Department of Internal Medicine, Tenon Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Saint-Antoine Research Center (CRSA) INSERM UMRS 938, Sorbonne Université, Paris, France; National French Reference Centre for Auto-inflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA), Montpellier, France; Department of General Pediatrics, Versailles Hospital, Versailles, France.
Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Institut Imagine, Université Paris Cité, Paris, France.
J Invest Dermatol. 2024 Jun;144(6):1282-1294.e8. doi: 10.1016/j.jid.2023.12.007. Epub 2023 Dec 19.
A20 haploinsufficiency is an autoinflammatory disease caused by defective inactivation of the NF-κB pathway. We conducted a systematic literature review of articles reporting patients with TNFAIP3 sequence variants from 2016 to August 2023 following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data from 177 patients from 65 articles were retrieved (108 women). The principal features were mucosal ulcers (n = 129); fever (n = 93) followed by gastrointestinal (n = 81); skin features (n = 76); autoimmunity (n = 61), including thyroiditis (n = 25) and lupus (n = 16); and joint involvements (n = 54). Five patients had died at the time of publication. In 54 of 63 patients, CRP was significantly elevated during flares, with a median of 51 mg/l. The most commonly used treatment included corticosteroids and nonsteroidal anti-inflammatory drugs (n = 32), TNF blockers (n = 29), colchicine (n = 28), and methotrexate (n = 14). TNFAIP3 variants impacted the ovarian tumor domain in 92 cases and a Zinc finger domain in 68 cases. Geographic origin, reported sex, and variant type significantly impacted phenotype. A better understanding of the wide A20 haploinsufficiency phenotype could facilitate the diagnosis process. Much remains to be elucidated about pathogenesis and treatment to improve outcome in patients with A20 haploinsufficiency.
A20 单倍体不足是一种自身炎症性疾病，由 NF-κB 通路的缺陷失活引起。我们按照 PRISMA（系统评价和荟萃分析的首选报告项目）指南对 2016 年至 2023 年 8 月期间报告 TNFα 诱导蛋白 3（TNFAIP3）序列变异患者的文献进行了系统综述。从 65 篇文章中检索到 177 名患者的数据（108 名女性）。主要特征是黏膜溃疡（n=129）；发热（n=93），其次是胃肠道（n=81）；皮肤特征（n=76）；自身免疫（n=61），包括甲状腺炎（n=25）和狼疮（n=16）；以及关节受累（n=54）。在发表时，有 5 名患者已经死亡。在 63 名患者中的 54 名患者中，在疾病发作时 CRP 显著升高，中位数为 51mg/L。最常用的治疗方法包括皮质类固醇和非甾体抗炎药（n=32）、TNF 阻滞剂（n=29）、秋水仙碱（n=28）和甲氨蝶呤（n=14）。TNFAIP3 变异影响 92 例卵巢肿瘤结构域和 68 例锌指结构域。地理起源、报告性别和变异类型对表型有显著影响。更好地了解广泛的 A20 单倍体不足表型可以促进诊断过程。在 A20 单倍体不足患者的发病机制和治疗方面仍有许多需要阐明的地方，以改善患者的预后。
