Recent advances in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease.
OBJECTIVE
The discovery of Kaposi sarcoma herpesvirus (KSHV) led to recognition of KSHV-associated multicentric Castleman disease (MCD) as a distinct lymphoproliferative disorder. The pathogenesis of KSHV-MCD is attributed to proliferation of KSHV-infected B cells, production of KSHV-encoded viral interleukin 6 by these cells, and dysregulation of human interleukin 6 and interleukin 10. This article reviews advances in the field of disease pathogenesis and targeted therapies.


RESULTS
Our understanding of the pathogenesis of KSHV-MCD has increased in recent years and improved therapies have been developed. Recent studies demonstrate that the anti-CD20 monoclonal antibody, rituximab, as well as virus-activated cytotoxic therapy using high-dose zidovudine and valganciclovir, can control symptoms and decrease adenopathy. With treatment, 1-year survival now exceeds 85%. Interestingly, even in the absence of pathologic findings of MCD, KSHV-infected patients may have inflammatory symptoms, excess cytokine production, and elevated KSHV viral load similar to KSHV-associated MCD. The term KSHV-associated inflammatory cytokine syndrome has been proposed to describe such patients.


CONCLUSIONS
Recent advances in targeted therapy have improved outcomes in KSHV-MCD, and decreased need for cytotoxic chemotherapy. Improved understanding of the pathogenesis of KSHV-MCD and KSHV-associated inflammatory cytokine syndrome is needed, and will likely lead to additional advances in therapy for these disorders.
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. uldrickts@mail.nih.gov
Thomas S
TS
Uldrick
Mark N
MN
Polizzotto
Robert
R
Yarchoan
D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D005871:Castleman Disease / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D000069283:Rituximab; D000077562:Valganciclovir; D015215:Zidovudine / Q000627:therapeutic use
D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D015215:Zidovudine; D000069283:Rituximab; D000077562:Valganciclovir; D015774:Ganciclovir