Download - La importancia de la prevención de alergia a los alimentosrespyn2.uanl.mx/especiales/2005/ee-11-2005/documentos/40.pdf · Eczema Allergic Rhinitis Recurrent Asthma Wheezing Secondary

La importancia de la prevención de alergia a los alimentos

Ricardo Sorensen, MDChairman,

Department of PediatricsLSUHSC

Department of Pediatrics

LSUHSC

AllergyAllergy

IgE Mediated

Non-Atopic Atopic

Food allergyAllergic rhinitisAllergic asthma

Single food allergyVenom reactionDrug reaction

Celiac diseaseNARESIgG – mediated

alveolitis

Non-IgE Mediated

EosinophilicgastroenteropathiesAtopic dermatitis

Food hypersensitivity

Non-allergic (non-immune)food hypersensitivity

Food allergy

IgE-mediated food allergy

Non-IgE-mediated food allergy

CLASSIFICATION OF CLINICAL MANIFESTATIONS

CLASSIFICATION OF CLINICAL MANIFESTATIONS

A. Clinical course1. Occasional ingestion ---

Acute manifestations2. Frequent ingestion ---

Chronic symptomsB. Location of symptoms

1. Gastrointestinal2. Gastrointestinal and distal3. Distal manifestations only

A. Clinical course1. Occasional ingestion ---

Acute manifestations2. Frequent ingestion ---

Chronic symptomsB. Location of symptoms

1. Gastrointestinal2. Gastrointestinal and distal3. Distal manifestations only

•Gastrointestinal Manifestations of Food Allergy•Gastrointestinal Manifestations of Food Allergy

IgE Non-IgE Acute Chronicmediated mediated

Perioral + +

Vomit + + + +

Diarrhea + + + +

Abdominal Pain + + + +

•Systemic Manifestations of Food Allergy•Systemic Manifestations of Food Allergy


Anaphylaxis + +

Respiratory Manifestations of Food AllergyRespiratory Manifestations of Food Allergy


Throat tightness + +

Rhinitis + + +

Asthma + + +

Skin Manifestations of Food AllergySkin Manifestations of Food Allergy


Urticaria + + + + +Angioedema + ++ +Atopic dermatitis + + + + + +


Urticaria + + + + +Angioedema + ++ +Atopic dermatitis + + + + + +

Atopic Dermatitis: SignificanceAtopic Dermatitis: Significance

The most common chronic skin disease in children.Atopic dermatitis in the U.S.• Prevalence 10-20% overall†

• Affects 15 million Americans‡

• 17% prevalence by 6 months of age*• 7 million visits per year ‡

Up to 60% of children with severe atopic dermatitis have food hypersensitivity**

The most common chronic skin disease in children.Atopic dermatitis in the U.S.• Prevalence 10-20% overall†

• Affects 15 million Americans‡

• 17% prevalence by 6 months of age*• 7 million visits per year ‡

Up to 60% of children with severe atopic dermatitis have food hypersensitivity**† NIH- HHS Publication No. 03-4272, Rev April 2003‡ CDC Nat Ctr for Health Statistics Vital and Health Statistics Series, 1996, 13:134* Moore MM - Pediatrics - 01-MAR-2004; 113(3 Pt 1): 468-74

** Burkes et al. J Pediatr 1998, 132(1):132-610

† NIH- HHS Publication No. 03-4272, Rev April 2003‡ CDC Nat Ctr for Health Statistics Vital and Health Statistics Series, 1996, 13:134* Moore MM - Pediatrics - 01-MAR-2004; 113(3 Pt 1): 468-74

** Burkes et al. J Pediatr 1998, 132(1):132-610

Trends in Prevalence of Atopic DermatitisTrends in Prevalence of Atopic Dermatitis

0

5

10

15

20

25

1946 1958 1970 1996

% P

reva

lenc

e

0

5

10

15

20

25

1946 1958 1970 1996

% P

reva

lenc

e

*Secular trends in the UKEichenfield et al , 2003 Pediatrics 111: 608-16*Secular trends in the UKEichenfield et al , 2003 Pediatrics 111: 608-16

Atopic Dermatitis and Quality of LifeAtopic Dermatitis and Quality of Life

In infants• Itchiness & Irritability & Altered Sleep• Pain / Colic when associated to GI allergy• Stress associated to treatment• Disruption of family- child interactions

In children• Stress related to treatments• Disruption of daily routine• Sleep deprivation, nighttime scratching during all stages of sleep• Affects school, social interactions, personal relationships, and self-

consciousness

In infants• Itchiness & Irritability & Altered Sleep• Pain / Colic when associated to GI allergy• Stress associated to treatment• Disruption of family- child interactions

In children• Stress related to treatments• Disruption of daily routine• Sleep deprivation, nighttime scratching during all stages of sleep• Affects school, social interactions, personal relationships, and self-

consciousness

Howlett et al. Br J Dermatol 1999;140:381-4. Reuveni et al. Arch Pediatr Adoles Med 1999;153:249-53 Chamlin et al. Pediatrics 2004; 114(3); 607-11

Howlett et al. Br J Dermatol 1999;140:381-4. Reuveni et al. Arch Pediatr Adoles Med 1999;153:249-53 Chamlin et al. Pediatrics 2004; 114(3); 607-11

Increasing Prevalence of Asthma & Atopy

Increasing Prevalence of Asthma & Atopy

0

5

10

15

Eczema Hayfever Asthma

% P

reva

lenc

e (C

hild

ren

8-13

yrs

.)

1964 1989

0

5

10

15

Eczema Hayfever Asthma

% P

reva

lenc

e (C

hild

ren

8-13

yrs

.)

1964 1989

Ninan et al., 1992; BMJ 304: 873-75Ninan et al., 1992; BMJ 304: 873-75

Atopic Dermatitis: SignificanceAtopic Dermatitis: Significance

May be the first step in the Allergy March:the relationship between allergic manifestations throughout life

• Approximately 75- 80% of atopic dermatitis patients develop allergic rhinitis

• More than 50% of atopic dermatitis patients develop asthma

May be the first step in the Allergy March:the relationship between allergic manifestations throughout life

• Approximately 75- 80% of atopic dermatitis patients develop allergic rhinitis

• More than 50% of atopic dermatitis patients develop asthma

Leung DY - J Allergy Clin Immunol - 01-DEC-2003; 112(6 Suppl): S117Spergel J Allergy Clin Immunology 2003; 112 (6 Suppl): S 118-27Leung DY - J Allergy Clin Immunol - 01-DEC-2003; 112(6 Suppl): S117Spergel J Allergy Clin Immunology 2003; 112 (6 Suppl): S 118-27

Prevalence of Allergic Manifestations by AgePrevalence of Allergic Manifestations by Age

Adapted from Saarinen, 1995; Lancet. 346: 1065-69

0

10

20

30

40

1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Years

0

10

20

30

40

1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Years

SkinSkin

RespiratoryRespiratory

GIGI

Pathogenesis of Childhood AsthmaPathogenesis of Childhood AsthmaPathogenesis of Childhood Asthma

Genetics

Environ-ment

Age + Allergens

Tolerance

SensitizationFood allergyEczema

AllergicRhinitis

AsthmaRecurrentWheezing

Immunologic SensitizationImmunologic Sensitization

Immunologic sensitizationImmunologic sensitization

Re-exposure to sensitizing proteinRe-exposure to sensitizing protein

Manifestations of allergySigns and symptoms in target organs

Skin, GI, Lungs

Manifestations of allergySigns and symptoms in target organs

Skin, GI, Lungs

Food Allergies: 90% accounted for by 5 foodsFood Allergies: 90% accounted for by 5 foods

5 most common allergens in infants

Other

• Cow Milk• Soy• Wheat• Peanuts/Tree nuts• Egg

Cow milk protein: • the most common food antigen in infants• the most common protein used in infant formulas

Food Allergy — TreatmentFood Allergy — Treatment

Avoidance• Meticulous attention to labels• Education on sources of “hidden foods”

Extensive hydrolysate (hypoallergenic) formulasAmino acid formulas

Avoidance• Meticulous attention to labels• Education on sources of “hidden foods”

Extensive hydrolysate (hypoallergenic) formulasAmino acid formulas

Preventing Pediatric AllergyPreventing Pediatric Allergy

Allergy, particularly atopic dermatitis, is a significant health issue • High incidence in developed countries• Increasing incidence and prevalence• High costs of treatment• Impact on quality of life• Allergy March may greatly magnify the problem

Allergy, particularly atopic dermatitis, is a significant health issue • High incidence in developed countries• Increasing incidence and prevalence• High costs of treatment• Impact on quality of life• Allergy March may greatly magnify the problem

Primary Prevention is a PriorityPrimary Prevention is a Priority


Genetics

Environ-ment

Age + Allergens

Tolerance


AllergicRhinitis


EarlyIntervention


Genetics

Environ-ment

Age + Allergens

Tolerance


AllergicRhinitis


SecondaryPrevention


Genetics

Environ-ment

Age + Allergens

Tolerance


AllergicRhinitis


PrimaryPrevention

The StandardThe Standard

Nutritionally

Immunologically

Nutritionally

Immunologically

Historically, formulas have evolved to make cow’s milk nutritionally and functionally closer to human milk

Processed Whole

Cows Milk

Raw Cow Milk

“Formula”with Evaporated

Cow Milk

“Casein Predominant”

Formula

“WheyPredominant”

Formula

Protein size and AllergenicityProtein size and Allergenicity

High Molecular WeightHigh Molecular Weight Low Molecular WeightLow Molecular Weight

Potential for Hypersensitivity (Allergic Reaction)Potential for Hypersensitivity (Allergic Reaction)

Immune SystemImmune System

Hydrolysis Can Reduce Allergenicityof Cow Milk Proteins

Hydrolysis Can Reduce Allergenicityof Cow Milk Proteins

Median Molecular Weight of Infant FormulasMedian Molecular Weight of Infant Formulas

450 1,100

10,000

0

2,000

4,000

6,000

8,000

10,000

12,000

ExtensivelyHydrolyzed Casein

PartiallyHydrolyzed Whey

Whole ProteinCasein/Whey

Dalto

ns

Cumulative Incidence of Atopic Manifestations

Extensively Hydrolyzed Casein Formula vs Cow Milk Formula in Prevention Studies



p=0.025p=0.025

p<0.02p<0.02

p=0.032p=0.032p=NSp=NS

0

20

40

60

80

Von Berg 2003 Oldaeus 1997 Zeiger 1995 Mallet 1992

Cum

ulat

ive In

ciden

ce o

f AM

(%)

Extensively Hydrolyzed CaseinIntact Cow Milk

* Graph depicts only published, peer-reviewed, prospective trials. Studies up to 12 mo of Age ** For all extensively hydrolyzed casein formula studies, AM includes AD as one of the allergic outcomes assessed.*** 9 months: Oldaeus 1997; 12 months: Von Berg 2003, Zeiger 1995, Mallet 1992

Cumulative Incidence of Atopic Dermatitis




p=0.006p=0.006

p=0.007p=0.007p=NSp=NS

p=0.059p=0.059

p<0.005p<0.005

0

20

40

60

80

Von Berg2003

Oldaeus 1997 Zeiger 1995 Mallet 1992 Chandra1989

Cum

ulat

ive In

ciden

ce o

f AD

(%)

Extensively Hydrolyzed CaseinIntact Cow Milk

* Graph depicts only published, peer-reviewed, prospective trials. ** 9 months: Oldaeus 1997; 12 months: Von Berg 2003, Zeiger 1995, Mallet 1992; 18 months: Chandra 1989* Graph depicts only published, peer-reviewed, prospective trials.

** 9 months: Oldaeus 1997; 12 months: Von Berg 2003, Zeiger 1995, Mallet 1992; 18 months: Chandra 1989


Partially Hydrolyzed Whey Formula vs Cow Milk Formula in Prevention Studies



p=0.109p=0.109

p<0.05p<0.05

p<0.05p<0.05

p<0.05p<0.05

p=0.021p=0.021

p=NSp=NS p<0.001p<0.001

p=0.063p=0.063

p<0.05p<0.05

0

20

40

60

80

Becker 2004 Von Berg2003

Exl 2000 Chandra1997

Marini 1996 Vandenplas1995

de Seta 1994 Willems1993

Vandenplas1988

Cum

ulat

ive In

ciden

ce o

f AM

(%)

Partially Hydrolyzed WheyIntact Cow Milk

* Graph depicts only published, peer-reviewed, prospective trials with data collection at timepoints ≤12 months. ** For all studies except Becker 2004, AM includes AD as one of the allergic outcomes assessed; for Becker 2004, AM refers to asthma alone.

*** 4 months: Vandenplas 1988; 6 months: Exl 2000, De Seta 1994; 12 months: Becker 2004, Von Berg 2003, Chandra 1997, Marini 1996, Vandenplas 1995, Willems 1993

**** p-values in italics indicate that no p-value is reported in publication; p-value is based on calculated OR and CI

* Graph depicts only published, peer-reviewed, prospective trials with data collection at timepoints ≤12 months. ** For all studies except Becker 2004, AM includes AD as one of the allergic outcomes assessed; for Becker 2004, AM refers to asthma alone.

*** 4 months: Vandenplas 1988; 6 months: Exl 2000, De Seta 1994; 12 months: Becker 2004, Von Berg 2003, Chandra 1997, Marini 1996, Vandenplas 1995, Willems 1993

**** p-values in italics indicate that no p-value is reported in publication; p-value is based on calculated OR and CI





p=0.048p=0.048

p=0.004p=0.004

p<0.05p<0.05

p<0.02p<0.02p=NSp=NS p<0.05p<0.05

p>0.05p>0.05

p>0.05p>0.05

0.0

20.0

40.0

60.0

Von Berg2003

Chan 2002 Exl 2000 Chandra 1997 Marini 1996 Vandenplas1995

Tsai 1991 Vandenplas1988

Cum

ulat

ive In

ciden

ce o

f AD

(%)

Partially Hydrolyzed WheyIntact Cow Milk

* Graph depicts only published, peer-reviewed, prospective trials with data collection at timepoints ≤12 months. ** 4 months: Vandenplas 1988; 6 months: Exl 2000; 12 months: Von Berg 2003, Chandra 1997, Marini 1996, Vandenplas 1995, Tsai 1991

**** p-values in italics indicate that no p-value is reported in publication; p-value is based on calculated OR and CI****

* Graph depicts only published, peer-reviewed, prospective trials with data collection at timepoints ≤12 months. ** 4 months: Vandenplas 1988; 6 months: Exl 2000; 12 months: Von Berg 2003, Chandra 1997, Marini 1996, Vandenplas 1995, Tsai 1991

p-values in italics indicate that no p-value is reported in publication; p-value is based on calculated OR and CI

Effect of Hydrolyzed Cow Milk Formulafor Allergy Prevention the First Year of Life

The German Infant Nutritional Intervention (GINI) Study



Independent, government-sponsored study2,252 high-risk infants randomized at birth to: • Intact cow milk formula• Partially hydrolyzed whey formula• Extensively hydrolyzed casein formula• Extensively hydrolyzed whey formula

As needed, randomized formula was given to 6 months of age (no other foods besides breast milk)Allergic manifestations assessed at 1, 4, 8,12 mo• Atopic dermatitis• Allergic urticaria• Food allergy with manifestation in the GI tract

Independent, government-sponsored study2,252 high-risk infants randomized at birth to: • Intact cow milk formula• Partially hydrolyzed whey formula• Extensively hydrolyzed casein formula• Extensively hydrolyzed whey formula

As needed, randomized formula was given to 6 months of age (no other foods besides breast milk)Allergic manifestations assessed at 1, 4, 8,12 mo• Atopic dermatitis• Allergic urticaria• Food allergy with manifestation in the GI tract

Von Berg et al., 2003 J Allergy Clin Immunol 111(3): 533-40Von Berg et al., 2003 J Allergy Clin Immunol 111(3): 533-40





2,252 infants enrolled in the study:• 889 exclusively breastfed to 4 mo• 945 infants included in per protocol • 418 infants either non-compliant or drop-outs

• Extensively hydrolyzed casein had significantly higher number of non-compliant subjects than other formula groups (p=0.02)

Incidence of allergic manifestation at 12 months was 13%• 89% of all allergic manifestation was atopic dermatitis

12 month results published, 3-year publication pending, 6-year follow-up planned

2,252 infants enrolled in the study:• 889 exclusively breastfed to 4 mo• 945 infants included in per protocol • 418 infants either non-compliant or drop-outs

• Extensively hydrolyzed casein had significantly higher number of non-compliant subjects than other formula groups (p=0.02)

Incidence of allergic manifestation at 12 months was 13%• 89% of all allergic manifestation was atopic dermatitis

12 month results published, 3-year publication pending, 6-year follow-up planned

Von Berg et al., 2003 J Allergy Clin Immunol 111(3): 533-40Von Berg et al., 2003 J Allergy Clin Immunol 111(3): 533-40



3 Yr. GINI study : Findings not published. Results presented at ESPACI Meeting, 2003

0

5

10

15

20

25

Birth 12mo 24mo 36mo

Intact Cow MilkPartially Hydrolyzed WheyExtensively Hydrolyzed WheyExtensively Hydrolyzed Casein

Odds Ratio — Allergic ManifestationsExtensively Hydrolyzed Casein vs. Intact Cow Milk

Odds Ratio — Allergic ManifestationsExtensively Hydrolyzed Casein vs. Intact Cow Milk

Mallet 1992Mallet 1992

Von Berg 2003Von Berg 2003

Zeiger 1995Zeiger 1995

Oldaeus 1997Oldaeus 1997

0 0.5 1 1.5 2

* Published, peer-reviewed, prospective trials with data collection at timepoints ≤12 months. OR and CI shown in yellow are published values; OR in white and CI in yellow, dashed lines are calculated values.

** 9 months: Oldaeus 1997; 12 months: Von Berg 2003, Zeiger 1995, Mallet 1992

* Published, peer-reviewed, prospective trials with data collection at timepoints ≤12 months. OR and CI shown in yellow are published values; OR in white and CI in yellow, dashed lines are calculated values.


Odds Ratio — Atopic Dermatitis Extensively Hydrolyzed Casein vs. Intact Cow MilkOdds Ratio — Atopic Dermatitis

Extensively Hydrolyzed Casein vs. Intact Cow Milk

0 0.5 1 1.5 2

Mallet 1992Mallet 1992


Zeiger 1995Zeiger 1995

Oldaeus 1997Oldaeus 1997

Chandra 1989 ‡Chandra 1989 ‡

Osborn meta-analysis2003

Osborn meta-analysis2003

* Published, peer-reviewed, prospective trials with data collection at timepoints ≤12 months. OR and CI shown in black are published values; OR in white and CI in yellow, dashed lines are calculated values.


‡ Included in Osborn 2003

* Published, peer-reviewed, prospective trials with data collection at timepoints ≤12 months. OR and CI shown in black are published values; OR in white and CI in yellow, dashed lines are calculated values.



Odds Ratio — Allergic ManifestationsPartially Hydrolyzed Whey vs. Intact Cow Milk

Odds Ratio — Allergic ManifestationsPartially Hydrolyzed Whey vs. Intact Cow Milk

0 0.5 1 1.5 2

Chandra 1997 ‡Chandra 1997 ‡Exl 2000Exl 2000Von Berg 2003Von Berg 2003

Willems 1993 ‡Willems 1993 ‡

Vandenplas 1988 Vandenplas 1988

Vandenplas 1995 ‡Vandenplas 1995 ‡

Osborn meta-analysis 2003Osborn meta-analysis 2003

Marini 1996 Marini 1996

De Seta 1994 ‡De Seta 1994 ‡

* Graph depicts only published, peer-reviewed, prospective trials with data collection at timepoints ≤12 months. OR and CI shown in yellow are published values; OR in white and CI in yellow, dashed lines are calculated values.

** 4 months: Vandenplas 1988; 6 months: Exl 2000, De Seta 1994; 12 months: Von Berg 2003, Chandra 1997, Marini 1996,Vandenplas 1995, Willems 1993





Odds Ratio — Atopic DermatitisPartially Hydrolyzed Whey vs. Intact Cow Milk

Odds Ratio — Atopic DermatitisPartially Hydrolyzed Whey vs. Intact Cow Milk

0 0.5 1 1.5 2

Chandra 1997 ‡Chandra 1997 ‡Exl 2000Exl 2000


Tsai 1991‡Tsai 1991‡

Vandenplas 1988 Vandenplas 1988

Vandenplas 1995Vandenplas 1995

Osborn meta-analysis 2003Osborn meta-analysis 2003

Marini 1996 Marini 1996

De Seta 1994 ‡De Seta 1994 ‡

Chan 2002Chan 2002







Meta-Analysis: Formulas containingHydrolysed Protein for Prevention of Allergy

Osborn & Sinn, 2003 - The Cochrane Library

Meta-Analysis: Formulas containingHydrolysed Protein for Prevention of Allergy

Osborn & Sinn, 2003 - The Cochrane Library

Inclusion criteria• Randomized trials comparing use of hydrolyzed infant formula to

human milk or intact cow milk formula• ≥ 80% follow-up of subjects• 18 / 72 studies were eligible for inclusion

Main results• Prolonged feeding of hydrolyzed formula (PHF and EHF combined)

significantly reduced:• Allergy, eczema, cow’s milk allergy incidence in infancy• Asthma, food allergy prevalence in childhood

• No significant difference between PHF and EHF

Inclusion criteria• Randomized trials comparing use of hydrolyzed infant formula to

human milk or intact cow milk formula• ≥ 80% follow-up of subjects• 18 / 72 studies were eligible for inclusion

Main results• Prolonged feeding of hydrolyzed formula (PHF and EHF combined)

significantly reduced:• Allergy, eczema, cow’s milk allergy incidence in infancy• Asthma, food allergy prevalence in childhood

• No significant difference between PHF and EHF


Most studies done in high risk infants• No adequate standard public health mechanism to identify

infants at risk by family history• More than half of infants who develop allergies can not be

identified by family historyAcceptable cost effective strategies are needed for the general population

Most studies done in high risk infants• No adequate standard public health mechanism to identify

infants at risk by family history• More than half of infants who develop allergies can not be

identified by family historyAcceptable cost effective strategies are needed for the general population

Prevalence of atopic disease based on parental history

Prevalence of Parental Atopic History: 64% No Parental Hx 31% Uniparental 5% Biparental

Prevalence of Atopic Disease Total: 17.6% 9.6% 6.4% 1.6%

(10-15%) (20-30%) (30-40%)

Other refs: Halken S et al. Allergy 2000;55: 793-802Bousquet J. et al. J Allergy Clin Immunol 1986;78: 1019-1022;

Kjellman N. et al. Acta Paediatr Scan 1977;66: 565-71Exl BM, Nutr Res 2001;21: 355-79

Bergman, et al. Clinical and Experimental Allergy 1998; 28:905-907

Prevalence of Parental Atopic History: 64% 31% 5%

Prevalence of Atopic Disease in German Infants (total 17.6%):9.6% 6.4% 1.6%

For those who have a family history, there is no mandatory, standardized nor validated mechanism or tool to

elicit parental history

> 50% of children who develop allergy do not have a family history

Most Infants at risk for atopy go unidentified


Needed Strategy

Primary prevention measures applicable for the general population

Needed Strategy

Primary prevention measures applicable for the general population

RECOMMENDATIONS TO DECREASE THE ALLERGIC MARCH APPLICABLE TO ALL CHILDREN

RECOMMENDATIONS TO DECREASE THE ALLERGIC MARCH APPLICABLE TO ALL CHILDREN

• Breastfeeding, 4-12 months If supplements are needed: hydrolysate with proven efficacy No solids before 4 months of age No contact with tobacco smoke

Adapted from Yvan Vandenplas/ 4/03

• Breastfeeding, 4-12 months If supplements are needed: hydrolysate with proven efficacy No solids before 4 months of age No contact with tobacco smoke

Adapted from Yvan Vandenplas/ 4/03

Gracias por su atenciónGracias por su atención

Download - La importancia de la prevención de alergia a los alimentosrespyn2.uanl.mx/especiales/2005/ee-11-2005/documentos/40.pdf · Eczema Allergic Rhinitis Recurrent Asthma Wheezing Secondary

Top Related