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

Abstract

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 9 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.

Case Report: Rapid Recognition and Immune Modulation of Secondary HLH Due to Disseminated HSV Infection

“…Neonates have a quantitative immune deficiency due to low numbers of cytotoxic lymphocytes (16) and increased regulatory T cells (17). The relationship between HSV infection and HLH has been increasingly recognized (1,(18)(19)(20); however, controversy remains about whether this presentation truly represents HLH or is an "HLH mimic." Upon presentation, the patient was already in fulminant hepatic failure, so the authors decided to treat with immune suppression in an effort to mitigate further organ damage.…”

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

“…Studies were excluded if they did not discuss nHLH ( n = 280); aggregated nHLH patient data with all ages ( n = 83); provided insufficient detail and/or data describing a case of nHLH ( n = 28); and for other reasons ( n = 8). Two‐hundred‐five cases of nHLH from 142 articles were included in our analysis 12–152 …”

Epidemiology and Outcomes of Neonatal Hemophagocytic Lymphohistiocytosis

“…In another report of neonatal HLH, 7 out of 9 neonates had infection-triggered HLH with either HSV or entero virus ( 9 ). In addition, Takehara et al also reported a case of a neonate with disseminated HSV-1 infection complicated by HLH and multi-organ failure which was ultimately fatal ( 10 ). There are case reports of adenovirus triggered HLH in two neonates who eventually developed acute respiratory distress syndrome and cardiovascular failure before succumbing to illness despite being on extracorporeal membrane oxygenation support ( 11 ).…”