peanut allergy 2009

Narissara Suratannon,MD.Narissara Suratannon,MD.

OutlineOutline Epidermiology in western and eastern countriesEpidermiology in western and eastern countries

Cross reactivity of peanut among other legumes and tree nutCross reactivity of peanut among other legumes and tree nut

How roasting peanuts increase their allergenicityHow roasting peanuts increase their allergenicity

Diagnosis of peanut allergyDiagnosis of peanut allergy

Natural history of peanut allergyNatural history of peanut allergy

Factors associated developing of peanut allergyFactors associated developing of peanut allergy

New treatment of peanut allergy New treatment of peanut allergy

IntroductionIntroduction Food allergy is the leading cause of anaphylaxis in West

ern Europe and USA

In USA , food allergy accounts for :- 30,000 anaphylactic reactions- 2000 hospital admissions - 200 deaths

Peanuts and treenuts are the vast majority of life-threatening or fatal reactions to food

A.Wesley Burks.Lancet 2008; 371: 1538–46

EpidermiologyEpidermiology 2-4 fold increasing

Prevalence of sensitisation - In UK rose from 1.3 % to 3.2% [1989 and 1995] (Grundy.JACI 2002) - In US 8.6% [1988 – 1994] (Arbes JACI 2005)

Prevalence of clinical reactions- 0.5 to 1.0% in UK (Grundy.JACI 2002)

- 0.4 to 0.8% in US [1997-2002] (Sicherer.JACI 2003)

- 1.34% in Canada (Kagan JACI 2003)

- 1.9% in Australia ()

A.Wesley Burks.JACI 2009; 123 (2): 424–5

Parent-reported adverse food reactions in Hong Kong Chinese pre-schoolParent-reported adverse food reactions in Hong Kong Chinese pre-schoolers:epidemiology, clinical spectrum and risk factorsers:epidemiology, clinical spectrum and risk factors

Leung et al.Ped AI2009: 20: 339–346.

Chieng et al.Clinical and Experimental Allergy 2007:37:1055–61

LegumesLegumes

Bean

Pea

Lentil

Peanut

Lupine

LegumesLegumes

• Multiple sensitization appeared to be the rule

• Barnett et al screened sera from 40 patients with peanut allergy against 10 other legumes and demonstrated IgE binding to multiple legumes for 38% of patients (JACI1987;79:433-8)

• However, - clinical cross reactions are uncommonScott H. Sicherer,JACI 2001;108:881-90

Cros-allergenicity in the legume botanical family in Cros-allergenicity in the legume botanical family in children with food hypersensitivitychildren with food hypersensitivityJan Bernhisel-Broadbent, MD, and Huge A. Sampson, MDJan Bernhisel-Broadbent, MD, and Huge A. Sampson, MD

JACI 1989;83:435-40

• 82/186 (44%):

>= 1 positive SPT

• Clinical cross-

reaction:unlikely

to occur

• mild reactions

Clinical Cross-Reactions in Legume FamilyClinical Cross-Reactions in Legume Family

• Regional dietary habits may influence the epidemiology of legume allergy

• M ultiple legume allergy may occur on those who reacting to lupine,lentil, chickpea

• In France, 1 1 (4 4 %) of 2 4 had p ositive

skin test to lupine, and 7 of 8 subjects had positive oral challenge tests (Vautrin et al.JACI 1999;104:883-8)

Scott H. Sicherer,JACI 2001;108:881-90

Clinical Cross-Reactions in Legume FamilyClinical Cross-Reactions in Legume Family

However, in Italy; However, in Italy; lupine-enriched pasta can be tolerated by most subjects suffering from peanut allergy, only 2/12 children had 2/12 children had positive reactions positive reactions (Fiocchi et al.Clin Exp Aller 2009;article in press)

In Spain, 6/22 children with lent il allergy had reactions to chic

kpea,2/22 to other peas , and1/22 to green bean (Pascual et al.JACI 1999;103:154-8)

Co-allergy between peanut and tree nutCo-allergy between peanut and tree nut

• Isolated peanut allergy 3482 registrants(68%) • Isolated tree nut allergy by 464 (9%)• Allergy to both foods by 1203 (23%)

JACI 2001;108:128-32

JACI 2001;107:367-74

Prophylactically avoid tree nutsShould we recommend?

Varying results causing by different populations, Varying results causing by different populations, types of diagnosis types of diagnosis

No studies that document the reaction rate using No studies that document the reaction rate using blinded oral food challenges blinded oral food challenges

Complete avoidance of tree nuts was recommend Complete avoidance of tree nuts was recommend except one that were previously toleratedexcept one that were previously tolerated

Sicherer et al.JACI 2001;108:128-32

Reasons for Recommendation

Concerning that TN sensitivity appears to be severe and long-lived

The potential for cross contamination

It is often difficult to identify specific nuts in various processed foods

Sicherer et al.JACI 2001;108:128-32

Peanut Allergens

F ood allergens are- - 1070glycoproteins,

kd- wwwww-wwwwwww - resistant to heat, acid, an

d proteolysis which enablww wwww ww wwwwwwwww GI tract

Laurie A. Lee, A. Wesley Burks.Frontiers in Bioscience 2009; 14, 3361-71, Table from Middleton 7’th edition

Maillard reaction

JACI 2000;106:763-8

(MRPs)

JACI 2000;106:763-8 JACI 2001;107:1077-81

Clin Exp Aller.2000:30; 1540- 46

Clin Exp Aller.2000:30; 1540- 46

PatientPatient Pt. under 16 yr. who was Pt. under 16 yr. who was suspected FA (n=121) and from suspected FA (n=121) and from ALSPAC study who SPT +veALSPAC study who SPT +ve (n=40)(n=40)

InterventionIntervention What size of skin prick test and What size of skin prick test and which levels of specific IgE that which levels of specific IgE that will be correlate with oral will be correlate with oral challenge test challenge test

CompareCompare No compare groupNo compare groupOutcomeOutcome Wheal size >= 8 mm or >= 15 Wheal size >= 8 mm or >= 15

kUA/L of specific IgE was correlate kUA/L of specific IgE was correlate with positive oral challenge test of with positive oral challenge test of peanut allergypeanut allergy

Roberts et al.JACI2005;115:1291-6

PPV = 94.4%, S pecificity = 985. %, NPV = 573. % , sensitivity = 2 5 .4 %.

Roberts et al.JACI2005;115:1291-6

PPV of a specific IgE of 15-kUA/L = 91.3% Specificity = 96.8% , NPV = 53.0% , Sensitivity = 28.4%

Roberts et al.JACI2005;115:1291-6

Predictors for severe diseasesPredictors for severe diseases Broad epitope diversity (Median =9.5) tend to Broad epitope diversity (Median =9.5) tend to

more severe allergic reactions than who have more severe allergic reactions than who have few epitopes binding (Median =2) few epitopes binding (Median =2)

Shreffler et al.JACI 2004;113:776-82

Natural HistoryNatural History Mostly IgE-mediated reactions The mean age of diagnosis : - 1418months Symptoms occur following the first known peanut i

ngestion in 75% of wwwww wwwwwwww Almost always permanent

- Incidence in children = adults at the similar rate (Sicherer JACI 1999 from US digital phone survey)

- After 10 years pass, study groups still could not tolerate peanut (Bock and Atkins JACI 1989)

However, a subset of young peanut-allergic children (20%) indeed outgrows allergy

Laurie A. Lee, A. Wesley Burks.Frontiers in Bioscience 2009; 14, 3361-71David Fleischer.Current Allergy and Asth Reports 2007:7;175-81

JACI 2008;121:731-6

PatientPatient Children under 2 years who had Children under 2 years who had peanut allergy ; non-remitters (n= peanut allergy ; non-remitters (n= 218)218)

InterventionIntervention Find out what are predictors of Find out what are predictors of remission (clinical, lab tests)remission (clinical, lab tests)

CompareCompare Remitters (n=49)Remitters (n=49)

OutcomeOutcome Skin prick test >= 6 mm and Skin prick test >= 6 mm and specific IgE to peanut >= 3 kUA/L specific IgE to peanut >= 3 kUA/L before 2 years of age are predictors before 2 years of age are predictors of persistent peanut allergyof persistent peanut allergy

JACI 2008;121:731-6

Recurrent Peanut AllergyRecurrent Peanut Allergy

Estimated recurrent rates 7.9% Estimated recurrent rates 7.9% Risk : Consumed peanut infrequentlyRisk : Consumed peanut infrequently Recommendation : Foods should be consumed regularly Recommendation : Foods should be consumed regularly

and continue to carry a SIE until demenstrated persist and continue to carry a SIE until demenstrated persist tolerance for 1 or 2 yr.tolerance for 1 or 2 yr.

However, it is hard..However, it is hard.. Nearly half of outgrown patients : limited intake to products that Nearly half of outgrown patients : limited intake to products that

“may contain peanut”“may contain peanut” To incorporate peanut into their diet after years of strict To incorporate peanut into their diet after years of strict

avoidance : a way of life that difficult to changeavoidance : a way of life that difficult to change

David Fleischer.Current Allergy and Asth Reports 2007:7;175-81

Prevalence of peanut allergy was rising despite many Prevalence of peanut allergy was rising despite many strategiesstrategies

72 to 81% of presentation of peanut occur on first 72 to 81% of presentation of peanut occur on first exposure to peanutexposure to peanut

Others factors contributing for peanut allergy??Others factors contributing for peanut allergy??Failure to follow guideline??Failure to follow guideline??Delayed exposure strategies are failure??Delayed exposure strategies are failure??Other routes causing sensitization??Other routes causing sensitization??

Questions?Questions?

PatientPatient(questionaire, OC)(questionaire, OC)

Children with had peanut allergy Children with had peanut allergy aged under 38 months (n=49,36) aged under 38 months (n=49,36) from ALPSAC studyfrom ALPSAC study

InterventionIntervention Find factors associated with the Find factors associated with the development of peanut allergydevelopment of peanut allergy

CompareCompare Eczematous children without peanut Eczematous children without peanut allergy (n=70) , healthy controls allergy (n=70) , healthy controls (n=140)(n=140)

OutcomeOutcome Maternal peanut consumption , Maternal peanut consumption , positive cord-blood specific IgE to positive cord-blood specific IgE to peanut :not increased risk of PA peanut :not increased risk of PA but ..but ..

NEJM 2003:348;977-85

NEJM 2003:348;977-85

Failure to follow guideline??Failure to follow guideline??

In 2000, AAP, based on expert opinion, In 2000, AAP, based on expert opinion, suggested nursing mothers of at-risk infants to suggested nursing mothers of at-risk infants to eliminate peanuts from their diet and introduction eliminate peanuts from their diet and introduction of peanut should be delayed until 3 years of ageof peanut should be delayed until 3 years of age

In a survey of 957 mothers in UK In a survey of 957 mothers in UK (Hourihane et al. JACI 2007)(Hourihane et al. JACI 2007)

- 61% recalled hearing the advice about peanuts61% recalled hearing the advice about peanuts- 3.8 % stopped consuming peanuts while pregnant3.8 % stopped consuming peanuts while pregnant

A.Wesley Burks.Lancet 2008; 371: 1538–46

FAQ : prevalence of peanut allergy

10,786 children aged 4-19 years in 24 schools

(13 in UK, 11 in Israel)

8,600 children

1960 not-returned

226 was excluded

Israel = 4657

UK = 3943

FFQ : mothers & infants consumption questionnaire

Mothers of Jewish infants aged 8-14 months (n=176)

Israel = 99

UK = 77

Du Toit et al.JACI 2008;122:984-91

81.8%

JACI 2008;122:984-91

• 47/81 children with questionaire-based diagnosis of PA underwent

clinical assessment; 36/47 (77%) had PA , the rest are peanut tolerant

JACI 2008;122:984-91

JACI 2008;122:984-91

The largest and most significant difference between UK and Isarel was in age of introduction of peanut (P<0.001)

Du loit et al.JACI 2008;122:984-91

Could different methods of preparing peanut Could different methods of preparing peanut be responsible for different rates?be responsible for different rates?

Du loit et al.JACI 2008;122:984-91

Summery : there was a strong inverse association between peanut consumption in infancy and prevalence of PA in childhood

PatientPatient Eczematous children with peanut Eczematous children with peanut allergy aged under 48 months (n= allergy aged under 48 months (n= 133)133)

InterventionIntervention (questionnaire (questionnaire

before SPT)before SPT)

Peanut exposure during first year Peanut exposure during first year of life during pregnancy, lactation of life during pregnancy, lactation and household peanut and household peanut consumptionconsumption

CompareCompare Eczematous children with egg Eczematous children with egg allergy but not sensitize to peanut allergy but not sensitize to peanut (n=160) , healthy controls (n=160) , healthy controls (n=150)(n=150)

OutcomeOutcome Levels of peanut exposure by Levels of peanut exposure by different routes between groupsdifferent routes between groups

Fox et al.JACI 2009;123:417-23

Diagnosis of PA : SPT wheal > 8 mm, a Diagnosis of PA : SPT wheal > 8 mm, a specific IgE > 15 kUA/L or positive DBPCFC specific IgE > 15 kUA/L or positive DBPCFC

** ** *

0 , 1.1, 2.4 g 0 , 0.6 , 0.9 g

** P<0.001 ** P<0.001 1.9 , 6.9 ,18.8 g

* P=0.009

***

*** P=0.002

฿ ฿

฿=NS

Fox et al.JACI 2009;123:417-23

Fox et al.JACI 2009;123:417-23

Comments for this paperComments for this paper

• Is it truely possible to discriminate between household

and peanut consumption??

• Maternal consumption was included in household

consumptions

4 male , 9-13 years , did DBPCFC to confirmed diagnosis 4 male , 9-13 years , did DBPCFC to confirmed diagnosis and pretreatment threshold dosesand pretreatment threshold doses

OIT was done by peanut flour mixed with yogurt dose 5-800 OIT was done by peanut flour mixed with yogurt dose 5-800 mg , conventional protocolmg , conventional protocol

Increasing dose every 2 weeksIncreasing dose every 2 weeks

Maintainace dose 800 mg protein after post OIT challengeMaintainace dose 800 mg protein after post OIT challenge

Follow-up studies are required to examine the duration and frequency of maintenance therapy required to induce long-term tolerance

Clark et al.Allergy 2009.Feb 17; ePub ahead of Print

Clark et al.Allergy 2009.Feb 17; ePub ahead of Print

6 weeks after final dose

Clark et al.Allergy 2009.Feb 17; ePub ahead of Print

Take Home MessageTake Home Message Indicence of peanut allergy seems to be Indicence of peanut allergy seems to be

rising without explanationrising without explanation

Peanut and other legumes : clinical Peanut and other legumes : clinical cross-reactions are unlikely to occurcross-reactions are unlikely to occur

Peanut and treenut : no DBPC study but Peanut and treenut : no DBPC study but still should recommend to avoid still should recommend to avoid

Take Home MessageTake Home Message Factors associated developing peanut allergyFactors associated developing peanut allergy

- Soybean consumption in early infant- Soybean consumption in early infant- Applying peanut oil in eczematic skin- Applying peanut oil in eczematic skin- Delayed consumption in infancy ??- Delayed consumption in infancy ??- Enviromnental exposure via household - Enviromnental exposure via household

consumption??consumption??

SOTI seems to be promising treatmentSOTI seems to be promising treatment