Successful rituximab treatment of severe pemphigus vulgaris resistant to multiple immunosuppressants.
Successful rituximab treatment of severe pemphigus vulgaris resistant to multiple immunosuppressants.
复制标题
利妥昔单抗成功治疗对多种免疫抑制剂耐药的严重寻常型天疱疮。
DOI：
10.1080/00015550410024111
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发表时间：
2005
影响因子：
3.6
通讯作者：
T. Tüting
中科院分区：
文献类型：
--
作者：
J. Wenzel;R. Bauer;T. Bieber;T. Tüting
先生，寻常型天疱疮(PV)是一种自身免疫性疾病，以水泡和广泛的皮肤和粘膜侵蚀为特征。这种疾病是由抗体介导的，主要针对表皮细胞黏附分子Desmoglein 1和3。全身皮质类固醇是公认的一线治疗方法，但由于众所周知的副作用，其使用受到限制，特别是在长期治疗中。为了减少这些副作用，近年来已经试验了几种与其他免疫抑制药物的联合应用，例如硫唑嘌呤、甲氨蝶呤、霉酚酸酯、环磷酰胺、静脉免疫球蛋白、血浆置换和光分离。不幸的是，多重耐药方案的存在，给治疗带来了复杂的挑战。我们在此报告一位55岁女性患PV长达13年的病例。她需要持续接受甲基强的松龙治疗，剂量约为每天20毫克，以防止广泛起泡。硫唑嘌呤(2 mg/kg体重/天，疗程1年)、环磷酰胺(1.5 mg/kg体重/天，疗程6个月)、甲氨蝶呤(25 mg/周静脉滴注)。治疗8个月后，霉酚酸酯3g/d，连用1年，静脉注射丙种球蛋白(2 g/kg体重/周期，3个周期)均不能改善临床症状，也不能预防复发。由于长期的类固醇治疗，她患有严重的库欣综合征，包括骨质疏松症，导致两个脊椎骨折，身高减少了约9厘米。她患有类固醇诱导的糖尿病、青光眼和动脉高血压，并经历了一次细菌败血症，需要重症监护治疗。当广泛的新皮损出现时(图1a)，我们决定用抗CD20单抗美妥昔单抗(MabThera)治疗这位患者，因为最近有报道成功治疗顽固性PV(1-4)。我们在5周内应用了4个周期的600 mg利妥昔单抗(相当于375 mg/m体表)。加用小剂量甲基强的松龙(8 mg/d)口服治疗。值得注意的是，她的皮肤损伤在最后一次利妥昔单抗周期后的第二到第六周之间消失(图1B)。同时，间接免疫荧光法检测的抗上皮抗体效价从1：160下降到1：40。流式细胞仪检测外周血B细胞数由正常降至2个/ml，未见严重的临床副作用。在临床随访期间(现在3个月)，没有新的病变出现。甲基强的松龙剂量可减至6 mg/d。我们在这位非常顽固的患者身上的发现支持利妥昔单抗治疗重症PV的临床疗效。进一步的预期控制
Sir, Pemphigus vulgaris (PV) is an autoimmune disease characterized by blisters and widespread erosions involving skin and mucous membranes. The disorder is mediated by antibodies, predominantly directed against the epidermal cell adhesion molecules desmoglein 1 and 3. Systemic corticosteroids are the established first-line treatment, but their use is limited due to the well known side effects, especially in long-term treatment. To reduce these side effects, several combinations with other immunosuppressive drugs have been tested in recent years, e.g. azathioprine, methotrexate, mycofenolate mofetil, cyclophosphamide, intravenous immunoglobulins, plasmapheresis and photopheresis. Unfortunately, multiresistant courses exist and present a complex therapeutic challenge. We present here the case of a 55-year-old woman suffering from PV for 13 years. She needed continuous treatment with methylprednisolone doses around 20 mg/ day to prevent widespread blistering. Treatment with azathioprine (2 mg/kg body weight/day for 1 year), cyclophosphamide (1.5 mg/kg body weight/day for 6 months), methotrexate (25 mg/week i.v. for 8 months), mycofenolate mofetil (3 g/day for 1 year) and intravenous immunoglobulins (three cycles of IntraglobinCP using 2 g/kg body weight per cycle) did not improve the clinical picture and was not able to prevent recurrences. Due to long-term steroid treatment, she had severe Cushing’s syndrome including osteoporosis leading to two vertebral fractures with a loss of about 9 cm of her body height. She suffered from steroid-induced diabetes mellitus, glaucoma and arterial hypertension, and experienced an episode of bacterial sepsis necessitating intensive care treatment. When widespread new lesions developed (Fig. 1a) we decided to treat this patient with anti-CD20 monoclonal antibody rituximab (MabThera), as successful treatment of recalcitrant PV had recently been reported (1–4). We applied four weekly cycles of 600 mg rituximab (corresponding to 375 mg/m body surface) within 5 weeks. Additional low-dose oral treatment with methylprednisolone was performed (8 mg/day). Remarkably, her skin lesion cleared up between the second and sixth weeks after the last rituximab cycle (Fig. 1b). Simultaneously, the titre of anti-epithelial antibodies, detected by indirect immunofluorescence, declined from 1:160 to 1:40. Peripheral B cells, counted by flow cytometry, decreased from normal numbers to 2 cells/ml. Severe clinical side effects were not observed. During the clinical follow-up period (now 3 months) no new lesions have appeared. Methylprednisolone dosage could be reduced to 6 mg/day. Our findings in this extremely recalcitrant patient support the clinical efficacy of rituximab for the treatment of severe PV. Further prospective controlled