De Novo Human Herpesvirus 8 Tumors Induced by Rituximab in Autoimmune or Inflammatory Systemic Diseases

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, is involved in KS and other tumors, including multicentric Castleman's disease and primary effusion lymphoma. Rituximab (RTX) is currently used for the treatment of several autoimmune or inflammatory diseases and humoral organ transplant rejection. De novo HHV-8 tumors induced by RTX used for these indications have not been reported previously. This study was undertaken to evaluate de novo HHV-8 tumors induced by RTX.

In this retrospective study, we investigated the clinical, virologic, and pathologic features of 5 HIV-negative male patients with HHV-8 tumors induced by RTX therapy.

Patients were all immunocompromised by previous treatments, which consisted of steroids and/or immunosuppressive agents, and received RTX for insufficient response, disease progression, or transplant rejection. They developed HHV-8 tumors a median of 4 months after beginning treatment with RTX (range 3-13 months). Four patients had at least 1 risk factor for HHV-8, including a high Fitzpatrick skin phototype (of >3) (n = 3) and homosexuality (n = 1). Four patients developed KS (all 4 had skin lesions and 2 had visceral involvement), and 1 patient developed a solid primary effusion lymphoma. RTX was discontinued in all patients, and immunosuppressants were reduced when feasible. After a median follow-up of 20 months, 2 patients died. Remission of KS was complete in 1 patient and partial in 1 patient, and 1 patient had progression.

Our findings indicate that patients who have a high skin phototype and are at risk of HHV-8 should be carefully screened for HHV-8 before RTX therapy. The safety of RTX, especially in nonlymphomatous disorders, should be carefully evaluated in patients at risk of HHV-8 tumors.