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Food Allergy in Children Guest Editors HEMANT P. SHARMA, MD, MHS ROBERT A. WOOD, MD MAX J. COPPES, MD, PhD, MBA PEDIATRIC CLINICS OF NORTH AMERICA www.pediatric.theclinics.com April 2011 • Volume 58 • Number 2 SAUNDERS an imprint of ELSEVIER, Inc. W.B.SAUNDERSCOMPANY ADivisionofElsevierInc. 1600JohnF.KennedyBoulevard(cid:2)Suite1800(cid:2)Philadelphia,Pennsylvania19103-2899 http://www.theclinics.com THEPEDIATRICCLINICSOFNORTHAMERICAVolume58,Number2 April2011ISSN0031-3955,ISBN-13:978-1-4557-0786-7 Editor:KerryHolland DevelopmentalEditor:DonaldMumford (cid:2)2011ElsevierInc.Allrightsreserved. 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GOALSTATEMENT ThegoalofthePediatricClinicsofNorthAmericaistokeeppracticingphysiciansandresidentsuptodatewithcurrentclin- icalpracticeinpediatricsbyprovidingtimelyarticlesreviewingthestate-of-the-artinpatientcare. ACCREDITATION ThePediatricClinicsofNorthAmericaisplannedandimplementedinaccordancewiththeEssentialAreasandPoliciesofthe AccreditationCouncilforContinuingMedicalEducation(ACCME)throughthejointsponsorshipoftheUniversityOfVirginia SchoolOfMedicineandElsevier.TheUniversityOfVirginiaSchoolofMedicineisaccreditedbytheACCMEtoprovidecon- tinuingmedicaleducationforphysicians. TheUniversityofVirginiaSchoolofMedicinedesignatesthiseducationalactivityforamaximumof15AMAPRACategory 1Credits(cid:3)foreachissue,90creditsperyear.Physiciansshouldonlyclaimcreditcommensuratewiththeextentoftheir participationintheactivity. TheAmericanMedicalAssociationhasdeterminedthatphysiciansnotlicensedintheUSwhoparticipateinthisCMEactivity areeligibleforamaximumof15AMAPRACategory1Credits(cid:3)foreachissue,90creditsperyear. Creditcanbeearnedbyreadingthetextmaterial,takingtheCMEexaminationonlineathttp://www.theclinics.com/home/ cme,andcompletingtheevaluation.Aftertakingthetest,youwillberequiredtoreviewanyandallincorrectanswers. Followingcompletionofthetestandevaluation,yourcreditwillbeawardedandyoumayprintyourcertificate. FACULTYDISCLOSURE/CONFLICTOFINTEREST TheUniversityofVirginiaSchoolofMedicine,asanACCMEaccreditedprovider,endorsesandstrivestocomplywiththe AccreditationCouncilforContinuingMedicalEducation(ACCME)StandardsofCommercialSupport,CommonwealthofVir- giniastatutes,UniversityofVirginiapoliciesandprocedures,andassociatedfederalandprivateregulationsandguidelines ontheneedfordisclosureandmonitoringofproprietaryandfinancialintereststhatmayaffectthescientificintegrityandbal- anceofcontentdeliveredincontinuingmedicaleducationactivitiesunderourauspices. TheUniversityofVirginiaSchoolofMedicinerequiresthatallCMEactivitiesaccreditedthroughthisinstitutionbedeveloped independentlyandbescientificallyrigorous,balancedandobjectiveinthepresentation/discussionofitscontent,theories andpractices. Allauthors/editorsparticipatinginanaccreditedCMEactivityareexpectedtodisclosetothereadersrelevantfinancial relationshipswithcommercialentitiesoccurringwithinthepast12months(suchasgrantsorresearchsupport,employee, consultant,stockholder,memberofspeakersbureau,etc.).TheUniversityofVirginiaSchoolofMedicinewillemployappro- priatemechanismstoresolvepotentialconflictsofinteresttomaintainthestandardsoffairandbalancededucationtothe reader.QuestionsaboutspecificstrategiescanbedirectedtotheOfficeofContinuingMedicalEducation,UniversityofVir- giniaSchoolofMedicine,Charlottesville,Virginia. ThefacultyandstaffoftheUniversityofVirginiaOfficeofContinuingMedicalEducationhavenofinancialaffiliationstodisclose. Theauthors/editorslistedbelowhaveidentifiednofinancialorprofessionalrelationshipsforthemselvesortheir spouse/partner: LeeABricker,MD;JosephL.CallesJr,MD;L.LeeCarlisle,MD;MadelineA.Chadehumbe,MD;BantuChhangani,MD;Cyn- thiaL.Feucht,PharmD,BCPS(GuestEditor);NevilleH.Golden,MD;DonaldE.Greydanus,MD,DrHC(ATHENS)(Guest Editor);CarlaHolloway,(AcquisitionsEditor);IliyanIvanov,MD;IanKodish,MD,PhD;JonMcClellan,MD;AhsanNazeer, MD;DilipR.Patel,MD,FAACPDM,FAAP,FSAM,FACSM(GuestEditor);HelenD.Pratt,PhD;KarenRheuban,MD(Test Author);RuqiyaShamaTareen,MD;LibbieStansifer,MD;andTiffanyThomas,MD. Theauthors/editorslistedbelowidentifiedthefollowingprofessionalorfinancialaffiliationsforthemselvesortheir spouse/partner: EvelynAttia,MDisanindustryfundedresearch/investigatorforEliLilly&Co. RobertL.Findling,MDreceivesgrant/researchsupport,isaconsultant,andisontheSpeakers’BureauforBristol-Myers Squibb,Johnson&Johnson,andShire;receivesgrant/researchsupportandisaconsultantforAbbott,Addrenex,AstraZe- neca,Forest,GSK,Lilly,Otsuka,Pfizer,Schering-Plough,SupernusPharmaceuticals,andWyeth;isaconsultantforBiovail, KemPharm,Lundbeck,Novartis,Noven,Organon,Sanofi-Aventis,Sepracore,Solvay,andValidus;andreceivesgrant/re- searchsupportfromNeuropharm. ManmohanK.Kamboj,MDisontheSpeakers’BureauforPfizer. GabrielKaplan,MDisontheSpeakers’BureauforShire,isaconsultantforCommonhealthHoboken,andisemployedby UniversityMedicalCenter. JeffreyH.Newcorn,MDisanindustryfundedresearch/investigatorforShire,OrthoMcNeilJanssen,andEliLilly,andis aconsultantandisontheAdvisoryCommittee/BoardforShire. CarolRockhill,MD,PhD,MPHisanindustryfundedresearch/investigatorforSeasideTherapeutics. SherylRyan,MDisontheSpeaker’sBureauforMerckPharmaceuticals. ChrisVarley,MDisontheSpeaker’sBureauforNovartis. DisclosureofDiscussionofNon-FDAApprovedUsesforPharmaceuticalProductsand/orMedicalDevices TheUniversityofVirginiaSchoolofMedicine,asanACCMEprovider,requiresthatallfacultypresentersidentifyanddisclose anyoff-labelusesforpharmaceuticalandmedicaldeviceproducts.TheUniversityofVirginiaSchoolofMedicinerecom- mendsthateachphysicianfullyreviewalltheavailabledataonnewproductsorprocedurespriortoclinicaluse. TOENROLL ToenrollinthePediatricClinicsofNorthAmericaContinuingMedicalEducationprogram,callcustomerserviceat1-800- 654-2452orvisitusonlineatwww.theclinics.com/home/cme.TheCMEprogramisavailabletosubscribersforanadditional feeof$223.00 This page intentionally left blank FoodAllergyinChildren Contributors GUEST EDITORS HEMANTP.SHARMA,MD,MHS AssociateChief,DivisionofAllergyandImmunology,CenterforCancerandBlood Disorders,Children’sNationalMedicalCenter;AssistantProfessorofPediatrics, GeorgeWashingtonUniversity,Washington,DC ROBERTA.WOOD,MD Chief,DivisionofPediatricAllergyandImmunology,TheJohnsHopkinsHospital; ProfessorofPediatrics,TheJohnsHopkinsUniversitySchoolofMedicine;Professor ofInternationalHealth,TheJohnsHopkinsBloombergSchoolofPublicHealth, Baltimore,Maryland MAXJ.COPPES,MD,PhD,MBA SeniorVicePresident,CenterforCancerandBloodDisorders,Children’sNational MedicalCenter;ProfessorofOncology,MedicineandPediatrics,GeorgetownUniversity; ClinicalProfessorofPediatrics,GeorgeWashingtonUniversity,Washington,DC AUTHORS SEEMAS.ACEVES,MD,PhD AssistantProfessor,PediatricsandMedicine;Director,EosinophilicGastrointestinal DisordersClinic,DivisionofAllergyandImmunology,DepartmentsofPediatricsand Medicine,UniversityofCalifornia,SanDiego,RadyChildren’sHospital,SanDiego, California S.HASANARSHAD,DM,FRCP ProfessorofAllergyandClinicalImmunology,IIIResearchDivision,Universityof Southampton,Southampton;Director,TheDavidHideAsthmaandAllergyResearch Centre,Newport,IsleofWight,UnitedKingdom KIRSTENBEYER,MD Klinikfu¨rPa¨diatrie(Pneumo/Immunol),Charite´,CampusVirchow-Klinikum,Berlin,Germany A.WESLEYBURKS,MD Chief,DivisionofPediatricAllergyandImmunology,DepartmentofPediatrics; Kiser-ArenaProfessorofPediatrics,DukeUniversitySchoolofMedicine,Durham, NorthCarolina JEAN-CHRISTOPHCAUBET,MD DivisionofPediatricAllergyandImmunology,PediatricsMountSinaiSchoolofMedicine, NewYork,NewYork;DepartmentofChildandAdolescent,UniversityHospitalsofGeneva andMedicalSchooloftheUniversityofGeneva,Geneva,Switzerland STACYCHIN,MD Fellow,DivisionofPediatricAllergyandImmunology,DepartmentofPediatrics,Duke UniversitySchoolofMedicine,Durham,NorthCarolina vi Contributors RENATAR.COCCO,MD ClinicalResearcher,DivisionofAllergy,ClinicalImmunologyandRheumatology, DepartmentofPediatrics,FederalUniversityofSa˜oPaulo,Sa˜oPaulo,Brazil GEORGEDUTOIT,FRCPCH(UK) DivisionofAsthma,AllergyandLungBiology,Guy’sandStThomas’NationalHealth ServiceFoundationTrust,theMedicalResearchCouncilandAsthmaUKCentrein AllergicMechanismsofAsthma,King’sCollegeLondon,London,UnitedKingdom PHILIPPEA.EIGENMANN,MD PediatricAllergyUnit,Children’sHospital,UniversityHospitalofGeneva,Geneva, Switzerland KIRSIM.JA¨RVINEN,MD,PhD AssistantProfessor,DivisionofPediatricAllergyandImmunology,Department ofPediatrics,JaffeInstituteforFoodAllergy,TheMountSinaiSchoolofMedicine, NewYork,NewYork JACOBD.KATTAN,MD ClinicalFellow,DivisionofPediatricAllergyandImmunology,DepartmentofPediatrics, JaffeInstituteforFoodAllergy,TheMountSinaiSchoolofMedicine,NewYork,NewYork CORINNEKEET,MD AssistantProfessorofPediatrics,DivisionofPediatricAllergyandImmunology, DepartmentofPediatrics,JohnsHopkinsSchoolofMedicine,Baltimore,Maryland JENNIFERS.KIM,MD AssistantProfessorofPediatrics,DivisionofAllergyandImmunology,MountSinai SchoolofMedicine,NewYork,NewYork GIDEONLACK,FRCPCH(UK) DivisionofAsthma,AllergyandLungBiology,Guy’sandStThomas’NationalHealth ServiceFoundationTrust,theMedicalResearchCouncilandAsthmaUKCentrein AllergicMechanismsofAsthma,King’sCollegeLondon,London,UnitedKingdom DARLENEK.MANSOOR,MD,MS AttendingPhysician,DivisionofAllergyandImmunology,CenterforCancerandBlood Disorders,Children’sNationalMedicalCenter;AssistantProfessorofPediatrics, GeorgeWashingtonUniversity,Washington,DC KIMMUDD,RN,MSN ResearchNurse/ProgramCoordinator,JohnsHopkinsDivisionofPediatricAllergy andImmunology,JohnsHopkinsHospital,Baltimore,Maryland ANTONELLAMURARO,MD,PhD Professor,DepartmentofPediatrics,FoodAllergyCentre,VenetoRegion,University ofPadua,Padua,Italy ANNANOWAK-WEGRZYN,MD AssociateProfessor,DepartmentofPediatrics,JaffeFoodAllergyInstitute,MountSinai SchoolofMedicine,NewYork,NewYork JONATHANO’BHOURIHANE,MB,DM,FRCPI Professor,DepartmentofPaediatricsandChildHealth,ClinicalInvestigationsUnit,Cork UniversityHospital,UniversityCollegeCork,Wilton,Cork,Ireland Contributors vii JAE-WONOH,MD,PhD DepartmentofPediatrics,HanyangUniversityKuriHospital,Seoul,Korea HEMANTP.SHARMA,MD,MHS AssociateChief,DivisionofAllergyandImmunology,CenterforCancerandBlood Disorders,Children’sNationalMedicalCenter;AssistantProfessorofPediatrics, GeorgeWashingtonUniversity,Washington,DC SCOTTH.SICHERER,MD ProfessorofPediatrics,DivisionofAllergyandImmunology,MountSinaiSchool ofMedicine,NewYork,NewYork CARINAVENTER,PhD,RD NHIRPostDoctorateResearchFellow,UniversityofPortsmouth,Portsmouth;Senior AllergyDietitian,TheDavidHideAsthmaandAllergyResearchCentre,Newport, IsleofWight,UnitedKingdom BRIANP.VICKERY,MD Instructor,DivisionofPediatricAllergyandImmunology,DepartmentofPediatrics, DukeUniversitySchoolofMedicine,Durham,NorthCarolina JULIEWANG,MD DivisionofPediatricAllergyandImmunology,PediatricsMountSinaiSchoolofMedicine, NewYork,NewYork ROBERTA.WOOD,MD Chief,DivisionofPediatricAllergyandImmunology,TheJohnsHopkinsHospital; ProfessorofPediatrics,TheJohnsHopkinsUniversitySchoolofMedicine;Professor ofInternationalHealth,TheJohnsHopkinsBloombergSchoolofPublicHealth, Baltimore,Maryland JAIMELIOUWOLFE,MD DivisionofGastroenterology,DepartmentofSurgery,Children’sNationalMedicalCenter, Washington,DC This page intentionally left blank FoodAllergyinChildren Contents Preface:FoodAllergyinChildren xv Hemant P.Sharma,RobertA.Wood,andMaxJ.Coppes ClinicalPresentationsofFoodAllergy 315 DarleneK.MansoorandHemantP.Sharma Foodallergiesareimmune-mediatedresponsestofoodproteins.Because ofdifferencesintheunderlyingimmunologicmechanisms,therearevarying clinicalpresentationsoffoodallergy.Thisarticlediscussesthemanifesta- tions of IgE-mediated disorders, including urticaria and angioedema, rhinoconjunctivitis, asthma, gastrointestinal anaphylaxis, generalized ana- phylaxis, food-dependent exercise-induced anaphylaxis, and oral allergy syndrome. It also reviews the presentations of mixed IgE- and cell-medi- ateddisorders,includingatopicdermatitisandeosinophilicgastrointestinal disorders. Finally, the manifestations of cell-mediated food allergies are discussed, including dietary protein-induced proctitis and proctocolitis, food protein-induced enterocolitis syndrome, celiac disease, and food- induced pulmonaryhemosiderosis. EpidemiologyofFoodAllergy 327 CarinaVenterandS.HasanArshad Food allergy (FA) is perceived as a common problem, especially during childhood. Accurate assessment of incidence and prevalence of FA has beendifficulttoestablish,however,duetolackofuniversallyaccepteddi- agnosticcriteria.AlthoughmanyfoodsarereportedtocauseIgE-mediated FA,moststudiesfocuson4commonfoodgroups:cow’smilk,hen’segg, peanut/treenuts,andfish/shellfish.Theremaybevariationinthepreva- lenceofFAinregionsoftheworldandalikelyincreaseinprevalencehas beenobservedinrecentdecades.Thiscannotbestatedwithconfidence, however,withouttheuseofconsistentmethodologyanddiagnosticcriteria. DiagnosticTestingintheEvaluationofFoodAllergy 351 PhilippeA.Eigenmann,Jae-WonOh,andKirstenBeyer Food-related symptoms arefrequent in childhood, and pediatricians are oftenrequestedtoinitiateafoodallergydiagnosticworkup.Acarefulhis- toryisthecornerstoneforassessingwhethertestsareneededandwhich diagnostic procedures are most appropriate. Skin prick tests should be performedonlyaccordingtostandardproceduresbyaskilledhealthpro- fessional. Determining serum IgE levels (in vitro tests) are available for a wide range of foods. Of utmost importance is the need to correlate testresultstotheclinicalpicture.Whenaconclusioncannotbereached, oralfoodchallengesshouldbeperformedforadefinitediagnosis. PathophysiologyofFoodAllergy 363 BrianP.Vickery,StacyChin,andA.WesleyBurks Inthisarticlewereviewthepathophysiologyoffoodallergy,whichaffects 4%ofUSchildrenand2%ofadults,andisincreasinginprevalence.Most

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