Baldo Francesco, Erkens Remco G A, Mizuta Mao, Rogani Greta, Lucioni Federica, Bracaglia Claudia, Foell Dirk, Gattorno Marco, Jelusic Marija, Anton Jordi, Brogan Paul, Canna Scott, Chandrakasan Shanmuganathan, Cron Randy Q, De Benedetti Fabrizio, Grom Alexei, Heshin-Bekenstein Merav, Horne AnnaCarin, Khubchandani Raju, Ozen Seza, Quartier Pierre, Ravelli Angelo, Shimizu Masaki, Schulert Grant, Scott Christiaan, Sinha Rashmi, Ruperto Nicolino, Swart Joost F, Vastert Sebastiaan, Minoia Francesca
Pediatric Immuno-Rheumatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
ASST Gaetano Pini, Milan, Italy.
Rheumatology (Oxford). 2025 Jan 1;64(1):32-44. doi: 10.1093/rheumatology/keae391.
To assess current treatment in macrophage activation syndrome (MAS) worldwide and to highlight any areas of major heterogeneity of practice.
A systematic literature search was performed in both EMBASE and PubMed databases. Paper screening was done by two independent teams based on agreed criteria. Data extraction was standardized following the PICO framework. A panel of experts assessed paper validity, using the Joanna Briggs Institute appraisal tools and category of evidence (CoE) according to EULAR procedure.
Fifty-seven papers were finally included (80% retrospective case-series), describing 1148 patients with MAS: 889 systemic juvenile idiopathic arthritis (sJIA), 137 systemic lupus erythematosus (SLE), 69 Kawasaki disease (KD) and 53 other rheumatological conditions. Fourteen and 11 studies specified data on MAS associated to SLE and KD, respectively. All papers mentioned glucocorticoids (GCs), mostly methylprednisolone and prednisolone (90%); dexamethasone was used in 7% of patients. Ciclosporin was reported in a wide range of patients according to different cohorts. Anakinra was used in 179 MAS patients, with a favourable outcome in 83% of sJIA-MAS. Etoposide was described by 11 studies, mainly as part of HLH-94/04 protocol. Emapalumab was the only medication tested in a clinical trial in 14 sJIA-MAS, with 93% of MAS remission. Ruxolitinib was the most reported Janus kinase inhibitor in MAS.
High-dose GCs together with IL-1 and IFNγ inhibitors have shown efficacy in MAS, especially in sJIA-associated MAS. However, the global level of evidence on MAS treatment, especially in other conditions, is still poor and requires standardized studies to be confirmed.
评估全球范围内巨噬细胞活化综合征（MAS）的当前治疗情况，并突出实践中主要存在异质性的领域。
在EMBASE和PubMed数据库中进行了系统的文献检索。由两个独立的团队根据商定的标准进行论文筛选。按照PICO框架对数据提取进行了标准化。一组专家使用乔安娜·布里格斯研究所的评估工具和根据欧洲抗风湿病联盟（EULAR）程序的证据类别（CoE）来评估论文的有效性。
最终纳入了57篇论文（80%为回顾性病例系列），描述了1148例MAS患者：889例系统性幼年特发性关节炎（sJIA）、137例系统性红斑狼疮（SLE）、69例川崎病（KD）和53例其他风湿性疾病。分别有14项和11项研究明确了与SLE和KD相关的MAS数据。所有论文均提及糖皮质激素（GCs），主要是甲泼尼龙和泼尼松龙（90%）；7%的患者使用了地塞米松。根据不同队列，环孢素在广泛的患者中被报道。阿那白滞素用于179例MAS患者，在83%的sJIA-MAS患者中取得了良好疗效。11项研究描述了依托泊苷，主要作为HLH-94/04方案的一部分。emapalumab是在14例sJIA-MAS患者的临床试验中测试的唯一药物，93%的MAS患者病情缓解。鲁索替尼是MAS中报道最多的Janus激酶抑制剂。
大剂量GCs联合IL-1和IFNγ抑制剂在MAS中已显示出疗效，尤其是在与sJIA相关的MAS中。然而，关于MAS治疗的全球证据水平，特别是在其他疾病中的证据水平仍然很低，需要进行标准化研究来证实。
