Characteristics and outcomes of Kaposi sarcoma herpesvirus (KSHV)-associated inflammatory cytokine syndrome (KICS)

KSHV inflammatory cytokine syndrome (KICS) is characterized by KSHV infection and severe inflammatory symptoms and signs (elevated cytokines, C-reactive protein, and KSHV viremia), without evidence of other causes. The primary objective was to evaluate KICS natural history after exclusion of other inflammatory disorders, including multicentric Castleman disease (MCD) and, in a revised working definition, primary effusion lymphoma (PEL). Participants with KICS were treated for concurrent Kaposi sarcoma (KS) and/or received KICS-directed treatment with rational therapies used in other KSHV-associated disorders (KAD), such as rituximab, tocilizumab or high-dose valganciclovir/azidothymidine. KICS response was evaluated using clinical benefit response criteria (KICS-CBR). Baseline inflammatory cytokines were compared between those with KICS and participants with other KAD: PEL, MCD with KS, or KS alone. Seventy-three participants were enrolled from 2011 to 2022. Following exclusion of other inflammatory processes, 35 (34 with HIV) had KICS, and all but 1 had concurrent stage T1 KS. Among patients with KICS, 11 (43%) received rituximab [with liposomal doxorubicin (8) or paclitaxel (3) for concurrent KS] and 55% (95% confidence interval (CI): 23-83%) had a response per KICS-CBR. Interleukin (IL)-10, IL-6 and IL-1b levels were higher among those with KICS as compared to KS alone. The median overall survival among participants with KICS was 5.7 years (95% CI: 5.7 years - not reached). KICS is a diagnosis of exclusion from PEL and MCD. Nearly all patients with KICS have advanced KS and it is associated with significant morbidity and mortality. Rituximab may benefit a subset of participants with KICS. NCT01419561