title: Human herpesvirus 8-related Castleman disease in the absence of HIV infection.
abstract: BACKGROUND
  Castleman disease (CD) in the context of human immunodeficiency virus (HIV) infection is well described. It is almost always multicentric (MCD) and linked to human herpesvirus 8 (HHV-8). There are limited published data surrounding HHV-8-related CD among HIV-negative patients.
  
  
  METHODS
  From January 1995 through June 2012, we identified in a single center 18 HIV-seronegative patients with HHV-8-related CD. We report on their clinical, pathological, and laboratory features.
  
  
  RESULTS
  All cases were multicentric. Patients were aged 42-83 years and were referred with a relapsing remitting syndrome of fever (94%), constitutional symptoms (100%), peripheral lymphadenopathy (100%), splenomegaly (72%), hepatomegaly (50%), and edema (28%). Kaposi sarcoma was observed in 9 cases. Anemia and serum markers of inflammation were present in all cases. Polymerase chain reaction for HHV-8 DNA was positive on blood samples in all cases, whereas only 12 of 16 patients tested had positive HHV-8 serology at diagnosis. All cases showed the classic histological features of MCD, and LANA-1 immunostaining identified HHV-8-infected plasmablasts in 16 of 16 tested cases. Reactive hemophagocytic syndrome (44%), autoimmune hemolytic anemia (33%), and lymphoma (22%) were the commonest associated complications. Remission was obtained with etoposide in 13 of 15 cases. Rituximab allowed prolonged remission off therapy in 10 cases. Death occurred in 3 patients not treated with rituximab. These features were similar to those described in HIV-positive HHV-8-related MCD. Comparison between these 18 cases and 12 HIV-negative HHV-8-unrelated MCD cases showed marked discrepancies.
  
  
  CONCLUSIONS
  HHV-8-associated MCD may be considered as a single clinicopathological entity regardless of HIV status.
authors.affiliation: Department of Clinical Immunology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris and Univ Paris Diderot.
authors.forename: A
authors.initials: A
authors.lastname: Dossier
authors.forename: V
authors.initials: V
authors.lastname: Meignin
authors.forename: C
authors.initials: C
authors.lastname: Fieschi
authors.forename: D
authors.initials: D
authors.lastname: Boutboul
authors.forename: E
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: L
authors.initials: L
authors.lastname: Galicier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia; D005871:Castleman Disease / Q000209:etiology* / Q000473:pathology* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006678:HIV; D006566:Herpesviridae Infections / Q000150:complications* / Q000473:pathology* / Q000821:virology; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D004279:DNA, Viral