Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Department of Women's and Children's Health, Institute of Translational Medicine, Alder Hey Children's Hospital, Eaton Road, Liverpool, L12 2AP, UK.
Pediatr Nephrol. 2018 Jan;33(1):25-39. doi: 10.1007/s00467-016-3559-2. Epub 2017 Jan 6.
The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of disorders characterized by necrotizing inflammation of the small to medium vessels in association with autoantibodies against the cytoplasmic region of the neutrophil. Included in this definition are granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome). AAV are chronic, often relapsing diseases that can be organ or life threatening. Despite immunosuppression, the morbidity and mortality remain high. Renal involvement contributes significantly to the morbidity with high numbers of patients progressing to end-stage kidney disease. Current therapies have enabled improvements in renal function in the short term, but evidence for long-term protection is lacking. In MPA, renal involvement is common at presentation (90%) and often follows a more severe course than that seen in paediatric GPA. Renal biopsy remains the 'gold standard' in diagnosing ANCA-associated glomerulonephritis. While GPA and MPA are considered separate entities, the two are managed identically. Current treatment regimens are extrapolated from adult studies, although it is encouraging to see recruitment of paediatric patients to recent vasculitis trials. Traditionally more severe disease has been managed with the 'gold standard' treatment of glucocorticoids and cyclophosphamide, with remission rates achieved of between 70 and 100%. Other agents employed in remission induction include anti-tumor necrosis factor-alpha therapy and mycophenolate mofetil. Recently, however, increasing consideration is being given to rituximab as a therapy for children in severe or relapsing disease, particularly for those at risk for glucocorticoid or cyclophosphamide toxicity. Removal of circulating ANCA through plasma exchange is a short-term measure reserved for severe or refractory disease. Maintenance therapy usually involves azathioprine. The aim of this article is to provide a comprehensive review of paediatric AAV, with a focus on renal manifestations, and to highlight the recent advances made in therapeutic management.
抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）是一组以小至中等血管坏死性炎症为特征的疾病，与抗中性粒细胞胞浆抗体有关。该定义包括肉芽肿性多血管炎（GPA，以前称为韦格纳肉芽肿病）、显微镜下多血管炎（MPA）和嗜酸性肉芽肿性多血管炎（以前称为变应性肉芽肿性血管炎）。AAV 是慢性的，常反复发作的疾病，可导致器官损害或危及生命。尽管进行了免疫抑制治疗，但其发病率和死亡率仍然很高。肾脏受累是导致发病率升高的主要原因，许多患者进展为终末期肾病。目前的治疗方法可在短期内改善肾功能，但缺乏长期保护的证据。在 MPA 中，肾脏受累在发病时很常见（90%），且通常比儿科 GPA 更为严重。肾活检仍然是诊断 ANCA 相关性肾小球肾炎的“金标准”。虽然 GPA 和 MPA 被认为是两种不同的实体，但它们的治疗方法相同。目前的治疗方案是从成人研究中推断出来的，尽管看到儿科患者参与最近的血管炎试验令人鼓舞。传统上，更严重的疾病采用糖皮质激素和环磷酰胺的“金标准”治疗，缓解率在 70%至 100%之间。在缓解诱导中还使用其他药物，包括抗肿瘤坏死因子-α治疗和霉酚酸酯。然而，最近，越来越多的人考虑将利妥昔单抗作为严重或复发性疾病儿童的治疗药物，特别是对于那些有糖皮质激素或环磷酰胺毒性风险的儿童。通过血浆置换清除循环中的 ANCA 是一种保留用于严重或难治性疾病的短期措施。维持治疗通常包括硫唑嘌呤。本文的目的是全面回顾儿科 AAV，重点介绍肾脏表现，并强调治疗管理方面的最新进展。
