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

Abstract

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

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.

Figures/Tables 4

Figure 1

Figure 2

Figure 3

Table 1

Timeline of disease course in children"

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。

Table 1

References 23

[1]	Aringer M. EULAR/ACR classification criteria for SLE[J]. Semin Arthritis Rheum, 2019, 49(3S): S14-S17.
[2]	Brocklebank V, Wood KM, Kavanagh D. Thrombotic microangiopathy and the kidney[J]. Clin J Am Soc Nephrol, 2018, 13(2): 300-317.
[3]	Bayer G, von Tokarski F, Thoreau B, et al. Etiology and outcomes of thrombotic microangiopathies[J]. Clin J Am Soc Nephrol, 2019, 14(4): 557-566.
[4]	Freedman SB, van de Kar N, Tarr PI. Shiga toxin-producing escherichia coli and the hemolytic-uremic syndrome[J]. N Engl J Med, 2023, 389(15): 1402-1414.
[5]	Mitsuiki N, Tamanuki K, Sei K, et al. Severe neonatal CMV infection complicated with thrombotic microangiopathy successfully treated with ganciclovir[J]. J Infect Chemother, 2017, 23(2): 107-110. doi: S1341-321X(16)30146-5 pmid: 27627852
[6]	Timmermans S, Abdul-Hamid MA, Vanderlocht J, et al. Patients with hypertension-associated thrombotic microangiopathy may present with complement abnormalities[J]. Kidney Int, 2017, 91(6): 1420-1425. doi: S0085-2538(16)30742-6 pmid: 28187980
[7]	National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents[J]. Pediatrics, 2004, 114(2Suppl 4th Report): 555-576.
[8]	Bamidele OF, Akintayo RO, Bojuwoye MO, et al. Throm-botic thrombocytopenic purpura as the first presentation in systemic lupus erythematosus[J]. Reumatologia, 2018, 56(4): 268-270.
[9]	Riancho-Zarrabeitia L, Martinez-Taboada V, Rua-Figueroa I, et al. Antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE) implies a more severe disease with more damage accrual and higher mortality[J]. Lupus, 2020, 29(12): 1556-1565.
[10]	Davin JC, van de Kar NC. Advances and challenges in the management of complement-mediated thrombotic microangiopathies[J]. Ther Adv Hematol, 2015, 6(4): 171-185.
[11]	Groot N, de Graeff N, Avcin T, et al. European evidence-based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative[J]. Ann Rheum Dis, 2017, 76(11): 1788-1796. doi: 10.1136/annrheumdis-2016-210960 pmid: 28630236
[12]	Fujimura Y, Matsumoto M. Registry of 919 patients with thrombotic microangiopathies across Japan: database of Nara Medical University during 1998-2008[J]. Intern Med, 2010, 49(1): 7-15.
[13]	Schmidt CQ, Schrezenmeier H, Kavanagh D. Complement and the prothrombotic state[J]. Blood, 2022, 139(13): 1954-1972.
[14]	Kidney Disease: Improving Global Outcomes Glomerular Diseases Work G. KDIGO 2021 clinical practice guideline for the management of glomerular diseases[J]. Kidney Int, 2021, 100(4S): S1-S276.
[15]	Muff-Luett M, Sanderson KR, Engen RM, et al. Eculizumab exposure in children and young adults: indications, practice patterns, and outcomes-a Pediatric Nephrology Research Consortium study[J]. Pediatr Nephrol, 2021, 36(8): 2349-2360. doi: 10.1007/s00467-021-04965-5 pmid: 33693990
[16]	中国罕见病联盟儿童非典型溶血尿毒综合征专业委员会. 中国儿童非典型溶血尿毒综合征诊治专家共识(2023版)[J]. 中华实用儿科临床杂志, 2023, 38(6): 401-412.
	China Alliance for Rare Diseases Pediatric Atypical Hemolytic Uremic Syndrome Committee. Consensus on the diagnosis and treatment of atypical hemolytic uremic syndrome in Chinese children(2023 edition)[J]. Zhonghua Shiyong Erke Linchuang Zazhi, 2023, 38(6): 401-412.
[17]	Kello N, Khoury LE, Marder G, et al. Secondary thrombotic microangiopathy in systemic lupus erythematosus and antiphospholipid syndrome, the role of complement and use of eculizumab: case series and review of literature[J]. Semin Arthritis Rheum, 2019, 49(1): 74-83.
[18]	Fakhouri F, Fila M, Hummel A, et al. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study[J]. Blood, 2021, 137(18): 2438-2449. doi: 10.1182/blood.2020009280 pmid: 33270832
[19]	Ardissino G, Possenti I, Tel F, et al. Discontinuation of eculizumab treatment in atypical hemolytic uremic syndrome: an update[J]. Am J Kidney Dis, 2015, 66(1): 172-173. doi: 10.1053/j.ajkd.2015.04.010 pmid: 26111906
[20]	Merrill SA, Brittingham ZD, Yuan X, et al. Eculizumab cessation in atypical hemolytic uremic syndrome[J]. Blood, 2017, 130(3): 368-372. doi: 10.1182/blood-2017-02-770214 pmid: 28461395
[21]	Fakhouri F, Fila M, Provot F, et al. Pathogenic Variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation[J]. Clin J Am Soc Nephrol, 2017, 12(1): 50-59.
[22]	Fakhouri F, Schwotzer N, Fremeaux-Bacchi V. How I diagnose and treat atypical hemolytic uremic syndrome[J]. Blood, 2023, 141(9): 984-995.
[23]	de Souza RM, Correa BHM, Melo PHM, et al. The treatment of atypical hemolytic uremic syndrome with eculizumab in pediatric patients: a systematic review[J]. Pediatr Nephrol, 2023, 38(1): 61-75.

Diagnosis, treatment, and reflection on pediatric systemic lupus erythematosus complicated by thrombotic microangiopathy

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