European Journal of Pediatrics

, Volume 163, Issue 9, pp 536–539

Identical twin brothers concordant for Langerhans’ cell histiocytosis and discordant for Epstein-Barr virus-associated haemophagocytic syndrome

  • Chun-Jung Chen
  • Tsyr-Yuh Ho
  • Jang-Jih Lu
  • Lai-Fa Sheu
  • Shih-Yi Lee
  • Chiung-Hsi Tien
  • Shin-Nan Cheng
Original Paper


We report on identical twin brothers, one of whom presented at 14 months of age with fever and clinical, laboratory and histological evidence of Epstein-Barr virus-associated haemophagocytic syndrome (EBV-AHS) and 4 months later with typical signs and symptoms of Langerhans’ cell histiocytosis (LCH). The other twin, without previous symptoms, also displayed at that time LCH associated with signs of recent EBV infection, but without symptoms of haemophagocytic syndrome. No mutation in the SH2D1A gene, as observed in X-linked lymphoproliferative disease, or in the perforin gene as observed in some cases of hereditary haemophagocytic syndrome, was found. Conclusion:the occurrence of haemophagocytic syndrome and Langerhans’ cell histiocytosis, although genetically based, can be triggered by environmental agents and viruses, in particular Epstein-Barr virus.


Epstein-Barr virus Haemophagocytic syndrome Langerhans’ cell histiocytosis Monozygotic twins 



chronic active Epstein-Barr virus infection


Epstein-Barr virus


EBV-associated haemophagocytic syndrome


haemophagocytic syndrome


hereditary haemophagocytic syndrome


X-linked lymphoproliferative disease


  1. 1.
    Aricò M, Nichols K, Whitlock JA, Arceci R, Haupt R, Mittler U, Kuhne T, Lombardi A, Ishii E, Egeler RM, Danesino C (1999) Familial clustering of Langerhans cell histiocytosis. Br J Haematol 107: 883–888CrossRefPubMedGoogle Scholar
  2. 2.
    Aricò M, Haupt R, Russotto VS, Bossi G, Scappaticci S, Danesino C (2001) Langerhans cell histiocytosis in two generations: a new family and review of the literature. Med Pediatr Oncol 36: 314–316CrossRefPubMedGoogle Scholar
  3. 3.
    Aricò M, Imashuku S, Clementi R, Hibi S, Teramura T, Danesino C, Haber DA, Nichols KE (2001) Hemophagocytic lymphohistiocytosis due to germline mutations in SH2D1A, the X-linked lymphoproliferative disease gene. Blood 9: 1131–1133CrossRefGoogle Scholar
  4. 4.
    Bernstrand C, Carstensen H, Jakobsen B, Svejgaard A, Henter JI, Olerup O (2003) Immunogenetic heterogeneity in single-system and multisystem Langerhans cell histiocytosis. Pediatr Res 54: 30–36CrossRefPubMedGoogle Scholar
  5. 5.
    Chu T, Jaffe R (1994) The normal Langerhans cell and the LCH cell. Br J Cancer 70: S4–S10Google Scholar
  6. 6.
    Egeler RM (1995) Clonality in Langerhan’s cell histiocytosis. BMJ 310: 804–805PubMedGoogle Scholar
  7. 7.
    Favara BE, Jaffe R, Egeler RM (2002) Macrophage activation and hemophagocytic syndrome in Langerhans cell histiocytosis: report of 30 cases. Pediatr Dev Pathol 5: 130–140PubMedGoogle Scholar
  8. 8.
    Goldberg J, Nezelof C (1986) Lymphohistiocytosis: a multi-factorial syndrome of macrophagic activation. Clinico-pathological study of 38 cases. Hematol Oncol 4: 275–289PubMedGoogle Scholar
  9. 9.
    Hesseling PB, Wessels G, Egeler RM, Rossouw DJ (1995) Simultaneous occurrence of viral-associated hemophagocytic syndrome and Langerhans cell histiocytosis: a case report. Pediatr Hematol Oncol 12: 135–141PubMedGoogle Scholar
  10. 10.
    Imashuku S, Hyakuna N, Funabiki T, Ikuta K, Sako M, Iwai A, Fukushima T, Kataoka S, Yabe M, Muramatsu K, Kohdera U, Nakadate H, Kitazawa K, Toyoda Y, Ishii E (2002) Low natural killer activity and central nervous system disease as a high-risk prognostic indicator in young patients with hemophagocytic lymphohistiocytosis. Cancer 94: 3023–3031CrossRefPubMedGoogle Scholar
  11. 11.
    Kasahara Y, Yachie A (2002) Cell type specific infection of Epstein-Barr virus (EBV) in EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection. Crit Rev Oncol Hematol 44: 283–294CrossRefPubMedGoogle Scholar
  12. 12.
    Katz AM, Rosenthal D, Jakubovic HR, Pai RK, Quinonez GE, Sauder DN (1991) Langerhans cell histiocytosis in monozygotic twins. J Am Acad Dermatol 24: 32–37PubMedGoogle Scholar
  13. 13.
    Klein A, Corazza F, Demulder A, Van Beers D, Ferster A (1999) Recurrent viral associated hemophagocytic syndrome in a child with Langerhans cell histiocytosis. J Pediatr Hematol Oncol 21: 554–556CrossRefPubMedGoogle Scholar
  14. 14.
    Ma X, Okamura A, Yosioka M, Ishiguro N, Kikuta H, Kobayashi K (2001) No mutations of SAP/SH2D1A/DSHP and perforin genes in patients with Epstein-Barr virus-associated hemophagocytic syndrome in Japan. J Med Virol 65: 358–361CrossRefPubMedGoogle Scholar
  15. 15.
    Neel JV, Major EO, Awa AA, Glover T, Burgess A, Traub R, Curfman B, Satoh C (1996) Hypothesis: “rogue cell”-type chromosomal damage in lymphocytes is associated with infection with the JC human polyoma virus and has implications for oncopenesis. Proc Natl Acad Sci USA 93: 2690–2695CrossRefPubMedGoogle Scholar
  16. 16.
    Scappaticci S, Danesino C, Rossi E, Klersy C, Fiori GM, Clementi R, Russotto VS, Bossi G, Aricò M (2000) Cytogenetic abnormalities in PHA-stimulated lymphocytes from patients with Langerhans cell histocytosis. AIEOP-Istiocitosi Group. Br J Haematol 111: 258–262CrossRefPubMedGoogle Scholar
  17. 17.
    Schmitt S, Wichmann W, Martin E, Zachmann M, Schoenle EJ (1993) Pituitary stalk thickening with diabetes insipidus preceding typical manifestations of Langerhans cell histiocytosis in children. Eur J Pediatr 152: 399–401PubMedGoogle Scholar
  18. 18.
    Stepp SE, Dufourcq-Lagelouse R, Le Deist F, Bhawan S, Certain S, Mathew PA, Henter JI, Bennett M, Fischer A, de Saint Basile G, Kumar V (1999) Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science 286: 1957–1959CrossRefPubMedGoogle Scholar
  19. 19.
    Willman CL, McClain KL (1998) A update on clonality, cytokines, and viral etiology in Langerhans cell histiocytosis. Hematol Oncol Clin North Am 12: 407–416PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Chun-Jung Chen
    • 1
  • Tsyr-Yuh Ho
    • 1
  • Jang-Jih Lu
    • 2
  • Lai-Fa Sheu
    • 3
  • Shih-Yi Lee
    • 2
  • Chiung-Hsi Tien
    • 1
  • Shin-Nan Cheng
    • 1
  1. 1.Department of Paediatrics, Tri-Service General HospitalNational Defence Medical CentreNeihu, Taipei Taiwan
  2. 2.Division of Clinical PathologyTri-Service General Hospital, National Defence Medical CentreTaipei Taiwan
  3. 3.Department of PathologyTri-Service General Hospital, National Defence Medical CentreTaipei Taiwan

Personalised recommendations