European Journal of Pediatrics

, Volume 164, Issue 5, pp 315–319 | Cite as

Occurrence of haemophagocytic lymphohistiocytosis at less than 1 year of age: analysis of 96 patients

  • Shinsaku ImashukuEmail author
  • Ikuyo Ueda
  • Tomoko Teramura
  • Kanako Mori
  • Akira Morimoto
  • Masahiro Sako
  • Eiichi Ishii
Original Paper


We analysed data of 96 infants (under 1 year of age) with haemophagocytic lymphohistiocytosis (HLH) from the registry of an HLH study conducted during 1986–2002 in Japan. The cases were classified into five groups. The diagnosis of familial HLH (FHL) as group 1 (n =27) was made with positive family history and/or recent molecular test for perforin and Munc13–4 mutations. Neonatal enterovirus- or herpes simplex virus-associated HLH as group 2a (n =7), Epstein-Barr virus–associated HLH (n =12) as group 2b, adenovirus- or cytomegalovirus-associated HLH as group 3 (n =9) were mostly diagnosed by viral isolation or by the detection of viral genome. Juvenile rheumatoid arthritis-associated macrophage activation syndrome was classified as group 4 (n =4) and the remaining without known triggers as group 5 (n =37). The peak onset age was 1–2 months for group 1, 1–2 weeks for group 2a, 12 months for group 2b, none for group 3, 9 months for group 4 and 2 months for group 5. Future novel diagnostic measures are required to define the precise nature of HLH in group 5. Conclusion:These data may provide useful information for neonatologists/ paediatricians in the differential diagnosis of haemophagocytic lymphohistiocytosis in early infancy.


Enterovirus Familial haemophagocytic lymphohistiocytosis Haemophagocytic lymphohistiocytosis Herpes simplex virus Onset age 







Epstein-Barr virus




familial haemophagocytic lymphohistiocytosis


haemophagocytic lymphohistiocytosis


herpes simplex virus


juvenile rheumatoid arthritis-associated macrophage activation syndrome


natural killer


stem cell transplantation


X-linked lymphoproliferative disease



The authors thank the many physicians who referred their patients to the HLH registration centre and who registered their patients in the HLH-94 international protocol study. The excellent secretarial assistance of Yasuko Hashimoto is acknowledged.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Shinsaku Imashuku
    • 1
    Email author
  • Ikuyo Ueda
    • 2
  • Tomoko Teramura
    • 1
  • Kanako Mori
    • 2
  • Akira Morimoto
    • 2
  • Masahiro Sako
    • 3
  • Eiichi Ishii
    • 4
  1. 1.Division of PaediatricsTakasago-Seibu HospitalTakasago City, Hyogo Prefecture Japan
  2. 2.Department of PaediatricsKyoto Prefectural University of MedicineKyoto Japan
  3. 3.Division of PaediatricsOsaka General HospitalOsaka Japan
  4. 4.Department of PaediatricsSaga UniversitySaga Japan

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