Igarashi Toru, Igarashi Tsutomu, Shimizu Akira, Itoh Yasuhiko
Department of Pediatrics, Nippon Medical School.
J Nippon Med Sch. 2013;80(5):396-400. doi: 10.1272/jnms.80.396.
Intravenous cyclophosphamide (IVCY) pulse therapy has been used for lupus nephritis since the latter half of the 1980s; it has been shown to be effective for lupus nephritis and vasculitis and has become a standard therapy for the diffuse proliferative type of lupus nephritis in adults. IVCY therapy has also come to be used in children. This paper reports the long-term outcomes of IVCY therapy in children.
Six female patients (age range, 13 to 18 years) with systemic lupus erythematosus (SLE) were enrolled in this retrospective study. Three patients had lupus nephritis (World Health Organization class IIb, IVa, IVc), 2 had central nervous system (CNS) lupus, and 1 had neither lupus nephritis nor CNS lupus. The mean pretreatment SLE disease activity index (SLEDAI) score was 18.8 ± 4.6. Cyclophosphamide (initial dose, 500 mg/m(2)) was administered intravenously each month for 6 months and then given every 3 months for maintenance. Prednisolone was given in dosages ranging from 5 to 60 mg/day, adjusted according to laboratory data and clinical symptoms. Levels of C3, C4, CH50, and creatinine; the SLEDAI score; and the SLE responder index were monitored and evaluated. The SLE responder index was considered to have improved if the SLEDAI score had decreased by 4 points or more after 52 weeks.
Prednisolone doses were reduced in all patients. Because methylprednisolone pulse therapy was administered before IVCY therapy, some patients had low titers of immunoglobin G antibodies against double-stranded DNA at the start of IVCY therapy. All patients had low serum creatinine levels. Proteinuria resolved in 1 of the 3 patients with lupus nephritis. The SLEDAI scores improved after 52 weeks in 5 of 6 patients (mean, 5.2 ± 2.6). No patients had severe bone marrow suppression or hemorrhagic cystitis during IVCY pulse therapy.
IVCY pulse therapy for SLE in children achieved good long-term outcomes with no serious adverse effects, such as digestive symptoms, bone marrow suppression, infection, and hemorrhagic cystitis. IVCY pulse therapy for children with SLE has recently been approved by the Ministry of Health, Labour and Welfare. Accordingly, this paper might become a guideline for this treatment.
自20世纪80年代后半期以来，静脉注射环磷酰胺（IVCY）脉冲疗法已用于狼疮性肾炎；已证明其对狼疮性肾炎和血管炎有效，并已成为成人弥漫性增殖型狼疮性肾炎的标准疗法。IVCY疗法也开始用于儿童。本文报告了IVCY疗法在儿童中的长期疗效。
本回顾性研究纳入了6例患有系统性红斑狼疮（SLE）的女性患者（年龄范围为13至18岁）。3例患者患有狼疮性肾炎（世界卫生组织IIb、IVa、IVc级），2例患有中枢神经系统（CNS）狼疮，1例既无狼疮性肾炎也无CNS狼疮。治疗前SLE疾病活动指数（SLEDAI）评分的平均值为18.8±4.6。环磷酰胺（初始剂量为500mg/m²）每月静脉注射1次，共6个月，然后每3个月给药1次进行维持治疗。泼尼松龙的给药剂量为每天5至60mg，根据实验室数据和临床症状进行调整。监测并评估C3、C4、CH50和肌酐水平、SLEDAI评分以及SLE反应指数。如果52周后SLEDAI评分降低4分或更多，则认为SLE反应指数有所改善。
所有患者的泼尼松龙剂量均有所减少。由于在IVCY治疗前进行了甲泼尼龙脉冲治疗，一些患者在IVCY治疗开始时抗双链DNA的免疫球蛋白G抗体滴度较低。所有患者的血清肌酐水平均较低。3例狼疮性肾炎患者中有1例蛋白尿消失。6例患者中有5例在52周后SLEDAI评分有所改善（平均值为5.2±2.6）。在IVCY脉冲治疗期间，没有患者出现严重的骨髓抑制或出血性膀胱炎。
儿童SLE的IVCY脉冲疗法取得了良好的长期疗效，且无严重不良反应，如消化系统症状、骨髓抑制、感染和出血性膀胱炎。儿童SLE的IVCY脉冲疗法最近已获得厚生劳动省的批准。因此，本文可能会成为这种治疗方法的指南。
