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

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.

• Authors: Lauren M Gerard, Katharine Xing, Ines Sherifi, John Granton, David Barth, Mohamed Abdelhaleem, Catherine Bergeron, Sheila Weitzman, Christine Cserti-Gazdewich
• Journal: International journal of hematology (Int J Hematol) Vol. 95 Issue 4 Pg. 445-50 (Apr 2012) ISSN: 1865-3774 [Electronic] Japan
• PMID: 22359105 (Publication Type: Case Reports, Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• Perforin
• Alemtuzumab

Topics

• Alemtuzumab
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Blastomyces (isolation & purification)
• Blastomycosis (complications, diagnosis)
• Epstein-Barr Virus Infections (complications, diagnosis)
• Herpesvirus 4, Human (isolation & purification)
• Humans
• Hypertension, Pulmonary (complications, microbiology, pathology)
• Lung (microbiology, pathology)
• Lymphohistiocytosis, Hemophagocytic (complications, drug therapy, genetics, virology)
• Male
• Middle Aged
• Mutation, Missense
• Perforin (genetics)