Synergistic Risks: The Impact of HIV on Kaposi Sarcoma and Lymphoma Incidence in Castleman's Disease
Authors: Elengickal Joseph , Sood Aditya , Pavy Michael , Hou Lilly , Aung Wint Yan , Varughese Vivek , Sangari Anish , Cooper Cody , Fanning Suzanne 
Published: December 2024

Background: Castleman's disease (CD) is an exceedingly rare heterogeneous lymphoproliferative disease. Disease classification is based on degree of involvement of lymph nodes, with unicentric CD involving only one lymph node while multicentric CD (MCD) involves multiple lymph nodes. Unicentric CD is typically a benign disorder, whereas multicentric CD is predominantly associated with HIV, HHV8 infection, and B symptoms, and carries a worse prognosis. A high prevalence of associated malignant conditions such as Kaposi Sarcoma and lymphomas have been observed among patients with MCD. The goal of this study is to further understand the association between HIV and MCD in the development of Kaposi Sarcoma (KS) and lymphoma.
Methods: This retrospective study utilized patient data from the TriNetX and US collaborative Network databases to complete two comparative studies. In both analyses, patients were matched on age, sex, race, ethnicity, homelessness, and socioeconomic/psychosocial circumstances using propensity matching based on demographic and ICD coded data. The study aimed to evaluate the association between HIV presence/absence in MCD patients and the incidence of mortality, KS, and Lymphoma, structured into two comparative assessments: MCD- HIV+ (A1) versus MCD+ HIV+ (A2) and MCD+ HIV- (B1) versus MCD+ HIV+ (B2). Measure of association analysis was conducted on matched cohorts to assess for risk.
Outcomes: Following matching, group A1 and A2 comprised 622 patients each (1244 total). The first analysis compared outcomes between HIV+ patients without MCD (Group A1) and with MCD (Group A2). The mortality risk for Group A1 and A2 was 9.06% and 12.9% respectively resulting in a risk difference of 3.9% (p=0.0225). The incidence of Kaposi Sarcoma was notably higher in Group A2 (12.5% vs 1.5%, risk difference 11.0%, p&lt;0.0001), as was the risk of Lymphoma (20.09% vs 3.02%, risk difference 17.07%, p=0.0001).
The second analysis compared the outcomes of MCD patients without HIV (Group B1) and with HIV (Group B2). Each group comprised 622 patients (1244 total). The mortality risk for Group B1 was 7.07%, and for Group B2 was 12.99% resulting in a risk difference of 5.15% (p=0.0021). Kaposi Sarcoma incidence was higher in Group B2 than group B1 (11.89% vs 1.6%, risk difference 10.29%, p&lt;0.0001), whereas the difference in Lymphoma risk (19.29% vs 17.36%, risk difference 1.93%, p=0.37) was not statistically significant.
Discussion: This study represents one of the largest retrospective reviews of MCD, and examines the relation between HIV and MCD particularly in the context of Kaposi Sarcoma and Lymphoma risks. There are several key findings from the analyses. Firstly, the study suggests a significantly increased risk of developing KS in patients with MCD and HIV. The risk of developing KS appears to be multiplicative when a patient is afflicted with both HIV and MCD compared with HIV or MCD alone. In contrast, while presence of MCD may affect the risk for lymphoma in patients with HIV, it does not appear HIV status in patients with MCD significantly affects their risk of developing lymphoma. This suggests a more limited effect of HIV infection on the development of lymphoma in patients with MCD. Additionally, the study demonstrates a significantly increased mortality risk during hospitalization for patients with both HIV and MCD. These findings underscore the heightened risk in patients with HIV-associated MCD. Through hospitalization data, this study was able to gather information on a large population of patients with the rare diagnosis of MCD and shed light on its association with HIV. This investigation highlights the critical need for targeted therapeutic strategies, vigilant surveillance, and further research for this vulnerable population.