective?
 Jewish children ages 4-19 living in London and Tel Aviv;
10,786 questionnaires/82% returned
 Questionnaires completed by high school students and
parents of primary school age pt
 Questionnaire positive pts confirmed with skin tests or
specific IgE (>95% + predictive value) or oral challenge
 Mothers questioned about solid food consumption during the
first year of life
Is Early Peanut Protective?
 Prevalence of peanut allergy in UK was 1.85% and in Israel was
0.17% (P<.001)
 Age of introduction of egg, soy, wheat, and tree nuts similar between
the 2 groups
 By 9 mos 69% of Israelis were eating peanut compared to 10% in
UK
 Median monthly consumption in infants 8-14 mos was 7.1 g in
Israel vs 0 g in UK (P<.001)
 Consumption 8 times monthly, mostly peanut butter
 Rate of peanut allergy was 10 times higher in UK children vs Israeli
children and was not explained by differences in gender, rate of
atopy, or socioeconomic status
Du Toit G, et al J Allerg Clin Immunol. 2008; 122:984-991
Is Early Egg Protective?
 2,589 Australian infants enrolled, age 11-15 months
 Egg allergy confirmed in 231 children
 Later introduction of egg associated with increased risk
 Compared to infants eating eggs at 4-6 months
 Odds ratio 1.6 for introduction at 10-12 months
 Odds ratio 3.4 for introduction after 12 months
 Duration of breastfeeding had no effect
How early is too early?
 503 infants being evaluated for suspected milk or egg allergy
301 infants with history of immediate reaction
202 infants with mod-severe AD and positive test
 Peanut sIgE of 5 or higher in 28% of patients
 Peanut consumption during pregnancy associated with a 3fold higher risk of sensitization
 Highest odds ratio of 4.99 in subgroup of 71 infants never
breastfed
Maternal diet during pregnancy
 Previous AAP recommendations
 Lactating mothers of high risk infants should avoid peanut and
nuts and consider eliminating milk, eggs, and fish
 2003 study – no effect of peanut intake
 2006 Cochrane review – no effect of maternal exclusion diet
 Current AAP recommendations
 Lack of evidence that maternal dietary restrictions during
pregnancy or lactation play a significant role
 Recent EP agrees…”does not recommend restricting maternal
diet during pregnancy or lactation as a strategy for preventing
the development or clinical course of food allergy”
LEAP study
Learning Early About Peanut Allergy
 500 children enrolled between 4-8 months of age
 History of egg allergy and/or atopic dermatitis
 No personal or family history of peanut allergy
 Randomized to intervention group fed peanut 3 times a week
or control group
 Skin and blood tests at 1, 2.5, and 5 years
 Oral challenge at 5 years of age
Food Allergies in School
“Fear and Allergies in the
Lunchroom”, 5 Nov 2007
What’s a parent to do?
 Peanut-free schools?
 Food allergy tables?
 How many Epi-Pens or
Twinjects?
 Where are they kept?
 When are they used?
 Skin contact?
 Airborne exposure?
Deaths in the U.S. in 2005 (all ages)
 Food allergies
 Lightning strikes
 Insect stings
 Malnutrition
 Accidental drowning
 Accidental poisoning
 Flu and pneumonia
18
48
82
3,003
3,976
23,618
63,001
Sources: National Center for Health Statistics, Centers for Disease Control and Prevention
Management of Food Allergies in
Schools
A patient in which of the following age groups is at greatest risk
of food-induced fatal anaphylaxis?
a) preschool students
b) elementary school students
c) high school students
Parents and food labels
 91 parents of children reviewed 23 product labels, asked to




name the food allergen present in the food product
7% (4 of 60) identified all 14 products containing milk
22% (6 of 17) identified all 7 products containing soy
54% (44 of 82) identified all 5 containing peanut
Results were better for egg and wheat
Food labeling for allergens
 Food Allergen Labeling and Consumer Protection Act
 Passed in 2004
 8 major food allergens
 Milk, egg, peanut, tree nuts, soy, wheat, fish, crustacean shellfish
 Highly refined oils and their derivatives are exempted
 Does not regulate voluntary disclaimers
 ‘may contain traces of….”, “made in the same factory as…..”
 20,241 manufactured food products-17% contained warning
 100 products with voluntary labeling regarding milk
 34 had detectable milk residues
o 61% -”may contain”
o 33% - “shared equipment” or “shared facility”
Food Allergies in School
Where do the majority of school-related anaphylactic food
reactions occur?
a) cafeteria
b) school bus
c) classroom
d) gym class
Self-administered epinephrine
 Two commercially available devices
 33-66 lbs – 0.15 mg
>66 lbs – 0.3 mg
 Kept on person vs in classroom vs in office ?
 When to use ? Hx asthma or prior episode?
 19% of food-induced episodes used 2nd dose
 25% of episodes occur without prior diagnosis
Peanut Butter at school
 30 school-aged children with peanut allergy
 DBPC inhalation challenge for 10 minutes
 No objective sx, one subjective SOB
 DBPC patch testing
 No systemic reactions, 40% mild local rash
 Various hand cleaning methods all effective except alcohol-based
hand sanitizers
Summary Statements
 For high risk infants, exclusive breastfeeding for 4 months vs
milk formula decreases atopic dermatitis and milk allergy in
first 2 years
 Infants with moderate to severe atopic dermatitis have a 3040% incidence of food allergy
 Exclusive breastfeeding for 3 months protects against
wheezing in early life, but not against allergic asthma
occurring beyond age 6
Summary Statements
 No convincing evidence for use of soy-based formula for allergy
prevention
 In high risk infants who are not exclusively breastfed for 4-6
months or are formula fed there is modest evidence that atopic
dermatitis may be delayed or prevented by use of hydrolyzed
formulas
 Extensively hydrolyzed more effective
 Higher cost should be considered
 No studies on use of amino acid-based formulas
 No current convincing evidence that delaying solid food beyond 4-
6 month of age is protective for allergic disease
 Including highly allergenic foods like fish, egg, and peanut
Food Allergy Update-2011
 Food allergies affect 5% of children
 A few foods account for >90% of reactions
 Accurate diagnosis includes history and careful interpretation
of in vivo and in vitro testing
 Encouraging studies regarding oral desensitization for milk
and peanut
 No significant evidence-based support for many current
infant feeding and school management practices
Questions?
References
Young MC, Munoz-Furlong A, Sicherer S. Management of food allergies in
schools: A perspective for allergists. J Allergy Clin Immunol 2009; 124:175182
Greer FR, Sicherer SH, Burks AW, et al. Effects of Early Nutritional
Interventions on the Development of Atopic Disease in Infants and
Children: The Role of Maternal Dietary Restriction, Breastfeeding,
Timing of Introduction of Complementary Foods, and Hydrolyzed
Formulas. Pediatrics 2008; 121 (1):183-190
Park A. Going Nuts Over Nut Allergies. Newsweek 9 March 2009:p 41-45
Sicherer SH and Sampson HA. Food Allergy. J Allergy Clin Immunol 2009; 125:1-10
Expert Panel. Guidelines for the Diagnosis and Management of Food Allergy
in the United States: Report of the NIAID-Sponsored Expert Panel. J
Allergy Clin Immunol Dec 2010; 126:S5-S56
Early feeding practices
 High-risk infants – 1 first-degree relative
 Partially hydrolyzed whey
 Good Start Supreme
 Partially hydrolyzed whey/casein
 Enfamil Gentlease
 Extensively hydrolyzed casein
 Nutramigen, Alimentum, Pregestimil
 Free amino acid-based
 Neocate, EleCare
GINI Study Conclusions
 Incidence of AD at 1 yr in exclusive breastfed, breast plus EH
formula, breast plus CM was 9.5%, 9.8%, and 14.8%
 At 3 yrs incidence was 6%, 6%, and 12%
 PH-whey more effective than EH-whey, neither as effective
as EH-casein
 Breast or breast plus EH formula reduce but do not prevent
majority of cases of AD
 No effect on incidence of asthma
German Infant Nutrition Intervention
Study
 2252 high risk infants enrolled by day 14
 Randomly assigned to supplements of one of 3 hydrolyzed
formulas or cow’s milk formula
 889 infants exclusively breastfed for 4 months
 945 introduced randomly to one of above
 No solids before 6 mos of age
 418 noncompliant or drop-outs, highest in the extensively
hydrolyzed casein group
Von Berg et al, J Allerg Clin Immunol 2003; 111: 533-540
Breastfeeding and prevention of Atopic
Dermatitis
 2001 meta-analysis of 18 prospective studies
 Over 4000 children followed for 1-5 yrs (4.5)
 Exclusive breastfeeding for 3 months protected against
development of AD
 Cohort as a whole (OR : 0.68)
 Infants with family history of allergy (OR : 0.58)
 No effect on infants with no family history of allergy
Breastfeeding and Asthma
 Meta-analysis in 2001 found exclusive breastfeeding was
protective
 Strongest with family history of atopy (OR 0.52)
 Cochrane review in 2002 found no effect
 More recent study distinguished between infant viral-induced
wheezing from asthma in older children with allergies and
PFT changes
 Increased risk of asthma at age 13 if breastfed
 Decreased of recurrent wheezing of infancy