Schmidt Enno, Bröcker Eva-Bettina, Goebeler Matthias
Department of Dermatology, University of Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany.
Clin Rev Allergy Immunol. 2008 Feb;34(1):56-64. doi: 10.1007/s12016-007-8021-6.
Autoimmune blistering diseases are associated with autoantibodies to desmosomal (pemphigus group) or hemidesmosomal proteins (autoimmune subepidermal blistering disorders) that are essential for the structural integrity of the epidermis and dermoepidermal junction. Treatment is usually based on systemic glucocorticosteroids, which are often combined with additional immunosuppressants such as azathioprine and mycophenolate mofetil or immunomodulators including dapsone, antibiotics, and intravenous immunoglobulins. These interventions are sometimes not sufficient to induce remission and/or may be associated with intolerable adverse events. In such situations, the anti-CD20 antibody rituximab has been successfully applied in recent years. Rituximab transitorily depletes CD20-positive B lymphocytes from the circulation. It has been employed in more than 1 million patients with CD20-positive non-Hodgkin's lymphoma and severe side effects were only rarely observed. Subsequently, the B cell-modulating effect of rituximab has encouraged its use in a variety of autoimmune diseases, including more than 40 patients with pemphigus. In addition, a few patients with bullous pemphigoid, mucous membrane pemphigoid, and epidermolysis bullosa acquisita have received rituximab. In the majority of these patients, clinical remission was induced; however, serious adverse events were considerable higher compared to both patients with non-Hodgkin's lymphoma or nonbullous autoimmune disorders like lupus erythematosus, dermatomyositis, and rheumatoid arthritis.
自身免疫性水疱病与针对桥粒蛋白（天疱疮组）或半桥粒蛋白（自身免疫性表皮下疱病）的自身抗体相关，这些蛋白对表皮和真皮表皮连接处的结构完整性至关重要。治疗通常基于全身性糖皮质激素，常与硫唑嘌呤、霉酚酸酯等其他免疫抑制剂或氨苯砜、抗生素和静脉注射免疫球蛋白等免疫调节剂联合使用。这些干预措施有时不足以诱导缓解和/或可能与无法耐受的不良事件相关。在这种情况下，抗CD20抗体利妥昔单抗近年来已成功应用。利妥昔单抗可暂时清除循环中的CD20阳性B淋巴细胞。它已被用于超过100万例CD20阳性非霍奇金淋巴瘤患者，很少观察到严重副作用。随后，利妥昔单抗的B细胞调节作用促使其在多种自身免疫性疾病中使用，包括40多名天疱疮患者。此外，一些大疱性类天疱疮、黏膜类天疱疮和获得性大疱性表皮松解症患者也接受了利妥昔单抗治疗。在这些患者中的大多数中，诱导了临床缓解；然而，与非霍奇金淋巴瘤患者或狼疮、皮肌炎和类风湿关节炎等非大疱性自身免疫性疾病患者相比，严重不良事件的发生率要高得多。
