药物超敏反应综合征 ppt课件

学习 汇报者 涂金伟 Drug inducedhypersensitivitysyndrome DIHS HISTORY Drug InducedHypersensitivitySyndrome DIHS wasfirstrecognizedin1950byChaiken inapatientusinganticonvulsant Later SaItzsteindescribedthiskindofdrugreactionaspseudolymphomaInthe1960swiththedevelopmentofcarbamazepine thediseasenamedantispasmodicsyndromeinadditiontoanticonvulsants diaphenylsulfone DDS allopurinol 别嘌醇 salazosulfapyridine 柳氮磺胺吡啶 anddapsone 氨苯砜 canalsocauseDIHS Defition Drug InducedHypersensitivitySyndrome DIHS isasevereandraresystemicreactiontriggeredbyadrug usuallyanantiepilepticdrug accompaniedbyfever lymphadenopathy hepatitis hematologicabnormalitieswitheosinophiliaandatypicallymphocytes andmayinvolveotherorganswitheosinophilicinfiltration causingdamagetoseveralsystems especiallytothekidneys heart lungs andpancreasischaracterizedbylateonset infectiousmononucleosis likesymptoms andherpesvirus6 HHV 6 reactivation Etiopathogenesis Drug deficiencyorabnormalityoftheepoxidehydroxylaseenzyme 环氧酶羟化酶 thatdetoxifiesthemetabolitesofaromaticamineanticonvulsants metabolicpathway Herpesvirus associatedsequentialreactivationofherpesvirusfamily Recently accumulatingevidencesuggeststhatotherHHVs suchasHSV EBV HHV 7andCMVmightbereactivatedduringthecourseofDIHS Gene NAT2andcertainhumanleukocyteantigen HLA alleles immuneresponse Clinicalmanifestations incubationperiod 2 6weeks Fever oftenhigh 38 5 40oC Rash Maculopapularrashdeveloping 3weeksafterstartingtherapywithalimitednumberofdrugs Thecutaneouseruptionconsistsofamorbilliformrash whichisalsocommoninotherlessseveredrugreactionsandbothpresentationsareindistinguishableTheface uppertrunkandupperextremitiesareinitiallyaffected withsubsequentprogressiontothelowerextremities Lymphadenopathy 2mm Themaculopapulareruptionlaterbecomesinfiltratedwithedematousfollicularaccentuat ion Swellingoftheface withmarkedperiorbitalinvolvement Vesiclesmayariseandfinevesiclesbyedemaofthedermiscanbepresent NonecrosisoftheepidermislikeTENoccurs exceptinrarecasesofoverlappingDRESS DIHSandTEN Smallsterileperifollicularpustulesandnonfollicularpustulesmayappear whicharedifferentfromacutegeneralizedexanthematouspustulosis anddoesnotpredominateonthemainfoldsoftheskin Overtimetherashbecomespurplish sharplylowerlimbsandtheresolutionisscaling Anotherformofpresentationisapictureofexfoliativedermatitis whichmaybeassociatedwithmucosalinvolvement suchascheilitis erosions pharygitisandenanthematousenlarged Varioushematologicabnormalities Leukocytosismaybehigh upuntil11 000leukocytes mm3 andeosinophiliareachesvalueshigherthan1500 mm3Hepatitis hepatomegaly ALT ASTincreased hepaticnecrosisMultiorganinvolvement myocarditis myositis pericarditis interstitialnephritis 11 ofcases necrotizinggranulomatousvasculitisinkidney braininvolvement encephalitisormeningitis colitisandthyroiditis themortalityrateisabout10 to20 mainlydiedofseverehepatitis Myocarditismaydevelopatthebeginningofthesyndromeorupto40daysafterinstallation Sym ptomsincludeheartfailure chestpain suddentachycardia dyspnea andhypotensioninearlyDRESS DIHS Renalinvolvementoccursinabout11 ofcases beingparticularlyevidentincasesarisingfromtheuseofallopurinol Therewasanincreaseinserumcreatinineandureaanddecreasedcreatinineclearance InurineItests increasedcontentofeosinophilscandeobserved Neurologicalcomplicationsincludemeningitisandence phalitis occursabout2to4weeksafteronsetofthedrugreactionpulmonaryinvolvementisrarelyreportedinDRESS DIHS Gastrointestinalbleedingmaybeanabruptcomplicationc ausedbyulcerscausedbyCMVEspeciallyincasesrelatedtoadvancedage renalimpairment jaundiceandhepatitiswithreactivationofCMV Incontrast caseswherethereisareactivationofEpstein Barrvirus EBV seemstohavelessaseverecourse butaremorelikelytohavelaterdevelopment usuallyafterseveralyears ofautoimmunediseasessuchasdiabetesmellitustype1andautoimmunehypothyroidism Auxiliaryexamination Completebloodcount ALT AST totalbilirrubin GGT alkalinephosphatase sodium potassium creatinineandcreatinineclearance 24hurineproteinandurinaryeosinophilcount CPK LDH ferritin triglycerides calciumandPTH bloodglucose TAPandTTPA lipase proteinelectrophore sis creactiveprotein quantitativePCRforHHV 6 7 EBVandCMV bloodculture anti nuclearfactor Diagnosticcaiteria 服用苯妥英钠药物史发热 以中高热为主 体温最高可达40 8oC皮疹 颜面部 躯干 四肢可见散在或弥漫分布的红色斑丘疹 高出皮面 压之不褪色 伴瘙痒 无脱屑及水泡 淋巴结肿大 颈部可扪及数枚直径约2 0 3 0cm的淋巴结腋下可扪及1 2枚直径约1 5 2 0cm的淋巴结腹股沟区可扪及1 2直径约1 5 2 0cm的淋巴结 肝炎 肝大 入院时肋下12cm 剑突下11cm10 15肋下8cm 剑突下8 5cm肝功 辅助检查 血常规 血氨 乳酸EB PCR 2 22 106血 痰 咽拭子 骨髓培养 阴性心肌标志物 免疫术前全套胸部平片 心脏彩超 胸腹部B超 Score 6 Differentialdiagnose SJS Johnson综合征 TEN 大疱性表皮松解坏死型药疹 SJS TENisdiagnosedbycharacteristicskinandmucosalmanifestations butnotbyorganinvolvement However DIHSisdiagnosedbasedonitscharacteristicclinicalcourse multipleorganinvolvementanddetectionofherpesvirusreactivationTheonsetofSJS TENwaswithin3weeksafterthestartofdrugadministrationin67 ofcases Incontrast DIHSdevelopedat2 6weeksin80 ofcases andoccurredmostfrequentlyat4 5weeks Complication Hemophagocyticsyndrome HPS canrarelybeobser vedinthecourseofDRESS DIHS HPSisassociatedwithandtriggeredbyvariousconditions includingviralinfections particularlyEBV malignanttu mors orautoimmunediseases WheninthecourseoftheDRESS DIHS HPSusuallyoccurstwoweeksaftertheonsetofdrugeruption Thereisadecreaseinwhitebloodcellsandplateletsthatisdetectedsimultaneouslywiththeelevationoflactatedehydrogenase LDH Bonemarrowaspiraterevealedhemophagocytosisfiguresinanincreasednumberofmacrophages Theincidenceofthissyndromeisestimatedtovaryfromonecaseamong1 000to10 000themortalityrateisabout10 to20 aspecifictherapymaybenecessary Treatment systemiccorticosteroids doseequaltoorgreaterthan1to1 5mg kg dayofprednisoneorequivalent withmarkedimprovementofsymptomsandlaboratoryparameters butseveraldaysafterthestartoftreatment Systemiccorticosteroidsshouldhavetheirdosereduced aftertheclinicalandlaboratorycontrolofthedisease slowlyover6 8weeksinordertopreventarecurrenceofthesymptomsofthedisease Abruptdeteriorationofvarioussymptomsisobservedwhenthewithdrawalisaccidentalorbyrapidreductionofthedosesofcorticosteroids TREATMENT Itshouldberememberedthattheimmunosuppressivetherapiesmayincreasetheriskofinfectiouscomplicationsandsepsis Physiciansshouldalsopayattentiontoaproperbalancebetweentheneedsofcorticosteroidsforreliefofsymptomsandclinicalsignsandtheirpossiblenegativeinterferenceonviralload Attention SpecialattentionshouldbegiventoapossiblereactivationofCMV EBV especiallyinpatientswithsevereDRESS DIHS themonitoringofliverfunctiontestsshouldbeperformedandappropriatetestsorderedtoruleouttheinvolvementofotherorganslikelungs thyroidandheart HighdosesofIVIG havetwoimmunologicaleffects i compensatesforthedecreaseinconcentrationofimmunoglobulinsinthepatient sbloodandthedefectsoftheimmuneprotectionagainstHHV 6 ii highdosesofIVIGhaveananti inflammatoryeffectthatcanregulateimmuneresponses asseeninthetreatmentofautoimmunediseases plasmaexchange especiallywithlowimmuneorseverecasesofinfectionandunfavorableimpactofGCtherapyandGCineffectiveinpatientswithsevereshocktherapy canbeinconjunctionwithIVIG OnceadayOr3timesinarow CsA CsAcaninhibit