Successful Treatment of Iatrogenic Multicentric Castleman’s Disease Arising Due to Recrudescence of HHV-8 in a Liver Transplant Patient

Abstract

We describe the case of a 59‐year‐old HIV‐negative male who developed multicentric Castleman's disease (MCD) 1 year postliver transplantation due to recrudescence of a pretransplant human herpesvirus‐8 (HHV‐8) infection. He presented with fevers, dry cough, weight loss and drenching night sweats. Routine investigations were all unremarkable. Computerized axial tomography (CT) scans showed splenomegaly and intra‐abdominal lymphadenopathy, confirmed by positron emission tomography. Cervical lymph node biopsies were consistent with MCD. The presence of HHV‐8 was confirmed on immunohistochemistry. Peripheral blood HHV‐8 quantitative polymerase chain reaction (qPCR) monitoring showed a threefold decrease in viremia in the first week of treatment with ganciclovir but had little impact on clinical symptoms. Reducing immunosuppression and switching to rituximab resolved clinical symptoms and produced a negative HHV‐8 qPCR result. Retrospective molecular testing of sera collected pre‐ and immediately posttransplantation confirmed preexisting HHV‐8 in the host. This is the first reported case of an HIV‐negative postliver transplant patient developing MCD that manifested as posttransplant lymphoproliferative disorder due to recrudescence of HHV‐8. We propose (1) the introduction of the term iatrogenic Castleman's disease (CD) for this and similar cases, (2) rituximab should be considered as a treatment option for CD and (3) consideration be given to a change to the World Health Organization classification of CD to incorporate such cases.

Human herpesvirus 6, 7, and 8 in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

“…It can be seen after primary HHV-8 infection or reactivation and typically presents with fevers, lymphadenopathy, hepatosplenomegaly, and cytopenias. MCD is commonly associated with increased IL-6 and IL-10 production (165,166). Less commonly, primary effusion lymphoma, an HHV-8 driven, non-Hodgkin, body cavity lymphoma, has been reported after SOT.…”

“…The initial approach to management of neoplastic and non-neoplastic HHV-8 associated disease relies on careful reduction or cessation of pharmacologic immunosuppression, though evidence to support efficacy in MCD or PEL is limited to case reports (114,144,165,(182)(183)(184). Decreasing immunosuppression alone can result in complete remission in up to 30% of…”

“…However, chemotherapy remains the first-line therapy as permitted by functional status and comorbid conditions (198). Case reports using antiviral medications (both systemic and intracavitary in PEL) coupled with immunosuppression reduction or CNI to mTOR inhibitor conversion have reported successful outcomes in MCD and PEL (165,167,197). Also, treatment of HHV-8 DNAemia and non-neoplastic manifestations using different antiviral agents as well as rituximab has been described and may be effective (109,157,160).…”

Viral infections associated with oral cancers and diseases in the context of HIV: a workshop report

“…As HHVs establish undetectable latent infections it is the presence of viraemia that appears immediately prior to clinical disease thus molecular assays (i.e. PCR assays) are useful for monitoring disease progression and treatment efficacy (Speicher et al , ). Viraemia can be determined from either plasma or peripheral blood mononuclear cells depending on whether the virus circulates as cell‐free intact virion or cell‐associated virus (Table ).…”