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Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3643-3653
Human Herpesvirus 8 Infection in Patients With POEMS
Syndrome-Associated Multicentric Castleman's Disease
Laurent Bélec,
Ali Si Mohamed,
François-Jerôme Authier,
Marie-Charlotte Hallouin,
Aye Myat Soe,
Sylvie Cotigny,
Philippe Gaulard, and
Romain K. Gherardi
From Groupe d'Etude et de Recherche sur le Nerf Et le Muscle
(GERMEN, EA 2347); Faculté de Médecine de Créteil,
Université Paris XII-Val de Marne; Département de
Pathologie, Hôpital Henri Mondor, Créteil; and INSERM U430
and Laboratoire de Virologie, Hôpital Broussais, Paris, France.
The polyneuropathy, organomegaly, endocrinopathy, M protein, skin
changes (POEMS) syndrome is a rare multisystemic disorder associated
with osteosclerotic myeloma and multicentric Castleman's disease
(MCD). Human herpesvirus type 8 (HHV-8) DNA sequences have been
detected in lymph nodes of about 40% of human immunodeficiency virus
(HIV)-negative patients with MCD, and in bone marrow stromal cells of
patients with multiple myeloma. Considering these data, we investigated
the presence of HHV-8 in 18 patients with POEMS syndrome (9 with MCD),
by nested polymerase chain reaction (N-PCR) to detect DNA sequenses in
various cells and tissues obtained by biopsy or at autopsy (13 patients, of whom 7 had MCD), and by an immunofluorescence assay to
detect anti-HHV-8 IgG antibodies in blood (18 patients, of whom 9 had
MCD). Detection of HHV-8 DNA was performed using three different N-PCR,
targeting nonoverlapping regions in open reading frame (ORF) 25 and
ORF26. Seven of 13 (54%) POEMS patients had HHV-8 DNA sequences in
their tissues, as assessed by all three N-PCR, and 9 of 18 (50%) had
circulating anti-HHV-8 antibodies. HHV-8 was mainly detected in the
subset of POEMS patients with MCD (6 of 7 [85%] for DNA sequences; 7 of 9 [78%] for antibodies). The percentage of positive N-PCR was higher in lymph nodes than in bone marrow samples (P < .02).
Sequencing of amplicons showed a homogeneous restricted variability in
the ORF26 region, characteristic of the minority subgroup B defined by
Zong, and responsible for isoleucine and glycine substitutions at amino
acid positions 134 and 167. These findings strongly suggest an
association of HHV-8 infection with POEMS syndrome-associated MCD.
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