Pemphigus湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科Structureofepidermis湘雅二醫(yī)院皮膚性病科PemphigusClinicalFeatures&PathogenesisEtiologyLaboratoryFindingsDiagnosisDifferentialDiagnosisTreatment湘雅二醫(yī)院皮膚性病科PhemphigusP.VulgarisP.VegetansP.FoliaceusP.ErythematosusDrug-inducedpemphigusParaneoplasticPemphigus,PNPIgAPemphigus湘雅二醫(yī)院皮膚性病科Middle-agedThin-walled,flaccid,easilyrupturedbullaeGeneralizedlesionBadconditionFatalPemphigusvulgaris湘雅二醫(yī)院皮膚性病科Bullouslesionsarisingfromapparentlynormalskinsurface.BullaeErosionCrust湘雅二醫(yī)院皮膚性病科Nikolsky’ssignTheupperlayersoftheepidermisareeasilymadetoslipbyslightpressureorrubbingbecauseoftheabsenceofcohesionintheskin.ItisalsoseeninStevens-Johnsonsyndrome,toxicepidermalnecrolysis,andepidermolysisbullosa.Phemphigus湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科inthelowerepidermisIntraepidermalblisterandcleftformationAcantholyticcells湘雅二醫(yī)院皮膚性病科acantholysisPhemphigus湘雅二醫(yī)院皮膚性病科acantholyticorTzankcellsPhemphigus湘雅二醫(yī)院皮膚性病科Pemphigusvegetans

Fungoidvegetationsorpapillomatousproliferations湘雅二醫(yī)院皮膚性病科Sharplydelineatinglesions湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科Groin,genitalia,perineum,axillaeareoftenaffected.湘雅二醫(yī)院皮膚性病科perinealviewshowingcharacteristichypertrophicflexuralvegetations.Notetheintactvesicles.湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科GeneralizedexfoliativeerythrodermaPemphigusFoliaceus

湘雅二醫(yī)院皮膚性病科CircumscribedpatchesoferythemaandcrustingPemphigusErythmatosus

湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科Thelesionsareusuallylocalizedoncheeks,foreheadandears.湘雅二醫(yī)院皮膚性病科scarringanderythemaaffectingbothcheeks湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科inthegranularlayerorbeneaththestratumcorneum湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科ETIOLOGYConceptofPemphigusIntraepidermalblistersAcantholysisNikolskysignAnautoimmunedermatoses??AntigenAntibodies湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科AntigenDsg2:所有有橋粒的組織Dsg3:表皮深層，粘膜全層Dsg1:表皮或粘膜淺層湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科AntigenPVAg:Dsg1,Dsg3;130KdaPFAg:Dsg1;160KdaCelladhesionmolecules湘雅二醫(yī)院皮膚性病科AntibodiesDIF:IgG&C3IIF:CirculatingICantibodyAbtitersoftenparalleldiseaseactivity湘雅二醫(yī)院皮膚性病科

DirectImmunofluorescentIgG&C3canbedetectedwithintheepidermaltissueintercellularantibodies湘雅二醫(yī)院皮膚性病科Animalmodel湘雅二醫(yī)院皮膚性病科Organculturemodel48hr72hr湘雅二醫(yī)院皮膚性病科P模型中纖溶酶原激活劑活性尿激酶可引起棘層松解抗尿激酶抗體能抑制模型中的棘層松解能抑制纖溶酶活性的抑肽酶等可抑制棘層松解0.2萬u/ml尿激酶48小時湘雅二醫(yī)院皮膚性病科Pathogenesis天皰瘡抗體角質(zhì)形成細(xì)胞Dsg1/Dsg3纖溶蛋白酶原激活物纖維蛋白酶系統(tǒng)活化細(xì)胞間粘合物質(zhì)降解棘刺松解湘雅二醫(yī)院皮膚性病科TreatmentCorticosteroidsImmunosuppressantsSupportivetherapyTopicaltreatment湘雅二醫(yī)院皮膚性病科Treatment皮質(zhì)類固醇激素用藥原則早期使用足量控制酌情減量維持要長ImmunosuppressantsAZP(Azathioprine)CTX(Cyclophosphamide)MTX(Methotrexate)CsAMMF(Mycophenolatemofetil)FK506(Tacrolimus)Tripterygiumglycosides湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科請思考：新的治療方法？湘雅二醫(yī)院皮膚性病科Treatment抑制纖溶酶活性止血芳酸0.5tid細(xì)胞水平針對抗原？針對產(chǎn)生抗體的B細(xì)胞克隆美羅華rituximab(Monoclonalanti-CD20antibody)；英利昔單抗Infliximab(TNF—α)造血干細(xì)胞移植湘雅二醫(yī)院皮膚性病科針對抗體抑制抗體生成吸附特異性抗體Immunoadsorption血漿置換PlasmapheresisIVIg:0.2-0.4g/kg/d*3-5d基因治療關(guān)閉產(chǎn)生抗體的B細(xì)胞克隆的基因阻止DNA轉(zhuǎn)錄阻止mRNA翻譯抗體湘雅二醫(yī)院皮膚性病科自體外周血干細(xì)胞移植治療難治性天皰瘡一例湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科Case132y/omanwithflaccidfluid-filledblisterfor2yearsandextensivepainfulerosionsfor2weeks.BeginwithOralerosion,progresstoinvolvethetrunkandextremities湘雅二醫(yī)院皮膚性病科Case1PET38.3℃BP145／110mmHg，lesions湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科Treatmentofcase1一般治療及護(hù)理甲基強(qiáng)地松龍80mg/d羅氏芬、雷尼替丁、鈣劑等局部處理：濕敷及搽藥湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科皰疹樣天皰瘡湘雅二醫(yī)院皮膚性病科環(huán)形或多環(huán)形紅斑，邊緣略隆起，水皰或丘皰疹。尼氏征陰性。瘙癢明顯。病程慢性，預(yù)后好。湘雅二醫(yī)院皮膚性病科藥物性天皰瘡可引起天皰瘡樣皮損的藥物D-青霉胺、卡托普利、呋塞米非那西林、砜類藥物皮損環(huán)狀、念珠狀紅斑水皰、大皰、鱗屑性斑塊湘雅二醫(yī)院皮膚性病科IgA天皰瘡角層下膿皰性皮病表皮內(nèi)嗜中性粒細(xì)胞浸潤性IgA皮病皮疹：皺褶部位，水皰、膿皰伴瘙癢，有融合傾向，環(huán)狀排列湘雅二醫(yī)院皮膚性病科副腫瘤性天皰瘡粘膜表現(xiàn)：頑固性糜爛性口炎及口腔粘膜潰瘍，可擴(kuò)展到扁桃體、食道、鼻咽粘膜、氣管、眼結(jié)膜、外生殖器。皮膚表現(xiàn)：瘙癢性、多形性、易變性。弛緩的或緊張的水皰，可伴糜爛苔蘚樣和多形紅斑樣皮損（靶形損害）軀干、四肢近端，掌跖也可受累，而頭面部皮膚不易受到損害湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科PNP伴發(fā)的腫瘤B淋巴細(xì)胞增生性疾病，包括霍奇金淋巴瘤、慢性淋巴細(xì)胞性白血病、Castlman病、肉瘤、胸腺瘤、Walden-strom巨淋蛋白血癥很少病例有潛在的非淋巴系統(tǒng)腫瘤，如胰腺癌、支氣管鱗癌、管內(nèi)乳腺瘤。湘雅二醫(yī)院皮膚性病科組織病理：（在皮損周圍正常皮膚粘膜取材）基底細(xì)胞上棘層松解，基底細(xì)胞空泡變性，表皮和表皮上部有角質(zhì)形成細(xì)胞壞死DIF：在表皮細(xì)胞表面有IgG沉積，同時基底膜帶有IgG及C3，呈顆粒狀或線狀沉積IIF：以正常人皮膚、猴食道作底物，與天皰瘡相同，可檢測到循環(huán)抗體。湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科家族性慢性良性天皰瘡Benignfamilialchronicpemphigus湘雅二醫(yī)院皮膚性病科家族性慢性良性天皰瘡Benignfamilialchronicpemphigus湘雅二醫(yī)院皮膚性病科家族性慢性良性天皰瘡Benignfamilialchronicpemphigus湘雅二醫(yī)院皮膚性病科皰疹樣皮炎DermatitisHerpetiformis湘雅二醫(yī)院皮膚性病科皰疹樣皮炎DermatitisHerpetiformis湘雅二醫(yī)院皮膚性病科皰疹樣皮炎DermatitisHerpetiformis湘雅二醫(yī)院皮膚性病科皰疹樣皮炎DermatitisHerpetiformis湘雅二醫(yī)院皮膚性病科妊娠皰疹Herpesgestationis湘雅二醫(yī)院皮膚性病科DifferentialdiagnosisBullousPemphigoid湘雅二醫(yī)院皮膚性病科TheelderlypeopleLarge,tensebullae;thedenudedareas:atendencytohealspontaneously.Itching,tensebullaeontheextremities湘雅二醫(yī)院皮膚性病科湘雅二醫(yī)院皮膚性病科Groin,axillae,theflexorsurfacesoftheforearms湘雅二醫(yī)院皮膚性病科Affectedback湘雅二醫(yī)院皮膚性病科Basementmembranezone,BMZhemidesmosomeLaminalucidaLaminadensaSublaminadensa湘雅二醫(yī)院皮膚性病科BPAg1:230KDantigenassembledinmacromolecularaggregateswithinthehemidesmosomesBPAg2：180KDantigenAtransmembraneglycoproteinwithbothintracellularandextracellularrelationshipswiththehemidesmosomes.湘雅二醫(yī)院皮膚性病科Subepidermalblisterwithinflammatoryinfiltrate(eosinophils)noacantholysis湘雅二醫(yī)院皮膚性病科 LinearIFalongtheBMZ.湘雅二醫(yī)院皮膚性病科OutlineofPemphigusVulgarisAcantholyticblistersformimmediatelyaboveepidermalbasalcells.PViscausedbyautoantibodiesagainstdesmoglein3,whichisadesmosomaladhesionfactorinKCs.Thepathogenesisinvolvesanti-desmogleinantibodies.湘雅二醫(yī)院皮膚性病科OutlineofPemphigusVulgarisThediseasemostfrequentlyoccursinthemiddle-agedandelderly.Ittendstomanifestasoralenanthema.Nikolsky’ssignispositive.Oralsteroidsandimmunosuppressantsarethefirst-linetreatment.湘雅二醫(yī)院皮膚性病科OutlineofPemphigusfolliaceusAutoantibodiesareproducedexclusivelyagainstdesmoglein1.Acantholysisandblisteringareseeninthesuperficialepidermis.Fragileblisters,scalinganderosion,accompaniedbycrusts,occursystemically.Lesionsarenotproducedinthemucosa.湘雅二醫(yī)院皮膚性病科OutlineofParaneoplasticpemphigusThediseaseaccompaniesmalignantorbenignneoplasm(lymphoproliferativediseasesinparticular).Severemucosallesionswitherosion,andvariouscutaneouslesions,appear.Autoantibodiesagainstseveralepid