Objectives The association between mutations in TNFAIP3, encoding the NF-kB regulatory protein A20, and a new autoinflammatory disease has recently been recognised. This study aims at describing the clinical phenotypes and disease course of patients with A20 haploinsufficiency (HA20). Methods Data for all cases from the initial publication, and additional cases identified through collaborations since, were collected using standardised data collection forms. Results A total of 16 patients (13 female) from seven families with a genetic diagnosis of HA20 were included. The disease commonly manifested in early childhood (range: first week of life to 29 years of age). The main clinical symptoms were recurrent oral, genital and/or gastrointestinal ulcers (16/16), musculoskeletal (9/16) and gastrointestinal complaints (9/16), cutaneous lesions (8/16), episodic fever (7/16), and recurrent infections (7/16). Clinical phenotypes varied considerably, even within families. Relapsing-remitting disease course was most common, and one patient died. Laboratory abnormalities included elevated acute-phase reactants and fluctuating presence of various autoantibodies such as antinuclear antibodies (4/10 patients tested) and anti-dsDNA (2/5). Tissue biopsy of different sites revealed non-specific chronic inflammation (6/12 patients tested), findings consistent with class V lupus nephritis in one patient, and pustules and normal results in two patients each. All patients were treated: 4/16 received colchicine and 12/16 various immunosuppressive agents. Cytokine inhibitors effectively suppressed systemic inflammation in 7/9 patients. Conclusions Early-onset recurrent oral, genital and/or gastrointestinal ulcers are the hallmark feature of HA20. Frequency and intensity of other clinical manifestations varied highly. Treatment regimens should be based on disease severity, and cytokine inhibitors are often required to control relapses.

中文翻译：

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A20 单倍体不足 (HA20)：新发现的 NF-kB 介导的自身炎症性疾病患者的临床表型和病程

目的 编码 NF-kB 调节蛋白 A20 的 TNFAIP3 突变与一种新的自身炎症性疾病之间的关联最近已被认识到。本研究旨在描述 A20 单倍剂量不足 (HA20) 患者的临床表型和病程。方法 使用标准化的数据收集表格收集最初发表的所有病例以及此后通过合作确定的其他病例的数据。结果 共纳入 7 个家族 16 例（13 名女性）的遗传诊断为 HA20 的患者。该疾病通常表现在儿童早期（范围：生命的第一周至 29 岁）。主要临床症状是复发性口腔、生殖器和/或胃肠道溃疡 (16/16)、肌肉骨骼 (9/16) 和胃肠道不适 (9/16)、皮肤病变 (8/16)、发作性发热 (7/16) 和反复感染 (7/16)。临床表型差异很大，即使在家庭内部也是如此。复发-缓解病程最常见，一名患者死亡。实验室异常包括急性期反应物升高和各种自身抗体的波动存在，例如抗核抗体（4/10 患者测试）和抗 dsDNA（2/5）。不同部位的组织活检显示非特异性慢性炎症（测试 6/12 患者），结果与 1 名患者的 V 级狼疮性肾炎一致，2 名患者的脓疱和正常结果。所有患者均接受治疗：4/16 接受秋水仙碱和 12/16 各种免疫抑制剂。细胞因子抑制剂有效抑制了 7/9 患者的全身炎症。结论 早发性复发性口服，生殖器和/或胃肠道溃疡是 HA20 的标志性特征。其他临床表现的频率和强度差异很大。治疗方案应基于疾病的严重程度，通常需要细胞因子抑制剂来控制复发。