International Journal of Hematology

, Volume 95, Issue 4, pp 445–450

Adult hemophagocytic lymphohistiocytosis with severe pulmonary hypertension and a novel perforin gene mutation

  • Lauren M. Gerard
  • Katharine Xing
  • Ines Sherifi
  • John Granton
  • David Barth
  • Mohamed Abdelhaleem
  • Catherine Bergeron
  • Sheila Weitzman
  • Christine Cserti-Gazdewich
Case Report

DOI: 10.1007/s12185-012-1029-6

Cite this article as:
Gerard, L.M., Xing, K., Sherifi, I. et al. Int J Hematol (2012) 95: 445. doi:10.1007/s12185-012-1029-6

Abstract

Adult hemophagocytic lymphohistiocytosis (HLH) is a rare and deadly hyperinflammatory syndrome presenting both diagnostic and therapeutic challenges. HLH may be primary, due to an underlying genetic abnormality, and/or secondary to infection, malignancy, or rheumatologic conditions. We describe a case of HLH-associated severe pulmonary hypertension paralleling Epstein–Barr virus (EBV) reactivation in a 52-year-old male in whom a novel perforin missense mutation was found (PRF1 1517C>T). Although intolerant of standard therapy (HLH-2004 protocol), a 6-week course of anti-CD52 (alemtuzumab) was associated with freedom-from-transfusion from weeks 4 to 13. However, 15 weeks after the onset of salvage therapy, he succumbed to polymicrobial sepsis despite treatment with prophylactic anti-infectives, with necropsy revealing disseminated blastomycosis and relapsed HLH. This case illustrates uncertainties in the relationships between pulmonary hypertension, a newly described PRF1 mutation, and possible pre-existing latent infectious risk factors (such as EBV or Blastomyces) in the pathogenesis and therapeutic perils of adult HLH.

Keywords

Hemophagocytic lymphohistiocytosis (HLH)HemophagocytosisAdultEpstein Barr Virus (EBV)EBV-HLHPulmonary hypertensionPerforinAlemtuzumabBlastomycosisBlastomyces dermatitidis

Copyright information

© The Japanese Society of Hematology 2012

Authors and Affiliations

  • Lauren M. Gerard
    • 1
  • Katharine Xing
    • 1
  • Ines Sherifi
    • 1
  • John Granton
    • 2
  • David Barth
    • 3
  • Mohamed Abdelhaleem
    • 4
  • Catherine Bergeron
    • 5
  • Sheila Weitzman
    • 6
  • Christine Cserti-Gazdewich
    • 3
  1. 1.Department of Internal MedicineUniversity of TorontoTorontoCanada
  2. 2.Division of Respirology, Faculty of Medicine, Mount Sinai and Women’s College HospitalUniversity Health Network, University of TorontoTorontoCanada
  3. 3.Laboratory Medicine Program, Division of Hematology, Department of Laboratory Hematology (Transfusion Medicine)Toronto General Hospital, University Health NetworkTorontoCanada
  4. 4.Department of Haematopathology (Molecular Haematopathology), Hospital for Sick ChildrenUniversity of TorontoTorontoCanada
  5. 5.Department of Laboratory Medicine and PathobiologyUniversity Health Network, University of TorontoTorontoCanada
  6. 6.Department of Hematology/OncologyHospital for Sick ChildrenTorontoCanada