Department of Dermatology, University of Lübeck, Lübeck, Germany; Lübeck Institute for Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Lancet. 2019 Sep 7;394(10201):882-894. doi: 10.1016/S0140-6736(19)31778-7.
Pemphigus consists of a group of rare and severe autoimmune blistering diseases mediated by pathogenic autoantibodies mainly directed against two desmosomal adhesion proteins, desmoglein (Dsg)1 and Dsg3 (also known as DG1 and DG3), which are present in the skin and surface-close mucosae. The binding of autoantibodies to Dsg proteins induces a separation of neighbouring keratinocytes, in a process known as acantholysis. The two main pemphigus variants are pemphigus vulgaris, which often originates with painful oral erosions, and pemphigus foliaceus, which is characterised by exclusive skin lesions. Pemphigus is diagnosed on the basis of either IgG or complement component 3 deposits (or both) at the keratinocyte cell membrane, detected by direct immunofluorescence microscopy of a perilesional biopsy, with serum anti-Dsg1 or anti-Dsg3 antibodies (or both) detected by ELISA. Corticosteroids are the therapeutic mainstay, which have recently been complemented by the anti-CD20 antibody rituximab in moderate and severe disease. Rituximab induces complete remission off therapy in 90% of patients, despite rapid tapering of corticosteroids, thus allowing for a major corticosteroid-sparing effect and a halved number of adverse events related to corticosteroids.
天疱疮是一组罕见且严重的自身免疫性水疱病，由致病性自身抗体介导，这些自身抗体主要针对两种桥粒黏附蛋白，即桥粒芯糖蛋白 1（Dsg）1 和桥粒芯糖蛋白 3（也称为 DG1 和 DG3），它们存在于皮肤和黏膜表面。自身抗体与 Dsg 蛋白结合会诱导相邻角质形成细胞分离，这一过程称为棘层松解。两种主要的天疱疮变异型是寻常型天疱疮，常由口腔疼痛性糜烂开始；落叶型天疱疮，其特征为仅皮肤损伤。天疱疮的诊断基于病变周围活检的直接免疫荧光显微镜检查，检测到角质形成细胞膜上的 IgG 或补体成分 3 沉积（或两者兼有），同时通过 ELISA 检测到血清抗 Dsg1 或抗 Dsg3 抗体（或两者兼有）。皮质类固醇是主要的治疗方法，近年来，在中重度疾病中补充了抗 CD20 抗体利妥昔单抗。利妥昔单抗可诱导 90%的患者停药完全缓解，尽管皮质类固醇迅速减量，但仍能显著减少皮质类固醇相关不良反应的发生。
