Pediatric Allergy

Pediatric Allergy Prevention and Management

Change in Direction During the Past Three Years • Understanding of the importance of immunological sensitization and tolerance • Recognition that tolerance not sensitization is the critical step in allergy prevention • Finding that exposure to the allergenic food at the optimum age is probably a critical step in allergy prevention • Recognition that tolerance can be induced after allergy has been established – leading to important measures for allergy management

Prevention of Food Allergy in Clinical Practice Significant change in directives within the past 3 years: • Previously: Avoidance of allergen to prevent sensitization (allergen-specific IgE) • Current: Active stimulation of the immature immune system to induce tolerance of the antigens in food ________________ Rautava et al 2005

Diet During Pregnancy • Current directive: the atopic mother should strictly avoid her own allergens and replace the foods with nutritionally equivalent substitutes • There are no indications for mother to avoid other foods during pregnancy • A nutritionally complete, well-balanced diet is essential • Authorities recommend avoidance of excessive intake of highly allergenic foods such as peanuts and nuts to prevent “allergen overload”, but there is no scientific data to support this _______________ Kramer et al 2006

Implications of Research Data • Exclusive breast-feeding with exclusion of mother’s and baby’s allergens will reduce signs of allergy in the first 1-2 years • Reduction or prevention of early food allergy by breast-feeding does not seem to have long-term effects on the development of asthma and allergic rhinitis • Other benefits of breast-feeding far outweigh any possible negative effects on allergy: exclusive breast-feeding for 4-6 months is strongly encouraged

Summary of 2008 AAP Guidelines for Allergy Management [Greer et al 2008] • There is no convincing evidence that women who avoid highly allergenic foods, or other foods during pregnancy and breast-feeding lower their child’s risk of allergies • For high-risk for allergy infants (one first-degree relative with established allergy), exclusive breast-feeding for at least 4 months prevents or delays the occurrence of atopic dermatitis (eczema), cow’s milk allergy, and wheezing in early childhood • There is a lack of evidence that exclusive breast-feeding has any positive effect on the development of asthma in older children _____________ Greer et al 2008 ____________________ Sicherer and Burks 2008

Summary of 2008 AAP Guidelines continued • In infants at high risk for allergy who are not exclusively breast-fed for 4-6 months there is modest evidence that the onset of atopic disease (allergy), especially eczema, may be delayed or prevented by the use of hydrolyzed formulas • Extensively hydrolyzed formulas have a greater protective effect than partially hydrolyzed formulas

Summary of 2008 AAP Guidelines continued • There is no good evidence that soy-based infant formulas have any preventive effect on the development of allergy • There is little evidence that delaying the timing of the introduction of solid foods beyond 4-6 months of age prevents the occurrence of allergy _____________________ Thygaran and Burks 2008

Infant Formulae for the Allergic BabyCurrent Recommendations • Modest evidence that allergy may be delayed or prevented by the use of hydrolyzed formulas compared with formula of intact cow’s milk proteins • Cow’s milk based formula if there are no signs of milk allergy • Partially hydrolysed (phf) whey-based formula if there are no signs of milk allergy • Extensively hydrolysed (ehf) casein based formula if milk allergy is proven _________________ Greer et al AAP 2008 Von Berg et al 2007

Recommendations for Introduction of Solids to High Risk for Allergy Infants • Little evidence that delaying the introduction of complementary foods beyond 4-6 months of age prevents allergy • Introduction of solid foods should be individualized • Foods should be introduced one at a time in small amounts • Mixed foods containing various potential food allergens should not be given unless tolerance to each ingredient has been assessed __________________ Greer et al AAP 2008 ___________________________________ European Food Safety Authority EFSA 2009

Introduction of Solid Foods in Relationship to Celiac Disease • Results suggest that in high risk for celiac disease infants introduction of gluten-containing grains before 3 months or after 7 months increases incidences of development of CD1 • Introduction of gluten while breast-feeding offers protection or delays onset of celiac disease in at-risk infants2 • Recommendations: • Introduce gluten grains in small amounts between 4 and 6 months while infant is breastfed • Continue breast-feeding for a further 2-3 months _______________ 1Norris et al 2005 _____________ 2Guandalini 2007

Introduction of Peanuts • Directives from pediatric societies (1998 - 2007) recommended avoidance of peanuts by mothers during pregnancy and lactation, and delaying introduction of peanuts until after 2 or even 3 years of age • Research indicates that incidence of peanut allergy in children rose dramatically in the years following release of these directives • Recent research suggests: • Avoidance of peanuts reduced development of tolerance • Early exposure leads to reduced incidence of peanut allergy _________________ Hourihane et al 2007

Introduction of Peanuts Study (n=10,786) among primary school age Jewish children in UK and Israel • Prevalence of peanut allergy (PA): • In UK: 1.85% • In Israel: 0.17% • Median monthly consumption of peanut in infants aged 8 – 14 months: • In UK: 0 • In Israel: 7.1 g • Difference not due to atopy, genetic background, social class, or peanut allergenicity • Israeli infants consume peanuts in high quantities during the first year of life ______________ Du Toit et al 2008

Introduction of Fish • Historically, fish consumption during infancy was considered to be a risk factor for allergy • Recent research indicates otherwise: • Regular fish consumption during the first year of life associated with a reduced risk for allergic disease by age 4 years (n=4089)1 • Babies of mothers who frequently consumed fish (2-3 times per week or more) during pregnancy had one third less food sensitivities than those whose mothers did not consume fish during pregnancy2 _____________ 1Kull et al 2006 _______________ 2Calvani et al 2006

Introduction of Fish Study (n= 5,000); 20.9% developed eczema by 1 year: • Babies who were fed fish before nine months of age were 24% less likely to develop eczema by age 1 year • Omega-3 content of fish did not seem to influence the outcome • The age at which egg and milk were introduced did not affect development of eczema • Breast-feeding did not have any significant impact on development of eczema ____________ Alm et al 2009

The Natural History of Food Allergy • Food allergy most often begins in the first 1 to 2 years of life • Child is sensitized to the food protein by the immune system developing allergen-specific IgE to that protein • Sensitization does not necessarily mean that the child will develop symptoms when that food is eaten • Over time most food allergy is lost _________ Wood 2003

Development of Tolerance • 25% of infants lost all food allergy symptoms after 1 year of age • Most infants will outgrow milk allergy by 3 years of age, but may become intolerant to other foods • Tolerance of specific foods : After 1 year: • 26% decrease in allergy to: • Milk Soy  Peanut • Egg  Wheat • 2% decrease in allergy to other foods

Prognosis Age at which milk was tolerated by milk-allergic children: • 28% by 2 years of age • 56% by 4 years of age • 78% by 6 years of age • About 25% of food allergic children develop respiratory allergies • Allergy to some foods more often than others persists into adulthood: • Peanut Tree nuts Seeds • Shellfish Fish

University of Portsmouth UK • Milk allergy outgrown: • ¾ by 3 years • Egg allergy outgrown: • ½ by 3 years • Of 272 allergic babies, only 60 (22%) were allergic at age 3 years • In these the most common allergies were: • Peanuts (11) • Eggs (9) • Milk (4) • Wheat, Brazil nut; Almond (2 each) • Hazelnut, Cashew, Corn (1 each) • None were allergic to tomato or fish at age 3 years _____________ Savage et al 2007

Induction of Oral Tolerance • Tolerance to a specific food can be induced by oral administration of the offending food by process of “low dose continuous exposure” • Designated (SOTI: specific oral tolerance induction) • Starting with very low dosages • Gradually increasing daily dosage up to the equivalent of the usual daily intake • Followed by daily maintenance dose __________________ Niggemann et al 2006

Desensitization to Cow’s Milk • 18 children with confirmed CMA >4 years of age underwent SOTI • Starting dose 0.05 ml cow’s milk • Increased to 1 ml on first day • Increasing dosage weekly up to a daily dose of 200-250 ml • Results: 16/18 tolerated 200-250 ml milk • Length of process median 14 weeks (range 11-17 weeks) • Tolerance has been maintained for >1 year _______________ Zapatero et al 2008

Oral Tolerance Induction to Milk, Egg, and Peanut • 36% of children with IgE-mediated allergy to cow’s milk and hen’s egg developed permanent tolerance of the foods after a median 21 months specific oral tolerance induction (SOTI)1 • 4 peanut-allergic children underwent SOTI: • Daily doses of peanut flour starting at 5 mg peanut protein • 2-weekly dosage increase up to 800 mg protein • All subjects tolerated at least 10 whole peanuts (2.38 g protein) on post-intervention challenge2 ______________ 1Staden et al 2007 ____________ 2Clark et al 2009

Progression of Peanut Allergy • Peanut allergy, like many early food allergies, can be outgrown • In 2001 pediatric allergists in the U.S. reported that about 21.5 per cent of children will eventually outgrow their peanut allergy1 • Those with a mild peanut allergy, as determined by the level of peanut-specific IgE in their blood, have a 50% chance of outgrowing the allergy2 • Only about 9% of patients are reported to outgrow their allergy to tree nuts3 __________________ 1Skolnick et al 2001 2Fleischer et al 2003 3Fleischer et al 2005

Maintaining Tolerance of Peanut • When there is no longer any evidence of symptoms developing after a child has consumed peanuts, it is preferable for that child to eat peanuts regularly, rather than avoid them, in order to maintain tolerance to the peanut • Children who outgrow peanut allergy are at risk for recurrence, but the risk has been shown to be significantly higher for those who continue to avoid peanuts after resolution of their symptoms _________________ Fleischer et al 2004

Take Home Message • Allergy prevention emphasizes inducing tolerance rather than avoiding sensitization • Beginning of tolerance to foods may occur in utero or during breast-feeding • Restriction of maternal diet to avoid highly allergenic foods during pregnancy or lactation is contraindicated • Unless either mother or baby is allergic to them

Take Home Message • Exclusive breast-feeding should continue to 4-6 months of age • Complementary foods (solids) should be introduced no later than 6 months of age • Gluten-containing foods should be introduced not later than 6 months of age while breast-feeding continues

Take Home Message • Management of established food allergy includes: • Accurate identification of the allergenic food(s) • Careful avoidance of the food allergens – especially if there is any risk of anaphylaxis • Avoidance of unnecessary food restrictions

Take Home Message • Provision of complete balanced nutrition by substituting foods of equal nutritional value • Monitoring the child’s response at intervals to determine when the food allergy has been outgrown • Maintenance of tolerance by feeding tolerated foods regularly

Invitation to Further Information www.allergynutrition.com Joneja, J.M.Vickerstaff Dealing with Food Allergies in Babies and Children Bull Publishing Company, Boulder, Colorado. October 2007

Pediatric Allergy