title: 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.affiliation: Department of Internal Medicine, University of Toronto, Toronto, Canada. lauren.gerard@utoronto.ca
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Gerard
authors.forename: Katharine
authors.initials: K
authors.lastname: Xing
authors.forename: Ines
authors.initials: I
authors.lastname: Sherifi
authors.forename: John
authors.initials: J
authors.lastname: Granton
authors.forename: David
authors.initials: D
authors.lastname: Barth
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdelhaleem
authors.forename: Catherine
authors.initials: C
authors.lastname: Bergeron
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.forename: Christine
authors.initials: C
authors.lastname: Cserti-Gazdewich
mesh_terms: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001758:Blastomyces / Q000302:isolation & purification; D001759:Blastomycosis / Q000150:complications / Q000175:diagnosis; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000175:diagnosis; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D054353:Perforin / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D054353:Perforin; D000074323:Alemtuzumab