Can plasma HHV8 viral load be used to differentiate multicentric Castleman disease from Kaposi sarcoma?

Abstract

We measured plasma human herpesvirus 8 (HHV8) DNA load in consecutive patients presenting with HIV-associated multicentric Castleman disease (MCD) and in contemporaneous patients who had Kaposi sarcoma (KS), lymphoma or other diagnoses. All 11 patients with MCD had detectable plasma HHV8 DNA compared with 18 (72%) of 25 patients with KS, none with lymphoma and one of 38 patients with other diagnoses. Detectable plasma HHV8 DNA levels were higher among MCD patients, median (interquartile range [IQR]) = 43,500 (5200-150,000) copies/mL, when compared with those with KS, median (IQR) = 320 (167-822) copies/mL and those with lymphoma and other diagnoses (one-way analysis of variance; P = 0.0303). Using receiver operating characteristic analysis, a cut-off of >1000 copies HHV8 DNA/mL of plasma helped to discriminate between MCD and other diagnoses, with a specificity of 94.7% and a negative predictive value of 97.3%. The level of HHV8 viraemia, while not diagnostic, may aid discrimination between patients with MCD and those with KS and other systemic illnesses.

The clinical application of plasma Kaposi sarcoma herpesvirus viral load as a tumour biomarker: results from 704 patients

“…This study has explored the role of plasma KSHV as a tumour marker in KSHV‐associated diseases. The use of plasma KSHV as a diagnostic marker in PLWH appears to be limited and this larger study contradicts previous reports that suggested that the KSHV viral load was able to differentiate between the three main KSHV‐associated pathologies [5–7]. These earlier publications suggested that the highest KSHV viral levels were detected in those with KSHV‐associated lymphomas, then in those with MCD, and the lowest levels were found in those with KS.…”

“…As a diagnostic biomarker, it has been postulated that the KSHV viral load is able to differentiate between different KSHV‐associated pathologies, with the highest levels in KSHV‐associated lymphomas, then in MCD, and the lowest levels in KS [5–7]. Numerous published studies have shown that KSHV is almost always detectable in the blood of patients with active MCD and that levels of KSHV DNA correlate with symptomatic disease [8–14].…”

Vironome of Kaposi sarcoma associated herpesvirus-inflammatory cytokine syndrome in an AIDS patient reveals co-infection of human herpesvirus 8 and human herpesvirus 6A

“…This represents the highest KSHV viral load on record (Table 1). By comparison KS patients (Polstra et al, 2003, Sayer et al, 2011) typically have a mean KSHV viral load of 1000 copies / ml (range 151 – 26,915), PEL patients (Simonelli et al, 2009) of 10,284 copies / ml (range 2,558 – 36,300) and MCD (Simonelli et al, 2009) of 4,400 copies / ml (range 600 – 1,678,000). KS malignancies are AIDS defining, but rarely associated with high-level virus replication.…”

Clinical and experimental study of castleman disease in children

“…At present, it is generally believed that interleukin‐6 (IL‐6) produced by the lymph nodes plays a very important role in the occurrence and development of CD . Several studies reported that the occurrence of MCD in adults was closely related to HHV8 infection in AIDS patients , but controversy exists between MCD and HHV8 in patients without HIV infection . Recently, Sandrine Leroy et al found that MCD was closely related to HHV8 infection in a meta‐analysis of 32 children with a history of MCD.…”

“…Pediatr Blood Cancer DOI 10.1002/pbc Several studies reported that the occurrence of MCD in adults was closely related to HHV8 infection in AIDS patients [11,12], but controversy exists between MCD and HHV8 in patients without HIV infection [13]. Recently, Sandrine Leroy et al [14] found that MCD was closely related to HHV8 infection in a meta-analysis of 32 children with a history of MCD.…”