Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Technology Development, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, 292-0818, Chiba, Japan.
Int J Hematol. 2020 Jan;111(1):131-136. doi: 10.1007/s12185-019-02738-3. Epub 2019 Sep 23.
Hemophagocytic lymphohistiocytosis (HLH) occurs in neonates with disseminated infection of herpes simplex virus (HSV). Little has been reported on the control of rapid HLH progression. We studied the cytokine profile and genetic basis of two index cases with divergent outcomes after early treatment of type 2 HSV infection. One survivor had fever and elevated serum levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), interferon (IFN)-β, and IFN-γ at diagnosis. The other neonate had no fever or TNF-α production, but significant IL-6 or IFN responses during the treatment course, and died 19 days after birth. Among 16 reported cases of neonatal HSV-HLH including index cases, eight deceased neonates experienced significantly less fever at presentation (p = 0.028), lower platelet counts (p = 0.019), and lower ratios of soluble IL-2 receptor (sIL-2R) to ferritin levels (p = 0.044) than eight survivors. The 100-day overall survival rates were significantly higher in patients with fever (p = 0.004), > 100 × 10/L of platelet counts (p = 0.035) or > 20 of sIL-2R/ferritin ratio at diagnosis (p = 0.004). The first febrile and cytokine responses to HSV infection predict the early outcome of neonatal HSV-HLH.
噬血细胞性淋巴组织细胞增生症（HLH）发生于单纯疱疹病毒（HSV）播散性感染的新生儿。对于迅速进展的 HLH 的控制，相关报道较少。我们研究了两例 2 型 HSV 感染早期治疗后结局不同的指数病例的细胞因子谱和遗传基础。幸存者在诊断时发热，血清肿瘤坏死因子（TNF）-α、白细胞介素 6（IL-6）、干扰素（IFN）-β和 IFN-γ水平升高。另一个新生儿无发热或 TNF-α产生，但在治疗过程中有明显的 IL-6 或 IFN 反应，并在出生后 19 天死亡。在包括指数病例在内的 16 例新生儿 HSV-HLH 报道病例中，8 例死亡新生儿在就诊时发热（p=0.028）、血小板计数（p=0.019）和可溶性白细胞介素 2 受体（sIL-2R）与铁蛋白比值（p=0.044）均显著降低。发热（p=0.004）、血小板计数＞100×10/L（p=0.035）或 sIL-2R/铁蛋白比值＞20（p=0.004）的患者 100 天总生存率显著较高。
第一发热和细胞因子反应对新生儿 HSV-HLH 的早期预后有预测作用。
