NIH Research-Leeds Musculoskeletal Biomedical Research Unit (NIHR-LMBRU) and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner Building, St. James's University Hospital, Beckett Street, Leeds, United Kingdom.
Department of Rheumatology, Pinderfields Hospital, Wakefield, United Kingdom.
JCI Insight. 2016 May 5;1(6):e86336. doi: 10.1172/jci.insight.86336.
Some adult patients presenting with unexplained pyrexia, serositis, skin rashes, arthralgia, myalgia, and other symptoms commonly found in autoinflammatory disorders may not fit a specific diagnosis, either because their clinical phenotype is nondiagnostic or genetic tests are negative. We used the term undifferentiated systemic autoinflammatory disorder (uSAID) to describe such cases. Given that well-defined autoinflammatory diseases show responses to IL-1 blockade, we evaluated whether anakinra was useful for both diagnosing and treating uSAID patients.
We performed a retrospective analysis of consecutive patients presenting with uSAID between 2012-2015 who were treated with the recombinant IL-1 receptor antagonist anakinra. uSAID was diagnosed after excluding malignancy, infection, and pathogenic mutations in known hereditary fever syndromes (HFS) genes and where clinical criteria for adult onset Still's disease (AOSD) were not met.
A total of 11 patients presented with uSAID (5 males and 6 females), with a mean time to diagnosis of 3.5 years (1-8 years). Patients were unresponsive or only partially controlled on disease-modifying antirheumatic drug (DMARD)/steroid treatment. Anakinra controlled symptoms within 4-6 weeks of starting treatment in 9 of 11 cases. Two patients discontinued therapy - one due to incomplete response and another due to severe injection-site reactions.
This retrospective case series demonstrates that the spectrum of poorly defined autoinflammatory disorders that show responsiveness to anakinra is considerable. Anakinra seems a viable treatment option for these patients, who are unresponsive to standard steroid/DMARD treatments. Moreover, given the mechanisms of action, response to anakinra implicates underlying IL-1 dysregulation in the disease pathogenesis of responding uSAIDs patients.
一些表现为不明原因发热、浆膜炎、皮疹、关节炎、肌痛和其他自身炎症性疾病常见症状的成年患者，可能无法明确诊断，这可能是因为其临床表型不具有诊断意义，或者基因检测结果为阴性。我们使用“未分化系统性自身炎症性疾病（uSAID）”来描述此类病例。鉴于明确的自身炎症性疾病对 IL-1 阻断有反应，我们评估了 anakinra 是否对 uSAID 患者的诊断和治疗都有用。
我们对 2012-2015 年间连续就诊的 uSAID 患者进行了回顾性分析，这些患者均接受了重组 IL-1 受体拮抗剂 anakinra 治疗。uSAID 的诊断是在排除恶性肿瘤、感染和已知遗传性发热综合征（HFS）基因中的致病性突变，以及不符合成人斯蒂尔病（AOSD）临床标准后作出的。
共有 11 例患者表现为 uSAID（5 例男性和 6 例女性），平均确诊时间为 3.5 年（1-8 年）。患者对疾病修饰抗风湿药物（DMARD）/类固醇治疗无反应或仅部分控制。在 11 例患者中，有 9 例在开始治疗的 4-6 周内症状得到控制。有 2 例患者停止了治疗 - 1 例是因为不完全反应，另 1 例是因为严重的注射部位反应。
这项回顾性病例系列研究表明，对 anakinra 有反应的不明原因自身炎症性疾病谱相当广泛。anakinra 似乎是这些对标准类固醇/DMARD 治疗无反应的患者的可行治疗选择。此外，鉴于其作用机制，对 anakinra 的反应表明，对反应性 uSAID 患者的疾病发病机制存在潜在的 IL-1 失调。
