Infant Food AllergiesInfant Food AllergiesWhere Are We Now?Where Are We Now?

Janice Joneja Ph.D., RDJanice Joneja Ph.D., RD

2

Food Allergy in the Past 7 YearsFood Allergy in the Past 7 Years

Nearly 4% of North Americans have food Nearly 4% of North Americans have food allergies, many more than recorded in the allergies, many more than recorded in the pastpast Incidence of food allergy much higher in Incidence of food allergy much higher in

children (>8%) than adults (<2%)children (>8%) than adults (<2%) Prevalence of peanut allergy doubled in Prevalence of peanut allergy doubled in

American children younger than 5 years of American children younger than 5 years of age in the years 2002 - 2007age in the years 2002 - 2007

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Food Allergy in the Past 7 Food Allergy in the Past 7 YearsYears

Prevalence of Prevalence of food allergyfood allergy highest in infants and toddlers highest in infants and toddlers Cow’s milk allergy incidence: 2.5% of infantsCow’s milk allergy incidence: 2.5% of infants Up to 8% of children under 3 years have allergy to a Up to 8% of children under 3 years have allergy to a

limited number of foods:limited number of foods: Cow’s milk Cow’s milk Wheat Wheat Egg Egg Shellfish Shellfish Soy Soy Fish Fish Peanut Peanut Tree nuts Tree nuts

For every child who actually had a food allergy, over three more For every child who actually had a food allergy, over three more children were believed wrongly by their parents to suffer from the children were believed wrongly by their parents to suffer from the conditioncondition

______________Venter et al 2008

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Age Relationship Between Food Allergy and AtopyAge Relationship Between Food Allergy and Atopy

1 2 32 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Age (in years)

0

Rel

ativ

e In

cide

nce

Asthma

Rhinitis

Eczema

Food Allergy

Anaphylaxis

Effect of Food Allergens Effect of Air-borne Allergens

5

Historical PerspectiveHistorical Perspective Sensitization to food allergens was thought to Sensitization to food allergens was thought to

be the start of the “allergic march”be the start of the “allergic march”Food allergyFood allergy

Atopic dermatitis/eczemaAtopic dermatitis/eczema

AsthmaAsthmaRhinitisRhinitis

Reducing sensitization to foods was therefore Reducing sensitization to foods was therefore considered the essential first step in allergy considered the essential first step in allergy preventionprevention

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Historical PerspectiveHistorical Perspective Measures of prevention were all designed to Measures of prevention were all designed to avoid avoid

sensitizationsensitization to allergens during what were to allergens during what were considered the most vulnerable periods:considered the most vulnerable periods: Intra-uterine lifeIntra-uterine life From birth to 2-3 yearsFrom birth to 2-3 years

This meant reduction in This meant reduction in exposureexposure to highly allergenic to highly allergenic foods:foods: Mother’s diet during pregnancy and lactationMother’s diet during pregnancy and lactation Delay in introduction of highly allergenic foods during Delay in introduction of highly allergenic foods during

weaningweaning In spite of these stringent measures to prevent allergy, In spite of these stringent measures to prevent allergy,

incidence of all types of allergies have increased incidence of all types of allergies have increased significantlysignificantly

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Change in Direction During the Past Change in Direction During the Past Five YearsFive Years

Understanding of the importance of immunological Understanding of the importance of immunological sensitizationsensitization and and tolerancetolerance

Recognition that Recognition that tolerancetolerance not not sensitizationsensitization is the is the critical step in allergy preventioncritical step in allergy prevention

Finding that Finding that exposureexposure to the allergenic food at an to the allergenic food at an optimum stage is probably a critical step in optimum stage is probably a critical step in allergy allergy preventionprevention

Recognition that tolerance can be induced after Recognition that tolerance can be induced after allergy has been established – leading to important allergy has been established – leading to important measures for measures for allergy managementallergy management

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Allergy is a Response of the Immune SystemAllergy is a Response of the Immune System

Our immune systems are designed to protect Our immune systems are designed to protect the body from invasion by foreign materialsthe body from invasion by foreign materials

All foods contain proteins – derived from All foods contain proteins – derived from plants and animals – all of which are foreign to plants and animals – all of which are foreign to the human bodythe human body

In order for food to be absorbed, metabolized, In order for food to be absorbed, metabolized, and utilized by the body, the immune system and utilized by the body, the immune system needs to be “educated” that the foreign needs to be “educated” that the foreign material is safematerial is safe

________Herz 2008

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Education of the Immune SystemEducation of the Immune System

Involves a complex series of immunological Involves a complex series of immunological reactions controlled by T cell lymphocytes (T reactions controlled by T cell lymphocytes (T cells)cells)

T helper (Th) cells detect foreign proteins T helper (Th) cells detect foreign proteins (antigens) in any form(antigens) in any form

T cells then trigger a series of immunological T cells then trigger a series of immunological reactions, mediated by cytokines reactions, mediated by cytokines (the “control (the “control chemicals” of the immune system) chemicals” of the immune system)

_________Joneja 2007

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T-helper Cell SubclassesT-helper Cell Subclasses There are two subclasses of T-helper cellsThere are two subclasses of T-helper cells

Th1Th1 Th2Th2

Each Th cell type produces its own specific Each Th cell type produces its own specific set of cytokinesset of cytokines

The types of cytokines generated determine The types of cytokines generated determine the resulting immune responsethe resulting immune response

Th1 principally Th1 principally INF-INF- Th2 principally Th2 principally IL-4IL-4

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Role of T-helper Cell SubtypesRole of T-helper Cell Subtypes

Th1 Th1 triggers the triggers the protective responseprotective response to a to a pathogenpathogen such as a virus or bacterium such as a virus or bacterium

IgM, IgG, IgAIgM, IgG, IgA antibodies are produced antibodies are produced

Th2Th2 is responsible for the allergic is responsible for the allergic ((hypersensitivityhypersensitivity)) reaction reaction IgEIgE antibodies are produced antibodies are produced

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T cells involved in Oral ToleranceT cells involved in Oral Tolerance T cell response depends on the type of T helper cell T cell response depends on the type of T helper cell

that is activatedthat is activated Latest research indicates that T cells that produce a Latest research indicates that T cells that produce a

cytokine called TGF-cytokine called TGF- are important in inducing oral are important in inducing oral tolerancetolerance Sometimes called Th3 cellsSometimes called Th3 cells

T cells that produce IL-10 and IL-13 may also be T cells that produce IL-10 and IL-13 may also be involved in toleranceinvolved in tolerance

These also regulate immune response to resident These also regulate immune response to resident microflora, preventing the usual immune microflora, preventing the usual immune inflammatory response to microorganismsinflammatory response to microorganisms

___________________Strobel and Mowat 2006

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Oral ToleranceOral Tolerance

““Education” of the T cells to not respond to that food Education” of the T cells to not respond to that food protein when it enters via the oral route – called protein when it enters via the oral route – called oral oral tolerancetolerance

Contrasts with the Contrasts with the active immune responsesactive immune responses needed needed to protect the gut against continual bombardment by to protect the gut against continual bombardment by invading pathogens and their products (toxins, etc)invading pathogens and their products (toxins, etc)

Also contrasts with the Also contrasts with the reduced responsivenessreduced responsiveness to the to the millions of microorganisms that are permanent millions of microorganisms that are permanent residents of the large bowelresidents of the large bowel

T cells involved in these processes are called T cells involved in these processes are called regulator T cells (Tregulator T cells (Tregreg))

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Prevention of Food Allergy in Clinical Prevention of Food Allergy in Clinical PracticePractice

Significant changeSignificant change in directives within the past 5 in directives within the past 5 years:years:

Previously: Previously: Avoidance of allergen to Avoidance of allergen to prevent prevent

sensitizationsensitization (allergen-specific IgE) (allergen-specific IgE) Current: Current:

Active stimulation of the immature Active stimulation of the immature immune system to immune system to induce toleranceinduce tolerance of the of the antigens in foodantigens in food

________________Rautava et al 2005

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Factors Predictive of Allergy:Factors Predictive of Allergy:High and Low risk GroupsHigh and Low risk Groups

Many factors investigated as possible Many factors investigated as possible predictive markers for allergypredictive markers for allergy

Only significant variable in studies:Only significant variable in studies:Family history of allergyFamily history of allergy (all types) (all types)

High risk for allergy:High risk for allergy: One first degree relative with diagnosed One first degree relative with diagnosed

allergy (IgE-mediated) of any typeallergy (IgE-mediated) of any type First-degree relative: parent or siblingFirst-degree relative: parent or sibling

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Does Atopic Disease Start in Fetal Does Atopic Disease Start in Fetal Life?Life?

Fetal cytokines are skewed to the Th2 type Fetal cytokines are skewed to the Th2 type of responseof response

Suggested that this may guard against Suggested that this may guard against rejection of the “foreign” fetus by the rejection of the “foreign” fetus by the mother’s immune systemmother’s immune system

IgE occurs from as early as 11 weeks IgE occurs from as early as 11 weeks gestation and can be detected in cord bloodgestation and can be detected in cord blood

_____________Jones et al 2000

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Does Atopic Disease Start in Fetal Life? Does Atopic Disease Start in Fetal Life? (continued)(continued)

At birth neonates have low At birth neonates have low INF-INF- and tend and tend to produce the cytokines associated with to produce the cytokines associated with Th2 response, especially Th2 response, especially IL-4IL-4

So why do all neonates not have allergy?So why do all neonates not have allergy?

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Does Atopic Disease Start in Fetal Life? Does Atopic Disease Start in Fetal Life? (continued)(continued)

New research indicates that the immune New research indicates that the immune system of the mother may play a very system of the mother may play a very important role in important role in expressionexpression of allergy in of allergy in the neonate and infantthe neonate and infant

IgG crosses the placenta; IgE does notIgG crosses the placenta; IgE does not Certain sub-types of IgG (IgG1; IgG3) can Certain sub-types of IgG (IgG1; IgG3) can

inhibit IgE responseinhibit IgE response

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Significance in PracticeSignificance in Practice

Food proteins demonstrated to cross the Food proteins demonstrated to cross the placenta and can be detected in amniotic placenta and can be detected in amniotic fluidfluid

Exposure to small quantities of food Exposure to small quantities of food antigens from mother’s diet thought to antigens from mother’s diet thought to tolerize the fetustolerize the fetus, by means of IgG1 and , by means of IgG1 and IgG3, within a “protected environment”IgG3, within a “protected environment”

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Immune Response of the Allergic MotherImmune Response of the Allergic Mother

Atopic mother’s immune system may Atopic mother’s immune system may dictate the response of the fetus to antigens dictate the response of the fetus to antigens in uteroin utero

The allergic mother may be incapable of The allergic mother may be incapable of providing sufficient IgG1 and IgG3 to providing sufficient IgG1 and IgG3 to downregulate (depress) fetal IgE downregulate (depress) fetal IgE

There is no convincing evidence that There is no convincing evidence that sensitization to sensitization to specificspecific food allergens is food allergens is initiated prenatallyinitiated prenatally

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Diet During PregnancyDiet During Pregnancy

Current directive: the atopic mother should strictly Current directive: the atopic mother should strictly avoid her own allergens and replace the foods with avoid her own allergens and replace the foods with nutritionally equivalent substitutesnutritionally equivalent substitutes

There are There are no indicationsno indications for mother to avoid other for mother to avoid other foods during pregnancyfoods during pregnancy

A nutritionally complete, well-balanced diet is A nutritionally complete, well-balanced diet is essentialessential

Authorities recommend avoidance of Authorities recommend avoidance of excessiveexcessive intake intake of highly allergenic foods such as peanuts and nuts to of highly allergenic foods such as peanuts and nuts to prevent “allergen overload”, but there is no scientific prevent “allergen overload”, but there is no scientific data to support thisdata to support this

_______________Kramer et al 2006

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Breast-feeding and AllergyBreast-feeding and Allergy

Studies indicating that breast-feeding is Studies indicating that breast-feeding is protective against allergy report:protective against allergy report: A definite improvement in infant eczema and A definite improvement in infant eczema and

associated gastrointestinal complaints when associated gastrointestinal complaints when baby is exclusively breast-fedbaby is exclusively breast-fed

Reduced risk of asthma in the first 24 months Reduced risk of asthma in the first 24 months of lifeof life

__________________Kirjavainen et al 2002

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Breast-feeding and AllergyBreast-feeding and Allergy

Other studies are in conflict with these Other studies are in conflict with these conclusions: conclusions: Some report no improvement in symptomsSome report no improvement in symptoms Some suggest symptoms get worse with breast-Some suggest symptoms get worse with breast-

feeding and improve with feeding of feeding and improve with feeding of hydrolysate formulaehydrolysate formulae

Japanese study suggests that breast-feeding Japanese study suggests that breast-feeding increases the risk of asthma at adolescence increases the risk of asthma at adolescence

Why the conflicting resultsWhy the conflicting results??

_______________Miyake et al 2003

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Immunological Factors in Human Milk that Immunological Factors in Human Milk that may be Associated with Allergy:may be Associated with Allergy:

Cytokines and ChemokinesCytokines and Chemokines

Atopic mothers tend to have a higher level of the Atopic mothers tend to have a higher level of the cytokines and chemokines associated with allergy in cytokines and chemokines associated with allergy in their breast milktheir breast milk

Those identified include:Those identified include:IL-4IL-4 IL-5IL-5IL-8IL-8 IL-13IL-13Some chemokines (e.g. RANTES)Some chemokines (e.g. RANTES)

Atopic infants do not seem to be protected from Atopic infants do not seem to be protected from allergy by the breast milk of atopic mothersallergy by the breast milk of atopic mothers

___________________________Snijders et al 2007 KOALA study

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Immunological Factors in Human Milk Immunological Factors in Human Milk that may be Associated with Allergy: that may be Associated with Allergy:

TGF-TGF-11 Cytokine, transforming growth factor-Cytokine, transforming growth factor-1 (1 (TGF-TGF-

11) promotes tolerance to food components in the ) promotes tolerance to food components in the intestinal immune responseintestinal immune response

TGF-TGF-11 in mother’s colostrum may influence the in mother’s colostrum may influence the type and intensity of the infant’s response to food type and intensity of the infant’s response to food allergensallergens

A normal level of A normal level of TGF-TGF-11 is likely to facilitate is likely to facilitate tolerance to food encountered by the infant in tolerance to food encountered by the infant in mother’s breast milk and later to formulae and mother’s breast milk and later to formulae and solidssolids

______________Rigotti et al 2006

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Implications of Research DataImplications of Research Data

Exclusive breast-feeding with exclusion of Exclusive breast-feeding with exclusion of mother’s and baby’s allergens will reduce signs of mother’s and baby’s allergens will reduce signs of allergy in the first 1-2 years; specifically:allergy in the first 1-2 years; specifically: Cow’s milk allergyCow’s milk allergy EczemaEczema

Reduction or prevention of early food allergy by Reduction or prevention of early food allergy by breast-feeding does not seem to have long-term breast-feeding does not seem to have long-term effects on the development of asthma and allergic effects on the development of asthma and allergic rhinitisrhinitis

Other benefits of breast-feeding far outweigh any Other benefits of breast-feeding far outweigh any possible negative effects on allergy: exclusive possible negative effects on allergy: exclusive breast-feeding for 4-6 months is strongly breast-feeding for 4-6 months is strongly encouragedencouraged

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Summary of 2008 AAP Guidelines for Allergy Summary of 2008 AAP Guidelines for Allergy Management Management [Greer et al 2008][Greer et al 2008]

There is no convincing evidence that women There is no convincing evidence that women who avoid highly allergenic foods, or other who avoid highly allergenic foods, or other foods during pregnancy and breast-feeding foods during pregnancy and breast-feeding lower their child’s risk of allergieslower their child’s risk of allergies

For high-risk for allergy infants (one first-For high-risk for allergy infants (one first-degree relative with established allergy), degree relative with established allergy), exclusive breast-feeding for at least 4 months exclusive breast-feeding for at least 4 months prevents or delays the occurrence of atopic prevents or delays the occurrence of atopic dermatitis (eczema), cow’s milk allergy, and dermatitis (eczema), cow’s milk allergy, and wheezing in early childhoodwheezing in early childhood

_____________Greer et al 2008

____________________Sicherer and Burks 2008

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Preventive Effect of Breast-feeding:Preventive Effect of Breast-feeding:KOALA StudyKOALA Study

Longer duration of breastfeeding is associated with Longer duration of breastfeeding is associated with lower risk for eczema in non-atopic motherslower risk for eczema in non-atopic mothers

Slightly lower risk for mothers with allergy but no Slightly lower risk for mothers with allergy but no asthmaasthma

Longer duration of breastfeeding reduced risk for Longer duration of breastfeeding reduced risk for wheezing in infants: possibly due to reduction in wheezing in infants: possibly due to reduction in respiratory infectionsrespiratory infections

There is a lack of evidence that exclusive or There is a lack of evidence that exclusive or prolonged breast-feeding has any positive effect on prolonged breast-feeding has any positive effect on the development of asthma in older childrenthe development of asthma in older children

___________________________Snijders et al 2007 KOALA study

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Summary of 2008 AAP Guidelines Summary of 2008 AAP Guidelines continuedcontinued

In infants at high risk for allergy who are not In infants at high risk for allergy who are not exclusively breast-fed for 4-6 months there is exclusively breast-fed for 4-6 months there is modest evidence that the onset of atopic modest evidence that the onset of atopic disease (allergy), especially eczema, may be disease (allergy), especially eczema, may be delayed or prevented by the use of hydrolyzed delayed or prevented by the use of hydrolyzed formulasformulas

There is no good evidence that soy-based There is no good evidence that soy-based infant formulas have any preventive effect on infant formulas have any preventive effect on the development of allergythe development of allergy

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Preventive Effect of Hydrolyzed Infant Preventive Effect of Hydrolyzed Infant FormulaeFormulae

No evidence of any reduction in allergy with No evidence of any reduction in allergy with hydrolyzed formula compared to breastfeedinghydrolyzed formula compared to breastfeeding

Limited evidence that prolonged feeding with Limited evidence that prolonged feeding with hydrolyzed formula compared to cow’s milk reduces hydrolyzed formula compared to cow’s milk reduces incidence of CMA and eczemaincidence of CMA and eczema

No evidence that hydrolyzed formulas have any No evidence that hydrolyzed formulas have any effect on the development of rhinitis and asthma latereffect on the development of rhinitis and asthma later

Extensively hydrolyzed cow’s milk (Ehf) formulas Extensively hydrolyzed cow’s milk (Ehf) formulas marginally better than partially hydrolyzed whey marginally better than partially hydrolyzed whey (Phf) in prevention (Phf) in prevention

_________________________________Osborn and Sinn 2009 Cochrane Review

__________________________Von Berg et al GINI Study 2009

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Infant Formulae for the Allergic BabyInfant Formulae for the Allergic BabyCurrent RecommendationsCurrent Recommendations

Cow’s milk based formula if there are no signs Cow’s milk based formula if there are no signs of milk allergyof milk allergy

Partially hydrolysed (phf) whey-based formula Partially hydrolysed (phf) whey-based formula if there are no signs of milk allergy in high risk if there are no signs of milk allergy in high risk for allergy groupfor allergy group

Extensively hydrolysed (ehf) casein based Extensively hydrolysed (ehf) casein based formula if milk allergy is proven formula if milk allergy is proven

_________________Greer et al AAP 2008Von Berg et al 2007

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Recommendations for Introduction of Solids Recommendations for Introduction of Solids to High Risk for Allergy Infantsto High Risk for Allergy Infants

Little evidence that delaying the introduction of Little evidence that delaying the introduction of complementary foods beyond 4-6 months of age complementary foods beyond 4-6 months of age prevents allergyprevents allergy

Introduction of solid foods should be individualizedIntroduction of solid foods should be individualized Foods should be introduced one at a time in small Foods should be introduced one at a time in small

amountsamounts Mixed foods containing various potential food Mixed foods containing various potential food

allergens should not be given unless tolerance to each allergens should not be given unless tolerance to each ingredient has been assessedingredient has been assessed

____________________Greer et al AAP 2008

_____________________Thygaran and Burks 2008

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Introduction of Solid Foods in Introduction of Solid Foods in Relationship to Celiac DiseaseRelationship to Celiac Disease

Results suggest that in high risk for celiac disease Results suggest that in high risk for celiac disease infants introduction of gluten-containing grains infants introduction of gluten-containing grains before 3 months or after 7 months increases before 3 months or after 7 months increases incidences of development of CDincidences of development of CD11

Introduction of gluten while breast-feeding offers Introduction of gluten while breast-feeding offers protection or delays onset of celiac disease in at-risk protection or delays onset of celiac disease in at-risk infantsinfants22

Recommendations: Recommendations: Introduce gluten grains in small amounts between 4 and 6 Introduce gluten grains in small amounts between 4 and 6

months while infant is breastfedmonths while infant is breastfed Continue breast-feeding for a further 2-3 monthsContinue breast-feeding for a further 2-3 months

Similar results for wheat allergySimilar results for wheat allergy33

_______________1Norris et al 2005

______________2Guandalini 2007

____________3Poole et al 2006

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Introduction of PeanutsIntroduction of Peanuts

Directives from pediatric societies (1998 - 2007) Directives from pediatric societies (1998 - 2007) recommended avoidance of peanuts by mothers recommended avoidance of peanuts by mothers during pregnancy and lactation, and delaying during pregnancy and lactation, and delaying introduction of peanuts until after 2 or even 3 years of introduction of peanuts until after 2 or even 3 years of ageage

Research indicates that incidence of peanut allergy in Research indicates that incidence of peanut allergy in children rose dramatically in the years following children rose dramatically in the years following release of these directivesrelease of these directives

Recent research suggests:Recent research suggests: Avoidance of peanuts reduced development of toleranceAvoidance of peanuts reduced development of tolerance Early exposure leads to reduced incidence of peanut allergyEarly exposure leads to reduced incidence of peanut allergy

_________________Hourihane et al 2007

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Introduction of PeanutsIntroduction of PeanutsStudy (n=10,786) among primary school age Jewish Study (n=10,786) among primary school age Jewish

children in UK and Israelchildren in UK and Israel Prevalence of peanut allergy (PA):Prevalence of peanut allergy (PA):

In UK:In UK: 1.85%1.85% In Israel:In Israel: 0.17%0.17%

Median monthly consumption of peanut in infants Median monthly consumption of peanut in infants aged 8 – 14 months:aged 8 – 14 months: In UK:In UK: 00 In Israel:In Israel: 7.1 g7.1 g

Difference not due to atopy, genetic background, Difference not due to atopy, genetic background, social class, or peanut allergenicitysocial class, or peanut allergenicity

Israeli infants consume peanuts in high quantities Israeli infants consume peanuts in high quantities during the first year of lifeduring the first year of life

______________Du Toit et al 2008

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Introduction of FishIntroduction of Fish

Historically, fish consumption during infancy was Historically, fish consumption during infancy was considered to be a risk factor for allergyconsidered to be a risk factor for allergy

Recent research indicates otherwise:Recent research indicates otherwise: Regular fish consumption during the first year of life Regular fish consumption during the first year of life

associated with a reduced risk for allergic disease by age 4 associated with a reduced risk for allergic disease by age 4 years (n=4089)years (n=4089)11

Babies of mothers who frequently consumed fish (2-3 Babies of mothers who frequently consumed fish (2-3 times per week or more) during pregnancy had one third times per week or more) during pregnancy had one third less food sensitivities than those whose mothers did not less food sensitivities than those whose mothers did not consume fish during pregnancyconsume fish during pregnancy22

_____________1Kull et al 2006

_______________2Calvani et al 2006

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Introduction of FishIntroduction of Fish

Study (n= 5,000); 20.9% developed eczema by 1 year: Study (n= 5,000); 20.9% developed eczema by 1 year: Babies who were fed fish before nine months of age Babies who were fed fish before nine months of age

were 24% less likely to develop eczema by age 1 yearwere 24% less likely to develop eczema by age 1 year Omega-3 content of fish did not seem to influence the Omega-3 content of fish did not seem to influence the

outcomeoutcome The age at which egg and milk were introduced did The age at which egg and milk were introduced did

not affect development of eczemanot affect development of eczema Breast-feeding did not have any significant impact on Breast-feeding did not have any significant impact on

development of eczemadevelopment of eczema____________Alm et al 2009

____________________________Hibbeln et al 2007 ALSPAC study

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The Natural History of Food AllergyThe Natural History of Food Allergy

Food allergy most often begins in the first 1 to Food allergy most often begins in the first 1 to 2 years of life2 years of life

Child is sensitized to the food protein by the Child is sensitized to the food protein by the immune system developing allergen-specific immune system developing allergen-specific IgE to that proteinIgE to that protein

Sensitization does not necessarily mean that Sensitization does not necessarily mean that the child will develop symptoms when that the child will develop symptoms when that food is eatenfood is eaten

Over time most food allergy is lostOver time most food allergy is lost_________Wood 2003

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PrognosisPrognosis Most children outgrow early food allergyMost children outgrow early food allergy

John’s Hopkins Children’s Center USAJohn’s Hopkins Children’s Center USA Milk allergy outgrown:Milk allergy outgrown:

20% by 4 years20% by 4 years 42% by 8 years42% by 8 years 79% by 16 years79% by 16 years

Egg allergy outgrown:Egg allergy outgrown: 4% by 4 years4% by 4 years 37% by 10 years37% by 10 years 68% by 16 years68% by 16 years

Allergy to some foods more often than others persists into Allergy to some foods more often than others persists into adulthoodadulthood:: PeanutPeanut Tree nuts Tree nuts SeedsSeeds ShellfishShellfish FishFish

______________Skripak et al 2007

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Induction of Oral ToleranceInduction of Oral Tolerance

Tolerance to a specific food can be induced by Tolerance to a specific food can be induced by oral administration of the offending food by oral administration of the offending food by process of “low dose continuous exposure”process of “low dose continuous exposure”

Designated (SOTI: specific oral tolerance Designated (SOTI: specific oral tolerance induction)induction)

Starting with very low dosagesStarting with very low dosages Gradually increasing daily dosage up to the Gradually increasing daily dosage up to the

equivalent of the usual daily intakeequivalent of the usual daily intake Followed by daily maintenance doseFollowed by daily maintenance dose

__________________Niggemann et al 2006

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_____________Calvani et al 2010

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Desensitization to Desensitization to Cow’s MilkCow’s Milk

18 children with confirmed CMA >4 years of age 18 children with confirmed CMA >4 years of age underwent SOTIunderwent SOTI

Starting dose 0.05 ml cow’s milkStarting dose 0.05 ml cow’s milk Increased to 1 ml on first dayIncreased to 1 ml on first day Increasing dosage weekly up to a daily dose of 200-Increasing dosage weekly up to a daily dose of 200-

250 ml250 ml Results: 16/18 tolerated 200-250 ml milkResults: 16/18 tolerated 200-250 ml milk Length of process median 14 weeks (range 11-17 Length of process median 14 weeks (range 11-17

weeks)weeks) Tolerance has been maintained for >1 yearTolerance has been maintained for >1 year_______________Zapatero et al 2008 41

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Oral Tolerance Induction to Oral Tolerance Induction to Milk, Egg, and PeanutMilk, Egg, and Peanut

36% of children with IgE-mediated allergy to 36% of children with IgE-mediated allergy to cow’s cow’s milkmilk and and hen’s egghen’s egg developed permanent tolerance of developed permanent tolerance of the foods after a median 21 months specific oral the foods after a median 21 months specific oral tolerance induction (SOTI)tolerance induction (SOTI)11

4 peanut-allergic children underwent SOTI:4 peanut-allergic children underwent SOTI: Daily doses of Daily doses of peanut flourpeanut flour starting at 5 mg peanut protein starting at 5 mg peanut protein 2-weekly dosage increase up to 800 mg protein2-weekly dosage increase up to 800 mg protein All subjects tolerated at least 10 whole peanuts (2.38 g All subjects tolerated at least 10 whole peanuts (2.38 g

protein) on post-intervention challengeprotein) on post-intervention challenge22

______________1Staden et al 2007

______________22Clark et al 2009 42

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Progression of Peanut AllergyProgression of Peanut Allergy

Peanut allergy, like many early food allergies, can be Peanut allergy, like many early food allergies, can be outgrownoutgrown

In 2001 pediatric allergists in the U.S. reported that In 2001 pediatric allergists in the U.S. reported that about 21.5 per cent of children will eventually about 21.5 per cent of children will eventually outgrow their peanut allergyoutgrow their peanut allergy11

Those with a mild peanut allergy, as determined by Those with a mild peanut allergy, as determined by the level of peanut-specific IgE in their blood, have a the level of peanut-specific IgE in their blood, have a 50% chance of outgrowing the allergy50% chance of outgrowing the allergy22

Only about 9% of patients are reported to outgrow Only about 9% of patients are reported to outgrow their allergy to tree nutstheir allergy to tree nuts33

__________________1Skolnick et al 20012Fleischer et al 20033Fleischer et al 2005 43

44

Maintaining Tolerance of PeanutMaintaining Tolerance of Peanut

When there is no longer any evidence of When there is no longer any evidence of symptoms developing after a child has consumed symptoms developing after a child has consumed peanuts, it is preferable for that child to peanuts, it is preferable for that child to eat eat peanuts regularlypeanuts regularly, rather than avoid them, in , rather than avoid them, in order to maintain tolerance to the peanutorder to maintain tolerance to the peanut

Children who outgrow peanut allergy are at risk Children who outgrow peanut allergy are at risk for recurrence, but the risk has been shown to be for recurrence, but the risk has been shown to be significantly higher for those who significantly higher for those who continue to continue to avoid peanutsavoid peanuts after resolution of their symptoms after resolution of their symptoms

_________________Fleischer et al 2004

44

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Probiotics and Allergy PreventionProbiotics and Allergy Prevention

Probiotics and prebiotics may change the colonic Probiotics and prebiotics may change the colonic microflora of the neonatemicroflora of the neonate

Theory: Theory: Change from Th2 to Th1 response in the neonatal period is Change from Th2 to Th1 response in the neonatal period is

required to reduce potential for allergyrequired to reduce potential for allergy This change is mediated by contact with micro-organismsThis change is mediated by contact with micro-organisms Non-allergic children have a predominance of lactobacilli Non-allergic children have a predominance of lactobacilli

and bifidobacteriaand bifidobacteria Atopic children tend to have more clostridia and lower Atopic children tend to have more clostridia and lower

levels of bifidobacterialevels of bifidobacteria Probiotics could be used to change the “atopic” to a more Probiotics could be used to change the “atopic” to a more

“non-atopic flora”“non-atopic flora”____________Ozdemir 2010

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Studies on Probiotics in Allergy PreventionStudies on Probiotics in Allergy Prevention

Some studies indicate a positive outcome in Some studies indicate a positive outcome in reducing the incidence of allergy:reducing the incidence of allergy: Lactobacillus F19 in cereals fed to infants from 4 Lactobacillus F19 in cereals fed to infants from 4

to 13 months of age reduced the incidence of to 13 months of age reduced the incidence of eczemaeczema11

Other studies showed no effect:Other studies showed no effect: Bifidobacterium + Lactobacillus rhamnosus daily Bifidobacterium + Lactobacillus rhamnosus daily

for the first 6 months in at risk infants had no for the first 6 months in at risk infants had no effect compared to placeboeffect compared to placebo22

____________________

1 West et al 2009___________________

2 Soh et al 2009

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Current Status of Probiotics in Current Status of Probiotics in Allergy PreventionAllergy Prevention

Beneficial effects of probiotic therapy depends on:Beneficial effects of probiotic therapy depends on: Type of bacteria selectedType of bacteria selected Dosage of the bacteria delivered to the digestive tractDosage of the bacteria delivered to the digestive tract Method of delivery of the bacteria to the GI tract (in Method of delivery of the bacteria to the GI tract (in

formulae; in cereals)formulae; in cereals) Age of the individualAge of the individual Length of duration of deliveryLength of duration of delivery

Conclusion at the current state of research:Conclusion at the current state of research: Probiotics cannot be recommended generally for primary Probiotics cannot be recommended generally for primary

prevention of atopic diseaseprevention of atopic disease_____________Ozdemir 2010a

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Take Home MessageTake Home Message

Allergy prevention emphasizes inducing Allergy prevention emphasizes inducing tolerance rather than avoiding sensitizationtolerance rather than avoiding sensitization

Beginning of tolerance to foods may occur in Beginning of tolerance to foods may occur in utero or during breast-feedingutero or during breast-feeding

Restriction of maternal diet to avoid highly Restriction of maternal diet to avoid highly allergenic foods during pregnancy or lactation allergenic foods during pregnancy or lactation is contraindicatedis contraindicated

Unless either mother or baby is allergic to Unless either mother or baby is allergic to themthem

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Take Home MessageTake Home Message

Management of established food allergy Management of established food allergy includesincludes:: Accurate identification of the allergenic Accurate identification of the allergenic

food(s)food(s) Careful avoidance of the food allergens – Careful avoidance of the food allergens –

especially if there is any risk of anaphylaxisespecially if there is any risk of anaphylaxis Avoidance of unnecessary food restrictionsAvoidance of unnecessary food restrictions

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Take Home MessageTake Home Message

Provision of complete balanced Provision of complete balanced nutrition by substituting foods of equal nutrition by substituting foods of equal nutritional valuenutritional value

Monitoring the child’s response at Monitoring the child’s response at intervals to determine when the food intervals to determine when the food allergy has been outgrownallergy has been outgrown

Maintenance of tolerance by feeding Maintenance of tolerance by feeding tolerated foods regularlytolerated foods regularly

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Invitation to Further InformationInvitation to Further Information

www.allergynutrition.com

Joneja, J.M.Vickerstaff Joneja, J.M.Vickerstaff Dealing with Food Allergies in Babies Dealing with Food Allergies in Babies and Childrenand Children Bull Publishing Company, Boulder, Colorado. Bull Publishing Company, Boulder, Colorado.

October 2007October 2007