Macrophage activation syndrome (MAS) is a potentially life-threatening complication of various inflammatory disorders, including multisystem inflammatory syndrome in children (MIS-C). MIS-C refractory to treatment should raise suspicion of MAS, which can be fatal if a definitive diagnosis is delayed. Unfortunately, there is a lack of data on MAS in children with MIS-C.

Our study aims to analyze the risk factors for the development of MAS in MIS-C, its clinical course and response to treatment, and identify predictive factors for pediatric intensive care.

We analyzed data from the Polish MIS-C registry of the MultiOrgan Inflammatory Syndromes COVID-19 Related Study. Patients were diagnosed according to the WHO MIS-C definition and treated according to national guidelines (Polish Pediatric Society) based on international consensus. MAS definition was based on 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis.

Two-hundred and seventy four children met the study inclusion criteria. Fifty-nine patients fulfilled MAS classification criteria, nine of which required admission to the pediatric intensive care unit (PICU). MIS-C patients with MAS were significantly older than patients without MAS (median 11.2 vs. 8.1 years). Multivariable analysis showed that age, symptoms characteristic of atypical Kawasaki disease, and skin erosions were significant factors associated with MAS in MIS-C patients. Analysis of laboratory parameters showed that on admission, MIS-C patients with MAS had significantly lower median lymphocyte and platelet counts, albumin and sodium levels, and higher median levels of C-reactive protein, procalcitonin, ferritin, D-dimers, triglycerides, serum creatinine, urea, and γ-glutamyl transpeptidase, and neutrophil count. Multivariate analysis showed that higher procalcitonin, ferritin, and fibrinogen levels at admission were predictive of MAS. Only elevated troponin level was a factor indicating a requirement of PICU hospitalization for children with MAS. MIS-C patients fulfilling MAS criteria were treated more often with intravenous immunoglobulins and steroids than children without MAS. Children with MAS more often required mechanical ventilation. None of the patients required biological agents.

The clinical course of MAS in MIS-C seems milder, treatment less aggressive, and the prognosis better than expected based on the current knowledge on MAS complicating other rheumatological diseases.

巨噬细胞活化综合征 (MAS) 是各种炎症性疾病的潜在危及生命的并发症，包括儿童多系统炎症综合征 (MIS-C)。对治疗无效的 MIS-C 应引起对 MAS 的怀疑，如果延迟明确诊断，这可能是致命的。不幸的是，缺乏 MIS-C 儿童的 MAS 数据。

我们的研究旨在分析 MIS-C 中 MAS 发展的危险因素、其临床过程和对治疗的反应，并确定儿科重症监护的预测因素。

我们分析了多器官炎症综合征 COVID-19 相关研究的波兰 MIS-C 登记处的数据。患者根据 WHO MIS-C 定义进行诊断，并根据基于国际共识的国家指南（波兰儿科学会）进行治疗。MAS 的定义基于 2016 年巨噬细胞激活综合征合并全身性幼年特发性关节炎的分类标准。

274 名儿童符合研究纳入标准。59 名患者符合 MAS 分类标准，其中 9 名需要入住儿科重症监护病房 (PICU)。患有 MAS 的 MIS-C 患者的年龄明显大于没有 MAS 的患者（中位数 11.2 岁对 8.1 岁）。多变量分析显示，年龄、非典型川崎病的症状特征和皮肤糜烂是与 MIS-C 患者 MAS 相关的重要因素。实验室参数分析显示，入院时，患有 MAS 的 MIS-C 患者的淋巴细胞和血小板计数、白蛋白和钠水平的中位数显着降低，而 C 反应蛋白、降钙素原、铁蛋白、D-二聚体、甘油三酯、血清的中位数水平较高肌酐、尿素和γ-谷氨酰转肽酶以及中性粒细胞计数。多变量分析表明，入院时较高的降钙素原、铁蛋白和纤维蛋白原水平可预测 MAS。只有肌钙蛋白水平升高是表明 MAS 儿童需要住院 PICU 的一个因素。与没有 MAS 的儿童相比，满足 MAS 标准的 MIS-C 患者更常接受静脉注射免疫球蛋白和类固醇治疗。MAS 患儿更常需要机械通气。没有患者需要生物制剂。MAS 患儿更常需要机械通气。没有患者需要生物制剂。MAS 患儿更常需要机械通气。没有患者需要生物制剂。

MIS-C 中 MAS 的临床病程似乎较温和，治疗的侵袭性较低，且预后好于目前对 MAS 与其他风湿病相关疾病的认识。