Food allergy: A practice parameter update (2014) - The American

53 Pages·2014·0.64 MB·English

Practice parameter
Food allergy: A practice parameter update—2014
HughA.Sampson,MD,SeemaAceves,MD,PhD,S.AllanBock,MD,JohnJames,MD,StacieJones,MD,
DavidLang,MD,KariNadeau,MD,PhD,AnnaNowak-Wegrzyn,MD,JohnOppenheimer,MD,
TamaraT.Perry,MD,ChristopherRandolph,MD,ScottH.Sicherer,MD,RonaldA.Simon,MD,
BrianP.Vickery,MD,andRobertWood,MD
ChiefEditors:HughA.Sampson,MD,andChristopherRandolph,MD
MembersoftheJointTaskForceonPracticeParameters:DavidBernstein,MD,JoannBlessing-Moore,MD,
DavidKhan,MD,DavidLang,MD,RichardNicklas,MD,JohnOppenheimer,MD,JayPortnoy,MD,
ChristopherRandolph,MD,DianeSchuller,MD,SheldonSpector,MD,StephenA.Tilles,MD,and
DanaWallace,MD
PracticeParameterWorkgroup:HughA.Sampson,MD(Chair),SeemaAceves,MD,PhD,S.AllanBock,MD,
JohnJames,MD,StacieJones,MD,DavidLang,MD,KariNadeau,MD,PhD,AnnaNowak-Wegrzyn,MD,
JohnOppenheimer,MD,TamaraT.Perry,MD,ChristopherRandolph,MD,ScottH.Sicherer,MD,
RonaldA.Simon,MD,BrianP.Vickery,MD,andRobertWood,MD
This parameter was developed bytheJointTaskForceon Because thisdocument incorporated the effortsofmany
Practice Parameters, representingtheAmerican Academyof participants,nosingleindividual,includingthosewhoservedon
Allergy,Asthma&Immunology (AAAAI);the American theJointTaskForce,isauthorizedtoprovideanofficialAAAAI
College ofAllergy,Asthma &Immunology (ACAAI); andthe or ACAAI interpretation of thesepracticeparameters. Any
JointCouncilofAllergy,Asthma&Immunology(JCAAI).The request for informationaboutor aninterpretation of these
AAAAI andthe ACAAI havejointly acceptedresponsibility practice parametersbythe AAAAIor ACAAI shouldbe
forestablishing‘‘FoodAllergy:Apracticeparameterupdate— directed to theExecutive Officesofthe AAAAI, ACAAI,and
2014.’’This isa complete andcomprehensivedocument at the JCAAI.These parameters arenot designedforuse by
currenttime.Themedical environmentis achangingone, and pharmaceuticalcompanies indrugpromotion.(JAllergy Clin
not all recommendations will be appropriatefor allpatients. Immunol2014;134:1016-25.)
oftheBoardofRegentsfortheAmericanCollegeofAllergy,Asthma&Immunology
Disclosureofpotentialconflictofinterest:H.A.Sampsonhasreceivedresearchsupport
(ACAAI);hasconsultantarrangementswithAstraZenecaandGenentech;hasreceived
fromtheNationalInstituteofAllergyandInfectiousDiseases(NIAID;AI44236and
paymentforlecturesfromGlaxoSmithKline,AstraZeneca,Genentech,andTEVA;
AI66738),theNational Institutes ofHealth (NIH;RR026134), andFoodAllergy
andhasreceivedtravelsupportfromTEVA.S.H.Sichererhasreceivedresearchsup-
ResearchandEducation(FARE);hasreceivedtravelsupportasthechairofPhARF
portfromtheNIAID,isamemberoftheAmericanBoardofAllergyandImmunology,
Awardreviewcommittee;hasconsultantarrangementswithAllerteinTherapeutics,
hasconsultantarrangementswithNovartisandFARE;andreceivesroyaltiesfrom
Regeneron,andtheDanoneResearchInstitute;andhasreceivedpaymentforlectures
UpToDate.R.A.Simonhasprovidedexperttestimonyforvariouslawfirms;has
fromThermoFisherScientific,UCB,andPfizer.S.Acevesisamemberofthemedical
receivedpaymentforlecturesfromMerck,Novartis,andCSL-Behring;holdspatents
advisorypanelfortheAmericanPartnershipforEosinophilicDisorders;hasreceived
fortheuseofsurfactantsinchronicrhinosinusitisandasthma;hasreceivedroyalties
researchsupportfromtheNationalInstitutesofHealth(NIAIDAI092135),theDepart-
from Wiley Blackwell and UpToDate; and has stock options in URXmobile.
mentofDefense,andtheAmericanAcademyofAllergy,Asthma&Immunology
B.P.VickeryhasreceivedresearchsupportfromtheNIH/NIAID(AI099083)and
(AAAAI)/AmericanPartnershipforEosinophilicDisorders;hasapatentheldbyUni-
theFoundationoftheACAAI.R.WoodhasconsultantarrangementswiththeAsthma
versity of California–San Diego for OVB licensed to Meritage Pharma; and has
andAllergyFoundationofAmerica,isemployedbyJohnsHopkinsUniversity,has
receivedtravelsupportfromtheNIHandtheFalkFoundation.S.A.Bockisonthe
receivedresearchsupportfromtheNIH,andreceivesroyaltiesfromUpToDate.The
medicaladvisoryboardforFARE.S.Joneshasreceivedresearchsupportfromthe
restoftheauthorsdeclarethattheyhavenorelevantconflictsofinterest.
NIH(COFAR),theNIH/NIAIDImmuneToleranceNetwork(A1-15416),andFood
We thank Anne Munoz-Furlong for review and helpful comments to ‘‘Section IX:
Allergy Research and Education. D. Lang is a speaker for Genentech/Novartis,
Managementinspecialsettings.’’
GlaxoSmithKline,andMerck;hasconsultantarrangementswithGlaxoSmithKline,
Correspondingauthor:SusanL.Grupe,JointTaskForceonPracticeParameters,50N
Merck,Aerocrine;andhasreceivedresearchsupportfromGenentech/Novartisand
BrockwaySt,#304,Palatine,IL60067.E-mail:[email protected].
Merck.A.Nowak-WegrzynisaspeakerforThermoFisherScientific,isontheadvi-
ReceivedforpublicationFebruary7,2014;revisedMay2,2014;acceptedforpublication
soryboardforNutricia,isontheDataSafetyMonitoringBoardforMerck,andhas
received research support from Nestl(cid:1)e (grant 0955), Nutricia, and the NIH. J. May6,2014.
AvailableonlineAugust28,2014.
Oppenheimerhas received research support from AstraZeneca,GlaxoSmithKline,
0091-6749/$36.00
Merck, Boehringer Ingelheim, Novartis, and MedImmune; has provided legal
(cid:1)2014AmericanAcademyofAllergy,Asthma&Immunology
consultation/expertwitnesstestimonyinmalpracticedefensecases;ischairmanof
http://dx.doi.org/10.1016/j.jaci.2014.05.013
theAmericanBoardofAllergyandImmunology;andhasconsultantarrangements
withGlaxoSmithKline,Mylan,Novartis,andSunovion.C.Randolphisamember
1016
JALLERGYCLINIMMUNOL SAMPSONETAL 1017
VOLUME134,NUMBER5
Key words: Food allergy, food allergen, cross-reactivity, DavidM.Lang,MD
adverse food reactions, IgE-mediated food allergy, eosinophilic Allergy/ImmunologySection
esophagitis RespiratoryInstitute
AllergyandImmunologyFellowshipTrainingProgram
ClevelandClinicFoundation
Previously published practice parameters of the Joint Task
Cleveland,Ohio
Force on Practice Parameters for Allergy and Immunology
are available at http://www.JCAAI.org or http://www.allergy
RichardA.Nicklas,MD
parameters.org.
DepartmentofMedicine
GeorgeWashingtonMedicalCenter
Washington,DC
CONTRIBUTORS
TheJointTaskForcehasmadeaconcertedefforttoacknowl- JohnOppenheimer,MD
edge all contributors to this parameter. If any contributors DepartmentofInternalMedicine
have been excluded inadvertently, the Task Force will ensure NewJerseyMedicalSchool
that appropriate recognition of such contributions is made sub- PulmonaryandAllergyAssociates
sequently. Morristown,NewJersey
JayM.Portnoy,MD
SectionofAllergy,Asthma&Immunology
WORKGROUP CHAIR Children’sMercyHospital
HughA.Sampson,MD DepartmentofPediatrics
JaffeFoodAllergyInstitute UniversityofMissouri–KansasCitySchoolofMedicine
DepartmentofPediatrics KansasCity,Missouri
IcahnSchoolofMedicineatMountSinai
NewYork,NewYork
DianeE.Schuller,MD
DepartmentofPediatrics
PennsylvaniaStateUniversityMiltonS.HersheyMedical
College
JOINT TASK FORCE LIAISON
Hershey,Pennsylvania
ChristopherRandolph
DepartmentofPediatrics/Allergy/Immunology
YaleAffiliatedHospitals SheldonL.Spector,MD
CenterforAllergy,Asthma,&Immunology DepartmentofMedicine
Waterbury,Connecticut UCLASchoolofMedicine
LosAngeles,California
JOINT TASK FORCE MEMBERS StephenA.Tilles,MD
DepartmentofMedicine
DavidI.Bernstein,MD
UniversityofWashingtonSchoolofMedicine
DepartmentsofClinicalMedicineandEnvironmental
Redmond,Washington
Health
DivisionofAllergy/Immunology
DanaWallace,MD
UniversityofCincinnatiCollegeofMedicine
DepartmentofMedicine
Cincinnati,Ohio
NovaSoutheasternUniversityCollegeofOsteopathic
Medicine
JoannBlessing-Moore,MD Davie,Florida
DepartmentsofMedicineandPediatrics
StanfordUniversityMedicalCenter
DepartmentofImmunology PARAMETER WORKGROUP MEMBERS
PaloAlto,California SeemaAceves,MD,PhD
EosinophilicGastrointestinalDisordersClinic
DivisionofAllergy,Immunology
DavidA.Khan,MD
DepartmentsofPediatricsandMedicine
DepartmentofInternalMedicine
UniversityofCalifornia,SanDiego
UniversityofTexasSouthwesternMedicalCenter
RadyChildren’sHospital
Dallas,Texas
SanDiego,California
1018 SAMPSONETAL JALLERGYCLINIMMUNOL
NOVEMBER2014
S.AllanBock,MD ScottH.Sicherer,MD
DepartmentofPediatrics DepartmentofPediatrics
NationalJewishHealth PediatricAllergyandImmunology
Denver,Colorado IcahnSchoolofMedicineatMountSinai
DepartmentofPediatrics JaffeFoodAllergyInstitute
UniversityofColoradoSchoolofMedicine NewYork,NewYork
Aurora,Colorado
RonaldA.Simon,MD
DivisionofAllergy,Asthma&Immunology
JohnM.James,MD ScrippsClinic
PrivateClinicalPractice DepartmentofExperimental&MolecularMedicine
ColoradoAllergyandAsthmaCenters,PC ScrippsResearchInstitute
FortCollins,Colorado LaJolla,California
BrianP.Vickery,MD
StacieJones,MD
DepartmentofPediatrics
DepartmentofPediatrics
UniversityofNorthCarolinaSchoolofMedicine
AllergyandImmunology
ChapelHill,NorthCarolina
UniversityofArkansasforMedicalSciences
ArkansasChildren’sHospital
RobertWood,MD
LittleRock,Arkansas
DepartmentofPediatricsandInternationalHealth
DivisionofPediatricAllergyandImmunology
JohnsHopkinsUniversitySchoolofMedicine
DavidM.Lang,MD
Baltimore,Maryland
Allergy/ImmunologySection
DivisionofMedicine
AllergyandImmunologyFellowshipTrainingProgram
TABLE OF CONTENTS
ClevelandClinicFoundation
Cleveland,Ohio
I. Classification of major food allergens, cross-reactivities,
genetically modified foods, and clinical implications
KariNadeau,MD,PhD
A. Classification
DepartmentofAllergy,AsthmaandImmunology
B. Cross-reactivity
StanfordUniversitySchoolofMedicine
C. Genetically modified organisms in foods and the
Stanford,California
potential for allergenicity
II. Mucosal immune responses induced by foods
AnnaNowak-Wegrzyn,MD III. The clinical spectrum of food allergy
DepartmentofPediatrics
A. Categories of adverse food reactions
JaffeFoodAllergyInstitute
B. Definitionsofspecificfood-inducedallergicconditions
DivisionofAllergyandImmunology
IcahnSchoolofMedicineatMountSinai IV. Prevalence, natural history, and prevention
NewYork,NewYork
A. Natural history
B. Prevention offood allergy
JohnOppenheimer,MD V. Adverse reactions to food additives
DepartmentofInternalMedicine VI. Diagnosis offood allergy, differential diagnosis, and
NewJerseyMedicalSchool diagnostic algorithm
PulmonaryandAllergyAssociates
A. Diagnosis of IgE-mediated food allergy
Morristown,NewJersey
B. Non-IgE mediated: FPIES, allergic proctocolitis, and
enteropathy
TamaraT.Perry,MD C. Eosinophilic esophagitis
DepartmentofPediatrics D. Eosinophilic gastroenteritis
AllergyandImmunologyDivision
VII. Management offood allergy and food-dependent,
UniversityofArkansasforMedicalSciences
exercise-induced anaphylaxis
ArkansasChildren’sHospital
VIII. Emerging therapies for food allergy
LittleRock,Arkansas
IX. Management in special settings
JALLERGYCLINIMMUNOL SAMPSONETAL 1019
VOLUME134,NUMBER5
CLASSIFICATION OF RECOMMENDATIONS AND
EVIDENCE
Recommendation rating scale
Statement Definition Implication
Strongrecommendation(StrRec) Astrongrecommendationmeansthebenefitsofthe Cliniciansshouldfollowastrongrecommendationunlessa
recommendedapproachclearlyexceedtheharms clearandcompellingrationaleforanalternative
(orthattheharmsclearlyexceedthebenefitsinthecase approachispresent.
ofastrongnegativerecommendation)andthatthe
qualityofthesupportingevidenceisexcellent(grade
AorB).*Insomeclearlyidentifiedcircumstances,
strongrecommendationsmightbemadebasedonlesser
evidencewhenhigh-qualityevidenceisimpossibleto
obtainandtheanticipatedbenefitsstronglyoutweighthe
harms.
Moderate(Mod) Arecommendationmeansthebenefitsexceedtheharms Cliniciansshouldalsogenerallyfollowarecommendation
(orthattheharmsexceedthebenefitsinthecaseofa butshouldremainalerttonewinformationandsensitive
negativerecommendation),butthequalityofevidenceis topatientpreferences.
notasstrong(gradeBorC).*Insomeclearlyidentified
circumstances,recommendationsmightbemadebased
onlesserevidencewhenhigh-qualityevidenceis
impossibletoobtainandtheanticipatedbenefits
outweightheharms.
Weak(Weak) Anoptionmeansthateitherthequalityofevidencethat Cliniciansshouldbeflexibleintheirdecisionmaking
existsissuspect(gradeD)*orthatwell-donestudies regardingappropriatepractice,althoughtheymightset
(gradeA,B,orC)*showlittleclearadvantagetoone boundsonalternatives;patientpreferenceshouldhavea
approachversusanother. substantialinfluencingrole.
Norecommendation(NoRec) Norecommendationmeansthereisbothalackofpertinent Cliniciansshouldfeellittleconstraintintheirdecision
evidence(gradeD)*andanunclearbalancebetween makingandbealerttonewpublishedevidencethat
benefitsandharms. clarifiesthebalanceofbenefitversusharm;patient
preferenceshouldhaveasubstantialinfluencingrole.
Category of evidence B Directly based on category II evidence or extrapolated
recommendation from category I evidence
Ia Evidence from meta-analysis of randomized controlled
C Directly based on category III evidence or extrapolated
trials
recommendation from category I or II evidence
Ib Evidence from at least 1 randomized controlled trial
D Directly based on category IV evidence or extrapolated
IIa Evidence from at least 1 controlled study without
recommendation from category I, II, or III evidence
randomization
LB Laboratory based
IIb Evidence from at least 1 other type of quasiexperimental
NR Not rated
study
III Evidence from nonexperimental descriptive studies, such
as comparative studies
SUMMARY OF CONFLICT OF INTEREST
IV Evidence from expert committee reports or opinions or
DISCLOSURES
clinical experience of respected authorities or both
Thefollowingisasummaryofinterestsdisclosedonworkgroup
members’conflictofinterestdisclosurestatements(notincluding
Strengthofrecommendation*
information concerning family member interests). Completed
A Directly based on category I evidence conflictofinterestdisclosurestatementsareavailableonrequest.
Workgroupmember Disclosures
HughA.Sampson,MD AllerteinTherapeutics–Consultant
FoodAllergyResearchandEducation(FARE)–MedicalAdvisoryBoard,unpaid
Novartis–Consultant,unpaid
DBVScientificAdvisoryBoard,unpaid
ThermoFisherScientific–EAACItravelexpensesandhonorarium
UCB–XXNationalCongressoftheMexicanPediatricSpecialistsinClinicalImmunology
andAllergy–Travelexpensesandhonorarium
NationalInstituteofAllergyandInfectiousDiseases(NIAID)–Researchgrant
FARE–Researchgrant
UniversityofNebraska(FARRP)–Consultant
AllergyandAsthmaFoundationofAmerica–Consultant
(Continued)
1020 SAMPSONETAL JALLERGYCLINIMMUNOL
NOVEMBER2014
(Continued)
Workgroupmember Disclosures
SeemaAceves,MD,PhD MeritagePharma–Patentroyalties
S.AllanBock,MD FoodAllergyandAnaphylaxisNetwork—MedicalAdvisoryBoard
NationalJewishHealth–Researchaffiliate
JohnJames,MD AmericanBoardofAllergyandImmunology–MedicalAdvisoryBoard
ParentsofAsthmaticandAllergicChildren–MedicalAdvisoryBoard
StacieJones,MD NationalInstitutesofHealth(NIH)/NIAID–Researchgrant
NationalPeanutBoard–Researchgrant
FARE–Advisoryboard;researchgrant
Sanofi-Aventis–SteeringCommitteeMember
NIAIDSafetyMonitoringCommittee–Grantreview
NIAIDStudySection–AdHocReview
AAAAI–Speaker
IndianaUniversityMedicalSchoolandRileyChildren’sHospital–Speaker
SpanishSocietyofAllergy&ClinicalImmunology(SEAIC),Madrid,Spain–Speaker
OregonAllergy,Asthma&ImmunologySociety–Speaker
DavidLang,MD Tera–Speaker
Sanofi-Aventis–AdvisoryBoard
Merck–AdvisoryBoard;speaker
Astra-Zeneca–Speaker
Genentech–Speaker
GlaxoSmithKline–Speaker
Genentech/Novartis–Researchgrant
KariNadeau,MD,PhD NIAID–Researchgrant
FARE–Researchgrant
AnnaNowak-Wegrzyn,MD Merck–AdvisoryBoard
FARE–Grant
Nestle–Grant
NewYorkAllergyandAsthmaSociety–ExecutiveCommitteeMember
JohnOppenheimer,MD
TamaraT.Perry,MD NIH/NHLBI–Researchgrant
NIH/NIAID–Researchgrant
NIHNationalCenterforMinorityHealthDisparities–Researchgrant
ARCenterforClinicalandTranslationResearch–Researchgrant
ChristopherRandolph,MD GlaxoSmithKline–Consultant;speaker;honorarium;researchgrant
Astra–Consultant;AdvisoryBoard;speaker;honorarium;researchgrant
Merck-Consultant;speaker;honorarium;researchgrant
Genentech/Novartis-Consultant;speaker;honorarium;researchgrant
Baxter–Speaker
Dyax–Researchgrant
Dey–Speaker
Alcon-Speaker;honorarium;researchgrant
ISTA(Bepreve)–Speaker;honorarium
Sunovion(Sepracor)–Speaker
CSFBehring–Speaker
Pharmaxis–Providedadvertisement
TEVA–Speaker;researchgrant
ConnecticutAllergySociety–Officer
ScottH.Sicherer,MD AmericanAcademyofPediatrics–Officer
AmericanBoardofAllergyImmunology–BoardMember
AAAAI–Speaker
JournalofAllergyandClinicalImmunology/JACI-InPractice–AssociateEditor
NIH/NIAID–Grants
FARE–Consultant
FoodAllergyResearchandEducation–Medicaladvisor/consultant
Novartis-Consultant
RonaldA.Simon,MD Novartis–Speakers’bureau
Novartis–Researchsupport
Merck–Speakers’bureau
GlaxoSmithKline–Speakers’bureau
(Continued)
JALLERGYCLINIMMUNOL SAMPSONETAL 1021
VOLUME134,NUMBER5
(Continued)
Workgroupmember Disclosures
BrianP.Vickery,MD Cephalon–Researchgrant
ThrasherResearchFund–Researchgrant
WallaceResearchFoundation–Researchgrant
AmericanCollegeofAllergy,Asthma&Immunology–Grant
AmericanLungAssociation–Grant/SteeringCommitteeMember
NIH/NIAID–Grant
RobertWood,MD FARE—MedicalAdvisoryBoard
AllergyandAsthmaFoundationofAmerica–Consultant
NIH–Researchsupport
AmericanBoardofAllergyandImmunology–BoardofDirectors
AmericanBoardofPediatrics–BoardofDirectors
AmericanAcademyofAllergy,Asthma&Immunology(AAAAI)–BoardofDirectors
Resolution of nondisqualifying interests parameter that addresses recent advances in the field of food
TheJointTaskForcerecognizesthatexpertsinafieldarelikely allergy and the optimal methods of diagnosis and management
tohaveintereststhatcouldcomeintoconflictwithdevelopmentof basedonanassessmentofthemostcurrentliterature.TheChair
acompletelyunbiasedandobjectivepracticeparameter.Aprocess (Hugh A. Sampson, MD) invited workgroup members to
hasbeendevelopedtopreventpotentialconflictsfrominfluencing participateintheparameterdevelopmentwhoareconsideredto
the final document in a negative way to take advantage of that beexpertsinthefieldoffoodallergy.Workgroupmembershave
expertise. beenvettedforfinancialconflictofinterestbytheJTF,andtheir
Attheworkgrouplevel,memberswhohaveapotentialconflict conflicts of interest have been listed in this document and are
ofinteresteitherdonotparticipateindiscussionsconcerningtopics postedontheJTFWebsiteathttp://www.allergyparameters.org.
relatedtothepotentialconflict,oriftheydowriteasectiononthat Thechargetotheworkgroupwastouseasystematicliterature
topic,theworkgroupcompletelyrewritesitwithouttheirinvolve- review in conjunction with consensus expert opinion and
menttoremovepotentialbias.Inaddition,theentiredocumentis workgroup-identified supplementary documents to develop a
reviewedbytheJointTaskForce,andanyapparentbiasisremoved practiceparameterthatevaluatesthecurrentstateofthescience
atthatlevel.Finally,thepracticeparameterissentforreviewboth regardingfoodallergy.
byinvitedreviewersandbyanyonewithaninterestinthetopicby
postingthedocumentontheWebsitesoftheACAAIandAAAAI.
PROTOCOL FOR FINDING EVIDENCE
The practice parameter on food allergy was last updated in
The NIAID guidelines were used to identify previously
20061andfocusedprimarilyonIgE-mediatedfoodallergy.Inthe
identified impactful studies on these topics. Additional Clinical
ensuingyears,therehavebeenconsiderableadvancesinthefield
reports were reviewed to ensure parity of expert opinion (AAP
in many areas, including our basic understanding offood aller-
and ICON). Additional PubMed searches were performed
gens,diagnostictesting,non–IgE-mediateddisorders,andman-
primarily to identify items in the literature after September
agementofvariousfood-inducedallergicreactions.In2010,the
2009 that were pertinent to update these topics. Meta-analyses
NIAID‘‘Guidelinesonthediagnosisandmanagementoffoodal-
werealwaysselectedwhenavailable.Gradingofeachreference
lergy’’werepublished,providingacomprehensivereviewofthe
wasperformedasapplicable(seethereferencelist),andoverall
scientificliteratureandexpertopiniononfoodallergy.2Giventhe
grades and strengths of recommendations were placed after the
manyadvancesinthefield,theJointTaskForceonPracticePa-
summary statements. Search terms include food allergy, food
rameters appointed a working group to review and update the
allergen, and each of the specific conditions reviewed in this
standing practiceparameters. Theworkinggroup relied heavily
parameter.
ontheNIAIDGuidelinesandfocusedonadvancessincethepub-
licationofthatlandmarkdocument.
SUMMARY STATEMENTS
THE JOINT TASK FORCE ON PRACTICE SummaryStatement1:Evaluatethepatientforpossiblefoodal-
PARAMETERS lergywiththeunderstandingthatarelativelysmallnumberofal-
The Joint Task Force on Practice Parameters (JTF) is a 13- lergenscauseahighproportionoffoodallergy(eg,cow’smilk,
membertaskforceconsistingof6representativesassignedbythe hen’segg,soy,wheat,peanut,treenuts,fish,andshellfish).See
AAAAI,6bytheACAAI,and1bytheJointCouncilofAllergy SummaryStatement48formanagement.[Strengthofrecommen-
and Immunology. This task force oversees the development of dation:Strong;BEvidence]
practice parameters, selects the workgroup chair or chairs, and Summary Statement 2: Advise patients who are allergic to
reviewsdraftsoftheparametersforaccuracy,practicality,clarity, certain specific foods about the risk of ingestion of similar
andbroadutilityoftherecommendationsforclinicalpractice. cross-reacting foods. Examples include ingestion of other tree
nutsinpatientswithtreenutallergy(eg,walnutandpecanorpis-
FOOD ALLERGY: A PRACTICE PARAMETER tachioandcashew),Crustaceainpatientswithcrustaceanseafood
UPDATE—2014 WORKGROUP allergy, vertebrate fish in patients with fish allergy, and other
TheFoodAllergy: APractice Parameter Update 2014Work- mammalianmilksinpatientswithcow’smilkallergy.[Strength
group was commissioned by the JTF to develop a practice ofrecommendation:Strong;CEvidence]
1022 SAMPSONETAL JALLERGYCLINIMMUNOL
NOVEMBER2014
SummaryStatement3:Avoidothermammalianmilks,suchas SummaryStatement14:Donotrecommendmaternalallergen
goat’smilk orsheep’smilk,in patientswithcow’smilkallergy avoidance or avoidance of specific complementary foods at
because of highly cross-reactive allergens. [Strength of recom- weaningbecausetheseapproacheshavenotprovedeffectivefor
mendation:Strong;BEvidence] primarypreventionofatopicdisease.[Strengthofrecommenda-
Summary Statement 4: Advise patients with seafood allergy tion:Weak;CEvidence]
that they are not at increased risk of a reaction to radiocontrast SummaryStatement15:Donotroutinelyrecommendsupple-
media. There is no documented relationship between non–IgE- mentationofthematernalorinfantdietwithprobioticsorprebi-
mediated anaphylactic reactions to radiocontrast media and otics as a means to prevent food allergy because there is
allergytofish,crustaceanshellfish,oriodine.[Strengthofrecom- insufficient evidence to support a beneficial effect. [Strength of
mendation:Strong;DEvidence] recommendation:Weak;CEvidence]
SummaryStatement5:TestforIgEantibodiesspecificforthe Summary Statement 16: Do not routinely recommend that
immunogenic oligosaccharide galactose-alpha-1, 3-galactose patients with chronic idiopathic urticaria (CIU) avoid foods
(alpha-gal) in patients who report a delayed systemic reaction containing additives. [Strength of recommendation: Strong; B
to red meat or unexplained anaphylaxis, particularly if they Evidence]
haveahistoryofprevioustickbites.[Strengthofrecommenda- SummaryStatement17:Donotroutinelyinstructasthmaticpa-
tion:Moderate;CEvidence] tientstoavoidsulfitesorotherfoodadditivesunlesstheyhavea
SummaryStatement6:Avoidallmammalianmeatsinpatients priorreactiontosulfites.Sulfitesaretheonlyfoodadditiveproved
with alpha-gal allergy because this oligosaccharide antigen is to trigger asthma. Although these reactions can be severe, even
widelyexpressedinmammaliantissues.[Strengthofrecommen- life-threatening in sensitive subjects, they are rare. [Strength of
dation:Moderate;CEvidence] recommendation:Strong;BEvidence]
SummaryStatement7:Evaluatepatientswithlatexallergyfor SummaryStatement18:Considernaturalfoodadditivesinthe
thepossibilityofcross-reactivitytobanana,avocado,kiwi,chest- evaluation of patients with a history of unexplained ingestant-
nut,potato,greenpepper,andotherfruitsandnuts.Individualized relatedanaphylaxis.[Strengthofrecommendation:Moderate;C
management isrecommended because clinical reactions caused Evidence]
bythiscross-reactivitycanrangefrommildtosevere.[Strength SummaryStatement19:Patientswhoexperienceanadversere-
ofrecommendation:Strong;CEvidence] action to food additives should be evaluated for sensitivity to
Summary Statement 8: Advise patients not to be concerned annatto and carmine. [Strength of recommendation: Strong;
aboutingestinggeneticallymodifiedfoodsgiventhecurrentstate AEvidence]
of knowledge and the US Food and Drug Administration’s SummaryStatement20:Cliniciansshouldbeawarethatavoid-
screening requirements to rule out allergenicity of genetically ancemeasuresareappropriateforpatientswithhistoriescompat-
modified foods. [Strength of recommendation: Weak; D ible with adverse reactions to an additive until diagnostic
Evidence] evaluation can be performed. [Strength of recommendation:
SummaryStatement9:Managenon–IgE-mediatedreactionsto Moderate;CEvidence]
foodswithappropriateavoidanceandpharmacotherapyasindi- Summary Statement 21: Clinicians should not recommend
cated with the understanding that the specific role of immunity food additive avoidance in their patients with hyperactivity/
(eg,IgA,IgM,IgG,andIgGsubclasses)intheseformsoffoodal- attentiondeficitdisorder.[Strengthofrecommendation:Strong;
lergyhasnotbeendemonstrated.[Strengthofrecommendation: AEvidence]
Strong;BEvidence] Summary Statement 22: The clinician should obtain a
Summary Statement 10: Determine whether the reported his- detailed medical history and physical examination to aid in the
toryoffoodallergy,whichoftenprovesinaccurate,andlaboratory diagnosisoffoodallergy.[Strengthofrecommendation:Strong;
dataaresufficienttodiagnosefoodallergyorwhetheranoralfood DEvidence]
challenge (OFC) is necessary. [Strength of recommendation: SummaryStatement23:TheclinicianshouldusespecificIgE
Strong;AEvidence] tests(skinpricktests,serumtests,orboth)tofoodsasdiagnostic
SummaryStatement11:Considerthenaturalcourseofallergies tools;however,testingshouldbefocusedonfoodssuspectedof
tospecificfoodswhendecidingonthefrequencyoffoodallergy provoking the reaction, and test results alone should not be
follow-upevaluations,recognizingthatallergiestocertainfoods considereddiagnosticoffoodallergy.[Strengthofrecommenda-
(milk, egg, wheat, and soy) generally resolve more quickly in tion:Strong;BEvidence]
childhoodthanothers(peanut,treenuts,fish,andshellfish).These Summary Statement 24: Component-resolved diagnostic
observationscouldsupportindividualizedfollow-up(ie,roughly testingtofoodallergenscanbeconsidered,asinthecaseofpea-
yearly re-evaluations of these allergies in childhood) with less nutsensitivity,butitisnotroutinelyrecommendedevenwithpea-
frequentretestingifresultsremainparticularlyhigh(eg,>20-50 nut sensitivity because the clinical utility of component testing
kU /L).[Strengthofrecommendation:Moderate;CEvidence] has not been fully elucidated. [Strength of recommendation:
A
Summary Statement 12: Encourage exclusive breast-feeding Weak;CEvidence]
forthefirst4to6monthsoflife.[Strengthofrecommendation: SummaryStatement25:TheclinicianshouldconsiderOFCsto
Weak;CEvidence] aid in the diagnosis of IgE-mediated food allergy. [Strength of
Summary Statement 13: For infants with a family history of recommendation:Strong;AEvidence]
atopy, consider a partially or extensively hydrolyzed infant for- SummaryStatement26:Ifclinicalhistoryisnotconsistentwith
mula for possible prevention of atopic dermatitis and infant anaphylaxis,performagradedOFCtoruleoutfoodallergy.Open
cow’s milk allergy if exclusive breast-feeding is not possible. food challenge is both cost- and time-efficient. [Strength of
[Strengthofrecommendation:Moderate;BEvidence] recommendation:Moderate;CEvidence]
JALLERGYCLINIMMUNOL SAMPSONETAL 1023
VOLUME134,NUMBER5
Summary Statement 27: If the diagnosis is still unclear after SummaryStatement39:Atrialoftwicedailyproteinpumpin-
open food challenge, then recommend a blind food challenge. hibitor (PPI) therapy for 8 weeks before diagnostic testing for
[Strengthofrecommendation:Moderate;BEvidence] EoEisrecommendedtoexcludegastroesophagealrefluxdisease
SummaryStatement28:Eliminationdietsanddietdiariescan (GERD) and PPI-responsive esophageal infiltration of eosino-
be used as an adjunctive means to diagnose food allergies but phils.[Strengthofrecommendation:Strong;CEvidence]
are not to be depended on solely for confirming a diagnosis. Summary Statement 40: The diagnosis of EoE should be
[Strengthofrecommendation:Weak;DEvidence] basedonthepresenceofcharacteristicsymptomsandendoscopic
Summary Statement 29: A diagnosis of food-dependent, features and the presence of 15 or more eosinophils per
exercise-inducedanaphylaxisshouldbeconsideredwheninges- high-power field quantified by a pathologist using hematoxylin
tionofcausalfoodorfoodsandtemporallyrelatedexerciseresult and eosin staining of esophageal biopsy specimens at 3400
insymptomsofanaphylaxis.Theclinicianshouldrecognizethat light microscopy. [Strength of recommendation: Strong; B
symptomsonlyoccurwithingestionofthecausalfoodorfoods Evidence]
proximatetoexerciseandthatingestionofthefoodintheabsence Summary Statement 41: Eosinophilic gastroenteritis (EGE)
ofexercisewillnotresultinanaphylaxis.[Strengthofrecommen- shouldbeconsideredaconstellationofclinicalsymptomsincom-
dation:Strong;BEvidence] binationwithgastric,smallintestine,and/orlargeintestineinfil-
SummaryStatement30:Theclinicianshouldconsiderthediag- tration of eosinophils at greater than the reported normal
nosis of oral allergy syndrome (pollen-food allergy) and obtain numbersofgastricandintestinaleosinophils.[Strengthofrecom-
specificIgEtestingtopollensinpatientswhoexperiencelimited mendation:Weak;DEvidence]
oropharyngeal symptoms after ingestion of food antigens that SummaryStatement42:Prescribeatargetedallergenelimina-
cross-react with pollen antigens. [Strength of recommendation: tiondietasthetreatmentforknownorstronglysuspectedfoodal-
Strong;BEvidence] lergy. Education about proper food preparation and the risks of
SummaryStatement31:AdiagnosisofIgE-mediatedcontact occult exposure is essential. [Strength of recommendation:
urticariashouldbeconsideredinpatientswithahistoryofimme- Strong;CEvidence]
diate urticarial rash at the site of contact with a food allergen. SummaryStatement43:Recommendconsultationwithanutri-
[Strengthofrecommendation:Weak;DEvidence] tionist for growing children in whom elimination diets might
SummaryStatement32:DonotroutinelyobtaintotalserumIgE affect growth, as well as those patients with multiple food al-
levelsforthediagnosisoffoodallergy.[Strengthofrecommenda- lergies, poor growth parameters, or both. Clinicians must be
tion:Strong;CEvidence] aware of the nutritional consequences of elimination diets and
SummaryStatement33:Donotperformintracutaneoustesting certainmedications,suchasesomeprazole,especiallyingrowing
for the diagnosis of food allergy (see discussion). [Strength of children. Specifically, identifying alternative dietary sources of
recommendation:Strong;BEvidence] calciumandvitaminDiscriticalforpatientswithmilkallergy.
Summary Statement 34: Unproved tests, including allergen- [Strengthofrecommendation:Strong;BEvidence]
specific IgG measurement, cytotoxicity assays, applied kinesi- Summary Statement44: Review recognition andtreatment of
ology, provocation neutralization, and hair analysis, should not IgE-mediated food-related allergic reactions with each patient
beusedfortheevaluationoffoodallergy.[Strengthofrecommen- and caregivers, as appropriate. Emphasis should be placed on
dation:Strong;CEvidence] prompt awareness of anaphylaxis and swift intervention.
Summary Statement 35: Although routine use of atopy patch [Strengthofrecommendation:Strong;CEvidence]
tests for diagnosis offood allergy is not recommended, the use Summary Statement 45: Discuss self-care management tech-
offood atopy patch tests in patients with pediatric eosinophilic niques,especiallywithhigh-riskpatients,(eg,adolescents,young
esophagitis(EoE)havebeendemonstratedtobevaluableinas- adults, and asthmatic patients), focusing on risk reduction and
sessing potential food triggers. [Strength of recommendation: recognition and treatment of anaphylaxis. [Strength of recom-
Moderate;CEvidence] mendation:Strong;CEvidence]
SummaryStatement36:Thephysicianshouldusethepatient’s SummaryStatement46:Useepinephrineasfirst-linemanage-
medicalhistory,responsetoatrialofeliminationofthesuspected mentforthetreatmentofanaphylaxis.[Strengthofrecommenda-
food,andOFCtoestablishadiagnosisoffoodprotein–induced tion:Strong;CEvidence]
enterocolitissyndrome(FPIES).However,whenthehistoryindi- SummaryStatement47:Ensurethatself-injectableepinephrine
catesthatinfantsorchildrenhaveexperiencedhypotensiveepi- is readily available to the patient and instruct the patient, care-
sodesormultiplereactionstothesamefood,adiagnosiscanbe giver, or both on the importance of its use and self-
based on a convincing history and absence of symptoms when administration,asrelevant.[Strengthofrecommendation:Strong;
thecausativefoodiseliminatedfromthediet.[Strengthofrecom- CEvidence]
mendation:Strong;BEvidence] SummaryStatement48:Evaluatechildrenwithfoodallergiesat
Summary Statement 37: The clinician should be aware that a regularintervals(1-2years),accordingtothepatient’sageandthe
gastrointestinalevaluationwithendoscopyandbiopsyisusually foodallergen,todeterminewhetherheorsheisstillallergic.If
notrequiredforthediagnosisofFPIESandallergicproctocolitis foodallergyisunlikelytochangeovertime,asinadults,periodic
withsymptomsthatrespondtoeliminationoftheoffendingfood re-evaluation(2-5years)isrecommended,dependingonthefood
andrecurwhenthefoodisreintroducedintothediet.[Strengthof allergy.[Strengthofrecommendation:Strong;CEvidence]
recommendation:Weak;CEvidence] Summary Statement 49: For patients with food-dependent,
SummaryStatement38:Measurementoffood-specificIgGand exercise-induced anaphylaxis, avoid food ingestion within 2 to
IgG antibodiesinserumarenotrecommendedforthediagnosis 4 hours of exercise for prevention of symptoms, and provide
4
ofnon–IgE-mediatedfood-relatedallergicdisorders.[Strengthof prompt treatment with onset of symptoms. [Strength of recom-
recommendation:Strong;BEvidence] mendation:Strong;CEvidence]
1024 SAMPSONETAL JALLERGYCLINIMMUNOL
NOVEMBER2014
SummaryStatement50:Managepollen-foodallergysyndrome inquiry should include adults and children. [Strength of recom-
ororalallergysyndromebydietaryavoidanceofrawfruits,veg- mendation:Strong;DEvidence]
etables,orbothbasedonthepatient’ssymptomprofileseverity. Summary Statement 64: Teach patients that ingestion, rather
Theextentoffoodavoidancedependsontheseverityoforopha- than casual exposure through the skin or close proximity to an
ryngeal symptoms. [Strength of recommendation: Strong; C allergen, is almost the only route for triggering severe allergic/
Evidence] anaphylacticreactions.[Strengthofrecommendation:Strong;C
Summary Statement 51: The clinician should understand Evidence]
thevariousclinicalpresentationsoftheseconditions(ie,FPIES/
proctocolitis/enteropathy), educate patients and care providers
about common food triggers, and recommend strict food PREFACE
avoidance of allergenic foods for symptom management. AsdefinedbytheNIAIDexpertpanel,foodallergyisdefined
[Strengthofrecommendation:Strong;CEvidence] here‘‘asanadversehealtheffectarisingfromaspecificimmune
Summary Statement 52: Usevolume replacement therapy for responsethatoccursreproduciblyonexposuretoagivenfood.’’2
theacutecaremanagementofpatientswithFPIES.[Strengthof Here, the term allergy is not limited to IgE-mediated immuno-
recommendation:Strong;BEvidence] logic reactions and is used to connote the induction of clinical
SummaryStatement53:SeepatientswithFPIESandallergic signs and symptoms, as opposed to sensitivity, which indicates
gastrointestinaldisordersatregularintervalsandconsiderrechal- thepresenceofIgEantibodiestoafood,oftenintheabsenceof
lengeinanappropriatemedicalfacilitybasedonthenaturalhis- clinicalsymptomatology.Althoughtheprevalenceoffoodallergy
tory of the specific disorder. [Strength of recommendation: overall and of allergy to specific foods is uncertain because
Strong;CEvidence] studies vary in methodological approaches,3,4 allergists who
SummaryStatement54:Considerserialtissuebiopsiesaspart havebeeninpracticeforatleastadecadehavebeenconfronted
ofdiseasemanagementinpatientswithEoE.Symptomsaloneor with an ever-growing number of patients with food allergy. On
endoscopywithoutbiopsycannotbeusedasanaccurategaugeof thebasisofarecentextensivereviewoftheliterature,foodallergy
EoE disease activity. [Strength of recommendation: Strong; C isestimatedtoaffectmorethan1%to2%andlessthan10%ofthe
Evidence] population.3 There are limited data to suggest that food allergy
SummaryStatement55:Considerassessmentforaeroallergen prevalencehasincreased,butnationalsurveyssuggestthatpeanut
sensitizationbecauseEoEcanbetriggeredbyaeroallergensinhu- allergyhastripledsincethelate1990s.5,6Inconsideringanumber
mansubjectsandanimalmodelsandtheremightbeaseasonality ofpublishedstudies,4,7,8itisapparentthatestimatesoffoodal-
to EoE diagnoses. [Strength of recommendation: Moderate; D lergyprevalencearehighestwhenbasedonself-report(approxi-
Evidence] mately 12%to 13%)comparedwithestimates basedon studies
SummaryStatement56:Considerfoodallergyevaluationwith usingtests,suchasOFCs(approximately3%).Thisobservation
bothskinprickandpatchtestingforEoEtoruleoutpossiblefood regardingadiscordanceofsuspectedandprovedfoodallergyun-
triggers.RememberthatpositiveserumspecificIgElevels,food derscorestheimportanceofusingproveddiagnosticmethodsto
skinpricktestresponses,andfoodpatchtestresultsarenotsuffi- evaluateindividualpatientssuspectedofahavingfoodallergy.
cienttodiagnosefoodtriggersforEoE.[Strengthofrecommen- The physician should apply information regarding epidemio-
dation:Moderate;CEvidence] logic features of food allergy when approaching diagnosis and
SummaryStatement57:Considertheuseoftargetedorempiric management,recognizingthatself-reportedfoodallergyismore
food-elimination diets or amino acid–based diets for successful common than proved food allergy, that food allergy is more
EoEtherapy.[Strengthofrecommendation:Strong;BEvidence] commoninchildren,thatalimitednumberoffoodsaccountfor
SummaryStatement58:Considertheuseofswallowedtopical mostsignificantfoodallergies,andthatfoodallergyoccursmore
esophagealcorticosteroidsforsuccessfulEoEtherapy.[Strength commonly in persons with other atopic diseases. There are a
ofrecommendation:Strong;AEvidence] number of epidemiologic features regarding food allergy that
Summary Statement 59: Referral to a gastroenterologist for mightbehelpfulinconstructingaprioriassessmentofriskand
esophagealdilationisrecommendedforhigh-gradestenosisbut considerationofpotentialtriggerswhenevaluatingindividualpa-
doesnotprovideinflammatorycontrol.[Strengthofrecommen- tients.Althoughmorethan170foodshavebeenidentifiedastrig-
dation:Moderate;CEvidence] gersoffoodallergy,thosecausingmostofthesignificantallergic
Summary Statement 60: Administer oral corticosteroids for reactions include peanut, tree nuts, fish, shellfish, milk, egg,
EGE as the preferred therapy. [Strength of recommendation: wheat, soy, and seeds.2,5,9-11 Food allergy (to foods other than
Weak;CEvidence] shellfish and fruits/vegetables) is more common in children
Summary Statement 61: Although immunotherapeutic ap- thaninadults.4,7,8,10-12Asdescribedelsewhereinthisparameter,
proaches, such as oral immunotherapy, in clinical trials milk,egg,wheat,andsoyallergiesaremorecommoninchildren
show promise in treating food allergy, they are not ready thaninadults.
for implementation in clinical practice at the present time Thereisahighco-occurrenceoffoodallergywithotheratopic
because of inadequate evidence for therapeutic benefit over diseases, including atopic dermatitis, asthma, and allergic
risks of therapy. [Strength of recommendation: Strong; rhinitis.2,6,13,14 In particular, children with moderate-to-severe
A Evidence] atopicdermatitisappeartohaveasignificantrisk(approximately
SummaryStatement62:Developawrittenactionplanfortreat- 35%)offoodallergy.13-15Therearenosimilarstudiesinadults,
ment of allergic reactions to food for adults and children. andthereforetheprevalenceofco-occurringfoodallergyinadults
[Strengthofrecommendation:Moderate;DEvidence] withatopicdermatitisisunknown.
SummaryStatement63:Inquireaboutandaddressbehavioral Cutaneous reactions to foods are some of the most common
changes because of bullying in patients with food allergy. This presentationsoffoodallergyandincludeIgE-mediated(urticaria,
JALLERGYCLINIMMUNOL SAMPSONETAL 1025
VOLUME134,NUMBER5
angioedema, flushing, and pruritus), cell-mediated (contact anaphylaxiscausethemostanxietyinpatientsandtheirfamilies.
dermatitis and dermatitis herpetiformis), and mixed IgE- and Theincidenceoffood-inducedanaphylaxisisunclear.The5US
cell-mediated(atopicdermatitis)reactions.Thesearedefinedas studies that have been conducted to estimate the prevalence of
follows: food-induced anaphylaxis have found wide differences in the
rates of hospitalization or emergency department visits for
d AcuteurticariaisacommonmanifestationofIgE-mediated
foodallergy,althoughfoodallergyisnotthemostcommon anaphylaxis, as assessed by International Classification of
Diseasescodesormedicalrecordreview,from1/100,000popu-
causeofacuteurticariaandisrarelyacauseofchronicur-
ticaria.16Urticariaisthemostcommonsymptominpatients lationtoashighas70/100,000population.25-29Theproportionof
experiencing food-induced anaphylaxis.17-19 anaphylaxiscasesthoughttobeduetofoodsinthesestudiesalso
d Angioedema most often occurs in combination with urti- variedwidely,rangingfrom13%to65%,withthelowestpercent-
cariaand,iffoodinduced,istypicallyIgEmediated.20An- agesfoundinthosestudieswithmorestringentdiagnosticcriteria
foranaphylaxis.Onestudyreportedthatthenumberofhospital-
gioedema is also a common symptom in patients with
anaphylaxis.17-19 izationsfor anaphylaxisincreasedwithincreasing age,whereas
another study reported total cases of anaphylaxis were almost
d Atopic dermatitis/atopic eczema is linked to a complex
twiceashighinchildrenasinadults.Thesevariationsmightbe
interaction between skin barrier dysfunction and environ-
mental factors, such as irritants, microbes, and aller- duetodifferencesinstudymethodsordifferencesinpopulations
gens.21-23 In some sensitized patients food allergens might studied. Although it is estimated that greater than 12 million
Americans have food allergies, data from the US Food and
be significant triggers for atopic dermatitis/atopic eczema,
Drug Administration’s National Electronic Injury Surveillance
especially ininfantsand youngchildren, inwhomfood al-
System of emergency department encounters suggest about
lergens are estimated to be a significant trigger in 30% to
40% of patients.21 125,000 visits per year for food-induced allergic reactions,
14,000visitsperyearforfood-inducedanaphylaxis,andapprox-
d Allergic contact dermatitis is a form of eczema caused by
cell-mediatedallergicreactionstochemicalhaptenspresent imately3,100hospitalizationsperyearrelatedtofoodallergy.26
Fatalities are rare and estimated to be less than 100 per year,
in some foods, either naturally (eg, mango) or as addi-
tives.24Clinicalfeaturesincludemarkedpruritus,erythema, withthemajorityoccurringduringthesecondthroughfourthde-
papules, vesicles, and edema. cadesoflife.30
ToreadthePracticeParameterinitsentirety,pleasedownload
d ContacturticariacausedbyfoodallergyisanIgE-mediated
theonlineversionofthisarticlefromwww.jacionline.org,www.
reaction caused by direct skin contact in a sensitized sub-
jcaai.org,orwww.allergyparameters.org.Pleasenotethatallref-
jects. Although common,reactions are typically not severe
erencescitedintheExecutiveSummarycanbefoundintheonline
and confined only to the site of contact.
document.Thereaderisreferredtotheonlineportionofthedocu-
Gastrointestinalreactionsarealsoafrequentmanifestationof ment formore detaileddiscussionof the comments made inthe
food allergy. However, the frequency and unpredictability of printedversion.