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Neonatal hemophagocytic lymphohistiocytosis associated with a vertical transmission of coxsackievirus B1

  • Case Report
  • Published:
Journal of Infection and Chemotherapy

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy with the background of hypercytokinemia. Early diagnosis and etoposide therapy are not established for affected newborns. An afebrile infant suffered from apnea 4 days after birth, showing leukocytosis, thrombocytopenia, coagulopathy, and cerebrospinal fluid pleocytosis. Serum levels of ferritin and sIL-2R were high. Bone marrow studies revealed activated/hemophagocytosing macrophages. Coxsackievirus B1 (CB1) was isolated from the throat and stool. Serum anti-CB1 antibody titers were elevated in the patient (4 → 16; 6 → 43 days after birth) and mother (128; 10 days after delivery). Normal expressions of perforin and CD107a precluded inherited HLH. The vertically transmitted CB1-HLH was successfully treated without administration of corticosteroid, cyclosporine, or etoposide. Serum cytokine levels showed dominant expression of monokines (IL-1β/6/8, and TNF-α) but not IFN-γ, which is the central player of inherited HLH. The cytokine profile might represent a unique pathophysiology of enterovirus-driven neonatal HLH.

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References

  1. Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Annu Rev Med. 2012;3:233–46.

    Article  Google Scholar 

  2. Risma K, Jordan MB. Hemophagocytic lymphohistiocytosis: updates and evolving concepts. Curr Opin Pediatr. 2012;24:9–15.

    Article  PubMed  CAS  Google Scholar 

  3. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–31.

    Article  PubMed  Google Scholar 

  4. Barre V, Marret S, Mendel I, Lesesve JF, Fessard CI. Enterovirus-associated haemophagocytic syndrome in a neonate. Acta Paediatr. 1998;87:469–71.

    Article  PubMed  CAS  Google Scholar 

  5. Lindamood KE, Fleck P, Narla A, Vergilio JA, Degar BA, Baldwin M, et al. Neonatal enteroviral sepsis/meningoencephalitis and hemophagocytic lymphohistiocytosis: diagnostic challenges. Am J Perinatol. 2011;28:337–46.

    Article  PubMed  Google Scholar 

  6. Suzuki N, Morimoto A, Ohga S, Kudo K, Ishida Y, Ishii E. Characteristics of hemophagocytic lymphohistiocytosis in neonates: a nationwide survey in Japan. J Pediatr. 2009;155:235–8.

    Article  PubMed  Google Scholar 

  7. Khetsuriani N, Lamonte-Fowlkes A, Oberst S, Pallansch MA. Enterovirus surveillance–United States, 1970–2005. MMWR Surveill Summ. 2006;55:1–20.

    PubMed  Google Scholar 

  8. Schwab I, Nimmerjahn F. Intravenous immunoglobulin therapy: how does IgG modulate the immune system? Nat Rev. 2013;13:176–89.

    Article  CAS  Google Scholar 

  9. Xu XJ, Tang YM, Song H, Yang SL, Xu WQ, Zhao N, et al. Diagnostic accuracy of a specific cytokine pattern in hemophagocytic lymphohistiocytosis in children. J Pediatr. 2012;160:984–90.

    Article  PubMed  CAS  Google Scholar 

  10. Yamada K, Yamamoto Y, Uchiyama A, Ito R, Aoki Y, Uchida Y, et al. Successful treatment of neonatal herpes simplex-type 1 infection complicated by hemophagocytic lymphohistiocytosis and acute liver failure. Tohoku J Exp Med. 2008;214:1–5.

    Article  PubMed  CAS  Google Scholar 

  11. Behrens EM, Canna SW, Slade K, Rao S, Kreiger PA, Paessler M, et al. Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J Clin Invest. 2011;121:2264–77.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Takahiro Yasumi (Department of Pediatrics, Kyoto University Hospital, Kyoto, Japan) and Prof. Eiichi Ishii (Department of Pediatrics, Ehime University Hospital, Toon, Japan) for their diagnostic support, and we appreciate the assistance of Dr. Brain Quinn for editing the English usage. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by a grant from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan

    Mitsuharu Fukazawa, Takayuki Hoshina, Etsuro Nanishi, Hisanori Nishio, Takehiko Doi, Shouichi Ohga & Toshiro Hara

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  1. Mitsuharu Fukazawa
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  2. Takayuki Hoshina
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  3. Etsuro Nanishi
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  4. Hisanori Nishio
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  5. Takehiko Doi
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  6. Shouichi Ohga
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  7. Toshiro Hara
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Correspondence to Takayuki Hoshina.

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Fukazawa, M., Hoshina, T., Nanishi, E. et al. Neonatal hemophagocytic lymphohistiocytosis associated with a vertical transmission of coxsackievirus B1. J Infect Chemother 19, 1210–1213 (2013). https://doi.org/10.1007/s10156-013-0629-2

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  • DOI: https://doi.org/10.1007/s10156-013-0629-2

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