Takehara Hiroki, Hirohata Koji, Mutoh Hiroshi, Irisa Chiharu, Kakiuchi Satsuki, Nishimura Riki, Oka Akira, Takahashi Naoto
Department of Pediatrics, The University of Tokyo Hospital.
Department of Neonatology, Tokyo Metropolitan Bokutoh Hospital.
Tohoku J Exp Med. 2019 Mar;247(3):149-152. doi: 10.1620/tjem.247.149.
Neonatal disseminated herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity; yet, the pathophysiology remains unclear. Here, we report a male infant with disseminated HSV type 1 (HSV-1) infection, complicated by hemophagocytic lymphohistiocytosis (HLH) and multiple organ failure. The infant, born at 39 weeks of gestation by normal delivery, developed fever (38.5˚C) with the high serum C-reactive protein levels on the 1st day of life, and exhibited tachypnea on the 3rd day. On the 5th day of life, the patient received mechanical ventilation and was transferred to our neonatal ICU. Real-time PCR for HSV-1 DNA revealed an extremely high serum concentration (1.0 × 10 copies/µL), and he was diagnosed with HSV-1 infection. Acyclovir (ACV) and corticosteroid pulse therapies with methylprednisolone were started. Continuous hemodiafiltration (CHDF) using cytokine-absorbing hemofilters was also initiated because of renal failure. These therapies, however, failed to control the disease, and the patient died on the 41st day of life. The dose of ACV on CHDF might not be adequate, although we could not measure the serum ACV concentrations. After the patient's death, we measured his serum cytokine concentrations taken four times during the clinical course. Serum concentrations of interleukin (IL)-6, IL-10, IL-1β, and interferon (IFN)-γ were elevated at the time of admission and were remarkably decreased by 10 days after treatment. In particular, the concentrations of IL-1β and IFN-γ were lower than the measurable ranges. It is therefore important to measure serum cytokine concentrations in real time to prevent excessive immune suppression.
新生儿播散性单纯疱疹病毒（HSV）感染是一种严重疾病，死亡率和发病率都很高；然而，其病理生理学仍不清楚。在此，我们报告一名患有播散性1型HSV（HSV-1）感染的男婴，并发噬血细胞性淋巴组织细胞增生症（HLH）和多器官功能衰竭。该婴儿通过正常分娩于孕39周出生，出生第一天出现发热（38.5˚C）且血清C反应蛋白水平升高，第三天出现呼吸急促。出生第五天，患者接受机械通气并转入我们的新生儿重症监护病房。HSV-1 DNA的实时PCR检测显示血清浓度极高（1.0×10拷贝/µL），他被诊断为HSV-1感染。开始使用阿昔洛韦（ACV）和甲泼尼龙进行糖皮质激素冲击治疗。由于肾衰竭，还启动了使用细胞因子吸附血液滤过器的持续血液透析滤过（CHDF）。然而，这些治疗未能控制病情，患者于出生第41天死亡。尽管我们无法测量血清ACV浓度，但CHDF时ACV的剂量可能不足。患者死亡后，我们测量了其临床过程中四次采集的血清细胞因子浓度。入院时血清白细胞介素（IL）-6、IL-10、IL-1β和干扰素（IFN）-γ浓度升高，治疗10天后显著下降。特别是，IL-1β和IFN-γ的浓度低于可测量范围。因此，实时测量血清细胞因子浓度对于预防过度免疫抑制很重要。
