醫(yī)、技學(xué)院(華盛頓醫(yī)療手冊培訓(xùn)-過敏和免疫學(xué))課件

HuiyingWangDepartmentofAllergyAllergyandClinicalImmunologyAnallergyisahypersensitivitydisorderoftheimmunesystem.Allergicreactionsoccurwhenaperson'simmunesystemreactstonormallyharmlesssubstancesintheenvironment.身體對一種或多種物質(zhì)的不正常反應(yīng)，而這些物質(zhì)對大多數(shù)人是無害的。Allergy變態(tài)反應(yīng)性疾病最早的記載古埃及國王Menses，與公元前3640年死于黃蜂叮咬Britannicus，羅馬皇帝Claudius之子，對馬過敏理查德三世吃了草莓得了急性蕁麻疹古羅馬哲學(xué)家,Lucretius提出有些東西對一些人來說是美食，對另一些人來說是毒藥變態(tài)反應(yīng)學(xué)起源1963年Gell和Coombs提出四型變態(tài)反應(yīng)疾病I型變態(tài)反應(yīng)—速發(fā)型變態(tài)反應(yīng)

IgE介導(dǎo)–肥大細胞脫顆?！交’d攣，毛細血管擴張，通透性增高，腺體分泌亢進

過敏性鼻炎，過敏性哮喘，過敏性休克II型變態(tài)反應(yīng)—細胞毒或溶細胞型變態(tài)反應(yīng)

IgG抗體或IgM抗體—結(jié)合的細胞溶解血液系統(tǒng)常見溶血性貧血，血小板減少性紫癜，粒性白細胞減少，輸血反應(yīng)，Rh因子不合引起的新生兒溶血，藥物過敏癥變態(tài)反應(yīng)學(xué)機制的研究III型變態(tài)反應(yīng)–抗原抗體復(fù)合物或免疫復(fù)合物型變態(tài)反應(yīng)

IgG或IgM抗體--抗原抗體復(fù)合物形成—SLE，RA，慢性腎小球腎炎IV型變態(tài)反應(yīng)–延緩型或遲發(fā)型變態(tài)反應(yīng)

細胞免疫，T淋巴細胞致敏后分化繁殖

接觸性皮炎，傳染性變態(tài)反應(yīng)，甲狀腺炎，移植排斥反應(yīng)變態(tài)反應(yīng)學(xué)機制的研究免疫系統(tǒng)基本功能免疫防御免疫自穩(wěn)與耐受免疫監(jiān)視感染自身免疫性和過敏性疾病腫瘤FIG1.Currentconceptofthepathogenesisofallergicreactions.Ingeneticallypredisposedindividuals,primaryexposuretoanallergenleadstoactivationofTH2lymphocytesandstimulationofIgEsynthesis.LaterexposurescauseimmediatemediatorreleaseandfurtheractivationofTH2cells,withresultingeosinophilandbasophilinflammation.Ag,Antigen.IgE介導(dǎo)的過敏反應(yīng)病理生理特點和意義組織胺—肥大細胞、嗜堿性細胞釋放，使平滑肌收縮、毛細血管擴張和通透性改變局部作用-水腫，風(fēng)團和紅斑風(fēng)團特點腸道癥狀的臨床特點診斷的意義（皮膚點刺試驗）全身作用-促使血壓下降，過敏性休克過敏性疾病的

兩個窘境

過敏性疾病的發(fā)病情況世界變態(tài)反應(yīng)組織(WAO)對30個國家進行調(diào)查研究結(jié)果顯示:在這些國家的12億總?cè)丝谥?22%(2億5千萬人)患有IgE介導(dǎo)的過敏性疾病。國際兒童哮喘及過敏性疾病調(diào)查研究（ISAAC）顯示，20年來過敏性疾病無論是發(fā)達國家和發(fā)展中國家都在增長。臺灣3個兒童里有一個哮喘。大陸地區(qū)廣州上海的中學(xué)、小學(xué)兒童過敏性鼻炎、哮喘的發(fā)病率都在增長。疾病無國界青霉素堅果類乳膠危機與應(yīng)對泥沼——層出不窮的過敏原我們能做什么？藥物治療特異性免疫治療AnaphylaxisEosinophiliaUrticariaandAngioedemaImmunodeficiencyAdverseDrugReactionsContentAnaphylaxisisarapidlydeveloping,life-threateningsystemicreactionmediatedbyimmunoglobulinE(IgE).Thepeakseverityisseenusuallywithin5to30minutes.

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

EtiologyFoodsHymenopterastings(bees,wasps,andfireants)MedicationsRadiocontrastmediaLatexrubberBloodproductsHemodialysisPhysicalfactors(coldtemperatureorexercise)Idiopathic萬物皆有可能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

細胞免疫體液免疫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