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4819 Hot Topics in Pediatric
Allergy and Immunology
Food, Drugs, & Bugs
Jennifer S. Kim MD FAAAAI
Assistant Professor of Pediatrics
Icahn School of Medicine at Mount Sinai
Jaffe Food Allergy Institute
New York, NY
Monday, February 25, 2013
Faculty Disclosure Information
SANOFI Anaphylaxis Advisory Board, Consultant
I do not intend to discuss an unapproved/investigative use
of a commercial product/device in my presentation.
FOOD ALLERGY
Allergy Testing: What’s New?
Baked Egg Diet
Natural History of Milk Allergy
Oral Immunotherapy
Allergy Testing:
Components
Diagnostic value of specific IgE to Ara h 2 to
predict peanut allergy in children is
comparable to a validated and updated
diagnostic prediction model
• Centre of Pediatric Allergy in the Wilhelmina
Children Hospital in The Netherlands
between 2008 and 2010
• 100 patients 47 allergic, 53 tolerant
• OFCs 81 DBPCFC, 19 open
• Median age 6 years; 65% males
Klemans RJ, Otte D, Knol M, et al. JACI 2013 Jan;131:157-63
Objectives
Dunn-Galvin model
• 6 predictors:
– Sex
– Age
– History
– Skin prick test
– Peanut sIgE
– Total IgE
Additional predictors
– Allergic rhinitis
– Atopic dermatitis
– sIgE to Ara h 1, 2, 3, 8
Klemans RJ, Otte D, Knol M, et al. JACI 2013 Jan;131:157-63
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Objectives
Dunn-Galvin model
• 6 predictors:
– Sex
– Age
– History
– Skin prick test
– Peanut sIgE
– Total IgE
Additional predictors
– Allergic rhinitis
– Atopic dermatitis
– sIgE to Ara h 1, 2, 3, 8
Klemans RJ, Otte D, Knol M, et al. JACI 2013 Jan;131:157-63 Klemans RJ, Otte D, Knol M, et al. JACI 2013 Jan;131:157-63
Ara h 2
Cutoff point
(kU/L)
Sensitivity
(%)
Specificity
(%)
>0.2 94 66
>5 55 98
sIgE to Ara h 2
did not
discriminate
among mild,
moderate, and
severe allergy
Klemans RJ, Otte D, Knol M, et al. JACI 2013 Jan;131:157-63
• Discriminative ability of Ara h 2 almost
comparable to updated prediction model
(containing 4 variables of original model)
A bioinformatics approach to
symptomatic peanut allergy• 62 DBPCFCs: 31 sx,
31 sensitized/tolerant
• Median peanut sIgE 2.2
(range 0.35-15.1)
• Mean age 7.5 years
• Specific IgE & IgG4 to
419 peptides Ara h 1-3
• Bioinformatic methods
applied for data
analysis
Lin J, Bruni FM, Fu Z, et al.
JACI 2012 May;129:1321-1328
Increasing Accuracy of
Peanut Allergy Diagnosis
by using Ara h 2• 5276 one-year-old infants in HealthNuts
population-based cohort study
• 200 subjects confirmed by peanut OFC
– 100 with peanut allergy
– 100 with peanut tolerance
• Median age 14 months at time of OFC
Dang TD et al, Tang M, Choo S, et al. JACI 2012 Apr;129:1056-63
Ara h 2 sIgE most predictive
Dang TD et al, Tang M, Choo S, et al. JACI 2012 Apr;129:1056-63
Ara h 2
Cutoff point
(kU/L)
Sensitivity
(%)
Specificity
(%)
>0.1 95 86
>1 60 97
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Dang TD et al, Tang M, Choo S, et al. JACI 2012 Apr;129:1056-63
The Utility of Peanut Components in
the Diagnosis of Peanut Allergy
Among Distinct Populations
• 167 subjects in 4 cohorts from US & Sweden
• Median age 11.7 years (IQR 7-15 years)
• Components measured at time of OFC
• PN-IgE most sensitive test (AUC 0.93)
• Ara h2 most specific (0.92) & best PPV (0.94)
Lieberman JA, Glaumann S, Batelson S, et al.
JACI: In Practice 2013 Jan;1:75-82
77%
57% non-reactive
Lieberman JA,
Glaumann S,
Batelson S, et al.
JACI: In Practice
2013 Jan;1:75-82
Stepwise
testing
approach
100%
PN sIgE & Ara h 2 IgE
did not correlate with
severity of reactions
on OFC
Ara h 2 (-) <0.35 kU/L
56 with +Ara h 2:
91% reactive
Evaluation of Ara h2 IgE thresholds in
the diagnosis of peanut allergy in a
clinical population (N=60)
ThresholdSensitivity,
% (95% CI)
Specificity,
% (95% CI)
PPV, %
(95% CI)
NPV, %
(95% CI)
% mis-
classified
ImmunoCAP Ara h 2
0.23 kUA/L92.3
(74.9-99.1)
60
(42.1-76.1)
63.2
(46-78.2)
91.3
(72-98.9)26.2
0.35 kUA/L88.5
(69.8-97.6)
71.4
(53.7-85.4)
69.7
(51.3-84.4)
89.3
(71.8-97.7)21.3
2 kUA/L23.1
(9.0-43.6)
94.3
(80.8-99.3)
75
(34.9-96.8)
62.3
(47.9-75.2)36.1
ISAC Ara h 2
0.3 ISU80.8
(60.6-93.4)
77.1
(59.9-89.6)
72.4
(52.8-87.3)
84.4
(67.2-94.7)21.3
Keet CA, Johnson K, Savage JH, et al. JACI: In Practice 2013 Jan;1:101-3
Mean age 7 yrs (range 3-19 yrs); PN sIgE range 0.4 – 21 kUA/L
Do systemic reactions occur with
isolated sensitization to Ara h 8?
• 144 children sens to Ara h 8 (≥0.35 kUA/L)
– but not Ara h 1, 2, 3 (<0.35)
• 89.5% (n=129)
non-reactive
• 9.7% (n=14)
oral symptoms
• 1 OFC with lip swelling, abd cramping
(Ara h 6 = 0.45; peanut 1.5 8.8 kUA/L )
Asarnoj A, Nilsson C, Lidholm J, et al. JACI 2012 Aug;130:468-72
Characteristic Range
Peanut <0.35 - 40
Ara h 8 <0.35 - 62
Birch 2 - >100
Age (y) 5-19
What’s the bottom line?Factors that make
component testing
LESS likely to be
informative
Factors that make
component testing
MORE likely to be
informative
A recent convincing
clinical reaction
Mild reactions or
no reaction history
Remote significant clinical
reaction in a patient with
PN-IgE ≥15
Remote clinical reaction with
development of birch
sensitization over time
PN-IgE >25 or <0.35 kUA/L PN-IgE 0.35-15 kUA/L
Lack of birch sensitization Birch sensitization
Younger children Older persons
SH Sicherer & RA Wood. Advances in Diagnosing Peanut Allergy
JACI: In Practice 2013 Jan; 1:1-13
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Baked egg diet
Lemon-Mulé H, Sampson HA, Sicherer SH et al. JACI 2008 Nov;122:977-983
Most children (70%) with egg allergy
are tolerant of baked egg
3 inconclusive
Follow-up Baked Egg StudyLeonard SA, Sampson HA, Sicherer SH, et al.
JACI 2012 Aug;130:473-80
RE, regular egg
BE, Baked egg
Leonard SA,
Sampson HA,
Sicherer SH, et al.
JACI 2012 Aug;
130:473-80
64%
26%
Regular egg tolerance was 12x
more likely to occur in baked egg
tolerant than in baked egg reactive
95% CI, 3.7-40.3, P < .001
Per-protocol group
~15x more likely to tolerate
regular egg than comparison
group over follow-up period
HR14.6
95% CI, 5.8-36.4; P < .0001
60%
28%
Criteria for selecting patients for
baked egg challenges
Leonard SA, Sampson HA, Sicherer SH, et al. JACI 2012 Aug;130:473-80
Egg white IgE 7 – 50 kUA/L
• Ingestion of baked egg may accelerate
tolerance development to natural/raw egg
• First 100 OFCs with regimented baked-
egg recipe in outpatient food allergy clinic
retrospectively evaluated
Outcomes of 100 consecutive
open, baked-egg oral food
challenges in the allergy office
Lieberman JA, Huang FR, Sampson HA, Nowak-Węgrzyn A.
JACI 2012 Jun;129:1682-4
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100 open baked-egg OFCs
Egg white
sIgE
Sensitivity
(%)
Specificity
(%)
PPV
(%)
NPV
(%)
<2.5 87 48 44 89
<5 56 69 46 77
<10 20 94 60 71
Lieberman JA, Huang FR, Sampson HA, Nowak-Węgrzyn A. JACI 2012 Jun;129:1682-4
Leonard SA, Sampson HA, Sicherer SH, et al JACI 2012 Aug;130:473-80
Lieberman JA, Huang FR, Sampson HA, Nowak-Węgrzyn A. JACI 2012 Jun;129:1682-4
Baked Egg Recipe
Natural History of Milk Allergy
The natural history of milk allergy in
an observational cohort
• CoFAR observational study of 244 children
(3-15 months) followed prospectively with
(1) convincing history of milk allergy with +SPT
and/or
(2) moderate-to-severe AD and +SPT to milk (n=24)
• Milk allergy resolved in 53%
by median 5.25 years
Wood RA, Sicherer SH, Vickery BP et al.
JACI published online 02 January 2013
Baseline
milk sIgE, kUA/L
<2
2 - 10
>10
Baseline
milk SPT, mm
<55 - 10
>10
Baseline AD
None/mild
Mod/severe
Wood RA, Sicherer SH,
Vickery BP et al.
JACI 2013
20 kUA/L, 7 mm, mod/severe AD
2 kUA/L, 4 mm, no/mild AD
20 kUA/L, 7 mm, no/mild AD
Composite Index
Web-based
milk-allergy
resolution
calculator at
cofargroup.org
Wood RA, Sicherer SH, Vickery BP et al. JACI 2013
May assist in counseling families as to prognosis of
young (<15 mo) child's milk allergy
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Oral Immunotherapy
• DBPC RCT of 55 children (5-11 yrs) with egg
allergy who received oral immunotherapy for up
to 22 months (median age of 7 years)
• Egg OIT provided protection by raising the
reaction threshold in majority and enabled
~25% to eat egg
• Reactions mostly mild (grade 1)
• ~15% unable to complete therapy, mostly due
to allergic reactions
• Mechanisms of OIT unknown
• Relationship to immune tolerance unknown
Conclusion: OIT is a highly
promising therapeutic interventionMilk OIT Cochrane Review
• up-to-date as of October 1, 2012
• 16 records included, representing 5 trials
• 196 patients studied (106 MOIT, 90 controls)
• No uniform protocol
• 62% in the MOIT group could tolerate full
serving of milk (~200 mL) compared to 8%
control (RR 6.61, 95% CI 3.51 to 12.44)
• None assessed patients off immunotherapy
• For every 11 patients, 1 required IM epiYeung JP, Kloda LA, McDevitt J et al.
Cochrane Database Syst Rev. 2012 Nov 14;11:CD009542
Outcome: Full desensitization
Yeung JP, Kloda LA, McDevitt J et al.
Cochrane Database Syst Rev. 2012 Nov 14;11:CD009542
Subgroup analysis of 4+ years
Yeung JP, Kloda LA, McDevitt J et al.
Cochrane Database Syst Rev. 2012 Nov 14;11:CD009542
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Cochrane Review of Peanut OITNurmatov U, Venderbosch I, Devereux G, Simons FE,
Sheikh A. Allergen-specific oral immunotherapy
for peanut allergy Cochrane Database Syst Rev
2012 Sep 12; 9: CD009014 1 small RCT qualified
“In view of the risk of adverse events and the lack of
evidence of long-term benefits, peanut OIT cannot
currently be recommended as a treatment for the
management of patients with IgE-mediated peanut
allergy. Larger RCTs are needed…”
Drugs
Safety of influenza vaccine for
egg-allergic patientsDes Roches A, Paradis L, Gagnon R et al.
JACI 2012 Nov;130:1213-1216
• Summary of 4172 patients
– 513 with severe allergy
• 4729 doses administered
• None developed anaphylaxis
• Risk of anaphylaxis (95% CI): 0-0.08%
– For severe egg allergy, 0-0.66%
Minimal Risk for TIV:
trivalent influenza vaccine• There is robust evidence that egg-allergic
patients, even those with severe allergy, can
be safely vaccinated in single dose
• PCP administers to persons with only hive
reactions to egg with 30-minute observation
• Allergist administers to persons with history
of mod – severe reactions from egg ingestion
with 30-minute observation
Exception: previous reaction to vaccine
Bugs
Risk factors for severe
Hymenoptera venom anaphylaxis
• Single-center, observational cohort
• 657 consecutive patients eligible for VIT
– mean age 44 years (range 6-84 years)
• 26.2% incidence of severe anaphylaxis
• 4 significant risk factors of severe
anaphylaxis identified (P < .001)
Stoevesandt J, Hain J, Kerstan A, Trautmann A. JACI 2012 Sep;130:698-704
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Absent
urticaria/
angioedema
may indicate
mastocytosis
( baseline
serum tryptase)
Cardiovascular
medication
might be
overestimated
risk factor in
venom-allergic
patients
> 11.4 μg/L
>65 years
Thank You
Educational Materials for Food AllergySicherer SH, Vargas PA, Groetch ME, et al.
J Pediatr 2012 Apr;160:651-6
Materials available online at no cost at
www.cofargroup.org