Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis

Motoshi Sonoda, Masataka Ishimura, Katsuhide Eguchi, Akira Shiraishi, Shunsuke Kanno, Noriyuki Kaku, Hirosuke Inoue, Yoshitomo Motomura, Masayuki Ochiai, Yasunari Sakai, Manabu Nakayama, Osamu Ohara, Shouichi Ohga

Research output: Contribution to journalArticle

Abstract

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 × 109/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.

Original languageEnglish
JournalInternational journal of hematology
DOIs
Publication statusAccepted/In press - Jan 1 2019

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Hemophagocytic Lymphohistiocytosis
Simplexvirus
Fever
Survival
Interferons
Interleukin-2 Receptors
Newborn Infant
Virus Diseases
Ferritins
Platelet Count
Survivors
Interleukin-6
Tumor Necrosis Factor-alpha
Cytokines
Herpes Simplex
Survival Rate
Parturition
Therapeutics
Infection
Serum

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

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title = "Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis",
abstract = "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 × 109/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.",
author = "Motoshi Sonoda and Masataka Ishimura and Katsuhide Eguchi and Akira Shiraishi and Shunsuke Kanno and Noriyuki Kaku and Hirosuke Inoue and Yoshitomo Motomura and Masayuki Ochiai and Yasunari Sakai and Manabu Nakayama and Osamu Ohara and Shouichi Ohga",
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TY - JOUR

T1 - Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis

AU - Sonoda, Motoshi

AU - Ishimura, Masataka

AU - Eguchi, Katsuhide

AU - Shiraishi, Akira

AU - Kanno, Shunsuke

AU - Kaku, Noriyuki

AU - Inoue, Hirosuke

AU - Motomura, Yoshitomo

AU - Ochiai, Masayuki

AU - Sakai, Yasunari

AU - Nakayama, Manabu

AU - Ohara, Osamu

AU - Ohga, Shouichi

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 × 109/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.

AB - 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 × 109/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.

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