Clinical management of human herpesvirus-8-related illnesses in solid organ transplant recipients

In solid organ transplant recipients (SOTRs), the oncogenic virus human herpesvirus-8 (HHV-8) also named Kaposi sarcoma herpesvirus (KSHV) causes four clinical diseases: Kaposi Sarcoma, Primary Effusion Lymphoma, Multicentric Castleman Disease (MCD), and KSHV inflammatory cytokine syndrome (KICS). This review outlines these clinical scenarios and discusses their management. Although HHV8-related disease in SOTR was first described more than three decades ago, there is a lack of data on treatment so much of the guidance is based on evidence in other immunodeficient patients, particularly people living with HIV. Whilst reduction of immunosuppression and switch from calcineurin inhibitors to mTOR inhibitors may be sufficient in early-stage post-transplant KS, systemic chemotherapy is necessary for advanced-stage KS and in KSHV-related lymphomas. For MCD and KICS, which usually follow primary HHV-8 infection, rituximab-based immunochemotherapy regimens are the cornerstone of treatment for these potentially lethal diseases. Although HHV-8 infection in SOTR is well recognized, it remains under-reported and greater awareness of the different clinical presentations of HHV-8 in this context is fundamental to improve outcomes.