4 APAPARI workshop foodallergy en (1)

To prevent food allergy…..Maternal avoidance of allergenic food did not prevent de velopment of allergic diseases and food sensitization.. To prevent food allergy…..Maternal avoidance of

What’s New in Food Allergy?

2017 APAPARI Workshop in Hanoi

Takao Fujisawa, MD PhD.

Allergy Center and Institute for Clinical Research Mie National Hospital

JAPAN

Food allergy is increasing

in the world

A survey in 2012 by World Allergy Organization (W AO) showed that the vast majority of countries rep orted an increase in food allergy prevalence in the preceding 10 years.

Prescott SL A global survey of changing patterns of food allergy burden in children World Allergy

Food allergy is on the rise

• Prevalence of self-reported peanut or tree nut allergy

increased more than 3-fold from 1997 to 2008 （ USA)

• Sicherer SH Us prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year

follow-up J Allergy Clin Immunol 2010;125:1322-1326.

• Retrospective analysis of referred children to allergy

specialists; 4-fold increase from 1995 to 2005 （ Australia)

• Mullins RJ Paediatric food allergy trends in a community-based specialist allergy practice,

1995-2006 The Medical journal of Australia 2007;186:618-621.

Food allergy is on the rise

School survey in Japan

(Ministry of Education and Science, Japan)

Prevention of food allergy

What’s New in Food Allergy?

A paradigm shift

To prevent food allergy…

Maternal avoidance of allergenic food

To prevent food allergy…

Maternal avoidance of allergenic food did not prevent de velopment of allergic diseases and food sensitization.

Milk sensitization (18month ）

Kramer MS, Kakuma R Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child Cochrane Database Syst Rev 2012; 9:CD000133.

Egg sensitization (18month ）

To prevent food allergy…

Maternal avoidance of allergenic food did not prevent de velopment of allergic diseases and food sensitization.

Kramer MS, Kakuma R Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child Cochrane Database Syst Rev 2012; 9:CD000133.

Gestational weight gain

Birthweight

To prevent food allergy…

The EP does not recommend restricting

maternal diet during pregnancy or

lactation as a strategy for preventing the

development or clinical course of FA.

Boyce Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report J Allergy Clin Immunol 2010; 126:1105-18.

To prevent food allergy…

• Solid foods should not be introduced into the diet of risk infants until 6 months of age,

high-with dairy products delayed until 1 year, eggs until 2 years , and peanuts, nuts, and fish until 3 years of age

• American Academy of Pediatrics Committee on Nutrition

Hypoallergenic infant formulas Pediatrics 2000; 106:346-9

Old recommendation

Resulting in

To prevent food allergy…

• Solid foods should not be introduced into the diet of

high-risk infants until 6 months of age,

with dairy products delayed until 1 year, eggs until 2

years , and peanuts, nuts, and fish until 3 years of age

• American Academy of Pediatrics Committee on Nutrition

Hypoallergenic infant formulas Pediatrics 2000; 106:346-9

Old recommendation

More egg allergy !!

Koplin JJ Can early introduction of egg prevent egg allergy in infants? A population-based study

J Allergy Clin Immunol 2010; 126:807-13.

To prevent food allergy…

LEAP study

LEAP-ON study

New paradigm: early consumption of peanut

To prevent food allergy…

Peanut allergy at 60 months

Peanut allergy at 72 months

LEAP study

LEAP-ON study

New paradigm: early consumption of peanut

To prevent food allergy…

General population

6 allergenic food from 3 months of age

Adherence=42.8%

New paradigm: early consumption of allergenic food

To prevent food allergy…

New paradigm: early consumption of heated egg

prevented egg allergy

Natsume O, Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial Lancet 2017; 389: 276- 286.

PETIT study

To prevent food allergy…

Allergenic food to babies ????

To prevent food allergy…

Allergenic food to babies…

* Maternal avoidance is not good.

* Early consumption is better than delayed introduction.

To prevent food allergy…

Allergenic food to babies…

* Maternal avoidance is not good.

* Early consumption is better than delayed introduction.

“Early egg or peanut introduction to the infant diet was associated with lower risk of developing egg or peanut allergy “Ierodiakonou D, Timing of Allergenic Food Introduction

to the Infant Diet and Risk of Allergic or Autoimmune Disease: A Systematic Review and Meta-analysis

JAMA 2016; 316: 1181-1192

To prevent food allergy…

Allergenic food to babies…

* Maternal avoidance is not good.

* Early consumption is better than delayed introduction.

We do not know, however,

- Who is the right target for novel intervention?

What’s New in Food Allergy?

Muraro A, Werfel T, Hoffmann-Sommergruber K, et al EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management

of food allergy Allergy 2014; 69: 1008-25.

Immunopathology-based classification

Clinical type of food allergy

Ebisawa M, Ito K, Fujisawa T, Japanese guidelines for food allergy 2017 Allergol Int

2017; 66: 248-264.

Clinical based classification

phenotype-Clinical types of food allergy

Neonatal Infantile gastrointestinal allergy

(Food-induced enterocolitis syndrome :FPIES)

Immediate type food allergy

Infantile atopic dermatitis associated with

food allergy

Food-dependent exercise-induced anaphylaxis

Oral allergy syndrome

Cell mediated/ IgE mediated

IgE mediated

IgE mediated

Pollen-food allergy syndrome

Ebisawa M, Ito K, Fujisawa T, Japanese guidelines for food allergy 2017 Allergol Int

2017; 66: 248-264.

Infantile atopic dermatitis is stron

gly associated with food sensitizat

ion

Flohr C,, Lack G Atopic Dermatitis and Disease Severity Are the Main Risk Factors for Food Sensitization in

Exclusively Breastfed Infants J Invest Dermatol 2013.

619 breast-fed infants at 3month old ） UK ）

Positive association between AD and sensitization with individual foods

Adjusted OREgg.9.48, 95% CI: 3.77–23.83Cow’s milk.9.11, 95% CI: 2.27–36.59, Peanut.4.09, 95% CI: 1.00–16.76,

P.0.05)

An infant with severe atopic dermatitis Think of food allergy

Common food allergens are differe

Common food allergens are differe

nt by age, by country (Asia)

Country Most common food triggers < 5 years Most common food triggers >=5 years China egg, cows milk, peanut, fish, shrimp, and fruit shellfish, peanut, egg, cow milk, fish

Thailand cows milk, shrimp, hen eggs, fish, crab, ant eggs, wheat shrimp, (crab, other shellfish and wheat)Taiwan cow’s milk, shrimp, fish, crab, peanut shrimp, crab, fish, mango, mollusc, milk, peanutKorea egg, cows milk, peanut, wheat, (soy and fish) egg (6-7 years) ,shellfish and fruits (12-13years),

nuts and grains

a cows milk and egg (no data) seafood, eggs, nuts

Malaysia cows milk, egg, peanut, tree nuts, sea food (no data) sea food, chicken, peanut, egg

Prescott SL A global survey of changing patterns of food allergy burden in children World Allergy Organ J 2013; 6: 21.

Diagnostic tests for IgE-mediated Food Allergy

onses

Specific IgE

Skin test (Prick test)

Basophil activation test (BAT)

Histamine release

CD203c expression

Food elimination test

Oral food challenge test

Allergen extract

Prick lancet Bifurcated needle

A+B2

Skin prick test

s Labelled anti-human IgE

（（（（（（（（（

Allergen-specific IgE (serum)

Substrate Fluorescent Measure fluorescence

Allergen

Solid surface

Specific IgE assay: ImmunoCAP

Interpretation of specific IgE tes

ts

Indicates sensitization to the allergen.

Positive allergen-specific IgE plus recent histories of the allergen-induced symptoms may be diagnostic.

(i.e little amount of Ara h 2 in peanut extract)

Concealed IgE-binding epitopes in solid-phased pr oteins

Probability curve

33

Ovomucoid-specific IgE to predict cooked egg OFC

IgE reactivity to allergen compon

disease eliciting IgE

Allergen components of plant origin

Pathogenesis-related

protein family 10 proteins

(PR-10)

Heat-labileOften cause local symptoms (OAS) Bet v 1Ara h 8

Pru p 1Mal d 1Profillins Great homology and cross-reactivity

Seldom cause severe symptoms

Bet v 2Ara h 9Pru p 4Mal d 4Non-specific lipid

transferprotein

(nsLTP)

Heat/digestion stableOften associated with systemic reactions Ara h 9Pru p 3

Mal d 3Cross-reactive

Scheurer S: Strong allergenicity of Pru av 3, the lipid transfer protein from cherry, is related

to high stability against thermal processing and digestion J Allergy

ClinImmunol2004;114:900-907.

Utilities of component-resolved

diagnostics

Detection of disease-eliciting IgE that binds to specific allergen component

is useful for the diagnosis.

Symptoms can be differentially cause

d by different components;

heat-labile proteins, such as Bet v 1-like cross-reactive proteins, cause oral allerg

y syndrome in pollinosis patients

Heat, digestion-stable proteins, such as LTP, cause systemic reactions

Ara h 2 is a major allergen in pean

ut

Ebisawa M, Moverare R, Sato S, Maruyama N, Borres MP, Komata T Measurement of Ara h 1-, 2-, and 3-specific IgE antibodies is

useful in diagnosis of peanut allergy in Japanese children Pediatr Allergy Immunol 2012; 23: 573-81.

Egg allergen components

Gal d 1 :ovomucoid

Gal d 2 :ovalbumin

Gal d 3 :ovotransferrin/conalbumin

Gal d 4 :lysozyme

Gal d 5 :livertinprotein in egg yolk,

chicken serum albumin

Major protein component, heat-labile

Strongly allergenic, heat-stable

Ovomucoid (Gal d 1)

Heat/digestion-stable protein

Allergenic in small amount

Higher ovomucoid IgE indicates intolerance to both raw and heated eggs.

Ando H, Borres MP, Urisu A: Utility of ovomucoid-specific IgEconcentrations in predicting symptomatic egg allergy J Aller

Oral food challenge

Objectives

Definitive diagnosis of a food allergy (i

dentification of the causative allergen)

Identification of the foods that have been proven

of sensitization but have not been ingested

Identification of foods suspected as causes of im mediate reaction

Definitive diagnosis of infantile atopic dermatitis associated with food

Evaluation of symptom-inducing threshold level

Ebisawa M, Ito K, Fujisawa T, Japanese guidelines for food allergy 2017 Allergol Int 2017; 66:

248-264.

Oral food challenge

Objectives

Determination of the safe intake quantit

y and judgement of tolerance acquisitio n

Determination of the safe intake quantity (Small t

Oral food challenge

What’s New in Food Allergy

Management of food allergy

Avoidance of allergenic food

“Necessity minimum” , based on correct diagnosis Diet for food allergy patients should,

be Safe

:No allergy symptoms including anaphylaxis

caused by “accidental “ingestion of offending food

contain necessary nutrition for growth

Not impair quality of life

Proper and prompt treatment for allergen- ind uced symptoms, especially anaphylaxis

Self injection of adrenalin (Epipen®)

Education of patients, families and schools

Oral food challenge

Scrambled Omelet Boiled

Pancake Donut

cookies Fried chicken

Boiled

30 min

How much milk in there ）

Pizza

Sliced cheese

Anaphylaxis ） WAO guidelines

Simons FE World Allergy Organization Guidelines for the Assessment and Management of

Anaphylaxis.

J Allergy Clin Immunol 2011; 127: e1-22.

Anaphylaxis ） WAO guidelines

Simons FE World Allergy Organization Guidelines for the Assessment and Management of

Anaphylaxis.

J Allergy Clin Immunol 2011; 127: e1-22.

Oral immunotherapy

What’s New in Food Allergy

Oral immunotherapy (OI

T)

OIT is defined as a treatment method for c

ases where the early acquisition of toleran

ce during the natural course cannot be anti cipated.

After a symptom induction threshold has b

een determined by OFC, causative foods ar

e taken under a physician's instruction aim

ing to acquire the conditions of increased t

hreshold or desensitization

The therapy is ultimately aimed at acquirin

g tolerance to the causative foods.

Ebisawa M, Ito K, Fujisawa T, Japanese guidelines for food allergy 2017 Allergol Int 2017; 66:

248-264.

Rush build-up (in hospital) Maintenanc

e dose (at home)

OFC threshold

Itoh-Nagato N, Inoue Y, Nagao M, Fujisawa T, Shimojo N, Iwata T Desensitization to a Whole Egg by Rush Oral Immunotherapy Improves Quality of Life of Guardians: A Multicenter, Randomized, Parallel-Group, Delayed-Start Design Study (submitted)

OFC after >2w re-elimination diet

Maintained desensitization levels

Reduced desensitization levels

Lost desentization levels

Itoh-Nagato N, Inoue Y, Nagao M, Fujisawa T, Shimojo N, Iwata T (submitted)

Induced symptoms,

sometimes anaphylaxis, are unavoidable during

(15.8%)

Food allergy diagnosis

Detailed clinical history =the most important Clinical classification

Careful interpretation of IgE tests

Oral food challenge=gold standard

Management of food allergy

Necessity minimum elimination diet