背景:巨噬细胞激活综合征(MAS),继发性噬血细胞性淋巴组织细胞增生症的一个例子,是风湿性疾病的潜在致命并发症。我们的目的是研究临床和实验室特征,治疗方案,以及与MAS相关的不同风湿性疾病在儿童中的结局。还研究了MAS的早期预警指标,以使临床医生能够及时准确地做出诊断。
方法:纳入2017年1月至2022年12月的55例风湿性疾病合并MAS患者。在疾病发作前收集临床和实验室数据,在诊断时,用MAS治疗后,并比较了系统性幼年特发性关节炎(sJIA)患者的数据,川崎病(KD),和系统性红斑狼疮(SLE)。建立随机森林模型,显示各变量的重要性得分存在显著差异。
结果:大多数(81.8%)MAS发生在基础疾病的初始诊断期间。与sJIA的活跃阶段相比,血小板计数,红细胞沉降率,sJIA-MAS中纤维蛋白原水平显著下降,而铁蛋白,铁蛋白/红细胞沉降率,天冬氨酸转氨酶,丙氨酸氨基转移酶,乳酸脱氢酶,D-二聚体水平显著升高。铁蛋白水平,铁蛋白/红细胞沉降率,血小板计数对sJIA-MAS的预测价值最大。sJIA-MAS组IL-18水平明显高于活动性sJIA组,而IL-6水平显著降低。大多数MAS患者采用甲基强的松龙脉冲联合环孢素治疗,没有死亡发生。
结论:血小板减少症,铁蛋白水平,铁蛋白/红细胞沉降率,天冬氨酸转氨酶水平升高可以预测sJIA患者MAS的发生。此外,我们的分析表明,IL-18在sJIA-MAS的MAS发病机制中起重要作用。
BACKGROUND: Macrophage activation syndrome (MAS), an example of secondary hemophagocytic lymphohistiocytosis, is a potentially fatal complication of rheumatic diseases. We aimed to study the clinical and laboratory characteristics, treatment schemes, and outcomes of different rheumatic disorders associated with MAS in children. Early warning indicators of MAS have also been investigated to enable clinicians to make a prompt and accurate diagnosis.
METHODS: Fifty-five patients with rheumatic diseases complicated by MAS were enrolled between January 2017 and December 2022. Clinical and laboratory data were collected before disease onset, at diagnosis, and after treatment with MAS, and data were compared between patients with systemic juvenile idiopathic arthritis (sJIA), Kawasaki disease (KD), and systemic lupus erythematosus (SLE). A random forest model was established to show the importance score of each variable with a significant difference.
RESULTS: Most (81.8%) instances of MAS occurred during the initial diagnosis of the underlying disease. Compared to the active stage of sJIA, the platelet count, erythrocyte sedimentation rate, and fibrinogen level in sJIA-MAS were significantly decreased, whereas ferritin, ferritin/erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and D-dimer levels were significantly increased. Ferritin level, ferritin/erythrocyte sedimentation rate, and platelet count had the greatest predictive value for sJIA-MAS. The level of IL-18 in the sJIA-MAS group was significantly higher than in the active sJIA group, whereas IL-6 levels were significantly lower. Most patients with MAS were treated with methylprednisolone pulse combined with cyclosporine, and no deaths occurred.
CONCLUSIONS: Thrombocytopenia, ferritin levels, the ferritin/erythrocyte sedimentation rate, and elevated aspartate aminotransferase levels can predict the occurrence of MAS in patients with sJIA. Additionally, our analysis indicates that IL-18 plays an important role in the pathogenesis of MAS in sJIA-MAS.