抗甲状腺药物致儿童抗中性粒细胞胞质抗体相关性血管炎3例并文献复习  

Antithyroid drugs-induced antineutrophil cytoplasmic antibody-associated vasculitis in children:report of three cases and literature review

作　　者：陈丽植[1] 吴靖宜 文思佳 林知朗 丘原全 王霁朏[2] 蒋小云[1] Chen Lizhi;Wu Jingyi;Wen Sijia;Lin Zhilang;Qiu Yuanquan;Wang Jifei;Jiang Xiaoyun(Department of Pediatric Nephrology and Rheumatology,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China;Department of Image,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第一医院小儿肾脏风湿病中心,广州510080 [2]中山大学附属第一医院影像科,广州510080

出　　处：《中华肾脏病杂志》2022年第3期177-188,共12页Chinese Journal of Nephrology

基　　金：广州市科技计划项目(202103000001)。

摘　　要：目的探讨抗甲状腺药物致儿童抗中性粒细胞胞质抗体(antineutrophil cytoplasmic antibody, ANCA)相关性血管炎(ANCA-associated vasculitis, AAV)的临床病理特点与预后。方法回顾性总结中山大学附属第一医院小儿肾脏风湿病中心3例抗甲状腺药物致儿童AAV的临床病理特点、治疗和转归情况, 并进行文献复习。结果 (1)共纳入3例患儿, 女2例, 男1例, 年龄分别为12.6岁、13.9岁和13.1岁。3例患儿起病前均有丙硫氧嘧啶(propylthiouracil, PTU)和/或甲巯咪唑(methimazole, MMI)使用史。3例患儿首诊原因均为面色苍白, 均有肾病水平蛋白尿、血尿和伴不同程度肾功能下降, 其中2例伴高血压。3例患儿均有肾外表现, 例1伴皮疹、关节痛和心功能不全;例2入院后反复抽搐, 累及脑;例3伴关节痛并累及肺。3例患儿p-ANCA和MPO-ANCA均阳性。3例患儿首次肾脏组织病理分别为硬化型、新月体型和混合型ANCA相关性肾炎, 例3治疗8个月后重复肾活检提示进展至硬化型。3例患儿均停用PTU或MMI, 予激素联合环磷酰胺冲击治疗, 例2和例3分别因急进性肾炎起病、复发(可疑肺出血)加用血浆置换, 例3复发后改用利妥昔单抗联合霉酚酸酯治疗。3例患儿经积极治疗后肾外症状均较快缓解, 例1和例2在治疗6个月后p-ANCA和MPO-ANCA转阴, 而例3则持续阳性。3例患儿分别随访24、10和12个月, 依次进展至慢性肾脏病(chronic kidney disease, CKD)2期(尿常规正常)、CKD 5期(在家猝死)和CKD 4期(仍肾病水平蛋白尿和镜下血尿)。(2)文献检索已报道的27例加上本中心报道的3例抗甲状腺药物致AAV患儿共30例, 29例患儿使用PTU(37.5±4.0)个月(1~96个月), 1例单独使用MMI 8个月出现AAV症状, 主要累及肾脏(28例, 93.3%)和肺(12例, 40.0%), 罕见累及脑(2例, 6.7%)。肾脏病理改变主要为新月体肾炎(5/23)和坏死性寡免疫复合物肾炎(11/23)。经停用抗甲状腺药物及激素和免疫抑制Objective To explore clinicopathological features and prognosis of antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV)in children induced by antithyroid drugs.Methods The clinicopathological features,treatment and prognosis of 3 children with AAV induced by antithyroid drugs in the Department of Pediatric Nephrology and Rheumatology of the First Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively,and the literatures were reviewed.Results(1)Among the 3 cases,there were 2 females and 1 male,whose ages were 12.6,13.9 and 13.1 years old,respectively.All patients had medication history of propylthiouracil(PTU)and/or methimazole(MMI)before onset.Initial manifestation was pallor and renal involvements with nephrotic proteinuria,hematuria and renal function abnormality,while 2 of them had hypertension.Extrarenal manifestations were also presented:case 1 presented with rash,arthralgia and cardiac insufficiency;case 2 had brain involvement with repeated convulsions;case 3 presented with arthralgia and lung involvement.They were all tested positive for p-ANCA and MPO-ANCA.Initial renal histopathology of the 3 cases were consistent with ANCA-associated glomerulonephritis,which were classified into sclerosis,crescentic and mixed class respectively.After 8 months of treatments,repeated renal biopsy of case 3 had demonstrated progression to sclerosis class.Antithyroid drugs(PTU or MMI)were discontinued in 3 cases,and the children were all treated with corticosteroid combined with intravenous pulse cyclophosphamide therapy.Plasma exchange was performed in case 2 and case 3 due to rapidly progressive glomerulonephritis and disease recurrence(suspected pulmonary hemorrhage),respectively.Case 3 was treated with rituximab combined with mycophenolate mofetil after recurrence.The extrarenal symptoms relieved quickly after treatments in all cases.P-ANCA and MPO-ANCA became negative in case 1 and case 2 after 6 months of treatments but they were persistently positive in case 3.Three cases were fo

关 键 词：丙硫氧嘧啶 甲巯咪唑 抗中性粒细胞胞浆抗体相关性血管炎 儿童 

分 类 号：R969[医药卫生—药理学]