Multicentric Castleman’s Disease in HIV Infection: a Systematic Review of the Literature

The objective of this study is to systematically review the epidemiology and the clinical and virologicaspects of multicentric Castleman’s disease in HIV-positive patients and to evaluate treatmentstrategies and outcome, especially in relation to HAART administration. The authors have conducteda systematic review of the English literature for all cases of newly diagnosed multicentric Castleman’sdisease in HIV-positive patients. The 25 studies which met the selection criteria included 84 HIVpositivepatients with multicentric Castleman’s disease (20 pre-HAART and 64 post-HAART era). Ofthem, the majority (90%) were men with 33 months median time from detection of HIV-positivity tomulticentric Castleman’s disease diagnosis in the HAART era. Fever and lymphadenopathy were themost common presenting symptoms and cytopenias, hypoalbuminemia, polyclonal hypergammaglobulinemiaand raised C-reactive protein the most frequently revealed laboratory findings. Kaposi’ssarcoma was present in 72% of the patients and respiratory system involvement in 34%. Althoughthe majority of cases reported were positive for human herpesvirus-8, none of the reviewed patientswas found to suffer from polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy,and skin changes (POEMS) syndrome. Of the 48 patients on HAART, 64% were already on HAART atmulticentric Castleman’s disease diagnosis, having a better immunologic profile and a lower incidenceof Kaposi’s sarcoma than the 35% of patients who initiated HAART after multicentric Castleman’sdisease diagnosis. Nevertheless, the two groups did not have significantly different mortalityrates (30 vs. 38%). At multicentric Castleman’s disease diagnosis, a wide range of CD4 counts wasrecorded, suggesting that disease presentation could occur at any CD4 count. With regard to treatment,the study confirmed the high rates of response with rituximab (anti-CD20 monoclonal). Monochemotherapyseems to give short-lived responses, which require maintenance to be sustained.Polychemotherapy with CHOP has given long-term remission in a subset of patients. Other regimensused in the treatment of HIV-related multicentric Castleman’s disease were antiviral agents, immunomodulatoryagents, and thalidomide. The fatality rate among HIV-related multicentric Castleman’sdisease cases reviewed was 44%, significantly lower than that of HIV-negative individuals (65%), whilemedian survival of the latter was 29 months longer than that of HIV-infected individuals. The fatalityrate among pre-HAART patients was 75 vs. 29% among HAART patients. Infection, multiorgan failure,Kaposi’s sarcoma, non-Hodgkin lymphoma and progressive multicentric Castleman’s disease werethe most often reported causes of death. In conclusion, multicentric Castleman’s disease is a lymphoproliferative disorder with an increasing prevalence in HIV-infected individuals. Even though lifeexpectancy in multicentric Castleman’s disease seems to have significantly improved in the HAARTera, it remains a disease with a poor prognosis and an increased incidence of non-Hodgkin lymphomain the HIV-context.