Guidelines for the Diagnosis and Management of Food Allergy in the United States

58 Pages·2010·1.02 MB·English

Guidelines for the Diagnosis and Management of Food
Allergy in the United States: Report of the NIAID-Sponsored
Expert Panel
Acknowledgments
PrimaryAuthors NIAID-SponsoredExpertPanelAuthors
JoshuaA.Boyce,MD S.HasanArshad,MBBS,MRCP,DM,FRCP
DivisionofRheumatology,ImmunologyandAllergy SchoolofMedicine
BrighamandWomen’sHospital UniversityofSouthampton
DepartmentofMedicineHarvardMedicalSchool Southampton,UK
Boston,Mass TheDavidHideAsthmaandAllergyResearchCentre
StMary’sHospital
AmalAssa’ad,MD
Newport,IsleofWight,UK
DivisionofAllergyandImmunology
SouthamptonUniversityHospitalNHSTrust
CincinnatiChildren’sHospitalMedicalCenter
Southampton,UK
UniversityofCincinnati
Cincinnati,Ohio
SamiL.Bahna,MD,DrPH
A.WesleyBurks,MD DepartmentofPediatrics
DivisionofAllergyandImmunology SectionofAllergyandImmunology
DepartmentofPediatrics LouisianaStateUniversityHealthSciencesCenter
DukeUniversityMedicalCenter Shreveport,La
Durham,NC
LisaA.Beck,MD
StacieM.Jones,MD DepartmentofDermatology
DivisionofAllergyandImmunology UniversityofRochesterMedicalCenter
DepartmentofPediatrics Rochester,NY
UniversityofArkansasforMedicalSciences
CarolByrd-Bredbenner,PhD,RD,FADA
ArkansasChildren’sHospital
DepartmentofNutritionalSciences
LittleRock,Ark
RutgersUniversity
HughA.Sampson,MD NewBrunswick,NJ
ElliotandRoslynJaffeFoodAllergyInstitute
DivisionofAllergyandImmunology CarlosA.CamargoJr,MD,DrPH
DepartmentofPediatrics DepartmentofEmergencyMedicine
MountSinaiSchoolofMedicine DivisionofRheumatology,AllergyandImmunology
NewYork,NY DepartmentofMedicine
MassachusettsGeneralHospital
RobertA.Wood,MD HarvardMedicalSchool
DivisionofAllergyandImmunology Boston,Mass
DepartmentofPediatrics
TheJohnsHopkinsUniversitySchoolofMedicine LawrenceEichenfield,MD
Baltimore,Md DivisionofPediatricandAdolescentDermatology
RadyChildren’sHospital
MarshallPlaut,MD
SanDiego,Calif
DivisionofAllergy,Immunology,andTransplantation
DepartmentsofPediatricsandMedicine
NationalInstituteofAllergyandInfectiousDiseases
UniversityofCalifornia,SanDiego
NationalInstitutesofHealth
SanDiego,Calif
Bethesda,Md
GlennT.Furuta,MD
SusanF.Cooper,MSc
SectionofPediatricGastroenterology,Hepatology,andNutrition
DivisionofAllergy,Immunology,andTransplantation
DigestiveHealthInstitute
NationalInstituteofAllergyandInfectiousDiseases
Children’sHospitalDenver
NationalInstitutesofHealth
Aurora,Colo
Bethesda,Md
DepartmentofPediatrics
MatthewJ.Fenton,PhD NationalJewishHealth
DivisionofAllergy,Immunology,andTransplantation Denver,Colo
NationalInstituteofAllergyandInfectiousDiseases DepartmentofPediatrics
NationalInstitutesofHealth UniversityofColoradoDenverSchoolofMedicine
Bethesda,Md Aurora,Colo
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S2 BOYCEETAL JALLERGYCLINIMMUNOL
DECEMBER2010
JonM.Hanifin,MD ScrippsClinic
DepartmentofDermatology SanDiego,Calif
OregonHealthandScienceUniversity
F.EstelleR.Simons,MD
Portland,Ore
DepartmentsofPediatricsandChildHealthandImmunology
CarolJones,RN,AE-C FacultyofMedicine
AsthmaEducatorandConsultant UniversityofManitoba
AllergyandAsthmaNetworkMother’sofAsthmatics Winnipeg,Manitoba,Canada
McLean,Va
StephenJ.Teach,MD,MPH
MonicaKraft,MD DivisionofEmergencyMedicine
DivisionofPulmonary,Allergy,andCriticalCareMedicine Children’sNationalMedicalCenter
DepartmentofMedicine Washington,DC
DukeUniversityMedicalCenter
BarbaraP.Yawn,MD,MPH,MSc
Durham,NC
DepartmentofResearch
BruceD.Levy,MD OlmstedMedicalCenter
PartnersAsthmaCenter Rochester,Minn
PulmonaryandCriticalMedicine DepartmentofFamilyandCommunityHealth
BrighamandWomen’sHospitalandHarvardMedicalSchool UniversityofMinnesotaSchoolofMedicine
Boston,Mass Minneapolis,Minn
PhilLieberman,MD
ContributingAuthor
DivisionofAllergyandImmunology
DepartmentofMedicine
JulieM.Schwaninger,MSc
UniversityofTennesseeCollegeofMedicine
DivisionofAllergy,Immunology,andTransplantation
Memphis,Tenn
NationalInstituteofAllergyandInfectiousDiseases
StefanoLuccioli,MD NationalInstitutesofHealth
OfficeofFoodAdditiveSafety Bethesda,Md
USFoodandDrugAdministration
CollegePark,Md CorrespondingAuthor
KathleenM.McCall,BSN,RN MatthewJ.Fenton,PhD
Children’sHospitalofOrangeCounty DivisionofAllergy,Immunology,andTransplantation
Orange,Calif NationalInstituteofAllergyandInfectiousDiseases
NationalInstitutesofHealth
LyndaC.Schneider,MD
Bethesda,Md
DivisionofImmunology
6610RockledgeDrive,Room3105
Children’sHospitalBoston
Bethesda,Md20892
Boston,Mass
Phone:[phone]
RonaldA.Simon,MD Fax:[phone]
DivisionofAllergy,AsthmaandImmunology E-mail:[email protected]
Sourcesoffunding
PublicationofthisarticlewassupportedbytheFoodAllergyInitiative.
Disclosureofpotentialconflictofinterest:
J.A.BoycehasservedontheAdvisoryBoardofGlaxoSmithKline.Hehasservedasaconsultantand/orspeakerforAltana,GlaxoSmithKline,andMerck.Hehasreceivedfunding/
grantsupportfromtheNationalInstitutesofHealth.
A.Assa’adholds,orislistedasaninventoron,USpatentapplication#10/566903,entitled‘‘Geneticmarkersoffoodallergy.’’ShehasservedasaconsultantforGlaxoSmithKlineandas
aspeakerfortheAmericanCollegeofAllergy,Asthma,andImmunology,theNorthEastAllergySociety,theVirginiaAllergySociety,theNewEnglandAllergySociety,andthe
AmericanAcademyofPediatrics.DrAssa’adhasreceivedfunding/grantsupportfromGlaxoSmithKline.
A.W.Burksholds,orislistedasaninventoron,multipleUSpatentsrelatedtofoodallergy.HeownsstockinAllerteinandMastCell,Inc,andisaminoritystockholderinDannonCo
Probiotics.HehasservedasaconsultantforActoGeniXNV,McNeilNutritionals,MeadJohnson,andNovartis.Hehasservedonthespeaker’sbureauforEpiPen/Dey,LP,andhas
servedonthedatamonitoringcommitteeforGenentech.HehasservedonanexpertpanelforNutricia.DrBurkshasreceivedfunding/grantsupportfromtheFoodAllergyand
AnaphylaxisNetwork,Gerber,MeadJohnson,andtheNationalInstitutesofHealth.
S.M.JoneshasservedasaspeakerandgrantreviewerandhasservedonthemedicaladvisorycommitteefortheFoodAllergyandAnaphylaxisNetwork.Shehasreceivedfunding/grant
supportfromDyaxCorp,theFoodAllergyandAnaphylaxisNetwork,MeadJohnson,theNationalPeanutBoard,andtheNationalInstitutesofHealth.
H.A.Sampsonholds,orislistedasaninventoron,multipleUSpatentsrelatedtofoodallergy.HeownsstockinAllerteinTherapeutics.Heistheimmediatepastpresidentofthe
AmericanAcademyofAllergy,Asthma,andImmunology.HehasservedasaconsultantforAllerteinTherapeutics,theAmericanAcademyofAllergy,Asthma,andImmunology,
theFoodAllergyInitiative,andScheringPlough.Hehasreceivedfunding/grantsupportforresearchprojectsfromtheFoodAllergyInitiative,theNationalInstitutesofHealth
(DivisionofReceiptandReferral,NationalInstituteofAllergyandInfectiousDiseases,NationalCenterforComplementaryandAlternativeMedicine),andPhadiaAB.Heisaco-
ownerofHerbalSpring,LLC.
R.A.Woodhasservedasaspeaker/advisoryboardmemberforGlaxoSmithKline,Merck,andDey.Hehasreceivedfunding/grantsupportfromGenentechandtheNationalInstitutesof
Health(NationalInstituteofAllergyandInfectiousDiseases).
S.H.Arshadhasreceivedfunding/grantsupportfromtheNationalInstitutesofHealthandtheNationalInstituteofHealthResearch,UK.
S.L.Bahnahasreceivedfunding/grantsupportfromGenentech.
L.A.Beckhasreceivedfunding/grantsupportfromtheAmericanAcademyofAllergy,Asthma,andImmunology,theNationalEczemaAssociation,andtheNationalInstitutesof
Health.
JALLERGYCLINIMMUNOL BOYCEETAL S3
VOLUME126,NUMBER6
C.Byrd-BredbennerownsstockinJohnson&Johnson.Shehasreceivedfunding/grantsupportfromtheUSDepartmentofAgriculture,theCannedFoodAlliance,andtheNewJersey
DepartmentofHealthandSeniorServices.
C.A.CamargoJrhasconsultedforDeyandNovartis.Hehasreceivedfunding/grantsupportfromavarietyofgovernmentagenciesandnot-for-profitresearchfoundations,aswellas
DeyandNovartis.
L.Eichenfieldhasreceivedfunding/grantsupportfromavarietyofnot-for-profitfoundations,aswellasAstellas,Ferndale,Johnson&Johnson,Novartis,Sinclair,Stiefel,and
TherapeuticsInc.
G.T.Furutahasservedasaconsultantand/orspeakertoCeptionTherapeuticsandTAP.Hehasreceivedfunding/grantsupportfromtheAmericanGastrointestinalAssociationandthe
NationalInstitutesofHealth.
J.M.HanifinhasservedasservedasaconsultantforALZA,Anesiva,Inc,BarrierTherapeutics,Inc,Milliken&Company,NordicBiotech,NovartisPharmaceuticalsCorporation,
ShionogiUSA,TaishoPharmaceuticalR&D,Inc,TeikokuPharmaUSA,Inc,UCB,YorkPharma,ZARS,Inc,andZymoGenetics.Hehasservedasaninvestigatororreceived
researchfundingfromALZA,AstellasPharmaUS,Inc,AsubioPharmaceuticals,Inc,Centocor,Inc,Corgentech,Novartis,NucrystPharmaceuticals,SeattleGenetics,andShionogi
USA.
M.Krafthasservedasaconsultantand/orspeakerforAstra-Zeneca,Genentech,GlaxoSmithKline,Merck,Novartis,andSepracor.Shehasreceivedfunding/grantsupportfrom
Genentech,GlaxoSmithKline,theNationalInstitutesofHealthandNovartis.
B.D.Levyholds,orislistedasaninventoron,USpatentapplications#20080064746entitled‘‘Lipoxinsandaspirin-triggeredlipoxinsandtheirstableanalogsinthetreatmentof
asthmaandinflammatoryairwaydiseases’’and#20080096961entitled‘‘Useofdocosatrienes,resolvinsandtheirstableanalogsinthetreatmentofairwaydiseasesandasthma.’’He
ownsstockinResolvyxPharmaceuticals.HehasservedasaconsultantforBayerHealthcareandResolvyxPharmaceuticals.DrLevyhasreceivedfunding/grantsupportfromthe
NationalInstitutesofHealth.
P.Liebermanhasservedasaconsultantand/orspeakertoDeyLaboratories,Novartis,Schering-Plough,AstraZenica,Merck,TEVA,Pfizer,MEDA,Alcon,Genentech,Intelliject,and
theFoodAllergyandAnaphylaxisNetwork.HeispastpresidentoftheAmericanAcademyofAllergy,Asthma,andImmunology.
L.C.Schneiderhasservedasaconsultant/clinicaladvisorfortheFoodAllergyInitiative.Shehasreceivedfunding/grantsupportfromavarietyofnot-for-profitresearchfoundations,as
wellasNovartisandtheNationalInstitutesofHealth.
R.A.SimonhasservedasaspeakerforDeyLaboratories,Genentech,GlaxoSmithKline,Merck,Novartis,andtheUSFoodandDrugAdministration.
F.E.R.Simonsholdsapatenton‘‘Fast-disintegratingepinephrinetabletsforsublingualadministration.’’Sheisapast-presidentoftheAmericanAcademyofAllergy,Asthma,and
ImmunologyandoftheCanadianSocietyofAllergyandClinicalImmunology.SheisamemberoftheadvisoryboardsofDey,Intelliject,andALK-Abello.Shehasreceivedfunding/
grantsupportfromAllerGen,theCanadianAllergy,AsthmaandImmunologyFoundation/AnaphylaxisCanada,andtheCanadianInstitutesofHealthResearch.
S.J.TeachhasservedasaspeakerforAstraZeneca.Hehasreceivedfunding/grantsupportfromtheAstraZenecaFoundation,Aventis,theChildHealthCenterBoard,theCNMC
ResearchAdvisoryCouncil,theNationalAssociationofChainDrugStoresFoundation,theNationalInstitutesofHealth(NationalInstituteofAllergyandInfectiousDiseases;
NationalHeart,Lung,andBloodInstitute),Novartis/Genentech,theRobertWoodsJohnsonFoundation,theUSCentersforDiseaseControlandPrevention,theUSPublicHealth
Service,andtheWashington,DC,DepartmentofHealth.
Theotherauthorshavedeclaredthattheyhavenoconflictofinterest.
S4 BOYCEETAL JALLERGYCLINIMMUNOL
DECEMBER2010
Preface
Food allergy is an immune-based disease that has become a knowledge,whichwillhelpfocusthedirectionoffutureresearch
serioushealthconcernintheUnitedStates.Arecentstudy1esti- inthisarea.
matesthatfoodallergyaffects5%ofchildrenundertheageof5 TheGuidelineswere developed overa2-yearperiodthrough
yearsand4%ofteensandadults,anditsprevalenceappearstobe the combined efforts of an Expert Panel and Coordinating
on the increase. The symptoms of this disease can range from Committee representing 34 professional organizations, federal
mildtosevereand,inrarecases,canleadtoanaphylaxis,asevere agencies,andpatientadvocacygroups.TheExpertPaneldrafted
and potentially life-threatening allergic reaction. There are no theGuidelinesusinganindependent,systematicliteraturereview
therapiesavailabletopreventortreatfoodallergy:theonlypre- andevidencereportonthestateofthescienceinfoodallergy,as
ventionoption for the patient is to avoid the food allergen, and well as their expert clinical opinion. The National Institute of
treatmentinvolvesthemanagementofsymptomsastheyappear. Allergy and Infectious Diseases (NIAID), a component of the
Andbecausethemostcommonfoodallergens—eggs,milk,pea- National Institutes of Health (NIH), provided funding for this
nuts, tree nuts, soy, wheat, crustacean shellfish, and fish—are projectandplayedapivotalroleasorganizerand‘‘honestbroker’’
highlyprevalentintheUSdiet,patientsandtheirfamiliesmust oftheGuidelinesproject.
remainconstantlyvigilant. AstheleadNIHinstituteforresearchonfoodallergy,NIAIDis
ThedevelopmentoftheGuidelinesfortheDiagnosisandMan- deeply committed to improving the lives of patients with food
agement of Food Allergy in the United States began in 2008 to allergyandisproudtohavebeeninvolvedinthedevelopmentof
meet a long-standing need for harmonization of best clinical these Guidelines. As our basic understanding of the human
practices relatedtofoodallergyacrossmedical specialties.The immunesystemandfoodallergyinparticularincreases,wehope
resulting Guidelines reflect considerable effort by a wide range totranslatethisinformationintoimprovedclinicalapplications.
of participants toestablish consensus and consistencyin defini- Although there are many challenges, the potential benefit for
tions, diagnostic criteria, and management practices. They humanhealthwillbeextraordinary.
provideconciserecommendationsonhowtodiagnoseandman-
age foodallergy andtreatacutefood allergyreactions.In addi- AnthonyS.Fauci,MD
tion,theyprovideguidanceonaddressingpointsofcontroversy Director
in patient management and also identify gaps in our current NationalInstituteofAllergyandInfectiousDiseases
JALLERGYCLINIMMUNOL BOYCEETAL S5
VOLUME126,NUMBER6
Guidelines for the Diagnosis and Management of Food
Allergy in the United States: Report of the NIAID-Sponsored
Expert Panel
Foodallergyisanimportantpublichealthproblemthataffects
childrenandadultsandmaybeincreasing inprevalence. Abbreviationsused
Despitetheriskofsevereallergicreactionsandevendeath, AAP: AmericanAcademyofPediatrics
thereisnocurrenttreatmentforfoodallergy:thedisease can ACD: Allergiccontactdermatitis
ACIP: AdvisoryCommitteeonImmunizationPractices
onlybemanagedbyallergenavoidance ortreatmentof
AD: Atopicdermatitis
symptoms.Thediagnosisandmanagementoffoodallergyalso
AP: Allergicproctocolitis
mayvaryfromone clinicalpracticesettingtoanother.Finally,
APT: Atopypatchtest
becausepatients frequentlyconfusenonallergicfoodreactions,
BP: Bloodpressure
suchasfoodintolerance,with foodallergies,thereisan CC: CoordinatingCommittee
unfoundedbeliefamongthepublicthatfoodallergyprevalence CDC: CentersforDiseaseControlandPrevention
ishigherthanittrulyis.Inresponsetotheseconcerns,the CI: Confidenceinterval
NationalInstituteofAllergy andInfectiousDiseases,working CMA: Cow’smilkallergy
with34professionalorganizations,federalagencies,andpatient COI: Conflictofinterest
advocacygroups,ledthedevelopment ofclinicalguidelinesfor DBPCFC: Double-blind,placebo-controlledfoodchallenge
DRACMA: DiagnosisandRationaleforActionagainstCow’sMilk
thediagnosisandmanagementoffoodallergy.TheseGuidelines
Allergy
areintended forusebyawidevarietyofhealthcare
EAACI: EuropeanAcademyofAllergyandClinicalImmunology
professionals,includingfamilypracticephysicians,clinical
EG: Eosinophilicgastroenteritis
specialists, andnursepractitioners.TheGuidelinesincludea
EGID: Eosinophilicgastrointestinaldisorder
consensus definitionforfoodallergy,discusscomorbid eHF: Extensivelyhydrolyzedinfantformula
conditionsoftenassociatedwithfoodallergy,andfocusonboth eHF-C: Extensivelyhydrolyzedcaseinformula
IgE-mediated andnon-IgE-mediatedreactionstofood. Topics eHF-W: Extensivelyhydrolyzedwheyinfantformula
addressedincludetheepidemiology,naturalhistory,diagnosis, EoE: Eosinophilicesophagitis
andmanagementoffoodallergy,aswellasthemanagementof EP: ExpertPanel
severesymptomsandanaphylaxis.TheseGuidelinesprovide43 FA: Foodallergy
FAAN: FoodAllergyandAnaphylaxisNetwork
concise clinicalrecommendationsandadditionalguidanceon
FALCPA: FoodAllergenLabelingandConsumerProtectionAct
pointsofcurrentcontroversyinpatientmanagement.Theyalso
FPIES: Foodprotein-inducedenterocolitissyndrome
identifygapsinthecurrentscientificknowledgetobeaddressed
GI: Gastrointestinal
throughfutureresearch.(JAllergyClin Immunol
GINI: GermanNutritionalInterventionStudy
2010;126:S1-S58.) GRADE: GradingofRecommendationsAssessment,Development
andEvaluation
Keywords: Food,allergy,anaphylaxis,diagnosis,diseasemanage-
ICD-9-CM: InternationalClassificationofDiseases,NinthRevision,
ment,guidelines
ClinicalModification
ICU: Intensive-careunit
IM: Intramuscular
SECTION 1. INTRODUCTION
IV: Intravenous
1.1. Overview MDI: Metered-doseinhaler
MMR: Measles,mumps,andrubella
Food allergy (FA) isan important public health problem that
MMRV: Measles,mumps,rubella,andvaricella
affectsadultsandchildrenandmaybeincreasinginprevalence.
NIAID: NationalInstituteofAllergyandInfectiousDiseases
Despitetheriskofsevereallergicreactionsandevendeath,there
NICE: NationalInstituteforHealthandClinicalExcellence
isnocurrenttreatmentforFA:thediseasecanonlybemanagedby
(England/Wales)
allergen avoidance or treatment of symptoms. Moreover, the NSAID: Nonsteroidalanti-inflammatorydrug
diagnosisofFAmaybeproblematic,giventhatnonallergicfood OAS: Oralallergysyndrome
reactions,suchasfoodintolerance,arefrequentlyconfusedwith pHF: Partiallyhydrolyzedinfantformula
FAs.Additionalconcernsrelatetothedifferencesinthediagnosis pHF-W: Partiallyhydrolyzedwheyformula
andmanagementofFAindifferentclinicalpracticesettings. PI: Packageinsert
Due to these concerns, the National Institute of Allergy and RCT: Randomizedcontrolledtrial
RR: Relativerisk
Infectious Diseases (NIAID), part of the National Institutes of
SAFE: Seeksupport,Allergenidentificationandavoidance,
Health, working with more than 30 professional organizations,
Followupwithspecialtycare,Epinephrinefor
emergencies
sIgE: Allergen-specificIgE
SPT: Skinpricktest
ReceivedforpublicationOctober12,2010;acceptedforpublicationOctober13,2010.
WAO: WorldAllergyOrganization
0091-6749
doi:10.1016/j.jaci.2010.10.007
S6 BOYCEETAL JALLERGYCLINIMMUNOL
DECEMBER2010
federal agencies, and patient advocacygroups, led the develop- development of the NICE guidelines is also very similar
mentof‘‘bestpractice’’clinicalguidelinesforthediagnosisand to that used to generate the EAACI and US Guidelines. It
management of FA (henceforth referred to as the Guidelines). is expected that NICE will release the final guidelines in
Basedonacomprehensivereviewandobjectiveevaluationofthe early 2011.
recentscientificandclinicalliteratureonFA,theGuidelineswere d In 2008, the World Allergy Organization (WAO) Special
developedbyanddesignedforallergists/immunologists,clinical Committee on Food Allergy identified cow’s milk allergy
researchers, and practitioners in the areas of pediatrics, family (CMA) as a topic that would benefit from a reappraisal
medicine, internal medicine, dermatology, gastroenterology, of the more recent literature and an updating of existing
emergencymedicine,pulmonaryandcriticalcaremedicine,and guidelines,whichsummarizedtheachievementsofthepre-
others. cedingdecadeanddealtmainlywithprevention.Itisinthis
The Guidelines focus on diseases that are definedas FA (see context that the WAO Diagnosis and Rationale for Action
section2.1)andincludebothIgE-mediatedreactionstofoodand against Cow’s Milk Allergy (DRACMA) was created.4
somenon-IgE-mediatedreactionstofood.TheGuidelinesdonot Theevidence-basedDRACMAguidelinescoverdiagnostic
discuss celiac disease, which is an immunologic non-IgE- algorithms, challenge-testing methodology, consideration
mediatedreactiontocertainfoods.Althoughthisisanimmune- of appropriate sensitization tests, and the limitations of
based disease involving food, existing clinical guidelines for diagnostic procedures for CMA. In addition, there is dis-
celiacdiseasewillnotberestatedhere.2,3 cussion of appropriate substitute feeding formulas that
Insummary,theGuidelines: can be used in various clinical situations, with consider-
ation, for example, of patient preferences, costs, and local
d Provide concise recommendations (guidelines numbered
availability.
1through43)toawidevarietyofhealthcareprofessionals
d In2006,anFApracticeparameterwaspublishedbyatask
on how to diagnose FA, manage ongoing FA, and treat
force established by the American College of Allergy,
acute FA reactions
Asthma and Immunology, the American Academy of
d Identify gaps in the current scientific knowledge to be ad-
Allergy, Asthma, and Immunology, and the Joint Council
dressed through future research
of Allergy, Asthma and Immunology.5 The document,
d Identify and provide guidance on points of current contro-
FoodAllergy:APracticeParameter,hasbeenanoutstand-
versy in patient management
ingresourcefortheallergyandimmunologyclinicalcom-
A companion Summary of the NIAID-Sponsored Expert munity,butmaynothavehadbroadimpactoutsideofthis
Panel Report has been prepared from the Guidelines. This community.
Summary contains all 43 recommendations, all ‘‘In summary’’
Notably, the new US Guidelines are specifically aimed at all
statements,definitions,1diagnostictableforFA,and1summary
healthcareprofessionalswhocareforadultandpediatricpatients
tableforthepharmacologicmanagementofanaphylaxis.Itdoes
with FA and related comorbidities. Thus, it is hoped that these
not contain background information, supporting evidence for
Guidelineswillhavebroadimpactandbenefitforallhealthcare
the recommendations and ‘‘In summary’’statements, and other
professionals.
summarytablesofdata.TheSummaryisnotintendedtobethe
sole source of guidance for the health care professional, who
1.3. How the Guidelines were developed
should consult the Guidelines for complete information.
1.3.1. The Coordinating Committee. NIAIDestablisheda
Finally, these Guidelines do not address the management of
Coordinating Committee (CC), whose members are listed in
patients with FA outside of clinical care settings (for example,
Appendix A, to oversee the development of the Guidelines; re-
schoolsandrestaurants)ortherelatedpublichealthpolicyissues.
view drafts of the Guidelines for accuracy, practicality, clarity,
Theseissuesarebeyondthescopeofthisdocument.
andbroadutilityoftherecommendationsinclinicalpractice;re-
view the final Guidelines; and disseminate the Guidelines. The
1.2. Relationship of the US Guidelines to other
CCmemberswerefrom34professionalorganizations,advocacy
guidelines
groups,andfederalagencies,andeachmemberwasvettedforfi-
Otherorganizationshaverecentlydeveloped,orarecurrently
nancialconflictofinterest(COI)byNIAIDstaff.PotentialCOIs
developing,guidelinesforFA.
werepostedontheNIAIDWebsiteathttp://www.niaid.nih.gov/
d TheEuropeanAcademyofAllergyandClinicalImmunol- topics/foodAllergy/clinical/Pages/FinancialDisclosure.aspx.
ogy (EAACI) has created a task force that is currently 1.3.2. The Expert Panel. The CC convened an Expert Panel
developing guidelines for the diagnosis and management (EP) in March 2009 that was chaired by Joshua Boyce, MD
of FA. The model for development of guidelines by this (BrighamandWomen’sHospital,Boston,Mass).Panelmembers
task force is very similar to that used to generate these werespecialistsfromavarietyofrelevantclinical,scientific,and
USGuidelines.FollowingcompletionoftheEAACIguide- publichealthareas(seeAppendixB).Eachmemberwasvettedfor
lines, additional efforts will be made to harmonize the US financialCOIbyNIAIDstaffandapprovedbytheCC.Potential
Guidelines with the EAACI guidelines. COIswerepostedontheNIAIDWebsiteprovidedinsection1.3.1.
d Clinical practice guidelines on FA in children and young The charge to the EP was to use an independent, systematic
people are being developed for use in the National Health literaturereview(seesection1.3.3),inconjunctionwithconsen-
ServiceinEngland,Wales,andNorthernIrelandbytheNa- susexpertopinionandEP-identifiedsupplementarydocuments,
tionalInstituteforHealthandClinicalExcellence(NICE). todevelopGuidelinesthatprovideacomprehensiveapproachfor
Theseguidelinesareintendedforusepredominantlyinpri- diagnosing and managing FA based on the current state of the
mary care and community settings. The model used for science.
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TheEPorganizedtheGuidelinesinto5majortopicareas: acompletelistofreferencesisavailableathttp://www.rand.org/
pubs/working_papers/WR757-1/.
d Definitions,prevalence,andepidemiologyofFA(section2)
1.3.4. Assessing the quality of the body of evidence.
d Natural history of FA and associated disorders (section 3)
Foreachkeyquestion,inadditiontoassessingthequalityofeach
d Diagnosis of FA (section 4)
oftheincludedstudies,RANDassessedthequalityofthebodyof
d Management of nonacute food-induced allergic reactions
evidence using the Grading of Recommendations Assessment,
and prevention of FA (section 5)
Development and Evaluation (GRADE) approach,8 which was
d Diagnosis and management of food-induced anaphylaxis
developedin2004.GRADEprovidesacomprehensiveandtrans-
and other acute allergic reactions to foods (section 6)
parentmethodologytodeveloprecommendationsforthediagno-
Subtopicsweredevelopedforeachofthese5broadtopicareas. sis,treatment,andmanagementofpatients.Inassessingthebody
1.3.3. The independent, systematic literature review of evidence, GRADE considers study design and other factors,
and report. RAND Corporation prepared an independent, suchastheprecision,consistency,anddirectnessofthedata.Us-
systematic literature review and evidence report on the state of ingthisapproach,GRADEthenprovidesagradeforthequalityof
thescienceinFA.RANDhadrespondedtotheNIAIDRequest thebodyofevidence.
for Proposal AI2008035, Systematic Literature Review and Based on the available scientific literature on FA, which in
EvidenceBasedReportonFoodAllergy,andwassubsequently someareaswasminimal,RANDusedtheGRADEapproachto
awardedthecontractinSeptember2008.Thecontract’sprincipal assess the overall quality of evidence for each key question
investigator wasPaulG.Shekelle, MD,PhD,aninternationally assigned by the EP and assigned a grade according to the
recognized expert in the fields of practice guidelines and followingcriteria9,10:
meta-analysis.
NIAIDandtheEPdevelopedanextensivesetofkeyquestions,6 d High—Furtherresearchisveryunlikelytohaveanimpact
on the quality of the body of evidence, and therefore the
whichwerefurtherrefinedindiscussionswithRAND.Literature
confidence in the recommendation is high and unlikely to
searcheswereperformedonPubMed,CochraneDatabaseofSys-
change.
tematicReviews,CochraneDatabaseofAbstractsofReviewsof
d Moderate—Furtherresearchislikelytohaveanimpacton
Effects,CochraneCentralRegisterofControlledTrials,andthe
the quality of the body of evidence and may change the
World Allergy Organization Journal, a relevant journal that is
recommendation.
notincludedinPubMed.Inmostcases,searcheswerelimitedto
d Low—Furtherresearchisverylikelytohavean important
theyears1988(January)to2009(September),withnolanguage
impactonthebodyofevidenceandislikelytochangethe
restrictions. Additional publications identified by the EP and
recommendation.
others involved in the review process alsowere included in the
RAND review if and only if they met the RAND criteria for AGRADE designationof ‘‘Low’’for the quality of evidence
inclusion. does not imply that an article is not factually correct or lacks
RANDresearchersscreenedalltitlesfoundthroughsearches, scientificmerit.Forexample,aperfectlydesignedandexecuted
as well as those that were submitted by the EP or NIAID. studyofatreatmentinasmallsamplethatisfromasinglesiteof
Screeningcriteriawereestablishedtofacilitatetheidentification highly selected patients might still yield an overall GRADE of
of articles concerning definitions, diagnoses, prevention, treat- ‘‘Low.’’ This is because a single small study is characterized as
ment, management, and other topics. Articles were included or ‘‘sparse’’data, and the patient population may not be represen-
excludedbasedonarticletypeandstudypurposeasfollows: tativeofthelargerpopulationofpatientswithFA.Eachofthese
factorsreducesthelevelofevidencefrom‘‘High,’’whichishow
d Article type
randomized controlled trial (RCT) evidence is designated ini-
– Included: Original research or systematic reviews
tially.Itisworthemphasizingthatthese2limitationsarenotof
– Excluded: Background or contextual reviews; nonsys-
thestudyperse,butofthebodyofevidence.Replicationofthe
tematic reviews; commentary; other types of articles
study’sresultonotherpopulationswouldresultinaGRADEof
d Study purpose ‘‘High.’’ItshouldbenotedthattheEPrecommendationsmadein
– Included: Incidence/prevalence/natural history; diagno- theseGuidelinesareoftenbasedonaGRADEclassificationofthe
sis; treatment/management/prevention qualityofevidenceas‘‘Low,’’thusnecessitatingmorecontribu-
– Excluded:NotaboutFA;aboutsomeaspectnotlistedin tiontotherecommendationfromexpertopinion.
the ‘‘included’’ category For additional information to understand the concept of
‘‘qualityofthebodyofevidence,’’pleaseseeAppendixC.
RANDscreenedmorethan12,300titles,reviewedmorethan
1.3.5.PreparationofdraftGuidelinesandExpertPanel
1,200 articles, abstracted nearly 900 articles, and included 348
deliberations. The EP prepared a draft version of the Guide-
articles in the final RAND report. Two RAND investigators
linesbasedontheRANDevidencereportandalsosupplementary
independentlyreviewedalltitlesandabstractstoidentifypoten-
documentsthatwereidentifiedbytheEPbutnotincludedinthe
tiallyrelevantarticles.Articlesthatmettheinclusioncriteriawere
independentlyabstractedbyasingleRANDinvestigator.Because RANDreport.
The supplementary documents contained information of sig-
ofthelargenumberofarticlesandtheshorttimeforthereview,
nificant value that was not included in the systematic literature
articles were not independently abstracted by 2 RAND investi-
gators (dual-abstracted). However, team members worked to- review due to the objective criteria for inclusion or exclusion
established by RAND, such as limits on demographics, study
gether closely and data were double-checked. Selected
population size, and study design. The EP used this additional
conclusions from the report have been published in a peer-
reviewed journal,7 and the full version of the report with information only to clarify and refine conclusions drawn from
S8 BOYCEETAL JALLERGYCLINIMMUNOL
DECEMBER2010
sourcesinthesystematicliteraturereview.Thesedocumentsare TheGuidelinesareintendedtoassisthealthcareprofessionalsin
denotedwithanasterisk(*)inReferences. making appropriate decisions about patient care in the United
Italsoshouldbenotedthatincludedreferencesareillustrative States.Therecommendationsarenotfixedprotocolsthatmustbe
ofthedataandconclusionsdiscussedineachsection,anddonot followed.HealthcareprofessionalsshouldtaketheseGuidelines
represent the totality of relevant references. For a full list of intoaccountwhenexercisingtheirclinicaljudgment.However,this
relevantreferences,thereadershouldrefertothefullversionof guidancedoesnotoverridetheirresponsibilitytomakedecisions
theRANDreport. appropriate to the circumstances of the individual patient, in
InOctober2009,theEPdiscussedthefirstwrittendraftversion consultation with the patient, guardian, or caregiver. Clinical
of the Guidelines and their recommendations. Following the judgment on the management of individual patients remains
meeting, the EP incorporated any panel-wide changes to the paramount.Healthcareprofessionals,patients,andtheirfamilies
recommendations within the draft Guidelines. These revised needtodevelopindividualtreatmentplansthataretailoredtothe
recommendationswerethensubjecttoaninitialpanel-widevote specificneedsandcircumstancesofthepatient.Thisdocumentis
to identify where panel agreement was less than 90%. Contro- intended as a resource to guide clinical practice and develop
versialrecommendationswerediscussedviateleconferenceand educationalmaterialsforpatients,theirfamilies,andthepublic.Itis
e-mail to achieve group consensus. Following discussion and notanofficialregulatorydocumentofanygovernmentagency.
revisionasnecessary,asecondvotewasheld.Allrecommenda-
tionsthatreceived90%orhigheragreementwereincludedinthe
SECTION 2. DEFINITIONS, PREVALENCE, AND
draftGuidelinesforpublicreviewandcomment.
Inadditiontothe43recommendations,sections3,5,and6ofthe EPIDEMIOLOGY OF FOOD ALLERGY
Guidelinescontain‘‘Insummary’’statements.Thesestatementsare
2.1. Definitions
intendedtoprovidehealthcareprofessionalswithsignificantinfor-
2.1.1. Definitions of food allergy, food, and food aller-
mationthatdidnotwarrantarecommendation,orareinplaceofa
gens.TheEPcametoconsensusondefinitionsusedthroughout
recommendationwhentheEPortheCCcouldnotreachconsensus.
theGuidelines.
All‘‘Insummary’’statementsreceived90%orhigheragreement.
A food allergy is defined as an adverse health effect arising
1.3.6. Public comment period and draft Guidelines
from a specific immune response that occurs reproducibly on
revision. ThedraftGuidelineswerepostedtotheNIAIDWeb
exposuretoagivenfood.
site in March 2010 for a period of 60 days to allow for public
Afoodisdefinedasanysubstance—whetherprocessed,semi-
review and comment. More than 550 comments were collected
processed,orraw—thatisintendedforhumanconsumption,and
andreviewedbytheCC,theEP,andNIAID.TheEPrevisedthe
includesdrinks,chewinggum,foodadditives,anddietarysupple-
Guidelinesinresponsetosomeofthesecomments.
ments.Substancesusedonlyasdrugs,tobaccoproducts,andcos-
FurtherdeliberationbetweentheCCandtheEPresultedinthe
metics (such as lip-care products) that may be ingested are not
revisionof5recommendations.Inaddition,section5.1.11,which
included.
discussesvaccinationinpatientswithallergytohen’segg(hence-
Food allergens are defined as those specific components of
forth referred to as egg), also underwent substantial revision to
foodoringredientswithinfood(typicallyproteins,butsometimes
bring it into better alignment with national vaccine policies.
also chemical haptens) that are recognized by allergen-specific
Consequently, the EP developed 1 recommendation for vaccina-
immunecellsandelicitspecificimmunologicreactions,resulting
tionwithMMRandMMRV,and3‘‘Insummary’’statementsfor
in characteristic symptoms. Some allergens (most often from
influenza, yellow fever, and rabiesvaccinations. All new recom-
fruitsandvegetables)causeallergicreactionsprimarilyifeaten
mendations and ‘‘In summary’’ statements were subjected to a
whenraw.However,mostfoodallergenscanstillcausereactions
panel-widevoteandachieved90%consensusormore.
evenaftertheyhavebeencookedorhaveundergonedigestionin
ThefinalGuidelineswerereviewedbytheCC.
thestomachandintestines.Aphenomenoncalledcross-reactiv-
1.3.7. Dissemination of the final Guidelines. The final
itymayoccurwhenanantibodyreactsnotonlywiththeoriginal
Guidelineswerepublishedandmadepublicallyavailableviathe
allergen,butalsowithasimilarallergen.InFA,cross-reactivity
Internet.
occurswhenafoodallergensharesstructuralorsequencesimilar-
itywithadifferentfoodallergenoraeroallergen,whichmaythen
1.4. Defining the strength of each clinical guideline
triggeranadversereactionsimilartothattriggeredbytheoriginal
TheEPhasusedtheverb‘‘recommends’’or‘‘suggests’’ineach
food allergen. Cross-reactivity is common,for example, among
clinical guideline. These words convey the strength of the
different shellfish and different tree nuts. (See Appendix D,
guideline,definedasfollows:
TableS-I.)
d Recommend is used when the EP strongly recommended Foodoils—suchassoy,corn,peanut,andsesame—rangefrom
for or against a particular course of action. very low allergenicity (if virtually all of the food protein is
d Suggest is used when the EP weakly recommended for or removedinprocessing)toveryhighallergenicity(iflittleofthe
against a particular course of action. foodproteinisremovedinprocessing).
2.1.2.Definitionsofrelatedterms.Thetermsallergyandal-
1.5. Summary
lergicdiseasearebroadlyencompassingandincludeclinicalcon-
The Guidelines present 43 recommendations by an indepen- ditionsassociatedwithalteredimmunologicreactivitythatmaybe
dent EP for the diagnosis and management of FA and food- eitherIgEmediatedornon-IgEmediated.IgEisauniqueclassof
inducedanaphylaxis.Three‘‘Insummary’’statementsprovidea immunoglobulinthatmediatesanimmediateallergicreaction.
briefreviewofUSnationalvaccinepolicyspecificallyrelatedto Thetermfoodhypersensitivityalsoisoftenusedtodescribe
vaccinationofpatientswitheggallergy. FA, although other groups have used this term more broadly to
JALLERGYCLINIMMUNOL BOYCEETAL S9
VOLUME126,NUMBER6
describeallotherfoodreactions,includingfoodintolerances.In Non-immunemediatedreactionsorfoodintolerancesinclude
theseGuidelines,theEPhasrefrainedfromusingthetermfood metabolic,pharmacologic,toxic,andundefinedmechanisms.In
hypersensitivity except for the term immediate gastrointestinal some cases, these reactions may mimic reactions typical of an
(GI)hypersensitivity,whichisIgEmediated. immunologic response. It is therefore important to keep these
Becauseindividualscandevelopallergicsensitization(asevi- food components or mechanisms in mind when evaluating
dencedbythepresenceofallergen-specificIgE(sIgE))tofoodal- adversefoodreactions.Mostadversereactionstofoodadditives,
lergens without having clinical symptoms on exposure to those suchasartificialcolors(forexample,FD&Cyellow5[tartrazine])
foods,ansIgE-mediatedFArequiresboththepresenceofsensiti- andvariouspreservatives(forexample,sulfites),havenodefined
zation and the development of specific signs and symptoms on immunologic mechanisms. These food components, as well as
exposuretothatfood.Sensitizationaloneisnotsufficienttode- otherfoodscontributingtofoodintolerances,arenotspecifically
fineFA. discussedintheseGuidelines.
AlthoughFAismostoftencausedbysIgE-mediatedreactions 2.1.3.Definitions of specificfood-induced allergiccon-
to food, the EP also considered literature relevant to reactions ditions.Anumberofspecificclinicalsyndromesmayoccurasa
likely mediated by immunologic but non-IgE-induced mecha- resultofFA,andtheirdefinitionsareasfollows:
nisms,includingfoodprotein-inducedenteropathy,exacerbations Food-inducedanaphylaxisisaseriousallergicreactionthatis
of eosinophilic GI disorders (EGIDs) (eosinophilic gastritis, rapidinonsetandmaycausedeath.12,13Typically,IgE-mediated
eosinophilicenteritis,eosinophiliccolitis,andeosinophilicgas- food-inducedanaphylaxisisbelievedtoinvolvesystemicmedia-
troenteritis), and food-induced allergic contact dermatitis. In tor release from sensitized mast cells and basophils. In some
theseconditions,sensitizationtofoodproteincannotbedemon- cases, such as food-dependent, exercise-induced anaphylaxis,
stratedbasedonsIgE.Thediagnosisofnon-IgE-mediatedFAis theabilitytoinducereactionsdependsonthetemporalassocia-
basedonsignsandsymptomsoccurringreproduciblyonexposure tion between food consumption and exercise, usually within 2
tofood,resolutionofthosesignsandsymptomswithspecificfood hours.
avoidance, and, most often, histologic evidence of an immuno- GI food allergies include a spectrum of disorders that result
logicallymediatedprocess,suchaseosinophilicinflammationof from adverse immunologic responses to dietary antigens. Al-
theGItract. though significant overlap may exist between these conditions,
TheseGuidelinesgenerally usethe termtoleratetodenotea several specific syndromes have been described. These are de-
condition where an individual has either naturally outgrown an finedasfollows:
FAorhasreceivedtherapyandnolongerdevelopsclinicalsymp-
d ImmediateGIhypersensitivityrefers toan IgE-mediated
tomsfollowingingestionofthefood.Thisabilitytotoleratefood
FAinwhichupperGIsymptomsmayoccurwithinminutes
doesnotdistinguish2possibleclinicalstates.Individualsmaytol-
and lower GI symptoms may occur either immediately or
eratefoodonlyforashortterm,perhapsbecausetheyhavebeen
witha delay of up toseveral hours.14,15 Thisis commonly
desensitizedbyexposuretothefood.Alternatively,theymayde-
seenasamanifestationofanaphylaxis.AmongtheGIcon-
veloplong-termtolerance.Thespecifictermtoleranceisusedin
ditions,acuteimmediatevomitingisthemost commonre-
theseGuidelinestomeanthatanindividualissymptomfreeafter
action and the one best documented as immunologic and
consumption of the food or upon oral food challenge weeks,
IgE mediated.
months,orevenyearsafterthecessationoftreatment.Theimmu-
d Eosinophilic esophagitis (EoE) involveslocalized eosino-
nological mechanisms that underlie tolerance in humans are philicinflammationoftheesophagus.16-18Insomepatients,
poorlyunderstood.
avoidance of specific foods will result in normalization of
Although many different foods and food components have
histopathology. Although EoE is commonly associated
been recognized as food allergens,11 these Guidelines focus on
with the presence of food-specific IgE, the precise causal
onlythosefoodsthatareresponsibleforthemajorityofobserved
role of FA in its etiology is not well defined. Both IgE-
adverse allergic or immunologic reactions. Moreover, foods or
and non-IgE-mediated mechanisms appear to be involved.
food components that elicit reproducible adverse reactions but
Inchildren,EoEpresentswithfeedingdisorders,vomiting,
do not have established or likely immunologic mechanisms are
reflux symptoms, and abdominal pain. In adolescents and
not considered food allergens. Instead, these non-immunologic
adults,EoEmostoftenpresentswithdysphagiaandesoph-
adverse reactions are termed food intolerances. For example,
ageal food impactions.
anindividualmaybeallergictocow’smilk(henceforthreferred
d Eosinophilicgastroenteritis(EG)alsoisbothIgE-andnon-
toasmilk)duetoanimmunologicresponsetomilkprotein,oral- IgE-mediatedandcommonlylinkedtoFA.15EGdescribesa
ternatively,thatindividualmaybeintoleranttomilkduetoanin-
constellationofsymptomsthatvarydependingonthepor-
ability to digest the sugar lactose. In the former situation, milk
tionoftheGItractinvolvedandapathologicinfiltrationof
protein is considered an allergen because it triggers an adverse
theGItractbyeosinophils,whichmaybelocalizedorwide-
immunologicreaction.Inabilitytodigestlactoseleadstoexcess
spread.EoEisacommonmanifestationofEG.
fluidproductionintheGItract,resultinginabdominalpainand
d Foodprotein-inducedallergicproctocolitis(AP)typically
diarrhea.Thisconditionistermedlactoseintolerance,andlactose
presentsininfantswhoseemgenerallyhealthybuthavevis-
isnotanallergenbecausetheresponseisnotimmunebased.
ible specks or streaks of blood mixed with mucus in the
Note: The words tolerance and intolerance are unrelated stool.15 IgE to specific foods is generally absent. The lack
terms, even though the spelling of the words implies that they
ofsystemicsymptoms,vomiting,diarrhea,andgrowthfail-
areopposites.
urehelpsdifferentiatethisdisorderfromotherGIFAdisor-
Adversereactionstofoodcanthereforebestbecategorizedas
ders that present with similar stool patterns. Because there
those involving immune-mediated or non-immune-mediated
are no specific diagnostic laboratory tests, the causal role
mechanisms,assummarizedinFig1.
S10 BOYCEETAL JALLERGYCLINIMMUNOL
DECEMBER2010
FIG1. Typesofadversereactionstofood
of food allergens such as those found in milk or soy is in- d Atopicdermatitis (AD),also knownas atopiceczema, is
ferred from a characteristic history on exposure. Many in- linked to a complex interaction between skin barrier dys-
fantspresentwhilebeingbreast-fed,presumablyasaresult function and environmental factors such as irritants, mi-
ofmaternallyingestedproteinsexcretedinbreastmilk. crobes, and allergens.20 Null mutations of the skin barrier
d Food protein-induced enterocolitissyndrome (FPIES)is proteinfilaggrinmayincreasetheriskfortranscutaneousal-
another non-IgE-mediated disorder that usually occurs in lergen sensitizationandthe developmentofFA insubjects
young infants and manifests as chronic emesis, diarrhea, with AD.21-23 Although the EP does not mean to imply
and failure to thrive. Upon re-exposure to the offending thatADresultsfromFA,theroleofFAinthepathogenesis
food after a period of elimination, a subacute syndrome and severity of this condition remains controversial.24 In
can present with repetitive emesis and dehydration.13,15 somesensitizedpatients,particularlyinfantsandyoungchil-
Milk and soy protein are the most common causes, al- dren, food allergens can induce urticarial lesions, itching,
thoughsomestudiesalsoreportreactionstootherfoods,in- andeczematousflares,allofwhichmayaggravateAD.19
cludingrice,oat,orothercerealgrains.Asimilarcondition d Allergic contact dermatitis (ACD) is a form of eczema
alsohasbeenreportedinadults,mostoftenrelatedtocrus- causedbycell-mediatedallergicreactionstochemicalhap-
tacean shellfish ingestion. tensthatareadditivestofoodsoroccurnaturallyinfoods,
d Oral allergy syndrome (OAS), also referred to as pollen- suchasmango.25Clinicalfeaturesincludemarkedpruritus,
associated FA syndrome, is a form of localized IgE- erythema, papules, vesicles, and edema.
mediated allergy, usually to raw fruits or vegetables, with d Contact urticaria can be either immunologic (IgE-medi-
symptoms confined to the lips, mouth, and throat. OAS ated reactions to proteins) or non-immunologic (caused
mostcommonlyaffectspatientswhoareallergictopollens. by direct histamine release).
Symptoms include itching of the lips, tongue, roof of the
Respiratory manifestations of IgE-mediated FA occur fre-
mouth,andthroat,withorwithoutswelling,and/ortingling
quently during systemic allergic reactions and are an important
of the lips, tongue, roof of the mouth, and throat. indicatorofsevereanaphylaxis.26However,FAisanuncommon
causeofisolatedrespiratorysymptoms,namelythoseofrhinitis
Cutaneous reactions tofoods are some of the most common
andasthma.
presentationsofFAandincludeIgE-mediated(urticaria,angioe-
Heinersyndromeisararediseaseininfantsandyoungchil-
dema,flushing,pruritus),cell-mediated(contactdermatitis,der-
dren.Causedprimarilybytheingestionofmilk,itischaracterized
matitis herpetiformis), and mixed IgE- and cell-mediated
bychronicorrecurrentlowerrespiratorysymptomsoftenassoci-
(atopicdermatitis)reactions.Thesearedefinedasfollows:
atedwith27,28:
d AcuteurticariaisacommonmanifestationofIgE-mediated
FA,althoughFAisnotthemostcommoncauseofacuteur- d Pulmonary infiltrates
ticariaandisrarelyacauseofchronicurticaria.19Lesionsde- d Upper respiratory symptoms
veloprapidlyafteringestingtheproblemfoodandappearas d GI symptoms
polymorphic, round, or irregular-shaped pruritic wheals, d Failure to thrive
ranginginsizefromafewmillimeterstoseveralcentimeters. d Iron-deficiency anemia
d Angioedema most often occurs in combination with urti- The syndrome is associated with non-IgE-mediated immune
caria and, if food induced, is typically IgE mediated. It is responses, such as precipitating antibodies to milk protein
characterized by nonpitting, nonpruritic, well-defined fractions. Evidence often exists of peripheral eosinophilia, iron
edematous swelling that involves subcutaneous tissues deficiency, and deposits of immunoglobulins and C3 in lung
(forexample,face,hands,buttocks,andgenitals),abdomi- biopsies in some cases. Milk elimination leads to marked
nalorgans,ortheupperairway.19Whentheupperairwayis improvement in symptoms within days and clearing of pulmo-
involved,laryngealangioedemaisamedicalemergencyre- naryinfiltrateswithinweeks.28Theimmunopathogenesisofthis
quiringpromptassessment.Bothacuteangioedemaandur- disorder is not understood, but seems to combine cellular and
ticaria are common features of anaphylaxis. immune-complexreactions,causingalveolarvasculitis.Insevere