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.