Pediatric AllergyPediatric Allergy

Prevention and ManagementPrevention and Management

Change in Direction During Change in Direction During the Past Three Yearsthe Past Three Years

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

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

Finding that Finding that exposureexposure to the allergenic to the allergenic food at the optimum age is probably a food at the optimum age is probably a critical step in critical step in allergy preventionallergy prevention

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

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Prevention of Food Allergy in Prevention of Food Allergy in Clinical PracticeClinical Practice

Significant changeSignificant change in directives within in directives within the past 3 years:the past 3 years:

Previously: Previously: Avoidance of allergen to Avoidance of allergen to prevent prevent sensitizationsensitization (allergen-specific (allergen-specific

IgE)IgE) Current: Current:

Active stimulation of the Active stimulation of the immature immature immune system to immune system to induce induce tolerancetolerance of the of the antigens in foodantigens in food________________

Rautava et al 2005 3

Diet During PregnancyDiet During Pregnancy

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

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

A nutritionally complete, well-balanced diet A nutritionally complete, well-balanced diet is essentialis essential

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

Kramer et al 2006 4

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 mother’s and baby’s allergens will reduce signs of allergy in the first 1-2 yearssigns of allergy in the first 1-2 years

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

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

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

2008]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

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

_____________Greer et al 2008

____________________Sicherer and Burks 2008

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Summary of 2008 AAP Summary of 2008 AAP Guidelines Guidelines continuedcontinued

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

Extensively hydrolyzed formulas Extensively hydrolyzed formulas have a greater protective effect than have a greater protective effect than partially hydrolyzed formulaspartially hydrolyzed formulas

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Summary of 2008 AAP Summary of 2008 AAP Guidelines Guidelines continuedcontinued

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

There is little evidence that delaying There is little evidence that delaying the timing of the introduction of the timing of the introduction of solid foods beyond 4-6 months of age solid foods beyond 4-6 months of age prevents the occurrence of allergyprevents the occurrence of allergy

_____________________Thygaran and Burks 2008

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Infant Formulae for the Infant Formulae for the Allergic BabyAllergic Baby

Current RecommendationsCurrent Recommendations Modest evidence that allergy may be Modest evidence that allergy may be

delayed or prevented by the use of delayed or prevented by the use of hydrolyzed formulas compared with hydrolyzed formulas compared with formula of intact cow’s milk proteinsformula of intact cow’s milk proteins

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

Partially hydrolysed (phf) whey-based Partially hydrolysed (phf) whey-based formula if there are no signs of milk allergyformula if there are no signs of milk allergy

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 Recommendations for Introduction of Solids to High Risk Introduction of Solids to High Risk

for Allergy Infantsfor Allergy Infants Little evidence that delaying the introduction Little evidence that delaying the introduction

of complementary foods beyond 4-6 months of of complementary foods beyond 4-6 months of age prevents allergyage prevents allergy

Introduction of solid foods should be Introduction of solid foods should be individualizedindividualized

Foods should be introduced one at a time in Foods should be introduced one at a time in small amountssmall amounts

Mixed foods containing various potential food Mixed foods containing various potential food allergens should not be given unless tolerance allergens should not be given unless tolerance to each ingredient has been assessedto each ingredient has been assessed

__________________Greer et al AAP 2008

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___________________________________European Food Safety Authority EFSA 2009

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

Introduction of gluten while breast-feeding Introduction of gluten while breast-feeding offers protection or delays onset of celiac offers protection or delays onset of celiac disease in at-risk infantsdisease in at-risk infants22

Recommendations: Recommendations: Introduce gluten grains in small amounts between Introduce gluten grains in small amounts between

4 and 6 months while infant is breastfed4 and 6 months while infant is breastfed Continue breast-feeding for a further 2-3 monthsContinue breast-feeding for a further 2-3 months

_______________1Norris et al 2005

_____________2Guandalini 200711

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 introduction of peanuts until after 2 or even 3 years of ageyears of age

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

Recent research suggests:Recent research suggests: Avoidance of peanuts reduced development of Avoidance of peanuts reduced development of

tolerancetolerance Early exposure leads to reduced incidence of peanut Early exposure leads to reduced incidence of peanut

allergyallergy_________________Hourihane et al 2007 12

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

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

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

Israeli infants consume peanuts in high Israeli infants consume peanuts in high quantities during the first year of lifequantities during the first year of life______________

Du Toit et al 200813

Introduction of FishIntroduction of Fish

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

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

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

Babies of mothers who frequently consumed fish Babies of mothers who frequently consumed fish (2-3 times per week or more) during pregnancy (2-3 times per week or more) during pregnancy had one third less food sensitivities than those had one third less food sensitivities than those whose mothers did not consume fish during whose mothers did not consume fish during pregnancypregnancy22

_____________1Kull et al 2006

_______________2Calvani et al 2006 14

Introduction of FishIntroduction of Fish

Study (n= 5,000); 20.9% developed eczema by 1 Study (n= 5,000); 20.9% developed eczema by 1 year: year:

Babies who were fed fish before nine months of Babies who were fed fish before nine months of age were 24% less likely to develop eczema by age were 24% less likely to develop eczema by age 1 yearage 1 year

Omega-3 content of fish did not seem to Omega-3 content of fish did not seem to influence the outcomeinfluence the outcome

The age at which egg and milk were introduced The age at which egg and milk were introduced did not affect development of eczemadid not affect development of eczema

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

____________Alm et al 2009 15

The Natural History of Food The Natural History of Food AllergyAllergy

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

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

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

Over time most food allergy is lostOver time most food allergy is lost

_________Wood 2003 16

Development of Development of ToleranceTolerance

25% of infants lost all food allergy 25% of infants lost all food allergy symptoms after 1 year of agesymptoms after 1 year of age

Most infants will outgrow milk allergy by Most infants will outgrow milk allergy by 3 years of age, but may become intolerant 3 years of age, but may become intolerant to other foodsto other foods

Tolerance of specific foods :Tolerance of specific foods :

After 1 year:After 1 year: 26% decrease in allergy to:26% decrease in allergy to:

MilkMilk Soy Soy PeanutPeanut

Egg Egg Wheat Wheat 2% decrease in allergy to other foods2% decrease in allergy to other foods 17

PrognosisPrognosis

Age at which milk was tolerated by milk-Age at which milk was tolerated by milk-allergic children:allergic children: 28% by 2 years of age28% by 2 years of age 56% by 4 years of age56% by 4 years of age 78% by 6 years of age78% by 6 years of age

About 25% of food allergic children About 25% of food allergic children develop respiratory allergiesdevelop respiratory allergies

Allergy to some foods more often than Allergy to some foods more often than others persists into adulthood:others persists into adulthood: PeanutPeanut Tree nuts Tree nuts

SeedsSeeds ShellfishShellfish FishFish

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University of Portsmouth University of Portsmouth UKUK

Milk allergy outgrown:Milk allergy outgrown: ¾ by 3 years¾ by 3 years

Egg allergy outgrown:Egg allergy outgrown: ½ by 3 years½ by 3 years

Of 272 allergic babies, only 60 (22%) were allergic Of 272 allergic babies, only 60 (22%) were allergic at age 3 yearsat age 3 years

In these the most common allergies were:In these the most common allergies were: Peanuts (11)Peanuts (11) Eggs (9)Eggs (9) Milk (4)Milk (4) Wheat, Brazil nut; Almond (2 each)Wheat, Brazil nut; Almond (2 each) Hazelnut, Cashew, Corn (1 each)Hazelnut, Cashew, Corn (1 each)

None were allergic to tomato or fish at age 3 yearsNone were allergic to tomato or fish at age 3 years

_____________Savage et al 2007

Induction of Oral Induction of Oral ToleranceTolerance

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

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

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

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

__________________Niggemann et al 2006

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Desensitization to Desensitization to Cow’s MilkCow’s Milk 18 children with confirmed CMA >4 years 18 children with confirmed CMA >4 years

of age underwent SOTIof age underwent 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 Increasing dosage weekly up to a daily dose

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

11-17 weeks)11-17 weeks) Tolerance has been maintained for >1 yearTolerance has been maintained for >1 year_______________Zapatero et al 2008 21

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 milkcow’s milk and and hen’s egghen’s egg developed developed permanent tolerance of the foods after a permanent tolerance of the foods after a median 21 months specific oral tolerance median 21 months specific oral tolerance induction (SOTI)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 starting at 5 mg

peanut proteinpeanut 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 All subjects tolerated at least 10 whole peanuts

(2.38 g protein) on post-intervention challenge(2.38 g protein) on post-intervention challenge22______________1Staden et al 2007

____________22Clark et al 2009 22

Progression of Peanut AllergyProgression of Peanut Allergy

Peanut allergy, like many early food Peanut allergy, like many early food allergies, can be outgrownallergies, can be outgrown

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

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

Only about 9% of patients are reported to Only about 9% of patients are reported to outgrow their allergy to tree nutsoutgrow their allergy to tree nuts33__________________

1Skolnick et al 20012Fleischer et al 20033Fleischer et al 2005 23

Maintaining Tolerance of Maintaining Tolerance of PeanutPeanut

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

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

_________________Fleischer et al 2004

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Take Home MessageTake Home Message Allergy prevention emphasizes inducing Allergy prevention emphasizes inducing

tolerance rather than avoiding tolerance rather than avoiding sensitizationsensitization

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

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

Unless either mother or baby is allergic Unless either mother or baby is allergic to themto them

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Take Home MessageTake Home Message

Exclusive breast-feeding should Exclusive breast-feeding should continue to 4-6 months of agecontinue to 4-6 months of age

Complementary foods (solids) should Complementary foods (solids) should be introduced no later than 6 be introduced no later than 6 months of agemonths of age

Gluten-containing foods should be Gluten-containing foods should be introduced not later than 6 months introduced not later than 6 months of age while breast-feeding of age while breast-feeding continuescontinues

Take Home MessageTake Home Message

Management of established food Management of established food allergy includesallergy includes:: Accurate identification of the Accurate identification of the

allergenic food(s)allergenic food(s) Careful avoidance of the food Careful avoidance of the food

allergens – especially if there is allergens – especially if there is any risk of anaphylaxisany risk of anaphylaxis

Avoidance of unnecessary food Avoidance of unnecessary food restrictionsrestrictions

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Take Home MessageTake Home Message Provision of complete balanced Provision of complete balanced

nutrition by substituting foods of nutrition by substituting foods of equal nutritional valueequal nutritional value

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

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

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Invitation to Further Invitation to Further InformationInformation

www.allergynutrition.com

Joneja, J.M.Vickerstaff Joneja, J.M.Vickerstaff Dealing with Food Dealing with Food Allergies in Babies and ChildrenAllergies in Babies and Children Bull Bull

Publishing Company, Boulder, Colorado. October Publishing Company, Boulder, Colorado. October 20072007