Gerstein Maya, Borgia R Ezequiel, Dominguez Daniela, Feldman Brian M, Liao Fangming, Levy Deborah M, Ng Lawrence, Abdelhaleem Mohamed, Silverman Earl D, Hiraki Linda T
M. Gerstein, MD, Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada, and Pediatric Rheumatology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
R.E. Borgia, MD, Division of Rheumatology, The Hospital for Sick Children, Toronto, and Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA.
J Rheumatol. 2021 Sep;48(9):1450-1457. doi: 10.3899/jrheum.200292. Epub 2020 Dec 1.
Macrophage activation syndrome (MAS), a life-threatening inflammatory complication, is increasingly recognized in childhood-onset systemic lupus erythematosus (cSLE). It can be a challenge to differentiate active cSLE from MAS. We generated decision rules for discriminating MAS from active cSLE in newly diagnosed patients.
We conducted a retrospective cohort study of consecutive, newly diagnosed, active cSLE patients with fever, requiring hospital admission to The Hospital for Sick Children from January 2003 to December 2007 (cohort 1) and January 2008 to December 2013 (cohort 2). All patients met ≥ 4 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria, and were steroid-naïve and infection-free. MAS was diagnosed based on expert opinion. Recursive partitioning was applied to each cohort to derive a decision rule based on clinical and laboratory features, distinguishing MAS from non-MAS cSLE. Each decision rule was applied to the alternate, independent cohort. Sensitivity and specificity of these decision rules were compared to existing criteria.
Cohort 1 (n = 34) and cohort 2 (n = 41) each had 10 patients with MAS. Recursive partitioning in cohort 1 identified ferritin ≥ 699 μg/L as the sole best discriminator between MAS and non-MAS patients (R = 0.48), and in cohort 2, ferritin ≥ 1107 μg/L was the best discriminator for MAS, followed by lymphocytes < 0.72 × 10/mm (R = 0.52). Cross-validation of our decision rules maintained 90-100% sensitivity and 65-85% specificity.
Our decision rule demonstrated improved performance compared to preliminary guidelines for MAS in cSLE from the Lupus Working Group of the Paediatric Rheumatology European Society and familial hemophagocytic lymphohistiocytosis diagnostic criteria. Validation in independent cohorts is required.
巨噬细胞活化综合征（MAS）是一种危及生命的炎症性并发症，在儿童期系统性红斑狼疮（cSLE）中越来越受到认可。区分活动性cSLE和MAS可能具有挑战性。我们制定了在新诊断患者中区分MAS和活动性cSLE的决策规则。
我们对2003年1月至2007年12月（队列1）以及2008年1月至2013年12月（队列2）期间连续新诊断的、有发热症状且需要入住病童医院的活动性cSLE患者进行了一项回顾性队列研究。所有患者均符合≥4条美国风湿病学会或系统性红斑狼疮国际协作临床标准，且未使用过类固醇且无感染。MAS根据专家意见进行诊断。对每个队列应用递归划分，以根据临床和实验室特征得出区分MAS和非MAS cSLE的决策规则。每个决策规则应用于另一个独立队列。将这些决策规则的敏感性和特异性与现有标准进行比较。
队列1（n = 34）和队列2（n = 41）各有10例MAS患者。队列1中的递归划分确定铁蛋白≥699μg/L是MAS和非MAS患者之间唯一最佳的鉴别指标（R = 0.48），而在队列2中，铁蛋白≥1107μg/L是MAS的最佳鉴别指标，其次是淋巴细胞<0.72×10/mm（R = 0.52）。我们决策规则的交叉验证保持了90 - 100%的敏感性和65 - 85%的特异性。
与欧洲儿科风湿病学会狼疮工作组的cSLE中MAS初步指南和家族性噬血细胞性淋巴组织细胞增生症诊断标准相比，我们的决策规则表现出更好的性能。需要在独立队列中进行验证。
