Department of Internal Medicine, Division of Rheumatology, Nagoya City University Hospital, Nagoya, Japan.
Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Mod Rheumatol. 2022 Jan 5;32(1):169-176. doi: 10.1080/14397595.2021.1899565.
Macrophage activation syndrome (MAS) developed under tocilizumab treatment poses a diagnostic challenge. This study aims to demonstrate the frequency and the clinical features of MAS developed in patients with adult-onset Still's disease (AOSD) receiving tocilizumab.
The consecutive AOSD patients treated with tocilizumab in our institution from April 2008 to March 2020 were studied. The frequency of clinically diagnosed MAS during tocilizumab treatment, their conformity to the several criteria relevant for MAS, and laboratory characteristics compared to AOSD flare were investigated.
Of the 20 AOSD patients treated with tocilizumab, six developed clinically diagnosed MAS, four immediately after starting tocilizumab and two after long-term treatment. Some of them had already met the MAS criteria before starting tocilizumab. At MAS diagnosis, although some did not meet the MAS criteria due to lack of fever and/or the lower ferritin levels, all consistently showed sharp increases in ferritin along with marked abnormal changes in two or more different markers of organ damage, unlike the AOSD flares.
MAS is not a rare complication in AOSD patients receiving tocilizumab. The clinical similarities between systemic AOSD and MAS, and substantial alterations in MAS features by inhibition of interleukin-6 signaling may limit the utility of the existing diagnostic/classification criteria in diagnosing MAS under tocilizumab treatment. The emergence of abnormalities in MAS-related organ damage markers with a rapid elevation of ferritin should be considered as MAS development in AOSD patients receiving tocilizumab even if the patients are afebrile or have relatively low ferritin levels.
托珠单抗治疗下发生的巨噬细胞活化综合征（MAS）带来了诊断挑战。本研究旨在展示接受托珠单抗治疗的成人Still 病（AOSD）患者中发生 MAS 的频率和临床特征。
研究了 2008 年 4 月至 2020 年 3 月期间在我院接受托珠单抗治疗的连续 AOSD 患者。研究了托珠单抗治疗期间临床诊断的 MAS 的频率、它们与 MAS 相关标准的一致性，以及与 AOSD 发作相比的实验室特征。
20 例接受托珠单抗治疗的 AOSD 患者中，有 6 例发生了临床诊断的 MAS，4 例在开始托珠单抗治疗后立即发生，2 例在长期治疗后发生。其中一些患者在开始托珠单抗治疗前已经符合 MAS 标准。在 MAS 诊断时，尽管由于缺乏发热和/或较低的铁蛋白水平，有些患者不符合 MAS 标准，但与 AOSD 发作不同，所有患者的铁蛋白均明显升高，同时两个或更多不同的器官损伤标志物出现明显异常改变。
MAS 是接受托珠单抗治疗的 AOSD 患者的一种罕见并发症。全身 AOSD 与 MAS 之间的临床相似性，以及白细胞介素-6 信号抑制对 MAS 特征的重大改变，可能限制了现有诊断/分类标准在托珠单抗治疗下诊断 MAS 的实用性。即使患者无发热或铁蛋白水平相对较低，在接受托珠单抗治疗的 AOSD 患者中，铁蛋白迅速升高伴 MAS 相关器官损伤标志物异常应被视为 MAS 发生。
