Gualdoni Guido A, Hofmann Georg A, Wohlfarth Philipp, Winkler Heide-Maria, Winkler Stefan, Haslacher Helmuth, Thalhammer Renate, Makristathis Athanasios, Ratzinger Franz, Burgmann Heinz
Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria.
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria.
J Clin Med. 2019 Apr 19;8(4):541. doi: 10.3390/jcm8040541.
Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening condition clinically presenting as SIRS (Systemic Inflammatory Response Syndrome). However, there is no comprehensive data concerning diagnostic algorithms, prevalence, outcome and biomarker performance in SIRS patients. We conducted a prospective observational cohort study on 451 consecutive patients fulfilling ≥2 SIRS criteria. The Hscore and the HLH-2004 criteria were used to determine the presence of sHLH, and the correlation of the screening-biomarkers ferritin, sCD25, and sCD163 with both scores was assessed. Out of 451 standard-care SIRS patients, five patients had high Hscores (≥169), suggesting incipient or HLH-like disease, and these patients were in urgent need for intensified therapy. However, none of these patients fulfilled five HLH-2004 criteria required for formal diagnosis. From the studied biomarkers, ferritin correlated strongest to both the HLH-2004 criteria and the Hscore (rs = 0.72, 0.41, respectively), and was the best predictor of 30-day survival (HR:1.012 per 100 μg/L, 95% CI: 1.004-1.021), when adjusted for patient's age, sex, bacteremia and malignant underlying-disease. Also, the HLH-2004 (HR per point increase: 1.435, 95% CI: 1.1012-2.086) and the Hscore (HR per point increase:1.011, 95% CI: 1.002-1.020) were independent predictors of 30-day-survival. The Hscore detected patients in hyperinflammatory states requiring urgent therapy escalation. Degrees of hyperinflammation, as assessed by ferritin and both HLH scores, are associated with worse outcomes.
继发性噬血细胞性淋巴组织细胞增生症（sHLH）是一种危及生命的疾病，临床上表现为全身炎症反应综合征（SIRS）。然而，目前尚无关于SIRS患者诊断算法、患病率、预后及生物标志物性能的全面数据。我们对451例符合≥2条SIRS标准的连续患者进行了一项前瞻性观察队列研究。采用Hscore和HLH - 2004标准来确定sHLH的存在，并评估筛查生物标志物铁蛋白、可溶性CD25（sCD25）和可溶性CD163（sCD163）与这两个评分的相关性。在451例接受标准治疗的SIRS患者中，有5例患者Hscore较高（≥169），提示存在早期或类HLH疾病，这些患者急需强化治疗。然而，这些患者均未满足正式诊断所需的5条HLH - 2004标准。在所研究的生物标志物中，铁蛋白与HLH - 2004标准和Hscore的相关性最强（rs分别为0.72和0.41），在对患者年龄、性别、菌血症和潜在恶性疾病进行校正后，是30天生存率的最佳预测指标（HR：每100μg/L为1.012，95%CI：1.004 - 1.021）。此外，HLH - 2004（每增加1分的HR：1.435，95%CI：1.1012 - 2.086）和Hscore（每增加1分的HR：1.011，95%CI：1.002 - 1.020）是30天生存率的独立预测指标。Hscore可检测出处于需要紧急升级治疗的高炎症状态的患者。通过铁蛋白和两个HLH评分评估的高炎症程度与较差的预后相关。
