Are Patients with HHV-8 Associated Castleman Disease Successfully Treated with Rituximab at Risk of Subsequently Developing HHV-8 Negative (Idiopathic) Castleman Disease?

Abstract

Multicentric Castleman disease (MCD) is a lymphoproliferative disorder characterized by lymph node histopathology and systemic symptoms. To our knowledge, there are no descriptions in the literature of long-term outcomes of human herpesvirus-8 (HHV-8)-associated MCD. We report a case of a 70-year-old male living with human immunodeficiency virus and a history of human herpesvirus-8 (HHV-8)-associated MCD. The patient reported having had low-grade fever for two weeks. Extensive workup revealed systemic lymphadenopathy without evidence of autoimmune disease or malignancy. Lymph node biopsy was consistent with HHV-8-negative idiopathic MCD (iMCD). The patient was subsequently scheduled for anti-interleukin-6 therapy. The present case is the first report of probable development of iMCD after long-term follow-up for HHV-8-associated MCD. The case illustrates the possible long-term consequences of MCD, suggesting the necessity of further research on the pathogenesis of CD. Given the uncertainty in the long-term outcomes of HHV-8-associated MCD, periodic surveillance of patients with a history of HHV-8-associated MCD is warranted. Prospective nationwide cohort studies comparing characteristics of HHV-8-associated MCD and iMCD would bring further insights. This is the first case describing the probable development of HHV-8-negative idiopathic MCD after HHV-8-associated MCD.Little is known of long-term outcomes of HHV-8-associated MCD and idiopathic MCD, necessitating periodic surveillance.HHV-8-negative idiopathic MCD patients are treated with siltuximab, an interleukin-6 inhibitor, unlike patients with HHV-8-associated MCD, who benefit most from rituximab.