医、技学院(华盛顿医疗手册培训-过敏和免疫学)课件

HuiyingWangDepartmentofAllergyAllergyandClinicalImmunologyAnallergyisahypersensitivitydisorderoftheimmunesystem.Allergicreactionsoccurwhenaperson'simmunesystemreactstonormallyharmlesssubstancesintheenvironment.身体对一种或多种物质的不正常反应，而这些物质对大多数人是无害的。Allergy变态反应性疾病最早的记载古埃及国王Menses，与公元前3640年死于黄蜂叮咬Britannicus，罗马皇帝Claudius之子，对马过敏理查德三世吃了草莓得了急性荨麻疹古罗马哲学家,Lucretius提出有些东西对一些人来说是美食，对另一些人来说是毒药变态反应学起源1963年Gell和Coombs提出四型变态反应疾病I型变态反应—速发型变态反应

IgE介导–肥大细胞脱颗粒—平滑肌痉挛，毛细血管扩张，通透性增高，腺体分泌亢进

过敏性鼻炎，过敏性哮喘，过敏性休克II型变态反应—细胞毒或溶细胞型变态反应

IgG抗体或IgM抗体—结合的细胞溶解血液系统常见溶血性贫血，血小板减少性紫癜，粒性白细胞减少，输血反应，Rh因子不合引起的新生儿溶血，药物过敏症变态反应学机制的研究III型变态反应–抗原抗体复合物或免疫复合物型变态反应

IgG或IgM抗体--抗原抗体复合物形成—SLE，RA，慢性肾小球肾炎IV型变态反应–延缓型或迟发型变态反应

细胞免疫，T淋巴细胞致敏后分化繁殖

接触性皮炎，传染性变态反应，甲状腺炎，移植排斥反应变态反应学机制的研究免疫系统基本功能免疫防御免疫自稳与耐受免疫监视感染自身免疫性和过敏性疾病肿瘤FIG1.Currentconceptofthepathogenesisofallergicreactions.Ingeneticallypredisposedindividuals,primaryexposuretoanallergenleadstoactivationofTH2lymphocytesandstimulationofIgEsynthesis.LaterexposurescauseimmediatemediatorreleaseandfurtheractivationofTH2cells,withresultingeosinophilandbasophilinflammation.Ag,Antigen.IgE介导的过敏反应病理生理特点和意义组织胺—肥大细胞、嗜碱性细胞释放，使平滑肌收缩、毛细血管扩张和通透性改变局部作用-水肿，风团和红斑风团特点肠道症状的临床特点诊断的意义（皮肤点刺试验）全身作用-促使血压下降，过敏性休克过敏性疾病的

两个窘境

过敏性疾病的发病情况世界变态反应组织(WAO)对30个国家进行调查研究结果显示:在这些国家的12亿总人口中,22%(2亿5千万人)患有IgE介导的过敏性疾病。国际儿童哮喘及过敏性疾病调查研究（ISAAC）显示，20年来过敏性疾病无论是发达国家和发展中国家都在增长。台湾3个儿童里有一个哮喘。大陆地区广州上海的中学、小学儿童过敏性鼻炎、哮喘的发病率都在增长。疾病无国界青霉素坚果类乳胶危机与应对泥沼——层出不穷的过敏原我们能做什么？药物治疗特异性免疫治疗AnaphylaxisEosinophiliaUrticariaandAngioedemaImmunodeficiencyAdverseDrugReactionsContentAnaphylaxisisarapidlydeveloping,life-threateningsystemicreactionmediatedbyimmunoglobulinE(IgE).Thepeakseverityisseenusuallywithin5to30minutes.

ClassificationAllergicIgE-mediatedanaphylaxisNonallergicanaphylaxis(usedtobecalledanaphylactoid)Cytotoxic-mediatedanaphylaxisImmunecomplex-complement-mediatedanaphylaxisIdiopathicDefinitionEpidemiologyIncidenceofanaphylaxisisapproximately50to2,000episodesper100,000person-yearswithalifetimeprevalenceof0.05%to2%.

EtiologyFoodsHymenopterastings(bees,wasps,andfireants)MedicationsRadiocontrastmediaLatexrubberBloodproductsHemodialysisPhysicalfactors(coldtemperatureorexercise)Idiopathic万物皆有可能RiskFactorsIgE-mediatedreactionsPrevioussensitizationandformationofantigen-specificIgEwithhistoryofanaphylaxis.Non-IgE-mediatedanaphylaxisMastocytosispatientsareathigherriskforfutureepisodesifnotrecognizedornotpremedicated.RadiocontrastsensitivityreactionsAge>50yearsPreexistingcardiovascularorrenaldiseaseHistoryofallergyHistoryofpreviousreactiontoradiocontrastmediaSensitivitytoseafoodoriodinedoesnotpredisposetoradiocontrastmediareactions.recognitionofpotentialtriggersandavoidanceisthebestprevention.Self-injectableepinephrineandpatientRadiocontrastsensitivityreactionsUseoflow-ioniccontrastmediaPremedicationbeforeprocedurePrednisone50mgPOgiven13,7,and1hourpriortoprocedureDiphenhydramine50mgPOgiven1hourbeforeprocedureH2blockermayalsobegiven1hourbeforeprocedurePremedicationisnot100%effectiveandappropriateprecautionsforhandlingareactionshouldbetaken.Prevention

MildanaphylaxisskinandsubcutaneoustissueonlyModerateanaphylaxisrespiratory,cardiovascular,orgastrointestinalinvolvementSevereanaphylaxishypoxia,hypotension,orneurologiccompromiseDiagnosticCriteriaAnaphylaxisduetopreformedIgEandreexposureNonallergicanaphylaxisRadiocontrastsensitivityreactionsRedman'ssyndromeMastocytosisIngestant-relatedreactionsFlushingsyndromespostmenopausalsymptoms,andalcoholuse.OtherformsofshockMiscellaneoussyndromessuchasC1esterase(C1INH)deficiencysyndrome,pheochromocytoma,neurologic(seizure,stroke),andcapillaryleaksyndromeIdiopathicDifferentialDiagnosis

Serumβ-tryptasepeaksat1houraftersymptomsbeginandmaybepresentupto6hours.EpicutaneousskintestingandRAST(radioallergosorbenttest)testingwhenavailabletoidentifytriggerallergens.DiagnosticTesting

Epinephrineshouldbeadministeredimmediately.Adult:0.3to0.5mlChild:0.1to0.3mlofa1:1,000solutioniminthelateralthigh,repeatedat10-to15-minuteintervalsifnecessary.0.5mLof1:1,000solutionsublinguallyincasesofmajorairwaycompromiseorhypotension.3to5mLof1:10,000solutionviacentralline.3to5mLof1:10,000solutiondilutedwith10mLofnormalsalineviaendotrachealtube.Protractedsymptomsthatrequiremultipledosesofepinephrine,anIVepinephrinedripmaybeuseful;theinfusionistitratedtomaintainadequatebloodpressure.Medications

Glucagon1-mg(1ampule)bolusandfollowedbyadripofupto1mg/hrcanbeusedtoprovideinotropicsupportforpatientswhoaretakingβ-adrenergicantagonists.Inhaledβ-adrenergicagonistsshouldbeusedtotreatresistantbronchospasm.Glucocorticoidshavenosignificantimmediateeffect.However,theymaypreventrelapseofseverereactions.Antihistaminesrelieveskinsymptomsbuthavenoimmediateeffectonthereaction.Theymayshortenthedurationofthereaction.Medications

Referralstoanallergistforfurtherevaluationshouldbeofferedtoallpatientswithahistoryofanaphylaxis.Moreimportantly,patientswithHymenopterasensitivityshouldbeevaluatedtodetermineeligibilityforvenomimmunotherapy.REFERRAL

Eosinophilia

Abroadvarietyofinfectious,allergic,neoplastic,andidiopathicdiseasesareassociatedwithincreasedbloodand/ortissueeosinophilia.Acceptedupperlimitsofnormalbloodeosinophiliavary.Avalue>600eosinophils/µLofbloodisabnormalinthevastmajorityofcases.Thedegreeofeosinophiliacanbecategorizedasmild(600to1,000cells/µL),moderate(1,500to5,000cells/µL),orsevere(>5,000cells/µL).Eosinophilsaretissue-dwellingcellsandaremostabundantinmucosaltissuessuchastherespiratoryandgastrointestinaltractsGENERALPRINCIPLES

Primaryeosinophilia

chronicmyeloiddisordersoracuteleukemiassecondaryeosinophilia

parasites,allergicdiseases,autoimmunedisorders,toxins,medications,andendocrinedisorders,suchasAddison'sdisease.IdiopathiceosinophiliaClassification

EosinophiliaassociatedwithatopicdiseaseInallergicrhinitis,nasaleosinophiliaismorecommonthanperipheralbloodeosinophilia.Nasaleosinophiliawithorwithoutbloodeosinophiliamaybeseeninasthma,nasalpolyposis,ornonallergicrhinitiswitheosinophiliasyndrome(NARES).NARESisasyndromeofmarkednasaleosinophiliaandnasalpolyps.Thesepatientsdonothaveahistoryofallergies,asthma,aspirinsensitivity,andhavenegativeskintestsandIgElevels.Atopicdermatitisisclassicallyassociatedwithbloodandskineosinophilia.Classification

Eosinophiliaassociatedwithpulmonaryinfiltrates.PIEsyndromesrefertothosediseaseswithpulmonaryinfiltratesandbloodeosinophiliaallergicbronchopulmonaryaspergillosis(ABPA)consistingofpulmonaryinfiltrates,proximalbronchiectasis,andasthma-anddrug-inducedpneumonitis.EosinophilicpneumoniasconsistofpulmonaryinfiltrateswithlungeosinophiliaacuteandchroniceosinophilicpneumoniasLofflersyndromeandtropicalpulmonaryeosinophiliaClassification

HIVParasiticinfectionEosinophiliaassociatedwithcutaneousdiseaseEosinophilicfasciitis/eosinophiliccellulitis/eosinophilicpustularfolliculitis/episodicangioedemawitheosinophiliaEosinophiliaassociatedwithmultiorganinvolvementDrug-inducedeosinophilia/Churg-Strausssyndrome(CSS)/Mastocytosis/Idiopathichypereosinophilicsyndrome(HES)/AcuteEosinophilicleukemia/Lymphoma/Atheroembolicdisease./ImmunodeficiencyClassification

Inindustrializednations,peripheralbloodeosinophiliaismostoftenduetoatopicdisease,whereashelminthicinfectionsarethemostcommoncauseofeosinophiliaintherestoftheworld.Epidemiology

Etiology

seetheclassificationPathophysiologyActivationofeosinophilsleadstothereleaseofstoredgranularcomponentssuchasmajorbasicproteins,eosinophilperoxidase,andeosinophilcationicprotein,whicharebelievedtoberesponsibleforthetissuedamageascribedtothesecells.Inaddition,theseactivatedcellsproducecytokinesthatcanexacerbatetheimmunologicreaction.Therearetwoapproachesthatareusefulforevaluatingeosinophilia,eitherbyassociatedclinicalcontext(Table1)orbydegreeofeosinophilia(Table2).DIAGNOSIS

Historycough,dyspnea,fever,oranysymptomsofcanceranyhistoryofrhinitis,wheezing,orrash.AcompletemedicationlistafulltravelhistoryfocusedoncountriesAnypetexposurePhysicalExaminationspecialfocusontheskin,upperandlowerrespiratorytracts,aswellascardiovascularandneurologicsystemsClinicalPresentationVariousconditionscanresultineosinophiliaassociatedwithpulmonaryinfiltratesTheetiologyofeosinophiliaassociatedwithcutaneouslesionsidiopathicHESbloodeosinophiliaof>1,500/µLfor>6monthswithassociatedorganinvolvement.DifferentialDiagnosis

LaboratoriesMildeosinophiliaassociatedwithsymptomsofrhinitisorasthmaskintesting.Stoolexaminationforovaandparasitesshouldbedoneonthreeseparateoccasionsserologictestsforantiparasiteantibodiesshouldalsobesent.CSSInthiscase,sinuscomputedtomography,nerveconductionstudies,andtestingforp-ANCAImagingChestx-raybronchoscopy/bronchoalveolarlavage(BAL)fluid/lungtissue.DiagnosticTesting

drugreactionHypereosinophilicsyndromePrimaryeosinophiliadisordersshouldbefollowedbyaspecialistanycasesofunresolvedorunexplainedeosinophiliawarrantevaluationbyanallergist-immunologist.TREATMENT

Primaryeosinophiliadisordersshouldbefollowedbyaspecialist;anycasesofunresolvedorunexplainedeosinophiliawarrantevaluationbyanallergist-immunologist..REFERRAL

Urticaria/Angioedema

DefinitionUrticaria(hives)areraised,flat-topped,well-demarcatedpruriticskinlesionswithsurroundingerythema.Centralclearingcancauseanannularlesionandisoftenseenafterantihistamineuse.Anindividuallesionusuallylastsminutestohours.Angioedemaisadeeperlesioncausingpainfulareasofskin-colored,localizedswelling.Itcanbefoundanywhereonthebody,butmostofteninvolvesthetongue,lips,oreyelids.Whenangioedemaoccurswithouturticaria,specificdiagnosesmustbeentertainedGENERALPRINCIPLES

Acuteurticariaanepisodelasting<6weeks.Usually,itiscausedbyanallergicreactiontoamedicationorfood,butitmayberelatedtounderlyinginfection,recentinsectsting,orexposure(contactorinhalation)toanallergen.Chronicurticariaepisodesthatpersistfor>6weeks.Therearemanypossiblecausesofchronicurticariaandangioedema,includingmedications,autoimmunity,self-careproducts,andphysicaltriggers.However,theetiologyremainsunidentifiedin>80%ofcases.Classification

Urticariaisacommonconditionthataffects15%to24%oftheU.S.populationatsometimeintheirlife.Chronicidiopathicurticariaoccursin0.1%oftheU.S.population,andtheredoesnotappeartobeanincreasedriskinpersonswithatopy.Angioedemagenerallylasts12to48hoursandoccursin40%to50%ofpatientswithurticaria.Epidemiology

Allergic:drugs,foods,inhalant,orcontactallergenTransfusionreactionsInfectionsInsectsAutoimmunediseasesMalignancyPhysicalurticaria:dermographism,cold,cholinergic,pressure,vibratory,solar,andaquagenicMastocytosisHereditarydiseasesIdiopathicEtiology

Mechanismsforinitiationofurticariaandangioedemadifferdependingontheclassificationandarenotfullyunderstood.However,thefinalcommonpathwayisthedegranulationofmastcellsorbasophilsandthereleaseofinflammatorymediators.Histamineistheprimarymediatorandelicitsedema(wheal)anderythema(flare).Pathophysiology

ClinicalPresentation/HistoryPhysicalExaminationDifferentialDiagnosisAllergicreaction/Physicalurticaria/Mastcellreleasabilitysyndromes/Urticarialvasculitis/specificentities/Hereditaryangioedema(HAE/C1esteraseinhibitor(C1INH)deficiencyDiagnosticTestingEpicutaneousskintestingandpatchtestingwhenindicated.Laboratories(CBC),ESR,urinalysis,andliverfunctiontests………C4levelDIAGNOSIS

identificationandavoidanceofspecificcauses.Allpotentialcausesshouldbeeliminated.hereditaryandacquiredangioedema,apromptassessmentofairwayiscriticalinespeciallythosepresentingwithalaryngealattack.MedicationsAsecond-generationoralantihistamineOralcorticosteroidsHereditaryandAcquiredAngioedema(DisorderofC1-inhibitor)C1-inhibitorreplacement(C1INHRP)isfirst-lineagentTREATMENT

AllpatientswithchronicurticariaorahistoryofanaphylaxisshouldbereferredtoanallergyspecialistforevaluationtoidentifypotentialallergicandautoimmunetriggersREFERRAL

Immunodeficiency

Primaryimmunodeficiencies(PIDs)aredisordersoftheimmunesystemthatresultinanincreasedsusceptibilitytoinfection.Secondaryimmunodeficienciesarealsodisordersofincreasedsusceptibilitytoinfectionbutareattributabletoanexternalsource.Definition

细胞免疫体液免疫Th1Th2Th17ThregNKcellsIgA,IgG,IgE,IgD,IgMPIDscanbeorganizedbythedefectiveimmunecomponents.HumoralimmunodeficiencyCommonvariableimmunedeficiency/X-linked(Bruton's)agammaglobulinemia/IgGsubclassdeficiency/IgAdeficiency/Hyper-IgE(Job)syndromeCell-mediatedimmunodeficiencyCombinedimmunodeficiencyInnateimmunesystemdefectsChronicgranulomatousdisease(CGD)ComplementdeficienciesClassification

Secondaryimmunodeficiencysyndromes,particularlyHIV/AIDS,arethemostcommonimmunodeficiencydisorders.MostPIDspresentinginadulthoodarehumoralimmunedefects.CVIDisthemostcommonsymptomaticPID,occurringwithafrequencyof1/10,000.Epidemiology

CVIDislargelyidiopathicHumoralimmunedeficienciesB-cellmaturation.AvarietyofgeneticmutationshavebeenassociatedwithspecificPIDsyndromes.Secondaryimmunodeficienciesmedications/infectiousagents(HIV)/malignancy/antibodyloss/autoimmunedisease/malnutrition/otherunderlyingdiseases(DM,cirrhosis,uremia).Etiology

ClinicalPresentationThehallmarkofPIDisrecurrentinfections.ImmunoglobulinA(IgA)deficiencyisthemostcommonimmunedeficiency,withaprevalenceof1in500people.In15%ofcases,anassociatedimmunoglobulinG(IgG)subclassdeficiencyispresent.elevatedlevelsofIgE.Amarkedincreaseintissueandbloodeosinophilsmayalsobeobserved.MutationsinSTAT3havebeenlinkedtodevelopmentofthisdisease(NEnglJMed2007;357(16):1608).DIAGNOSIS

Initialevaluationshouldfocusonidentifyingpossiblesecondarycausesofrecurrentinfectionsuchasallergy,medications,andanatomicabnormalities.CBCwithdifferential/HIVtest/quantitativeimmunoglobulinlevels/andcomplementlevels/BandTcellsB-cellfunctionApatientwithnormalorlowIgGandapoorresponsetoimmunizationisclassifiedashavingCVID.DiagnosticTestingIgAdeficiency:Nospecifictreatmentisavailable.CVIDshouldbetreatedwithIVIG.Replacementshouldbeinitiatedwith400mg/kg

Patients,especiallythosewithnodetectableIgA,needtohavevitalsignsmonitoredq15mininitiallybecauseanaphylaxisfromIgEanti-IgAantibodiescandevelopinthesepatients.Forthesepatients,itisbesttouseIVIGpreparationsthathaveverylowIgA.TREATMENT

AdverseDrugReactions

Adversedrugreactions(ADRs)areaverycommonproblem.OnlyasubsetofreactionsaremediatedimmunologicallyClassificationTypeAdrugreactionsTypeBdrugreactionsManydifferen