药物不良反应之皮肤表现

080830藥物不良反應之皮膚表現臺北市立聯合醫院皮膚科(和平)林瑞宜2020年5月3日星期日08083022:56:01演講大綱藥物不良反應之作用機轉過敏與非過敏如何診斷藥物過敏？藥物反應之作用之重要皮膚表現危險徵候08083022:56:01MechanismofAdverseDrugReactionsTypeA:藥理作用相關者(Pharmacological)依照藥理作用可預測者為已知之作用效果之擴大表現者常與劑量有關必須降低劑量者.TypeB:特質性或過敏性(idiosyncraticorallergic)依照藥物之藥理作用無法來預測者奇異的或特直性的不良反應常非單純之劑量相關反應(dose-responserelationship)發生不良反應時，誘因藥物常必須中止續用非用不可時，常須經過減敏步驟(Desensitization)08083022:56:01藥物過敏皮膚反應之診斷是否為藥物過敏之皮膚反應？Allergicorpseudoallergic?過敏或不良反應之類型為何？何種免疫反應？何種皮膚反應？誘發藥物為何？有無交互作用或交叉反應之藥物或情況？可能之預後嚴重性如何？08083022:56:01藥物反應之免疫作用機轉TypeI:IgEdependent(Anaphylaxis)蕁麻疹、血管性水腫、休克TypeII:Cytotoxic(Biological)天疱瘡Pemphigus,Thromobocytopenicpetechia,TypeIII:Immune-complex(Chemical,Connective)血管炎Vasculitis,血清病serumsickness,TypeIV:Cellmediated,DelayedtypeGranulomatous,Eczematous史帝芬─強生徵候群、毒性表皮壞死症(SIS-TEN)Th1-INFγ-Mono,Th2-IL-5-Eosin,IL-8PMN,CD4/808083022:56:01MechanismofFrugHypersensitivityAnnalsofInternalMedicine2003,139(8):68408083022:56:01判斷ADR之原因藥物及嚴重度一、臨床特徵原發皮疹之類型斑疹、丘疹、結節、膨疹、紫斑、水疱、膿疱皮疹之分布、數目及癢、痛等局部症狀有無波及粘膜併發症狀：全身性症狀發燒、關節痛內臟變化、多重器官淋巴腺腫痛08083022:56:01判斷ADR之原因藥物二、病程、時序應紀錄所有用藥史：種類及起訖過去，類似藥物、劑量變化其他可能交互作用之藥物，隱藏藥物藥物代謝相關之肝、腎功能變化開始發疹日期計算出服藥及發疹之間隔停藥後之反應再度使用之反應08083022:56:01皮膚藥物反應的簡單分類立即性或延遲性，自限性或持續性蕁麻疹及血管性水腫、休克發疹(exanthema):麻疹樣藥疹侷限性或汎發型(+粘膜?)發疹型多型性紅斑，水疱、黏膜(SJS/TEN)局部反應固定藥疹、光敏感性、水疱症、壞死等08083022:56:01SevereCutaneousADR08083022:56:01藥物反應的重要皮膚病變發疹樣藥疹：可能為下列之早期病變急性發疹樣膿疱症(AGEP)血管炎(血清病、免疫複合體病)紅皮症(剝脫性皮膚炎)伴隨系統症狀、嗜伊紅球症之藥疹(DRESS)SJS-TEN(毒性表皮壞死症)多型性紅斑SJSTEN08083022:56:01立即性反應：Anaphylaxis蕁麻疹Urticaria血管性水腫AngioedemaAnaphylaxis休克ADR之比例:Anaphylaxis30%Urticaria10%為藥物引起服藥至發疹間隔：分鐘至小時Mortality：5%常見原因藥物：β-lactam:Penicillins,Cephalosporins,NSAID,contrastmedia,monoclonalAby08083022:56:01發疹樣藥疹ExanthematousDrugEruption常見之藥物不良反應皮疹FromtrunktoextremitiesMaculopapulesorurticariamayconfluentPurpuraatankle,feet,waistMucosaisspared可能有少數毛囊性膿疱ADR之比例:Child10-20%,Adult50-70%服藥至發疹間隔：4(7)-14days08083022:56:01發疹樣藥疹ExanthematousDrugEruptionTypeIV,or非免疫性directbindingtoMHC-2inKC(sulfa)AminoPCinInfectiousmononucleosis可能為嚴重之藥疹的前驅危險徵候毛囊一致性膿疱，紫斑，Nikolsky’ssign,粘膜潰瘍系統性功能異常DDx:Viralexanthema,Toxicshocksyndrome,GVHD,Kawasaki’s,Still’s08083022:56:01發疹樣藥疹ExanthematousDrugEruption080830PerifollicularpapuleswithcentralpustulesExanthematousRashwithPurpura:Vasculitis08083022:56:01發疹樣藥疹ExanthematousDrugEruptionMortality：單純發疹樣藥疹為:0%其他進展？？？可能為嚴重之藥疹的前驅可能為嚴重之藥疹的前驅Hypereosinophilia:DRESSPalpablepurpura,arthritis:VasculitisFacialedema:DRESS,ErythrodermaMucosainvolvement:TEN,SJSPainfulskin:TEN08083022:56:01血管炎VasculitisPalpablepurpura可能伴隨蕁麻疹，發疹變化血清病、免疫複合體病(TypeIIIreaction)Dermato-arthritissyndromer/obacteremia/sepsisfirst可能波及多重器官ADR之比例:10%服藥至發疹間隔：7-21days,challenge3days08083022:56:01LeukocytoclasticVasculitis有硬結的紫斑Palpablepurpura表面有無壞死現象？有無血尿？CheckCBC,WBC/DCLFTRFTC3,C408083022:56:01血管炎VasculitisMortality：？？？常見原因藥物：Penicillins,NSAID(oral,topical)Sulfonamide,Cephalosporins,Anticonvulsant,Allopurinol,Thiazide,Bioproducts(G,M-CSF,biologics,etc.)08083022:56:01DRESS:DrugRasheswithEosinophiliaandSystemicSymptoms08083022:56:01DRESSHypersensitivitySyndrome伴隨系統症狀、嗜伊紅球症之藥疹伴隨系統症狀、嗜伊紅球症之藥疹DrugRash(Reaction)withEosinophiliaandSystemicSymptoms常與藥物之代謝有關，或病毒HHV-6,7Immune+,IL-5—Th2—eosinophilsADR之比例:70-90%服藥至發疹間隔：15-40days停藥後持續數週至數月Mortality：5-10%08083022:56:01DRESSHypersensitivitySyndromeFebrile(85%)mobilliformrash(75%)麻疹樣、浮腫、follicularaccentuation，水疱、膿疱、紫斑、紅皮症好發於臉、上軀幹及四肢；臉浮腫特徵SystemicinvolvementHepatitis,myocarditis,interstitialpneumonitis,nephritis,thyroiditisetc.LymphadenopathyRxofCorticosteroids:firstchoiceMayrelapseduringtapering08083022:56:01DRESSHypersensitivitySyndrome伴隨系統症狀、嗜伊紅球症之藥疹常與藥物之代謝有關：phenytoin(areneoxide)1:1000sulfonamide(hydoxylamine?)1:10,000常見原因藥物：AromaticAnticonvulsant(phenytoin,carbamazepine,phenobarbital)Allopurinol(inrenaldysfunction)Lamotrigine(esp.withValproate)Sulfonamide,dapsoneMinocycline,goldsalt080830急性發疹樣膿疱症AcuteGeneralizedExanthematousPustulosis(AGEP)臉部或腋下鼠蹊開始水腫性紅斑有非毛囊性小膿疱08083022:56:01急性發疹樣膿疱症(AGEP)AcuteGeneralizedExanthematousPustulosis急性發燒，與皮疹同時或更早臉部或腋下鼠蹊等部位浮腫開始數小時內快速擴散軀幹及上肢會波及粘膜皮疹為多樣性，癢或熱感水腫性紅斑上有非毛囊性小膿疱水腫、紫斑，水疱，靶型疹皮疹持續1-2週Mortality：1-2%08083022:56:01AGEP/EMtoPseudoephedrine08083022:56:01急性發疹樣膿疱症(AGEP)可能是敏感之recallreactionPatchtest:陽性率達80%Neutrophilia,IL-3,8,G-CSFfromTcellsADR之比例:70-90%服藥至發疹間隔：四天，一般為兩天內常見原因藥物：ß-lactame(PC,aminoPC,Cephalosporins)Macrolides,Calciumchannelblockers(esp.diltiazem)Sulfasalazine-COX2Inh08083022:56:01ErythrodermainAnticonvulsantHypersensitivitySyndrome08083022:56:01紅皮症(剝脫性皮膚炎)Exfoliativedermatitis,Erythroderma先局部皮疹，常由flexural開始，麻疹樣2-6天內擴展至全身(90%)臉部水腫Scaling：lamellar,crustybrannyHyper-/hypo-thermia,Tachycardia,CHFlymphadenopathyy,hepatomegalyEosinophiliaandlymphopeniaADR之比例:19%(5.5-42%)為藥物引起服藥至發疹間隔：wkstomons(epoprostenol)停藥後2-6wks緩解Mortality：?08083022:56:01紅皮症(剝脫性皮膚炎)常見原因藥物：Allopurinol,Ampicillin/Amoxicillin/Penicillins,(14%floxacillin)carbamazepine(ox-),phenobabital,phenytoindapsone,sulfasalazine,sulfonamide,clofazimine,omeprazole,phenothiazines,vancomycine