g. fevers, elevated levels of HHV8 were associated with low haemoglobin, sodium and albumin, and splenic enlargement. Stebbing et al. [30], showed that in 52 individuals with MCD, relapses were strongly associated with rising levels of HHV8 which predicted an attack (hazard ratio 2.9, 95% CI: 1.3–6.7). We suggest that histological confirmation requires immunocytochemical staining for HHV8 and IgM lambda (level of evidence 2B). We suggest that all patients should have their blood levels of HHV8 measured to support the diagnosis (level of evidence 2C). Following diagnosis, patients should have a CT of neck, chest, abdomen and pelvis. It is unclear whether a bone marrow biopsy to exclude

Enzalutamide nmr microlymphoma should be required where HLH is suspected. The role of functional imaging such as fluorodeoxyglucose positron emission tomography (FDG-PET) scans is uncertain although a small study [31], indicated that in individuals with active MCD, FDG-PET scans more frequently detected abnormal uptake Selleck BYL719 than CT. HIV-associated MCD is relatively uncommon and only recently recognized, so the incidence and prognosis are not well established. The precise effect of cART on incidence and prognosis is similarly unclear. Not only is MCD itself potentially fatal as a result of organ failure but it is also associated with an

increased incidence of non-Hodgkin lymphoma (NHL). In a prospective study of 60 HIV-infected individuals with MCD, 14 patients developed HHV8-associated NHL. Three patients had classic HHV8-positive, Epstein–Barr virus (EBV)-positive primary effusion lymphoma (PEL); five were diagnosed with HHV8-positive/EBV-negative visceral large B-cell lymphoma with PEL-like phenotype; and six developed plasmablastic lymphoma/leukaemia [21]. This is a 15-fold increase in lymphoma risk above that seen in the general HIV-infected population. In another study of 61 patients [32], at diagnosis, four patients (7%) had histological evidence of coexisting lymphoma, and one developed lymphoma 2 years after treatment. The incidence of lymphoma is 28 per

1000 patient-years. The pathogeneses of these lymphomas probably differ, with the plasmablastic type driven by the expansion of plasmablastic microlymphomas seen in MCD lesions [32,33]. In contrast, the PEL and PEL-like lymphomas Doxorubicin may be driven by the cytokine-rich environment with high levels of IL-6 and IL-10, which are known to enhance cell growth of PEL cell lines [34]. Cattaneo et al. [35], in a retrospective study showed that cART did not improve the outcome in HIV-related MCD. Thirty-five patients over a 21-year period (nine pre-cART and 26 post-cART) were compared. Overall survival of the entire series was 28 months without significant differences between pre- and post-cART era. Causes of death were evaluable in 18: non-Hodgkin lymphoma (NHL) (7), MCD (6), opportunistic infections (1), liver cirrhosis (1), acute myocardial infarction (1), KS (1) and therapy-related toxicity (1).