How I treat HIV-associated multicentric Castleman disease.

HIV-associated plasmablastic multicentric Castleman disease is an increasingly frequent diagnosis. Kaposi sarcoma herpesvirus is found in the monotypic polyclonal plasmablasts that characterize this disease. Unlike Kaposi sarcoma, the incidence does not correlate with CD4 cell count or use of highly active antiretroviral therapy. It is a relapsing and remitting illness, and diagnostic criteria are emerging that define disease activity based on the presence of a fever and raised C-reactive protein coupled with a list of clinical features. Treatment protocols increasingly stratify therapy according to performance status and organ involvement. I advocate rituximab monotherapy for good performance status patients without organ involvement and rituximab with chemotherapy for more aggressive disease. The success of antiherpesvirus agents in controlling active disease is limited, but valganciclovir may have a role as maintenance therapy in the future.

Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice.

Castleman's disease is a lymphoproliferative disorder thought to be related to deregulated production of IL-6. We have previously shown that mice lacking the trans-acting factor C/EBP beta, a transcriptional regulator of IL-6 and a mediator of IL-6 intracellular signaling, develop a pathology nearly identical to multicentric Castleman's disease, together with increasingly high levels of circulating IL-6. We describe here how the simultaneous inactivation of both IL-6 and C/EBP beta genes prevents the development of pathological traits of Castleman's disease observed in C/EBP beta-deficient mice. Histological and phenotypic analysis of lymph nodes and spleen of double mutant mice did not show either the lymphoadenopathy and splenomegaly or the abnormal expansion of myeloid, B and plasma cell compartments observed in C/EBP beta-/- mice, while B cell development, although delayed, was normal. Our data demonstrate that IL-6 is essential for the development of multicentric Castleman's disease in C/EBP beta-/- mice.