學習匯報者：涂金偉Drug-inducedhypersensitivitysyndrome(DIHS)HISTORYDrug-InducedHypersensitivitySyndrome(DIHS),wasfirstrecognizedin1950byChaiken,inapatientusinganticonvulsant.Later,SaItzsteindescribedthiskindofdrugreactionaspseudolymphomaInthe1960swiththedevelopmentofcarbamazepine,thediseasenamedantispasmodicsyndromeinadditiontoanticonvulsants,diaphenylsulfone(DDS).allopurinol(別嘌醇),salazosulfapyridine(柳氮磺胺吡啶)anddapsone(氨苯砜)canalsocauseDIHSDefitionDrug-InducedHypersensitivitySyndrome(DIHS)isasevereandraresystemicreactiontriggeredbyadrug(usuallyanantiepilepticdrug).accompaniedbyfever,lymphadenopathy,hepatitis,hematologicabnormalitieswitheosinophiliaandatypicallymphocytes,andmayinvolveotherorganswitheosinophilicinfiltration,causingdamagetoseveralsystems,especiallytothekidneys,heart,lungs,andpancreasischaracterizedbylateonset,infectiousmononucleosis-likesymptoms,andherpesvirus6(HHV-6)reactivation.EtiopathogenesisDrug:deficiencyorabnormalityoftheepoxidehydroxylaseenzyme(環氧酶羥化酶)thatdetoxifiesthemetabolitesofaromaticamineanticonvulsants(metabolicpathway)Herpesvirus:associatedsequentialreactivationofherpesvirusfamily.(Recently,accumulatingevidencesuggeststhatotherHHVs,suchasHSV,EBV,HHV-7andCMVmightbereactivatedduringthecourseofDIHS)Gene:NAT2andcertainhumanleukocyteantigen(HLA)alleles(immuneresponse)Clinicalmanifestationsincubationperiod(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,interstitial

nephritis

(11%ofcases),necrotizinggranulomatousvasculitisinkidney,brain

involvement(encephalitisormeningitis),colitisandthyroiditis.themortalityrateisabout10%to20%,mainlydiedofseverehepatitis

√Myocarditismaydevelopatthebeginningofthesyndromeorupto40daysafterinstallation.Sym-ptomsincludeheartfailure,chestpain,suddentachycardia,dyspnea,andhypotensioninearlyDRESS/DIHS.Renalinvolvementoccursinabout11%ofcases,beingparticularlyevidentincasesarisingfromtheuseofallopurinol.Therewasanincreaseinserumcreatinineandureaanddecreasedcreatinineclearance.InurineItests,increasedcontentofeosinophilscandeobserved.Neurologicalcomplicationsincludemeningitisandence-phalitis.occursabout2to4weeksafteronsetofthedrugreactionpulmonaryinvolvementisrarelyreportedinDRESS/DIHSGastrointestinalbleedingmaybeanabruptcomplicationc-ausedbyulcerscausedbyCMV

Especiallyincasesrelatedtoadvancedage,renalimpairment,jaundiceandhepatitiswithreactivationofCMV.Incontrast,caseswherethereisareactivationofEpstein-Barrvirus(EBV)seemstohavelessaseverecourse,butaremorelikelytohavelaterdevelopment(usuallyafterseveralyears)ofautoimmunediseasessuchasdiabetesmellitustype1andautoimmunehypothyroidismAuxiliaryexaminationCompletebloodcount,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服用苯妥英鈉藥物史發熱：以中高熱為主，體溫最高可達40.8oC皮疹：顏面部、軀干、四肢可見散在或彌漫分布的紅色斑丘疹，高出皮面，壓之不褪色，伴瘙癢，無脫屑及水泡。淋巴結腫大：頸部可捫及數枚直徑約2.0-3.0cm的淋巴結腋下可捫及1-2枚直徑約1.5-2.0cm的淋巴結腹股溝區可捫及1-2直徑約1.5-2.0cm的淋巴結

肝炎：肝大：入院時肋下12cm，劍突下11cm10.15肋下8cm，劍突下8.5cm肝功：

輔助檢查血常規：血氨、乳酸EB-PCR:2.22*106血、痰、咽拭子、骨髓培養：陰性心肌標志物、免疫術前全套胸部平片、心臟彩超、胸腹部B超

Score=6DifferentialdiagnoseSJS(Johnson綜合征)?TEN(大皰性表皮松解壞死型藥疹)SJS?TENisdiagnosedbycharacteristicskinandmucosalmanifestations,butnotbyorganinvolvement.However,DIHSisdiagnosedbasedonitscha