Severe polyneuropathy in HIV-negative human herpesvirus 8–associated multicentric Castleman disease successfully treated with rituximab and liposomal doxorubicin

Human herpesvirus 8-associated multicentric Castleman disease (HHV-8-associated MCD) is a rare lymphoproliferative disorder that typically occurs in immunocompromised patients with HIV infection. HHV-8-associated MCD is characterized by systemic inflammatory manifestations driven by viral interleukin-6, where neurological complications are uncommon. This contrasts with POEMS-associated MCD, which is HHV-8 negative and frequently complicated by polyneuropathy. A 56-year-old HIV-negative man presented with prolonged high-grade fever, severe anemia, multiple mildly enlarged lymph nodes, hepatosplenomegaly, pleural effusions, and ascites. He was initially diagnosed with idiopathic MCD and treated with tocilizumab; however, his condition was refractory and progressively worsened, with muscle weakness, distal sensory disturbance, and autonomic dysfunction. Nerve conduction studies demonstrated severe peripheral neuropathy with prominent axonal involvement. Subsequent evaluation revealed a markedly elevated plasma HHV-8 viral load, and immunohistochemistry of lymph node tissue demonstrated HHV-8-encoded latency-associated nuclear antigen-1-positive cells, leading to a definitive diagnosis of HHV-8-associated MCD. Given the aggressive disease course and poor performance status, treatment with rituximab plus liposomal doxorubicin was initiated. This led to rapid resolution of systemic inflammation, clearance of HHV-8 viremia, and marked improvement in both neurological symptoms and nerve conduction abnormalities. This case highlights that HHV-8-associated MCD can cause severe POEMS-like polyneuropathy even in HIV-negative patients and underscores the importance of distinguishing HHV-8-associated MCD from idiopathic MCD in patients who are refractory to interleukin-6-targeted therapy.