4819 Hot Topics in Pediatric Allergy and Immunology Food ... · 2/25/2013 · 4819 Hot Topics in...

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G:aaaai/committees/medical informatics/master ppt setup 03.ppt 1 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

Transcript of 4819 Hot Topics in Pediatric Allergy and Immunology Food ... · 2/25/2013 · 4819 Hot Topics in...

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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