目的 探讨CD20单克隆抗体(利妥昔单抗)治疗重症儿童系统性红斑狼疮(SLE)的有效性和安全性.方法 诊断依据1997年美国风湿病学会SLE的分类标准.纳入标准:年龄≤16岁,至少1个以上重要器官受累,SLEDA1评分＞10分,常规治疗反应欠佳.治疗方法:抗CD20单抗剂量375 mg/(m2·次),于第0、14天分次静脉输注.于CD20单抗治疗前及治疗后2周、1、3、6、12个月评估疗效,并监测不良反应.结果 共20例SLE患儿,男女比1∶3,年龄5～16岁,病程(3.0±2.5)年,平均随访(27.0±7.8)个月.10例狼疮脑病患儿谵妄、认知障碍等在1个月内明显改善；15例狼疮肾炎患儿中14例用药2～3个月后改善,1例无明显缓解；4例狼疮肺炎患儿用药1个月内症状减轻；18例血细胞减少患儿中16例在1个月内恢复.95％患儿(19/20)2周内B细胞清除,90％患儿(18/20)B淋巴细胞计数于1年内恢复.SLEDAI评分用药后明显降低,用药1年泼尼松剂量从( 45.0±4.7)mg/m2降至(12.0 ±2.7) mg/m2(P＜0.001).用药半年内5例患儿出现肺炎,其中2例重症肺炎分别为曲霉菌肺炎及卡氏肺囊虫肺炎,均治疗后好转,无死亡病例.随B细胞恢复,2例患儿分别于治疗15、18个月后病情反复,给予第2疗程抗CD20单抗后,1例病情再次缓解,另外1例病情缓解不明显.结论 抗CD20单抗治疗重症儿童SLE疗效肯定,耐受性较好,部分病例可能发生严重感染.%Objective To analyze the safety and efficacy of anti-CD20 monoclonal antibody in treatment of severe pediatric systemic lupus erythematosus (PSLE). Method The diagnosis of PSLE was made according to the criteria for the classification of systemic lupus erythematosus revised by the American College of Rheumatology in 1997. Severe cases with PSLE was selected by the following criteria:age ≤ 16 years,number of important organs involved ＞ 1,SLEDAI score ＞ 10 points and poor response to conventional immunosuppressive treatment.These patients received 2 doses of 375 mg/m2 rituximab (RTX),2 weeks apart.Clinical,laboratory findings and drug side effects were recorded at RTX initiation,2 weeks,1 month,3,6 and 12 months after infusion. Result A total of 20 patients. Male to female ratio was 1 ∶ 3,were enrolled.They were 5-16 years old. The course of disease was (3.0 ± 2.5) years (range:1 month-7 years),patients were followed up for 12-36 months[ median:(27.0 ± 7.8) months].Delirium and cognitive disorders were significantly improved in 10 cases of lupus eneephalopathy after 1 month. Lupus nephritis in children were eased slowly,14/15 patients with lupus nephritis were improved after 2-3 months,Four eases of lupus pneumonia were significantly improved within 1 month. Decreased blood cells counts were relieved at 1 month in 16/18 cases.Cellular immune function was assessed 2 weeks after application of anti-CD20 monoclonal antibody; we found B-cell clearance in 19 patients (95％).B lymphocyte count of 18 patients (90％) was restored within one year. SLEDAI score was reduced obviously. Dose of corticosteroid ranged from (45.0 ± 4.7 ) mg/m2 before drug use to ( 12.0 ± 2.7 ) mg/m212 months later ( P ＜ 0.001 ).After the drug use,5 patients had pneumonia within 6 months; 2 cases who suffered from aspergillus pneumonia and Pneumocystis carinii pneumonia respectively were severe. They accepted mechanical ventilation and anti-inflammatory support after being transferred to the intensive care unit,and their conditions improved at last. No death occurred.In 2 patients the disease recurred with B-cell recovery after 15 months and 18 months. Administration of another cycle of rituximab resulted in remission again in one case but not in the other.Conclusion Anti-CD20 monoclonal antibody is effective and safe in treatment of severe PSLE. But severe infections may occur in some cases.Focusing on prevention and early treatment can reduce the probability of adverse reactions.
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