The Bottom Line: The clinical manifestations of KICS are protean, and none are specific to the syndrome. Rather, they likely reflect common endpoints of proinflammatory cytokine deregulation in the setting of KSHV lytic replication and pathologic expression of KSHV encoded genes such as vIL-6. These symptoms may also be observed in other inflammatory states, and at times can be confused clinically with sepsis. KICS is therefore a diagnosis of exclusion, requiring pathologic exclusion of MCD; careful evaluation to exclude alternate explanations for the clinical manifestations, such as serious intercurrent infection; demonstration of systemic inflammation; and demonstration of KSHV viral activity.
Reference: Polizzotto MN, Uldrick TS, Duosho H, Yarchoan R. Clinical manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric castleman disease (KSHV-MCD) and the KSHV inflammatory cytokine syndrome. Frontiers in Microbiology. 2012; 3:73.
Summary: Its clinical manifestations resemble those of KSHV–multicentric Castleman disease (KSHV-MCD) but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV–MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV–MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some patients with severe KS or primary effusion lymphoma.
Like MCD that is unrelated to KSHV, the clinical presentation of KSHV–MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein.
Additional research is needed to better define the clinical spectrum of KICS and its relationship to KSHV–MCD. Research is also needed to better understand the pathogenesis and epidemiology of both KICS and KSHV–MCD, as well as the optimal therapy for both of these disorders.