KSHV, also called human herpesvirus-8, is the cause of a form of MCD called KSHV-MCD. KSHV-MCD is clinically similar to idiopathic MCD; in both, the clinical picture is characterized by fevers, weight loss, fatigue, edema, lymphadenopathy, splenomegaly, cytopenias, low albumin, and elevated C-reactive protein (CRP). The diagnosis of both is based on pathologic findings in lymph nodes, including the presence of plasmablasts. In idiopathic MCD, systemic manifestations are caused by overproduction of human interleukin-6 (hIL-6) and other cytokines by plasmablasts in affected lymphoid organs. KSHV encodes a mimic of hIL-6 called viral IL-6 (vIL-6). In KSHV-MCD, a subset of the lymph node plasmablasts are infected with KSHV, and a subset of these express vIL-6 and other lytic KSHV genes. We have studied 34 flares of KSHV-MCD and found that flares were often associated with an increase in hIL-6, vIL-6, or both; in 2 patients neither cytokine was elevated at the flare onset. Other elevated cytokines included IL-10, tumor necrosis factor alpha (TNF-[alpha]), and IL-1[beta]. Flares were also associated with an elevated viral load of KSHV. We also identified 6 patients with symptoms of KSHV-MCD, elevated KSHV viral load, and elevated vIL-6 but without pathologic findings of MCD; we have called this condition KSHV-associated inflammatory cytokine syndrome (KICS). KSHV-MCD is fatal if not treated. Based on the observation that zidovudine (AZT) and ganciclovir are activated to toxic moieties by KSHV lytic enzymes, we investigated a regimen of high-dose AZT and valganciclovir, a pro-drug of ganciclovir, in KSHV-MCD and showed that it had activity. Other information on the pathogenesis and treatment of these conditions will be presented.
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