Human Herpes Virus-6–Associated Encephalitis/Myelitis Mimicking Calcineurin Inhibitor–Induced Pain Syndrome in Allogeneic Stem Cell Transplantation Recipients

Goichi Yoshimoto, Yasuo Mori, Koji Kato, Takahiro Shima, Kohta Miyawaki, Yoshikane Kikushige, Kenjiro Kamezaki, Akihiko Numata, Takahiro Maeda, Katsuto Takenaka, Hiromi Iwasaki, Takanori Teshima, Koichi Akashi, Toshihiro Miyamoto

Research output: Contribution to journalArticle

Abstract

Human herpes virus-6 (HHV6)-associated myelitis and calcineurin inhibitor–induced pain syndrome (CIPS) are serious complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because these 2 complications cause similar sensory nerve–related symptoms, such as paresthesia, pruritus, and severe pain occurring around the engraftment, it can be difficult to differentially diagnose the 2 conditions. We retrospectively analyzed 435 recipients to distinguish clinical symptoms of these 2 complications. Twenty-four patients (5.5%) developed HHV6-associated encephalitis/myelitis; of these, 11 (2.5%) presented only with myelitis-related symptoms (HHV6-associated myelitis), which was confirmed by the detection of HHV6 DNA, and 8 (1.8%) had CIPS, with undetected HHV6 DNA. All patients with HHV6-associated myelitis or CIPS exhibited similar sensory nerve–related symptoms. Diagnostic images did not provide definite evidence specific for each disease. Symptoms of all patients with CIPS improved after switching to another immunosuppressant. Overall survival rate at 2 years for patients with HHV6-associated encephalitis/myelitis was significantly lower than that of CIPS (13.1% versus 29.2%; P =.049) or that of patients without HHV6-associated encephalitis/myelitis or CIPS (42.4%; P =.036), whereas there was no significant difference among the latter 2 groups (P =.889). The development of HHV6-associated encephalitis/myelitis but not CIPS was significantly associated with poor prognosis. Thus, transplant physicians should be aware that sensory nerve–related symptoms indicate early manifestations that might be correlated with reactivation of HHV6 or CIPS. Therefore, identification of HHV6 DNA is crucial for making a differential diagnosis and immediately starting appropriate treatments for each complication.

Original languageEnglish
Pages (from-to)2540-2548
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number12
DOIs
Publication statusPublished - Dec 1 2018

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Encephalitis Viruses
Myelitis
Calcineurin
Stem Cell Transplantation
Pain
Viruses
Encephalitis
DNA Viruses
Forensic Anthropology
Paresthesia
Hematopoietic Stem Cell Transplantation
Human Development
Pruritus
Immunosuppressive Agents
Differential Diagnosis
Survival Rate

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

@article{a642d66fb32c46a6b8a9ccf92e7c6dfb,
title = "Human Herpes Virus-6–Associated Encephalitis/Myelitis Mimicking Calcineurin Inhibitor–Induced Pain Syndrome in Allogeneic Stem Cell Transplantation Recipients",
abstract = "Human herpes virus-6 (HHV6)-associated myelitis and calcineurin inhibitor–induced pain syndrome (CIPS) are serious complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because these 2 complications cause similar sensory nerve–related symptoms, such as paresthesia, pruritus, and severe pain occurring around the engraftment, it can be difficult to differentially diagnose the 2 conditions. We retrospectively analyzed 435 recipients to distinguish clinical symptoms of these 2 complications. Twenty-four patients (5.5{\%}) developed HHV6-associated encephalitis/myelitis; of these, 11 (2.5{\%}) presented only with myelitis-related symptoms (HHV6-associated myelitis), which was confirmed by the detection of HHV6 DNA, and 8 (1.8{\%}) had CIPS, with undetected HHV6 DNA. All patients with HHV6-associated myelitis or CIPS exhibited similar sensory nerve–related symptoms. Diagnostic images did not provide definite evidence specific for each disease. Symptoms of all patients with CIPS improved after switching to another immunosuppressant. Overall survival rate at 2 years for patients with HHV6-associated encephalitis/myelitis was significantly lower than that of CIPS (13.1{\%} versus 29.2{\%}; P =.049) or that of patients without HHV6-associated encephalitis/myelitis or CIPS (42.4{\%}; P =.036), whereas there was no significant difference among the latter 2 groups (P =.889). The development of HHV6-associated encephalitis/myelitis but not CIPS was significantly associated with poor prognosis. Thus, transplant physicians should be aware that sensory nerve–related symptoms indicate early manifestations that might be correlated with reactivation of HHV6 or CIPS. Therefore, identification of HHV6 DNA is crucial for making a differential diagnosis and immediately starting appropriate treatments for each complication.",
author = "Goichi Yoshimoto and Yasuo Mori and Koji Kato and Takahiro Shima and Kohta Miyawaki and Yoshikane Kikushige and Kenjiro Kamezaki and Akihiko Numata and Takahiro Maeda and Katsuto Takenaka and Hiromi Iwasaki and Takanori Teshima and Koichi Akashi and Toshihiro Miyamoto",
year = "2018",
month = "12",
day = "1",
doi = "10.1016/j.bbmt.2018.07.017",
language = "English",
volume = "24",
pages = "2540--2548",
journal = "Biology of Blood and Marrow Transplantation",
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TY - JOUR

T1 - Human Herpes Virus-6–Associated Encephalitis/Myelitis Mimicking Calcineurin Inhibitor–Induced Pain Syndrome in Allogeneic Stem Cell Transplantation Recipients

AU - Yoshimoto, Goichi

AU - Mori, Yasuo

AU - Kato, Koji

AU - Shima, Takahiro

AU - Miyawaki, Kohta

AU - Kikushige, Yoshikane

AU - Kamezaki, Kenjiro

AU - Numata, Akihiko

AU - Maeda, Takahiro

AU - Takenaka, Katsuto

AU - Iwasaki, Hiromi

AU - Teshima, Takanori

AU - Akashi, Koichi

AU - Miyamoto, Toshihiro

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Human herpes virus-6 (HHV6)-associated myelitis and calcineurin inhibitor–induced pain syndrome (CIPS) are serious complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because these 2 complications cause similar sensory nerve–related symptoms, such as paresthesia, pruritus, and severe pain occurring around the engraftment, it can be difficult to differentially diagnose the 2 conditions. We retrospectively analyzed 435 recipients to distinguish clinical symptoms of these 2 complications. Twenty-four patients (5.5%) developed HHV6-associated encephalitis/myelitis; of these, 11 (2.5%) presented only with myelitis-related symptoms (HHV6-associated myelitis), which was confirmed by the detection of HHV6 DNA, and 8 (1.8%) had CIPS, with undetected HHV6 DNA. All patients with HHV6-associated myelitis or CIPS exhibited similar sensory nerve–related symptoms. Diagnostic images did not provide definite evidence specific for each disease. Symptoms of all patients with CIPS improved after switching to another immunosuppressant. Overall survival rate at 2 years for patients with HHV6-associated encephalitis/myelitis was significantly lower than that of CIPS (13.1% versus 29.2%; P =.049) or that of patients without HHV6-associated encephalitis/myelitis or CIPS (42.4%; P =.036), whereas there was no significant difference among the latter 2 groups (P =.889). The development of HHV6-associated encephalitis/myelitis but not CIPS was significantly associated with poor prognosis. Thus, transplant physicians should be aware that sensory nerve–related symptoms indicate early manifestations that might be correlated with reactivation of HHV6 or CIPS. Therefore, identification of HHV6 DNA is crucial for making a differential diagnosis and immediately starting appropriate treatments for each complication.

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