HHV-8-ASSOCIATED MULTICENTRIC CASTLEMAN DISEASE IN AN HIV CARRIER COMPLICATED BY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS AND TUMOR LYSIS SYNDROME: ATYPICAL PRESENTATIONS IN A RARE LYMPHOPROLIFERATIVE DISORDER

Abstract

Introduction/Objective: Human herpesvirus-8 (HHV-8)-associated multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder sometimes associated with acquired human immunodeficiency syndrome. Hemophagocytic lymphohistiocytosis (HLH) and tumor lysis syndrome (TLS) are unusual complications of MCD. Here, we presented a case report of an HIV patient with MCD who evolved for HLH and TLS, atypical presentations in this clinical setting. Methods: Data were obtained reviewing the medical record of a patient diagnosed and treated at the University of São Paulo (USP) in 2023. Case report: A 31 year-old man was admitted at the emergency department of HC-USP in June 2023 presenting multiple adenomegalies, recurrent fever and weight loss during the past 4 months. He had a previous diagnosis of HIV infection in regular treatment, with a T-CD4 lymphocyte count = 514 copies/mL. The patient was previously admitted in another service due to infectious complications, where he underwent an axillary lymph node biopsy, which showed lymphoid hyperplasia rich in interfollicular plasmocytes, compatible with a HHV-8-associated MCD, in addition to a spindle-cell neoplastic proliferation, supporting theconcomitant diagnosis of Kaposi's sarcoma (KS). He was submitted to up-front treatment based on prednisone 1 mg/kg/day. Upon admission at the HC-USP, he presented hepatosplenomegaly, ascites, and multiple lymph node enlargement. Laboratory evaluation revealed anemia, thrombocytopenia, hypoalbuminemia and marked increase in inflammatory tests, fulfilling criteria for MCD activity. After 10 days, he evolved with worsening of hepatosplenomegaly, progressive increase of direct bilirubin, pancytopenia, hyperferritinemia and hypertriglyceridemia. He also had TLS requiring dyalisis. Due to this presentation, a bone marrow evaluation was performed, which showed many figures of hemophagocytosis and high EBV viral load measured by qRT-PCR. The H-Score was applied to this case, with a result of 228 points, inferring 98-99% probability of HLH diagnosis, compatible with the previously formulated hypothesis. Promptly, methylprednisolone pulsotherapy was started at a dose of 1 g/day I.V. and etoposide 50 mg/m2/day I.V. for 3 days. Despite this approach, the patient presented an unfavorable evolution, evolving to death before the institution of up-front treatment for HHV-8-MCD. Discussion: HLH is a potentially lethal condition caused by macrophage hyperactivation following inflammatory, neoplastic or infectious triggers. Among the main causes, the HHV-8 virus highlights, particullarly in the context of immunosuppression. This virus is also involved in the pathogenesis of MCD and KS. There are, however, few reports of association between both disorders. Moreover, the association between MCD and TLS is also rare, since it is a non-neoplastic lymphoproliferative disease with low cellular turn-over. In view of the possible evolution to aggressive non-Hodgkin's lymphoma during the MCD's course, the TLS presence should prompt get to the search for concomitant DLBCL, which was not possible in this case due to the unfavorable premature evolution. Conclusion: This case showed that HLH and TLS, although rarely associated with MCD, can lead to serious organ dysfunctions with a potentially fatal course. Prompt recognition of both conditions is essential to establish early therapeutic measures that are crucial to ensure satisfactory clinical outcomes.