JohannesRing · AllergyinPractice Johannes Ring Allergy in Practice With a Foreword by Thomas Platts-Mills With149Figuresin175Partsand186Tables Prof.Dr.med.Dr.phil.JohannesRing KlinikundPoliklinikfürDermatologieundAllergologieamBiederstein desKlinikumsrechtsderIsarderTechnischenUniversitätMünchen BiedersteinerStraße29,D-80802München ISBN3-540-00219-7Springer-VerlagBerlinHeidelbergNewYork LibraryofCongressControlNumber:2004110368 Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeor partofthematerialisconcerned,specificallytherightsoftranslation,reprint- ing,reuseofillustrations,recitation,broadcasting,reproductiononmicrofilmor inanyotherway,andstorageindatabanks.Duplicationofthispublicationor partsthereofispermittedonlyundertheprovisionsoftheGermanCopyright LawofSeptember9,1965,initscurrentversion,andpermissionforusemustal- waysbeobtainedfromSpringer-Verlag.Violationsareliabletoprosecutionun- dertheGermanCopyrightLaw. Springer-VerlagBerlinHeidelbergNewYork SpringerisapartofSpringerScience+BusinessMedia http://www.springeronline.com ©Springer-VerlagBerlinHeidelberg2005 PrintedinGermany TitleoftheGermanedition: JohannesRing,AngewandteAllergologie.3.,neubearbeiteteAuflage Urban&VogelMedienundMedizinverlagsgesellschaftmbH&CoKG, München2004 ISBN3-89935-128-2 Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthis publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuch namesareexemptfromtherelevantprotectivelawsandregulationsandthere- forefreeforgeneraluse. Productliability:Thepublisherscannotguaranteetheaccuracyofanyinforma- tionabouttheapplicationofoperativetechniquesandmedicationscontainedin thisbook.Ineveryindividualcasetheusermustchecksuchinformationbycon- sultingtherelevantliterature. Editor:MarionPhilipp DeskEditor:IrmelaBohn ProductionEditor:JoachimW.Schmidt Coverdesign:eStudioCalamar,Spain Typesetting:FotoSatzPfeiferGmbH,D-82166Gräfelfing Printedonacid-freepaper–24/3150–543210 Preface µl · 5 ˆ [ * [ ˆ (ancientGreek) ”Avoidoverreactions”(principleofappliedallergology) Allergyis“in,”andhasbeenforsomeyearsnow.Theterm“allergy”is nolongeraforeignword.Inspiteofthis,allergiesarestillnotadequate- ly appreciated either by the general population or by the physicians’ community.Ontheonehand,allergyislikea“fashionabledisease”and anydisturbanceofwell-beingisregardedasallergy;ontheotherhand, very severe allergic conditions remain neglected, being left undiag- nosedanduntreated.Itisdifficulttofindtherightbalancebetweenthe extremes. After the first two editions of this book (1982 and 1988) sold over 20,000copies,thepublisherandauthordecidedtocollaborateonanew andtotallyrewrittenthirdedition.Inthisendeavortheoriginalaimofa verybriefandprecisebookletcontainingrelevantinformationforaller- gypracticewasnotforgotten.Thebookstartedasacollectionofshort informationleafletsforresidentsrotatingthroughtheAllergyDivision at Munich. It was Dr. J. Aumiller, chief editor of the Munich Medical Weekly,whothenpersuadedmetowriteaseriesofshortchaptersonal- lergyinpractice,andIamstillthankfulforthebrutalitywithwhichhe forcedmerigorouslytoshortenthetext!Inthisthirdedition,whichis publishedinbothGermanandEnglish,theauthoragainhadafightto findthemostlogicalmethodofclassification,adifficultyforeverycom- plexmedicalfield.Therearedifferentpossiblecriteriawhichcanbefol- lowedforaclassification: ) Accordingtoorgans(e.g.,allergyofthenose,eye,skin) ) Accordingtosymptoms(e.g.,urticaria,eczema,asthma) ) Accordingtopathomechanisms(e.g.,typesaccordingtoCoombs andGell) ) Accordingtoallergens(e.g.,foodallergy,animalproteinallergy, nickelallergy) ) Accordingtotheclinicalcourseandprognosis(e.g.,acuteorchronic allergies,life-threateningemergencies) ) Accordingtogeneticparameters(e.g.,familialallergies,sporadic allergies) ) Accordingtoage(e.g.,childhoodallergies,adultallergies) ) andmanymore Ifonepushedtheseclassificationstotheirlogicalextent,manyoverlaps andrepetitionswouldresult.Thelivingorganismisnotnecessarilylogi- cal,andevenlesssoinitspathophysiologicalvariants. VI Preface Nevertheless,weneedtostresstheimportanceofapreciseterminolo- gyintheindividualchapters;thisisnotasophisticatedphilosophybut ratherreflectstheinherentproblems,whichmaybeoverlookedatasu- perficialglance,butwhicharethedailybreadandbutterofseriousaller- gists. Furthermore,itwasimportantintheselectionofreferencesnotonly –asissooftenseennowadays–tolookthrough“threeyearsofMedline” butalsotoincludeimportantworkfromthepast.Therefore,Ipolitely askthereader–maybelikeonaholidaytrip–totrustthemoreorlessex- periencedguidanceoftheauthor;thisguidedtourwillbesubjective,but Ipromisetorelatethemostimportantpointsinashortandpreciseway. HereIwanttothankmanypeople.Firstlymyclinicalandexperimen- talteachersandmentors,Prof.Dr.med.Dr.h.c.mult.OttoBraun-Falco, themasterofexactclinicaldescription,theunforgettableProf.Dr.med. WalterBrendel,whogavemethespiritofenthusiasmforimmunology, Prof.Dr.med.habil.ErichFuchs,thegrandoldmanofGermanallergo- logyformanydiscussions,fruitfulcriticalremarksandalwaysenlight- eningexchangesofideasoverthedecades.Prof.Dr.med.AlaindeWeck hasgivenmemuchscientificinputandhassupportedmeonmywayinto the international allergy community. Dr. Eng Tan was my teacher as a “postdoc”attheScrippsClinicandResearchFoundationinLaJolla.To mypredecessorsatuniversitychairs,Prof.Dr.KarlheinzSchulzandProf. Dr.TheodorNasemanninHamburg-Eppendorf,Prof.Dr.med.Dr.phil. SiegfriedBorelliattheDepartmentofDermatology,BiedersteininMu- nich. I am thankful for the excellent tradition of clinical allergology whichIwasallowedtocontinue. I also want to thank my co-workers in allergology, Prof. Dr. med. BernhardPrzybilla,Priv.-Doz.Dr.med.DieterVielufattheLudigMaxi- miliansUniversity,andinHamburg,andProf.Dr.JürgenRakoskiand Priv.-Doz.Dr.UlfDarsowinthedailyworknowattheTechnicalUniver- sityofMunich.Thefollowingco-workershavehelpedinthepreparation ofsinglechapters: Prof.Dr.TorstenSchäfer(epidemiology),Prof.Dr.HeidrunBehrendt (allergy and environment, allergens), Priv.-Doz. Dr. Thilo Jakob, Dr. MartinMempel,Prof.Dr.MarkusOllert(pathophysiology,diagnostics, immunecomplexreactions),Dr.GregorWildiandMr.JanAl(rhinitis, asthma),Dr.AnkeGauger(urticaria),Dr.KnutBrockow(anaphylaxis), Dr.VolkerGrimmandMrs.ClaudiaKugler(foodallergy),Priv.-Doz.Dr. UlfDarsow(eczema),Priv.-Doz.Dr.BernadetteEberlein-König(photo- allergy,“ecosyndrome”),Dr.StephanieWeissenbacherandDr.Matthias Möhrenschlager(therapyandprevention),andDr.TheresiaRing(De- partmentofOphthalmology,LMU,“AllergyandtheEye”).Manythanks toJohannaGroschandtothenursesoftheDepartmentofDermatology andAllergyatBiedersteinfortheircontinuousandenthusiasticworkfor ourpatients! IwanttothankMrs.MarionPhilippandMrs.GabrieleM.Schröder (Springer, Heidelberg) for their professional help with the publishing andprintingandtoDr.ThomasPlatts-MillsfromCharlottesvilleforthe kindnessofhisforeword! Finally I want to thank my wife, Prof. Dr. med. Heidrun Behrendt, Preface VII headofthe“CentreforAllergyandEnvironment”(“ZAUM–Zentrum AllergieundUmwelt”),formanifoldsupport,beautifulelectronmicro- scope pictures and her everlasting contagious critical enthusiasm for allergyresearch! Munich,amBiederstein January2005 Prof.Dr.med.Dr.phil.JohannesRing Foreword AllergicdiseasehasbecomeamajoraspectofWesternSociety,bothin termsofmedicalmanagementandqualityoflife.Howeverunderstand- ingdiagnosisandmanagementbecomescomplexbecausenotonlyare theremultipleallergensourcesinvolvedbutalsoalargenumberofdis- eases.Hayfever,perennialrhinitis,chronicsinusdisease,urticara,atopic eczema,anaphylaxis,foodallergy,andasthmaeachaffectlargenumbers ofpatients.Becauseoftheoverallnumbers(15%–20%ofthepopula- tion)thereareinevitablyalargeproportionofpatientswhoareallergic orthinktheyareallergicandattributeothersymptomstothismecha- nism.Oneofthestrikingfeaturesofallergyisthateachdiseasevaries fromveryserioustotrivialwithnocleardistinction.Thusforeachofthe majorallergicdiseasestherearemanyindividualswhosesymptomsare notsufficienttogotoadoctorandalsopatientswhoselivesaremade miserableandeventhreatenedbythediseases.Understandingthefac- torswhichcontributetosuchaspectrumofallergicdiseaseisamajor challenge. Asthisbookexplainsaccuratediagnosisofsensitizationisessential. Withoutthis,itisnotpossibletomakearealisticassessmentoftherole ofallergyinthediseasenortoplantreatment.Foreachdiseasethereare multiplepotenzialallergensinvolvedandthemanagementstrategiesare different.Itisnotsurprisingthatassessmentandmanagementofallergic diseasebecomesconfusingtomanyofthehealthcareprofessionalswho havetocopewiththisproblem. ProfessorRingiswellknowninternationallyasanallergistandder- matologistwhohascontributedtoresearchonallergyforatleast25years (Heisalsofamousforawonderfulsenseofhumorwhichsadly,butwise- ly, doesn’t come through in the book). He has now published a book whichcoversawiderangeofdiseaseswhichareeitherallergicorimmu- nological and which provides a comprehensive approach to manage- ment.Inadditionthebookprovidesacompletereferencetocausesfor eachoftheconditionsassociatedwith“Allergie”.Overallitisausefuland veryhelpfulcontributiontotheliteratureofastillevolvingproblem. Johanneshasaverybroadviewofallergicdiseasebutbringsspecial expertisetoseveralareaswhichareoftenignoredorglossedover.Hehas mademajorcontributionstoourknowledgeoftheroleofallergensin atopiceczema.Inadditionhehasaprofoundknowledgeofotherforms ofskindisease.Thisaddsdepthandexcellentjudgmenttotheopinions expressed. He also includes a really useful chapter on pseudo-allergic X Foreword reactions.Thisisanimportantpartofdrugallergyandonetowhichhe hasoftencontributed.Itisperhapstheawarenessofotherrashes,pseu- do-allergicreactionsandanaphylactoidreactionsthataddsthegreatest strengthtothebook. InthelastfewyearsJohannesandhiscolleagueshaveestablishedthe “Centerforallergy andenvironment” (ZAUM –ZentrumAllergieund Umwelt)inMunich.Thisinstitutewhichisonlyfiveyearsoldhasalready madeitsmark.Dr.Behrendt’sworkontheinteractionbetweenairpol- lutantsandallergenparticlesiswellknownbutthisgroup’sworkona groupofleukotrienelikemoleculesderivedfrompollenhasopenedupa new area of allergy research. All this adds further depth to Dr. Ring’s understanding which is clearly evident in the book. Certainly those chaptersareapleasure. Notunexpectedly,JohannesRinghaswrittenanexcellentbookwhich coversawiderangeofallergicdisease.Thebookprovidesacomprehen- sivebutverywellplanneddescriptionofthediseasesthatareeithervery common or just common. His pragmatism comes through in all he writesresultinginareallyusefulguidetoanincreasinglycomplexfield. ThomasA.E.Platts-Mills,MD,PhD,FRCP OscarSwinefordJrProfessorofMedicine DivisionHeadofAsthmaandAllergicDisease Table of Contents 1 ClinicalManifestationandClassificationofAllergicDiseases 1 1.1 History.............................................. 1 1.2 ClinicalManifestationandDefinitionofAllergy ........... 2 1.3 ClassificationofAllergicDiseases ....................... 5 References ........................................... 7 2 PathophysiologyofAllergicReactions ................... 8 2.1 TheImmuneResponse ................................ 8 2.2 Antibodies........................................... 15 2.3 IgE-MediatedReaction ................................ 16 2.3.1 Mast-CellActivation .................................. 16 2.3.2 IgEandAtopy ........................................ 17 2.4 CytotoxicReactions(TypeII)........................... 18 2.5 ImmuneComplexReactions(TypeIII)................... 19 2.6 CellularHypersensitivity(TypeIV)...................... 19 2.7 LessFrequentTypesofAllergicReactions(TypesVandVI) 20 2.8 Pseudo-allergicReactions .............................. 20 2.9 MediatorsofAllergicReactions ......................... 20 2.9.1 Histamine ........................................... 20 2.9.2 Eicosanoids.......................................... 20 2.9.3 Leukotrienes ......................................... 23 2.9.4 Platelet-ActivatingFactor .............................. 23 2.9.5 Serotonin............................................ 24 2.9.6 ComplementSystem .................................. 24 2.9.7 MediatorsfromNeutrophilGranulocytes................. 25 2.9.8 MediatorsfromEosinophilGranulocytes ................. 25 2.9.9 Kallikrein-KininSystem ............................... 25 2.9.10 Tachykinins......................................... 26 2.10 SynopsisofMediatorReleaseandInactivation ............ 26 References ........................................... 27 3 GeneticsandEnvironmentintheDevelopmentofAllergy .. 30 3.1 GeneticsofAllergy.................................... 30 3.1.1 ClassicalGenetics..................................... 30 3.1.2 MolecularGenetics ................................... 31 References ........................................... 32 3.2 EpidemiologyofAllergicDiseases....................... 33 3.2.1 AtopicDiseases....................................... 33