儿童系统性红斑狼疮合并血栓性微血管病的诊治与思考

doi:10.12372/jcp.2025.24e1397

摘要/Abstract

摘要：

患儿，女，12岁，因“双下肢浮肿伴咳嗽40余天，确诊系统性红斑狼疮1个月”就诊。患儿外院肾穿刺结果提示狼疮性肾炎型（Ⅳ型）合并血栓性微血管病（TMA），经甲基泼尼松龙、环磷酰胺、贝利尤单抗治疗后，患儿仍存在重度高血压、肾功能损伤，血小板、血红蛋白、结合珠蛋白进行性下降，乳酸脱氢酶升高，外周血见破碎红细胞，入院后完善血管性血友病因子裂解酶活性正常，抗磷脂抗体阴性，可溶性c5-9明显升高。给予依库珠单抗治疗后，患儿病情好转，血红蛋白、血小板逐步回升，肾功能好转，随访病情稳定。本病例提示临床医师在系统性红斑狼疮(SLE)合并TMA治疗中，需尽早识别补体参与证据，及时启动依库珠单抗治疗，可极大改善患者远期预后。

关键词: 系统性红斑狼疮, 血栓性微血管病, 非典型尿毒综合征, 依库珠单抗

Abstract:

A 12-year-old female SLE patient with lupus nephritis (class Ⅳ) and TMA was admitted to our hospital. After treatments including blood purification, methylprednisolone and CTX pulse therapy, even belimumab infusion, she still exhibited renal dysfunction and abnormal blood tests including decreased levels in platelet count, hemoglobin and fragmented red blood cells. Further tests showed normal activity of the von Willebrand factor-cleaving protease, negative antiphospholipid antibodies, and significantly elevated soluble c5-9 levels. After initiating treatment with eculizumab, the patient's condition improved. The patient remained stable during a three-month follow-up. This case provides clinicians with insights into the treatment of SLE complicated by TMA. Early identification of complement involvement and prompt initiation of eculizumab treatment can significantly improve the patient's long-term prognosis.

Key words: systemic lupus erythematosus, thrombotic microangiopathy, atypical hemolytic uremic syndrome, eculizumab

倪佳佳, 朱亚菊, 金晶, 李皎宇, 郭桂梅. 儿童系统性红斑狼疮合并血栓性微血管病的诊治与思考[J]. 临床儿科杂志, 2025, 43(2): 150-156.

NI Jiajia, ZHU Yaju, JIN Jin, LI Jiaoyu, GUO Guimei. Diagnosis, treatment, and reflection on pediatric systemic lupus erythematosus complicated by thrombotic microangiopathy[J]. Journal of Clinical Pediatrics, 2025, 43(2): 150-156.

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患儿病程时间轴"

时间	临床表现及检查，药物治疗情况
入院前40天	患儿因系统性红斑狼疮、狼疮性肾炎、血栓性微血管病于外院行CRRT、甲基泼尼松龙、CTX冲击，
入院前2周	仍反复贫血、血小板减少，血压控制不佳，外院予氨氯地平、厄沙贝坦、呋塞米三联降压治疗，第二轮甲强龙、CTX冲击，并联合贝利尤单抗输注
入院时	贫血，浮肿，高血压，肉眼血尿。体格检查：体温：36.7 ℃，HR：88次/分，RR：20次/分，BP：161/110 mmHg，面色苍黄，双眼睑轻度浮肿，腹膨隆，腹部可见散在肥胖纹，双下肢凹陷性浮肿。血常规：WBC4.36×10⁹/L，Hb76 g·L^-1，Plt91×10⁹/L，Ret 8.21%，外周血可见破碎红细胞。尿常规：红细胞(镜检)满视野/HP，尿蛋白150.00 mg·dL^-1 感染炎症指标：CRP<8 mg·L^-1，PCT<0.05 ng·mL^-1，EBV/CMV/HSV/B19/风疹病毒、乙肝、丙肝、梅毒、艾滋阴性、结核抗体、T-spot均正常。肝肾功能：BUN17.2 mmol·L^-1，Cr110.9 μmol·L^-1，LDH558 U·L^-1。DIC：D-D二聚体1.15 mg·L^-1，纤维蛋白(原)降解产物3.55 mg·L^-1。免疫指标：ANA1:3200+，抗双链DNA、抗组蛋白抗体阳性，结合珠蛋白<0.07 g·L^-1，广谱抗人球蛋白试验：阴性。影像学：胸CT：两侧胸腔少量积液，心包积液。心彩色多普勒超声心动图：少量心包积液。治疗：泼尼松20 mg， bid+羟氯喹100 mg， bid，硝普钠0.5 μg·kg^-1·min^-1泵入+氨氯地平+厄沙贝坦+呋塞米降压
入院第3天	患儿血压降至120~135/70~85 mmHg，复查血小板、贫血、外周血破碎红细胞无改善，完善ADAMTS13活性正常，磷脂抗体、狼疮抗凝物筛查阴性，补体C3 0.58 g·L^-1明显降低，可溶性C5b-9浓度1569 ng·mL^-1明显升高，加用补体抑制剂依库珠单抗治疗
入院第8天	患儿血压稳定，监测PLT升至134×10⁹/L，Hb82 g·L^-1，外周血破碎红细胞消失，尿量稳定2000~2500 mL，尿色转清，停用硝普钠
入院第13天	血小板下降至89×10⁹/L，予CTX0.4g×2 d冲击治疗
入院第16天	PLT降至52×10⁹/L，Hb64 g·L^-1，予第三剂依库珠单抗900 mg治疗
入院第21天	PTL正常173×10⁹/L，Hb 81 g·L^-1，血肌酐73.6 umol·L^-1，血压稳定于（125~135/70~85 mmHg），尿量2 000~2 500 mL， c5b-9浓度降至132.59 μg·mL^-1，带药出院
出院后1月	血常规Hb126 g·L^-1，PLT194×10⁹/L，外周血未见破碎红细胞，血肌酐72 mol·L^-1。激素减为15 mg，bid+羟氯喹 100 mg，bid，CTX0.4g×2 d qmon+依库珠单抗900 mg， q2w
出院后3月	血压、尿量、尿色正常，血常规Hb138 g·L^-1，PLT211×10⁹/L，外周血未见破碎红细胞，血肌酐70 μmol·L^-1。

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