爱若华在皮肤科其他疾病的应用.docx
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爱若华在皮肤科其他疾病的应用.docx
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爱若华在皮肤科其他疾病的应用
Successfultreatmentofrecalcitranteczematousdermatitiswithleflunomide.
A.S.Boyd
JAmAcadDermatol.2013;69(3):
e148-149.
Notallpatientswitheczematousdermatitisrespondtoconservativetreatment,whichmeansthatsystemictherapiesorlighttherapymustbeconsidered.Leflunomidemaybeofbenefitinthesepatients.
A49-year-oldhealthywhitewomanpresentedwitha14-yearhistoryofeczematousdermatitisprimarilyaffectingherhandsandfeet.Herconditionfluctuated,withvesiclesandbullaedevelopingonthesidesofherfingersandsoles.Herplantardiseasewasvariablyincapacitating,withthickened,cracked,andpainfulskin,makingwalkingdifficult,leadingtosignificantweightgain.Shehadbeentreatedwithhighpotencytopicalsteroids,topicalpicrolimus,lacticacidandurea-containingcreams,oralantibiotics,oralketoconazole,andoralcorticosteroids.Noneelicitedmorethantemporaryrelief.Abiopsyspecimenofherleftsolewasobtained,andthehistopathologicresultswereconsistentwitheczematousoratopicdermatitis.
Anintramuscularinjectionoftriamcinolone40mgwasunhelpful,asweretopicalcoaltarandichthammol.Apatchtestrevealedallergiestofragrancemix,nickelsulfate,balsamofPeru,cobaltchloride,andcinnamaldehyde.Avoidanceofthesechemicalsfailedtoresultinimprovement.Thepatientwasprescribedmycophenolatemofetil500mgtwicedailywithonlymildimprovement.Becausenoreliefhadensuedafter4monthsandthepatientwasanxioustopursueotheroptions,themycophenolatemofetilwasdiscontinuedandthepatientwasprescribedazathioprine25mgdaily.Significantgastrointestinalupsetensuedalmostimmediately,andshestoppedtakingazathioprineafter1week.Becauselighttherapywasimpractical,leflunomide20mgdailywasprescribed.After1month,herhandswerelargelydisease-freeandherfeethadimproved.After2months,hersoleswereessentiallyclear.After5monthsoftherapy,themedicationwasreducedtoeveryotherday.Thepatient’sbloodworkwasunremarkable.After1yearoftreatment,sheremainsdisease-freeandthedrugisbeingtapered.Shehasresumedwalkingandhaslost35pounds.
Leflunomideisclassifiedasanoraldiseasemodifyingantirheumaticdrugandisusedinthetreatmentofbothrheumatoidandpsoriaticarthritis.Italsohasafavorabletrackrecordintreatingcutaneouspsoriasis,althoughitisnotconsideredafirst-linemedication.Thedruginhibitsdihydroorotatedehydrogenase,decreasingtheavailableintracellularpyrimidinesandmakingactivatedlymphocytesunabletoentertheSphaseofthecellcycle.Themostcommonsideeffectisdiarrhea,reportedin32%ofrheumatoidarthritispatients.Itcausestransaminaseelevationin2%to4%ofpatients,usuallywithinthefirst6monthsoftherapy.Itiscontraindicatedinpregnantwomenorwomenofchildbearingpotentialwhoarenotusingreliablecontraception.
Threepatientswithrecalcitrantatopicoreczematousdermatitistreatedwiththisdrughavebeenreported.Allimproved,with1patientbeingabletodiscontinueleflunomide.Eotaxin-3levelsandatopicdermatitisseverityhavebeenlinked.Thereisalsoevidencethateotaxinreleasebyeosinophilsisinhibitedbyleflunomideinvitro,leadingtospeculationthatthisrepresentsthedrug’smechanismofactioninatopicdermatitis.Aswithpsoriasis,leflunomideshouldnotbeconsideredafirst-linetreatmentoption;however,itdoesappeartobeeffectiveinsomepatientswithrecalcitrantdisease.
来氟米特成功治疗顽固性湿疹性皮炎
不是所有的湿疹性皮炎患者都对保守治疗有效,这也意味着需要考虑系统性治疗或光疗法,来氟米特或许能使这些病人受益。
一名49岁的健康白人女性有14年湿疹性皮炎病史,主要累及手足,病情波动明显,双手和双侧足底出现囊泡和大泡,足底病变复杂失去功能,伴有皮肤增厚、皲裂和皮肤疼痛(如图),由于难以行走,导致体重明显增加。
曾使用局部激素、吡美莫司、乳酸和尿素膏,口服抗生素、酮康唑和激素治疗,都只能暂时缓解病情,左脚底组织病理活检提示符合湿疹和特应性皮炎。
肌肉注射去炎松40mg,外用煤焦油和鱼石脂病情没有改善,皮肤过敏原检测提示对芳香化合物、硫酸镍、秘鲁香胶、氯化钴和肉桂醛过敏,但避免接触这些过敏原未没能使病情得到改善,使用吗替麦考酚酯500mg每日两次治疗,仅有轻微改善,由于在接下来的4个月病情没有改善,病人急于寻求其他治疗于是停用吗替麦考酚酯,并开始采用硫唑嘌呤25mg/d治疗,随即发生非常严重的胃肠道不适症状,于是在服用硫唑嘌呤一周后停药。
由于光疗无法实现,所以采用来氟米特20mg治疗,治疗1个月后,双手大部分病愈,双脚也明显好转,治疗2个月后,脚底病变基本痊愈,在治疗5个月后,开始改为隔天服药,血液检查未见异常,治疗一年后病情没有反复,药物逐渐减量,她重新开始行走,并减重35磅。
来氟米特作为口服病程改善抗风湿药物,被用于治疗类风湿关节炎和银屑病关节炎,在治疗银屑病方面尽管不是一线治疗用药但也有很好的记录。
来氟米特能抑制二氢乳清酸脱氢酶,减少细胞内嘧啶合成,抑制激活的淋巴细胞使其不能跨越细胞周期的S期,最常见的不良反应是腹泻,有报道称达到类风湿关节炎患者的32%。
在2%-4%患者中会发生转氨酶升高,常发生在治疗的前6个月内,在孕妇和没有采取避孕措施的育龄期妇女中禁用。
曾有报道称三名顽固性过敏性或湿疹性皮炎患者使用来氟米特治疗,均治疗好转,并且1名患者能停药。
嗜酸细胞活化趋化因子3水平和过敏性皮炎严重程度相关,在体外实验中,有实验表明来氟米特能抑制嗜酸性粒细胞释放嗜酸细胞活化趋化因子,因此,这可能是治疗特应性皮炎的机制。
来氟米特虽然不是治疗的一线用药,然而它确实对治疗一些顽固性疾病患者有效。
来氟米特治疗前、后对比
Leflunomideisapossibledeactivatorforvitiligo,apilotstudy.
S.S.Awad
JournaloftheEuropeanAcademyofDermatologyandVenereology.2012;26(9):
1173.
Invitiligopatientswithactivelyprogressivedisease,abundantTcellsweredetectedinthemarginoflesions.Targetingtheactivation⁄maturationofTcellsmayinterferewiththeautoimmunemediateddestructionofmelanocytesbyactivatedTcells.
Thispilotstudy,aimstoevaluatepossiblebeneficiaryeffectofLeflunomideasanimmune-modulatordrugintroducedtohaltvitiligoactivity.Leflunomideisaninhibitorofpyrimidinesynthesisandhasantiproliferativeandanti-inflammatoryactions.Leflunomideisknowntoinhibitlymphocyteactivation,cellmigrationandproliferation.ItpartiallyreducesIL-2productionandcompletelyinhibitsproliferationofstimulatedTcellsprincipallybyinhibitionofT-cellresponsivenesstoIL-2,andbyinhibitionofproteinTyrosinephosphorylationinTCells.
Atotalof30activevitiligopatientswereincludedinthestudy,18malepatientsand12femalepatients,withagerangingfrom16to56yearswithameanof29.2(±10.68SD).Thedurationofvitiligovariedfrom2weeksto30monthswithameanof7.45months(±7.23SD).Historyandgeneralexaminationsofthepatientsrevealeddiabetesmellitusinthreepatients,alopeciaareatainonepatient,hypertensioninonepatientandpsychologicalstressinfourpatients.Familyhistoryofvitiligowasnoticedin16patients.
Allpatientshadnon-segmentalvitiligoindifferentpartsofthebodyshowingnewlyevolvinglesionsand⁄orenlargingpatches,withinthelastmonth,withnomanifestationofstoppageonfirmedbyexaminationandarchiveddigitalimages.
Fifteenpatientswereusingsystemicsteroidsandhelio⁄photo-therapypriortothestudytocontroltheirdiseaseactivity,butwithnosuccess,theotherfifteenpatientswerenaiveanddidnotuseanyprecedingsystemicmedications.Detailedhistory,clinicalexaminationandlaboratoryinvestigationswereperformedatthebaselinevisit.Bloodand⁄orliverenzymesanomaliesexcludedtheircasesfromthestudy.Leflunomidetherapywasinitiatedinadoseof100mgdailyfor3daysasloadingdose,followedby20mgdailyfor6weeks.
Follow-upvisitswerescheduledeveryweek,wherediseaseprogresswasevaluatedandadverseeffectsweremonitoredtill12thweek,theendofthestudy.Significantstoppageofactivityandprogressofvitiligowasreportedin90%ofcasesandwasasearlyas2weeksoftherapyin13patients,3weeksin11patients,4weeksintwopatientsand5weeksinonepatient,withameanof2.6weeks(±0.7SD).
Significantpigmentationwasalsoobservedinmanypatientsbytheendofthestudy.Leflunomidecouldnotachievesignificanthaltingofthediseaseactivityinonlythreepatients(10%).
Duringthestudy,24patients(80%)didnotreportanycomplainsorshowadverseeffects,whileonlyonepatient(3.3%)hadhisliverenzymeselevatedattheendof6weekstreatment,andfivepatients(16.7%)hadsomegastriccomplainsrangingfrommilddiscomforttovomitingandoneofthemalsodevelopedlymphopeniaandhairfall.
Inthisstudy,LEFalsoprovedtomanagetheactivitynotonlyinnaivepatientsbutalsowhensystemicsteroidsfailedandprovedtobesuperiortothesteroidsinsuchcases.Steroidsarealsowellknownfordiabetic,hypertensiveandpsychogenicadverseeffectsandcouldbecontraindicatedinmanyvitiligopatients,demonstratingfurtherLEFbenefitsoversteroidsinsusceptibleindividuals.
Inconclusion,oncedailyleflunomideisaneffectiveandconvenienttreatmenttostopvitiligoprogressionwithtolerabilityandafavourablesafetyprofile.
来氟米特可能成为治疗白癜风的减活化剂,一项试点研究
活动性进展性白癜风患者,在病变的边缘可检测大量的T细胞。
靶向T细胞的活化/成熟可能干预T细胞激活由自身免疫介导的黑色素细胞结构的破坏。
这项试验研究旨在评估免疫调节剂来氟米特治疗活动性白癜风的疗效。
来氟米特是嘧啶合成抑制剂并具有抗增殖和抗炎作用。
来氟米特可抑制淋巴细胞的活化,细胞迁移和增殖。
它减少了部分IL-2产生并完全抑制了激活的T细胞的增殖,通过抑制活化T细胞对IL-2的反应还能抑制T细胞蛋白的酪氨酸磷酸化
共有30例活动性白癜风患者被纳入研究,男18例,女12例,年龄从16〜56岁,平均年龄为29.2岁(10.68±SD)。
白癜风病程从2周到30个月,平均7.45个月(7.23±SD)。
根据病史和查体发现糖尿病3例,斑秃患者1例,高血压1例,心理应激4例。
白癜风家族史发现16例。
所有患者均在身体的不同部位患有非节段型白癜风,表现为新的病变进展和斑块扩大。
在过去的一个月内,通过检查和影像学证实没有疾病停止进展的表现。
15例病人使用全身激素之前已经使用光照治疗控制其疾病活动度,但没有成功,另外15例患者没有使用任何前述全身用药。
在基线访问时详细询问病史并进行临床和实验室检查。
给予来氟米特前3天100mg/d的负荷剂量,以后给予20mg/d持续6周。
每周随访评估疾病进展和监测不良反应,直到第12周试验结束。
90%的病例白癜风的活动度和进展明显停止,治疗2周时有13例,3周有11例,4周2例病人,5周1例,平均为2.6周(0.7±SD)。
研究结束时在许多患者中观察到明显的色素沉着。
来氟米特也无法降低疾病活动度的只有3例(10%)。
在研究中,24例(80%)没有任何并发症或不良事件,而只有1例病人(3.3%)在治疗6周结束时肝酶升高,5例患者有一些胃部不适,从轻度不适到呕吐,其中1例患者淋巴细胞减少和脱发。
在本研究中,来氟米特不仅能够控制初治,也能控制全身激素治疗失败患者,而且疗效优于类固醇激素。
众所周知,激素治疗可能引起糖尿病,高血压和精神性等不事件,并可能在许多白癜风患者中被禁用,这表明在某些患者治疗中,LEF更优于激素。
总之,每日一次来氟米特是一种有效和方便的治疗,能够阻止白癜风病情的进展,并具有良好的安全性和耐受性。
Conversionfromtacrolimus/mycophenolicacidtotacrolimus/leflunomidetotreatcutaneouswartsinaseriesoffourpediatricrenalallograftrecipients.
NguyenL,McClellanRB,ChaudhuriA,etal
Transplantation.2012;94(5):
450-455.
BACKGROUND:
Thechallengeofimmunosuppressioninpediatricrenaltransplantationistobalancepreventingrejectionwhileavoidinginfectiouscomplications.Adermatologicalcomplicationofimmunosuppressionisviralwarts,whichcausesignificantdisfigurementandincreasetheriskofskinmalignancy.
METHODS:
Wepresentthreepediatricandadolescentrenalallograftrecipientswithmultiple,recalcitrantverrucaev
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