甲泼尼龙脉冲联合吗替麦考酚酯治疗儿童系统性红斑狼疮临床疗效分析

doi:10.13481/j.1671-587x.20180229

摘要/Abstract

摘要： 目的：探讨甲泼尼龙脉冲（MDP）联合吗替麦考酚酯（MMF）治疗儿童系统性红斑狼疮（SLE）的疗效及不良反应。方法：选择16例临床诊断为SLE、狼疮性肾炎（LN）、病理分级均为Ⅳ型弥漫性球性增生性肾小球肾炎的患儿，其中7例采用MDP联合MMF治疗，冲击间歇期口服小剂量糖皮质激素（GC），作为脉冲治疗组；9例采用口服GC移行减量治疗，作为传统治疗组。疗效评价系统为狼疮疾病活动指数（SLEDAI），分析2组患儿体质量指数（BMI）、眼压（IOP）、甘油三酯（TG）、空腹血糖（FBG）、血压（BP）和血钙（Ca），比较2组患儿治疗1年内的疗效及不良反应。结果：治疗后脉冲治疗组SLEDAI评分、补体C3和补体C4水平、24h尿蛋白定量均优于传统治疗组，其中治疗后3和6个月SLEDAI评分2组间比较差异有统计学意义（P<0.05），治疗后6个月血沉（ESR）和24h尿蛋白定量2组间比较差异有统计学意义（P<0.05），治疗后6和12个月补体C3水平2组间比较差异有统计学意义（P<0.05）。脉冲治疗组患儿治疗后BMI、IOP、TG和FBG低于传统治疗组，治疗后12个月BMI、IOP和TG水平2组间比较差异有统计学意义（P<0.05），治疗后6和12个月FBG水平比较差异有统计学意义（P<0.05）。脉冲治疗组患儿Ca高于传统治疗组，但差异无统计学意义（P>0.05）。治疗后脉冲治疗组患儿收缩压（SBP）及舒张压（DBP）高于传统治疗组，但差异无统计学意义（P>0.05）。2组患儿均未发生消化道溃疡、出血、穿孔，胰腺炎和心血管事件（如心律失常）等并发症。结论：与传统治疗方法比较，MDP联合MMF治疗SLE可早期快速控制症状，减轻脏器损害。以治疗1年为观察截点，其疾病活动度低于传统治疗，疗效优于口服GC移行减量联合免疫抑制剂治疗。且GC相关不良反应更少。

关键词: 狼疮性肾炎, 甲泼尼龙脉冲, 吗替麦考酚酯, 儿童, 系统性红斑狼疮

Abstract: Objective:To investigate the efficacy and side effects of combination of methylprednisolonepulse(MDP) and mycophenolate mofetil(MMF) in the treatment of systemic lupus erythematosus(SLE) in the children. Methods: A total of 16 cases of children with SLE,lupus nephritis(LN) and type Ⅳ diffuse glomerular mesangial proliferative glomerulonephritis diagnosed by pathology were selected.Among them 7 cases were given MDP combined with MMF,and received intermittently oral small dose of corticosteroids(GC), and they were used as pulse therapy group; 9 cases were given oral GC and transitional reduction,and they were used as traditional therapy group. SLEDAI was used for the evaluation of the curative effect,and body mass index(BMI),blood pressure(BP),intraocular pressure(IOP),triglycerides(TG),fasting blood glucose(FBG) and serum calcium(Ca) were analyzed during the treatment of 1 year and then the efficacies and side effects of the children in two groups were compared. Results: The SLEDAI scores,levels of complements C3 and C4,24 h urinary protein outcome of the children in pulse therapy group were better than those in traditional therapy group; the differences in SLEDAI scores were statistically significant after treating for 3 and 6 months between two groups(P<0.05); ESR and 24 h urinary protein outcome had significant differences after 6 months of treatment between two groups(P<0.05); the complement C3 difference was statistically significant between two groups(P<0.05) after 12 months of treatment.Compared with traditional therapy group,the BMI,IOP,TG,FBG of the children in pulse therapy group after treatment were decreased(P<0.05);the BMI,IOP and TG had significant differences after treating for 12 months between two groups(P<0.05);the differences in FBG were statistically significant after treating for 6 and 12 months between two groups(P<0.05).The Ca of the patients in pulse therapy group was higher than that in traditional therapy group,but there was no statistically significant difference(P>0.05). The SPB and DBP of the patients in pulse therapy group were higher than those in traditional therapy group,but the differences were not statistically significant(P>0.05).At the same time,gastrointestinal ulcers,bleeding,perforation,pancreatitis,cardiovascular events (such as cardiac arrhythmias) didn't occur in two groups. Conclusion: Compared with traditional therapy,the combined treatment of MDP and MMF can control the symptoms of SLE early and rapidly,and reduce the viscera damage.To choose 1 year after treatment as observation point,its disease activity is lower than the traditional therapy,and the curative effect is better than oral GC transitional reduction with immunosuppressant therapy.The GC-related side effects are lower than traditional therapy.

Key words: mycophenolate mofetil, systemic lupus erythematosus, lupus nephritis, children, methylprednisolone pulse

中图分类号:

R725

郭丽双, 刘金香, 王晶华, 潘璐, 徐萌, 刘聪聪, 杨思睿. 甲泼尼龙脉冲联合吗替麦考酚酯治疗儿童系统性红斑狼疮临床疗效分析[J]. 吉林大学学报(医学版), 2018, 44(02): 368-373.

GUO Lishuang, LIU Jinxiang, WANG Jinghua, PAN Lu, XU Meng, LIU Congcong, YANG Sirui. Analysis of curative effect of methylprednisolone pulse combined with mycophenolate mofetil in treatment of systemic lupus erythematosus in children[J]. Journal of Jilin University Medicine Edition, 2018, 44(02): 368-373.

参考文献

[1] Wright TB,Punaro M. Paediatric systemic lupus erythematosus:insights from translational research[J].Rheumatology,2017,56(1):i24-i31.
[2] Koutsokeras T,Healy T.Systemic lupus erythematosus and lupus nephritis[J].Nat Rev Drug Discov,2014,13(3):173-174.
[3] Brunner HI,Klein-Gite/man MS,Ying J,et al.Corticosteroid use in childhood-onset systemic lupus erythematosus-practice patterns at four pediatric rheumatology centers[J].Clin Exp Rheumatol,2009,27(1):155-162.
[4] 胡煜琳,刘代强.糖皮质激素联合小剂量环磷酰胺治疗重症系统性红斑狼疮效果分析[J].中国临床医生,2015,43(2):39-41.
[5] 顾珺,沈朝斌.儿童系统性红斑狼疮诊断与治疗研究现状[J].中华妇幼临床医学杂志:电子版,2017,13(4):378-383.
[6] Guiducci C,Gong M,Xu Z,et al.TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus[J].Nature,2010,465(7300):937-941.
[7] Dudhgaonkar S,Ranade S,Nagar J,et al.Selective IRAK4inhibition attenuates disease in murine lupus models and demonstrates steroid sparing activity[J].J Immunol,2017,198(3):1308-1319.
[8] 中华医学会风湿病学分会.系统性红斑狼疮诊断及治疗指南中华医学会风湿病学分会[J].中华风湿病学杂志,2010,14(5):342-346.
[9] Oon S,Wilson NJ,Wicks I,et al.Targeted therapeutics in SLE:emerging strategies to modulate the interferon pathway[J].Clin Transl Immunol,2016,5(5):e79.
[10] 葛安琪,秦少游,韩琳,等.以急性胰腺炎为首发症状的系统性红斑狼疮1例报告[J].临床肝胆病杂志,2017,33(11):2194-2195.
[11] 万钧,崔瑗,邝土光,等.以肺动脉高压为首发表现系统性红斑狼疮1例报告[J].中国实用内科杂志,2016,36(2):162-165.
[12] Lisnevskaia L,Murphy G,Isenberg D.Systemic lupus erythematosus[J].Lancet,2014,384(9957):1878-1888.
[13] Bennett L,Palucka AK,Arce E,et al.Interferon and granulopoiesis signatures in systemic lupus erythematosus blood[J].Exp Med,2003,197(6):711-723.
[14] 孙锋.不同剂量糖皮质激素治疗系统性红斑狼疮的临床效果分析[J].中国医药指南,2017,15(23):119-120.
[15] 曾凡钦.红斑狼疮的诊疗进展与展望[J].皮肤性病诊疗学杂志,2017,24(2):63-67.
[16] 张静,董晓蕾,蔡辉.系统性红斑狼疮临床研究进展[J].安徽医药,2017,21(11):1971-1974.
[17] Zabotti A,Baraldo M,Quartuccio L,et al.Optimizing the dose of mycophenolate mofetil for the maintenance treatment of lupus nephritis by therapeutic drug monitoring[J].Clin Rheumatol,2015,34(1):171-174.
[18] 邓江红,李彩凤.儿童系统性红斑狼疮治疗进展[J].中国实用儿科杂志,2016,31(1):67-71.
[19] 胡坚.儿童系统性红斑狼疮去激素化治疗的思考[J].中华实用儿科临床杂志,2016,31(21):1608-1611.
[20] 贾振祥,齐娅.常用糖皮质激素类药物不良反应总结分析[J].中国临床医药研究杂志,2007,164:59-60.
[21] Hong D,Cheng HX,Yu HQ,et al.Quantitative proteomic analysis of dexamethasone-induced effects on osteoblast differentiation,proliferation,and apoptosis in MC3T3-E1 cells using S1LAC[J].Osteoporos Int,2011,22(7):2175-2186.
[22] Zonana-Nacach A,Barr SG,Magder LS,et a1.Damage in systemic lupus erythematosus and its association with cortieosteroids[J].Arthritis Rheum,2000,43(8):1801-1808.