Royal Liverpool and Broadgreen University Hospital Trusts, Liverpool, UK.
Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
Clin Rheumatol. 2023 Dec;42(12):3189-3200. doi: 10.1007/s10067-023-06781-8. Epub 2023 Sep 27.
Immunoglobulin A (IgA) vasculitis (IgAV, also known as Henoch-Schoenlein purpura, HSP) is the most common vasculitis of childhood. It usually presents with a simple, self-limiting disease course; however, a small subset of patients may develop kidney involvement (IgAV-N) which occurs 4-12 weeks after disease onset and is the biggest contributor to long-term morbidity. Treatment currently targets patients with established kidney involvement; however; there is a desire to work towards early prevention of inflammation during the window of opportunity between disease presentation and onset of significant nephritis. There are no clinical trials evaluating drugs which may prevent or halt the progression of nephritis in children with IgAV apart from the early use of corticosteroids which have no benefit. This article summarises the latest scientific evidence and clinical trials that support potential therapeutic targets for IgAV-N that are currently being developed based on the evolving understanding of the pathophysiology of IgAV-N. These span the mucosal immunity, B-cell and T-cell modulation, RAAS inhibition, and regulation of complement pathways, amongst others. Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab. Further clinical trials, as well as pre-clinical scientific studies, are needed to identify mechanistic pathways as there may be an opportunity to prevent nephritis in this condition. Key Points • Kidney involvement is the main cause of long-term morbidity and mortality in IgA vasculitis despite the current treatment recommendations. • The evolving understanding of the pathophysiology of IgA vasculitis is allowing exploration of novel treatment options which target underlying immune pathways. • Novel treatments currently being trialled in IgA nephropathy may have benefit in IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-budesonide, B-cell modulators, and complement inhibitors. • Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with IgA vasculitis nephritis.
免疫球蛋白 A (IgA) 血管炎 (IgAV，也称为过敏性紫癜，HSP) 是儿童中最常见的血管炎。它通常表现为简单的、自限性的疾病过程；然而，一小部分患者可能会出现肾脏受累 (IgAV-N)，这发生在疾病发作后 4-12 周，是导致长期发病率的最大因素。目前的治疗方法针对已确诊的肾脏受累患者；然而，人们希望在疾病发作和发生明显肾炎之间的机会窗口期间，尽早预防炎症。除了早期使用皮质类固醇（没有益处）外，没有临床试验评估可能预防或阻止 IgAV 儿童肾炎进展的药物。本文总结了最新的科学证据和临床试验，这些证据和临床试验支持目前正在根据 IgAV-N 的病理生理学的不断发展而开发的 IgAV-N 的潜在治疗靶点。这些靶点涵盖黏膜免疫、B 细胞和 T 细胞调节、肾素-血管紧张素-醛固酮系统抑制以及补体途径调节等。可能考虑用于早期肾炎的新型药物包括曲氟布地奈德；B 细胞抑制剂，包括贝利尤单抗、替利塞普特、贝利木单抗、VIS649 和 BION-1301；B 细胞耗竭剂，如利妥昔单抗、奥法妥木单抗和硼替佐米；沙库巴曲缬沙坦；血管紧张素转换酶抑制剂 (ACE-Is)；以及补体途径抑制剂，包括阿伐卡潘、依帕考潘和那他珠单抗。需要进一步的临床试验和临床前科学研究来确定机制途径，因为有可能预防这种情况下的肾炎。要点 • 尽管有目前的治疗建议，但肾脏受累是 IgA 血管炎长期发病率和死亡率的主要原因。 • IgA 血管炎病理生理学的不断发展允许探索针对潜在免疫途径的新型治疗选择。 • 由于潜在病理生理学的相似性，目前正在 IgA 肾病中进行试验的新型治疗方法可能对 IgA 血管炎有益，例如曲氟布地奈德、B 细胞调节剂和补体抑制剂。 • 迫切需要进一步的研究，包括新型药物的临床试验，以改善 IgA 血管炎肾炎儿童的长期预后。
