皮肤学天疱疮

,大疱性皮肤病,天疱疮,天疱疮,复习Epidermis,Basal layer,Prickle layer,Granular layer,Horny layer,天疱疮,复习Desmosome,桥粒是表皮细胞之间重要的粘合性连接结构。,tonofilament,天疱疮,复习水疱和大疱,Vesicles & bullae,病因和发病机理 ETIOLOGY AND PATHOGENESIS,自身免疫性皮肤病 An autoimmune dermatoses抗原 antigen抗体 antibodies棘层松解 acantholysis,天疱疮是自身免疫性疾病Pemphigus is an autoimmune disease,在天疱疮患者有抗角质形成细胞间物质抗体，所针对的靶抗原是自身表皮组织。天疱疮常与其他自身免疫性疾病同时存在。皮质激素、免疫抑制剂、血浆置换疗法治疗有效。,天疱疮和自身抗原,桥粒芯糖蛋白 (Dsg) Dsg3: 基底/基底上KC Dsg1: 颗粒层KC,病名 自身抗体 靶抗原 分子量寻常型天疱疮（粘膜型） IgG Dsg3 130kD寻常型天疱疮（粘膜/皮肤型） IgG Dsg3 130kD Dsg1 160kD落叶型天疱疮 IgG Dsg1 160kD副肿瘤性天疱疮 IgG Dsg3 130kD Dsg1 160kD HD1/Plakin 500kD 桥粒斑蛋白(Dsp1) 250kD Dsp2 210kD BPAG1 230kD 桥粒壳蛋白(Envoplakin) 210kD 桥粒周蛋白(Periplakin) 190kD,天疱疮抗体Intercellular Antibodies,有器官和组织特异性，而无种属特异性。诱导动物天疱疮模型，皮损范围与所注入的天疱疮血清抗体滴度及注入量成正比。,人工培养皮块组织,天疱疮患者血清,基底层细胞间分离,1-2天,棘层细胞松解,3-4天,Passive transfer test,棘层松解 Acantholysis,天疱疮的病理特点是表皮内水疱及棘层细胞松解。病变早期有细胞间粘合物质崩解，细胞间隙增宽，后期有桥粒的破坏和消失，张力微丝破碎、排列紊乱。,Pathogenesis,天疱疮抗体,角质形成细胞,纤溶蛋白酶原激活物,纤维蛋白酶系统活化,细胞间粘合物质降解,棘层松解,病因,桥粒分离，细胞松解，水疱形成,天疱疮抗体,角质形成细胞,临床表现 Clinical features,五种类型寻常型天疱疮 P. Vulgaris增殖型天疱疮 P. Vegetans落叶型天疱疮 P. Foliaceus红斑型天疱疮 P. Erythematosus疱疹样天疱疮 P. Herpetiformis,寻常型天疱疮 Pemphigus vulgaris,年龄：中年人皮疹：薄壁、松弛性大疱，糜烂 、渗出、结痂，尼氏征阳性部位：躯干、四肢全身情况：差预后：不好,尼氏征 Nikolskys sign,又称棘层松解征。以手指轻推、压水疱，可使疱壁扩展，水疱加大；若稍用力推擦外观正常的皮肤，也可使表皮脱落或搓后不久出现水疱。The upper layers of the epidermis are easily made to slip by slight pressure or rubbing because of the absence of cohesion in the skin.,Nikolsky sign,主要见于寻常型天疱疮，还可见于 Stevens-Johnson 综合征, 中毒性表皮坏死症、剥脱性表皮松解症。The Nikolsky sign is also seen in Stevens-Johnson syndrome, toxic epidermal necrolysis, and epidermolysis bullosa.,寻常型天疱疮,bullae,erosions,Bullous lesions arising from apparently normal skin surface.,erosion,laccid bullae,crust,寻常型天疱疮,Hyperpigmented patches with no scarring,病例介绍 （A Case）,黄 某某，男，31岁，湖南新宁县人。全身皮肤反复起水疱2年，加重半月于2002.9.2日入院。患者2年前无诱因出现口腔糜烂，头部大疱，渐遍及全身，出现糜烂、结痂。当地诊断“天疱疮”，用激素（量不详）可暂时控制。半月前皮肤再次起疱，给予DXM 15mg/d, 效果欠佳后转入我院。,病例介绍 （A Case）,入院时情况：T38.3，BP145110mmHg，全身大片红色糜烂面 ，大量渗出，稍臭，表皮撕脱。四肢有散在正常皮岛，头面部多处糜烂、黑痂，双眼上睑大量黄色脓性分泌物，口唇糜烂和结痂，口腔粘膜多处糜烂面。,Extensive denuded areas,增殖型天疱疮Pemphigus vegetans,是寻常型天疱疮的异型。A variant of pemphigus vulgaris预后较好。Prognosis: relatively better,增殖型天疱疮 Pemphigus vegetans,皮疹特点：蕈样增殖和乳头瘤样增生。恶臭。部位：腋下、腹股沟、外生殖器等皱折部位。易继发感染。,Sharply delineated vegetating lesions,落叶型天疱疮 Pemphigus Foliaceus,皮损：水疱、广泛糜烂、叶状痂皮。部位：全身。常继发感染、衰竭。,Generalized exfoliative erythroderma,红斑型天疱疮 Pemphigus Erythmatosus,是落叶型天疱疮的良性型。皮疹：水疱、红斑、结痂。可向落叶型或寻常型转化。,Circumscribed patches of erythema and crusting,其他类型天疱疮,疱疹样天疱疮 IgA型天疱疮 药物诱导 副肿瘤性天疱疮,疱疹样天疱疮(pemphigus herpetiformis),环形或多环形红斑，边缘略隆起，水疱或丘疱疹。尼氏征阴性。瘙痒明显。病程慢性，预后好。,IgA型天疱疮,中老年女性皮肤皱褶部位红斑、水疱、瘙痒IgA型抗体,药物诱导的天疱疮,penicillamine, pecicillincaptoprilRifampin, thiopronine, interleukin-2Ultraviolet light, PUVA,副肿瘤性天疱疮 （Paraneoplastic pemthigus, PNP）,发生于皮肤粘膜的大疱性糜烂性皮肤病伴随潜在肿瘤。多形性皮损：红斑、大疱、糜烂、丘疹鳞屑性发疹、多形红斑样；粘膜损害重。免疫荧光沉淀：250、230、210、190kd片段。组织病理：表皮细胞间棘层松解、角质形成细胞坏死、空泡。预后差。,实验室检查 Laboratory Findings,细胞学检查 Cytology组织病理学检查 Histopathology免疫荧光学检查 Immunology,细胞学检查,棘层松解细胞（acantholytic or Tzank cells）细胞体大，球形，胞核大而深染，胞浆均匀嗜碱性。,The large nuclei are surrounded by a lightly staining halo in the cytoplasm.,组织病理学检查 Histopathology,表皮内水疱或裂隙形成Intraepidermal blister and cleft formation棘层松解细胞Acantholytic cells,寻常型或增殖型: 棘刺松解发生在基底层上方。,组织病理学检查 Histopathology,落叶型或红斑型: 棘刺松解发生在颗粒层或棘层上方。,直接免疫荧光（DIF）,IgG*,IgA*,IgM*,C3*,抗原+ 荧光标记抗体 荧光标记复合物,组织切片,荧光标记抗体,直接免疫荧光检查 Direct Immunofluorescent,直接免疫荧光表皮棘细胞间鱼网状荧光(intercellular antibodies),IgG & C3 can be detected within the epidermal tissue.,间接免疫荧光法（IIF）,血清,底物,（抗原）,荧光标记抗体,天疱疮抗原：豚鼠食道、正常人皮肤,病人,阳性,正常人,间接免疫荧光检查Indirect Immunofluorescent,间接免疫荧光天疱疮抗体（血循环中抗角朊细胞间物质抗体）Circulating IC antibody抗体滴度与病情严重程度平行Ab titers often parallel disease activity.,ELISA,针对桥粒芯糖蛋白3（DG3, desmoglein-3）针对桥粒芯糖蛋白1（DG1, desmoglein-1）,诊断 diagnosis,临床表现,组织病理,免疫荧光,诊断依据,治疗 Treatment,皮质类固醇激素Corticosteroids免疫抑制剂Immunosuppressants支持、对症治疗Supportive therapy 局部治疗Topical treatment,治疗 Treatment,皮质类固醇激素用药原则早期使用足量控制酌情减量维持要长,病例介绍（the Case）,一般治疗及护理甲基强地松龙80mg/d罗氏芬、雷尼替丁、钙剂等局部处理：湿敷及搽药,大疱性类天疱疮Bullous Pemphigoid,复习Basement membrane zone, BMZ,半桥粒,透明层,致密层,致密下层,大疱性类天疱疮Bullous Pemphigoid,BP was identified and named by Lever in 1953.An autoimmune dermatoses.,病因和发病机理 ETIOLOGY AND PATHOGENESIS,230KD antigen180KD antigen200KD antigen,Clinical Features,50岁以上者多见。厚壁、紧张、不易破的大疱，尼氏征阴性，可有程度不等的瘙痒。皮疹好发于躯干、四肢屈侧、腋窝和腹股沟，少数患者口腔粘膜受累。大多进展缓慢，若不及时治疗，皮疹可泛发全身，继发感染甚至死亡。,Histology,Subepidermal bulla, no acantholysisInflammatory infiltrate: eosinophils,Direct immunofluorescent,Linear IF is seen along the BMZ. IgG (80%) or C3 (100%) or both are found.,Direct immunofluorescent,BPAg1 (230KD): synthesized by keratinocyte and is an intracytoplasmic hemidesmosomal plaque proteinBPAg2 (180KD): a transmembranous hemidesmosomal protein with an extracellular collagen doma