天疱疮治疗-糖皮质激素

1.糖皮质激素作用机制2.天疱疮治疗中糖皮质激素应用3.糖皮质激素的不良反应天疱疮治疗——糖皮质激素

Thetreatmentofpemphigusisstillachallengingtask.Thechoiceforthebestregimenforeachtypeofpatient,basedontheextentofdisease,patients’comorbidities,controlofsideeffects,andfacilityofaccesstodrugs,whichmaybeexpensivesometimes,makestreatmentoptionsverylimitedincertaincases.PiresCAA,VianaVB,AraújoFC,MüllerSFR,OliveiraMS,CarneiroFRO.EvaluationofcasesofpemphigusvulgarisandpemphigusfoliaceusfromareferenceserviceinParástate,Brazil.AnBrasDermatol.2014;89(4):556-61.2天疱疮首选药物：局部or全身治疗一、糖皮质激素Glucocorticoids31.糖皮质激素类药物的分类根据来源

天然

：

可的松、氢化可的松

合成

：如泼尼松、地塞米松等4根据药理作用维持时间

短效

：可的松、氢化可的松<12h

中效

：泼尼松龙、曲安西龙12~36h

长效

：地塞米松、倍他米松>36h可的松、泼尼松

肝内转化→氢化可的松、泼尼松龙肝功能不全只能选用

氢化可的松、泼尼松龙

1.糖皮质激素类药物的分类52.药理作用1）抗炎作用2）免疫抑制作用3）抗毒作用4）抗休克作用5）血液与造血系统6）其它作用

6绝对禁忌症相对禁忌症现正患严重精神病和癫痫（非AID所至）活动性消化性溃疡新近胃肠吻合术角膜溃疡（非AID所至）抗菌药不能控制的感染如全身性霉菌感染

糖尿病

严重高血压

结核

精神病史

银屑病3.禁忌症7全身应用初始减量维持局部应用二、天疱疮治疗中糖皮质激素应用1.全身应用原则：早期应用、足量控制、合理减量、小量维持；起始控制阶段：量大从速；减量维持阶段：递减忌躁；临床常用口服：泼尼松、泼尼松龙、地塞米松；91.全身应用单纯累及口腔黏膜初始计量60~80mg/d多数情况下能在较短时间内控制损害用药后增量为原量1/3~1/2新疱发生糜烂明显有渗出病情控制后维持1~2周，然后逐渐减量10Thecombinationofcorticosteroidswithimunossupressants(azathioprine,cyclophosphamide,methotrexate,mycophenolatemofetil)hasshowngoodresultsincontrollingthedisease,whichallowedtoreducethedoseofcorticosteroid.MurrellDF,DickS,AhmedAR,AmagaiM,BarnadasMA,BorradoriL,etal.Consensusstatementondefinitionsofdisease,endpoints,andtherapeuticresponseforpemphigus.JAmAcadDermatol.2008;58:1043-6.111.全身应用--激素用量：初始计量皮肤范围-初始计量皮损面积<体表面积10%轻症40mg/d皮损面积=体表面积30%中症60mg/d皮损面积>体表面积50%重症口服剂量不超过120mg/d大剂量冲击治疗甲泼尼龙500~1000mg地塞米松100~200mg连续3d输注121.全身应用—激素用量：减量减药时机：口腔病损完全控制、原有糜烂面基本上为新生上皮覆盖后减药速度：开始快—后来慢13最初3~4周减药不超过原剂量1/6~1/5;7~10d减一次以后2~4w减一次减药过程中出现新病损：暂停减药因减药速度过快or骤然停药引起病损大面积复发果断增加用量重新给药1.全身应用—激素用量：减量141.全身应用—激素用量：维持用量时间：4~5年用量：Qod晨起15~20mg15二、局部应用轻型天疱疮：局部强效GC0.05%氯倍他索软膏涂抹患处bid病损内注射（复方倍他米松注射液）IntralesionalcorticosteroidinjectionsmaybeusedtotreatoralPVlesions,butthistypeoftherapyhasbeenassociatedwithscarringand/ormucosalatrophyBenLaghaN,PoulesquenV,RoujeauJC,etal.Pemphigusvulgaris:Acase-basedstudy.JCanDentAssoc.2005;71:667–672.161）长期大量应用引起的不良反应2）停药反应三、不良反应ThemostcommonGC-associatedAEsnotedinadultsinclude:osteoporosisandfractures;HPA-axissuppression;Cushingoidappearanceandweightgain;hyperglycemia/diabetes;CVDanddyslipidemia;myopathy;cataractsandglaucoma;psychiatricdisturbances;immunosuppression;aswellasotherGIanddermatologicevents.18医源性肾上腺皮质功能亢进症（库欣综合征）：长期应用超生理剂量后致糖代谢和盐水代谢紊乱的结果主要表现：满月脸、向心性肥胖、肌无力及肌萎缩、皮肤菲薄、痤疮、多毛、浮肿、低血钾、糖尿、易感染等19202122②萎缩、骨质疏松、骨缺血性坏死可使蛋白分解加速，合成减少，出现负氮平衡，使肌萎缩和骨质形成障碍

同时有促进甲状旁腺激素（PTH）分泌及抗维生素D作用，抑制成骨细胞活动，使破骨细胞活动增加，抑制骨基质蛋白质合成，增加钙、磷排泄，减少小肠对钙吸收，造成骨质疏松。儿童、绝经期妇女更易发生

宜补充维生素D、钙盐防止骨质疏松232.停药反应长期应用糖皮质激素，可通过负反馈作用，使内源性肾上腺皮质功能减退或萎缩，突然停药出现停药反应。a.医源性肾上腺皮质功能不全：

出现恶心

呕吐

食欲不振

肌无力

低血糖

低血压等24“反跳现象”：突然停药导致原发病复发或加重的现象“停药症状”：患者出现一些原来疾病没有的症状，如肌痛、肌强直、关节痛、

疲乏无力、情绪消沉、

发热等。2.停药反应25副反应&累计摄入量Manyadverseeffectsofglucocorticoidtreatment(suchasglucoseintoleranceandosteoporosis)arerelatedtocumulativetissueexposure.Wethereforesuggestdescribingthecumulativedose,especiallyinlongtermtherapy.Currentlythecalculationofcumulativedosesisusedratherforscientificreasons.26Insummary,wesuggestthatanappropriatedescriptionofagivenglucocorticoidtherapyregimenshouldfollowthisexample:Initiallyxmgprednisoneorallyonceaday(at800am)fortwoweeks,thenreducedtoymgprednisoneaday,followedby...(describeeachstepofreductionintermsofmgandtime)reachingzeroafterforexample,oneyear(overallduration).Thecumulativedosewaszmgprednisone.副反应&累计摄入量27糖尿病患者出现天疱疮时，激素的使用？Q&A·····全身使用强的松15mg/d，2周后症状明显减轻·······由于使用强的松后，血糖升高难以控制，后自行停用强的松·········空腹血糖8.6mmol/L，尿糖阴性···1.GC对糖尿病的影响1.Exogenouscorticosteroiduseisassociatedwithhyper-glycemia,andhigh-dosetherapyincreasesinsulinresistanceinpatientswithpre-existingandnew-onsetdiabetes.2.GCsalsoappeartohaveagreaterimpactonpostprandialcomparedtofastingglucoselevels29GC剂量对血糖影响TheeffectsofGCadministrationonglucoselevelsareobservedwithinhoursofsteroidexposure,andappeartobedose-dependent.Apopulation-basedstudyofover11,000patientsfoundthattheriskforhyperglycemiaincreasedsubstantiallywithincreasingdailysteroiddose;oddsratios(ORs)forhyperglycemiawere1.77,3.02,5.82and10.34for1–39mg/day,40–79mg/day,80–119mg/dayand≥120mg/dayofhydrocortisone-equivalent,respectively.HuscherD,ThieleK,Gromnica-IhleE,Gromnica-IhleE,HeinG,DemaryW,DreherR,ZinkA,ButtgereitF:Dose-relatedpatternsofglucocorticoid-inducedsideeffects.AnnRheumDis2009,68:1119–1124.30A监测先行The2013CanadianDiabetesAssociation(CDA)guidelinesrecommendthatglycemicparametersbemonitoredforatleast48hoursafterinitiationofGCtherapy,regardlessofwhetherornotthepatienthasdiabetes.Guidelinesforbloodglucosemonitoringpost-transplantsuggestweeklymonitoringforfourweeksaftertransplant,followedbybloodglucosechecksat3and6monthspost-transplant,thenannuallythereafter.311.CanadianDiabetesAssociation2013clinicalpracticeguidelinesforthepreventionandmanagementofdiabetesinCanada.2.B、临床实践《2013年中国2型糖尿病防治指南》3334referraltoamultidisciplinarydiabetesteam！①ThetreatmentofGC-induceddiabetesinchildrenisbestaccomplishedthroughthecombinedeffortsofamultidisciplinarypediatricdiabeteshealthcareteam。

②Whenpossible,referraltoamultidisciplinarydiabetesteamshouldbeconsidered.35《2013年中国2型糖尿病防治指南》36Summary—to病例1.首选口服糖皮质激素60~80mg/d2.检测血糖FBG、2hpostprandial根据血糖值请内分泌科会诊，胰岛素or降糖药的用量3.根据患者情况选取综合疗法—利妥昔单抗？等37Reference[1]BenLaghaN,PoulesquenV,RoujeauJC,etal.Pemphigusvulgaris:Acase-basedstudy.JCanDentAssoc.2005;71:667–672.[2]PiresCAA,VianaVB,AraújoFC,MüllerSFR,OliveiraMS,CarneiroFRO.EvaluationofcasesofpemphigusvulgarisandpemphigusfoliaceusfromareferenceserviceinParástate,Brazil.AnBrasDermatol.2014;89(4):556-61.[3]MurrellDF,DickS,AhmedAR,AmagaiM,BarnadasMA,BorradoriL,etal.Consensusstatementondefinitionsofdisease,endpoints,andtherapeuticresponseforpemphigus.JAmAcadDermatol.2008;58:1043-6.[4]HoJ,PacaudD:Secondarydiabetesinchildren.CanJDiab2004,28:400–405.[5]CanadianDiabetesAssociationClinicalPracticeGuidelinesExpertCommittee:CanadianDiabetesAssociation2013clinicalpracticeguidelinesforthepreventionandmanagementofdiabetesinCanada.CanJDiabetes2013,37(Suppl1):S1–S212.38Reference[6]Liuetal.:Apracticalguidetothemonitoringandmanagementofthecomplicationsofsystemiccorticosteroidtherapy.Allergy,Asthma&ClinicalImmunology20139:30.[7]《2013年中国2型糖尿病防治指南》