Department of Dermatology and Allergology, Philipps-Universität, D-35043 Marburg, Germany.
Br J Dermatol. 2012 Apr;166(4):844-52. doi: 10.1111/j.1365-2133.2011.10732.x.
Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs).
To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS.
We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status.
Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually.
The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus.
寻常型天疱疮（PV）是一种潜在危及生命的自身免疫性大疱性疾病，其特征为皮肤和黏膜水疱和糜烂。PV 的一线常用治疗方法是系统性皮质类固醇（CS）联合免疫抑制剂。在难治性病例中，免疫吸附（IA）和抗 CD20 抗体利妥昔单抗（Rtx）等新型治疗策略旨在直接干扰致病性自身抗体（auto-Abs）。
为了研究 IA 联合 Rtx 治疗难治性 PV 患者的长期疗效，我们通过监测自身免疫性大疱性皮肤病严重程度评分、针对桥粒芯糖蛋白 1 和 3（Dsg1 和 Dsg3）的 IgG 自身抗体(auto-Abs)以及系统性 CS 的剂量，评估治疗的临床反应。
我们回顾性分析了 10 例接受每 4 周 1 次 IA 治疗的难治性 PV 患者的临床和血清学参数，随后接受 1000mg 利妥昔单抗 2 次或 375mg/m²利妥昔单抗 4 次治疗。在 12 个月的随访期间，根据个体临床情况逐渐减少 CS 的剂量。
在首次 IA 治疗后 6 个月，10 例患者中有 8 例达到完全缓解，1 例部分缓解，1 例无反应。12 个月时，8 例中有 6 例达到完全缓解，1 例疾病稳定，1 例复发。总的来说，抗 Dsg3 IgG 和抗 Dsg1 IgG auto-Abs 与临床活动密切相关，CS 逐渐减少。
本研究结果表明，IA 联合 Rtx 可迅速诱导难治性天疱疮临床缓解和长期控制。
