Critically Severe Case of Neonatal Herpes with High Viral Load and Hemophagocytic Syndrome

Critically Severe Case of Neonatal Herpes with High Viral Load and Hemophagocytic Syndrome

HIROKI TAKEHARA,^1,2 KOJI HIROHATA,^1,2 HIROSHI MUTOH,¹ CHIHARU IRISA,¹ SATSUKI KAKIUCHI,¹ RIKI NISHIMURA,¹ AKIRA OKA¹ and NAOTO TAKAHASHI¹

¹Department of Pediatrics, The University of Tokyo Hospital, Tokyo, Japan
²Department of Neonatology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan

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℃) 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 × 10⁹ 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.

keywords —— acyclovir; continuous hemodiafiltration using a cytokine-absorbing hemofilter; cytokines; hemophagocytic lymphohistiocytosis; herpes simplex virus infection

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Tohoku J. Exp. Med., 2019, 247, 149-152

Correspondence: Hiroki Takehara, M.D., Department of Pediatrics, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Department of Neonatology, Tokyo Metropolitan Bokutoh Hospital, 4-23-15 Kotobashi, Sumida-ku, Tokyo 130-8575, Japan.

e-mail: h-takehara@umin.ac.jp