Concomitant administration of multiple drugs frequently causes severe pharmacokinetic or pharmacodynamic drug–drug interactions (DDIs) resulting in the possibility of enhanced toxicity and/or treatment failure. The activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), a drug efflux pump sharing localization and substrate affinities with CYP3A4, is a critical determinant of drug clearance, interindividual variability in drug disposition and clinical efficacy, and appears to be involved in the mechanism of numerous clinically relevant DDIs, including those involving dexamethasone. The recent increase in the use of high doses of dexamethasone during the COVID-19 pandemic have emphasized the need for better knowledge of the clinical significance of drug–drug interactions involving dexamethasone in the clinical setting. We therefore aimed to review the already published evidence for various DDIs involving dexamethasone in vitro in cell culture systems and in vivo in animal models and humans.

Kaposi sarcoma–associated herpesvirus (KSHV)/human herpesvirus 8–associated multicentric Castleman disease (MCD) is a polyclonal B-cell lymphoproliferative disorder that mainly occurs in immunocompromised hosts. The diagnosis relies on lymph node biopsy demonstrating KSHV-infected cells located in the mantle zone with a marked interfollicular plasma cell infiltration. Infected cells are large cells positive for immunoglobulin M (IgM), λ light chain, and CD38, described initially as infected plasmablasts. We show that IgM+λ+CD38high cells were also detectable in the peripheral blood of 14 out of 18 (78%) patients with active KSHV-MCD and absent in 40 controls. Using immunofluorescence and flow–fluorescence in situ hybridization, we demonstrate that these cells are KSHV infected and express both latent and lytic KSHV transcripts. These KSHV-infected viroblasts (KIVs) harbor a distinct phenotype compared with conventional plasmablasts. We also identified several putative mechanisms of immune escape used by KSHV, because KIVs displayed an overall decrease of costimulatory molecules, with a remarkable lack of CD40 expression and are interleukin-10–producing cells. The identification of this specific and easily accessible KSHV+ circulating population brings new elements to the understanding of KSHV-MCD but also raises new questions that need to be clarified.

Primary effusion lymphoma (PEL) is a rare B‐cell non‐Hodgkin lymphoma associated with Kaposi Sarcoma‐associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein‐Barr virus (EBV) in 60−80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow‐Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations.

Sarcoidosis is a systemic granulomatous disease with unpredictable evolution. Current biomarkers, including angiotensin-converting enzyme (ACE) and 1,25-OH vitamin D3, show limited accuracy. The soluble interleukin-2 receptor (sIL2R) reflects T-cell activation and may serve as a sensitive disease activity biomarker. To compare the diagnostic performance of sIL2R with ACE and 1,25-OH vitamin D3 for assessing sarcoidosis activity. A bicentrique retrospective study was conducted from November 2019 to January 2022 including 103 patients with confirmed sarcoidosis (WASOG criteria). Disease activity was defined by new clinical manifestations or therapy escalation. Serum sIL2R, ACE and 1,25-OH vitamin D3 were compared between active and inactive forms using ROC analysis. Among 103 patients (median age 51 years, 54.4% women), 60 (58%) had active disease. sIL2R levels were significantly higher in active patients (2096pg/mL vs 1337pg/mL; P<0.0001). sIL2R showed higher sensitivity (75%) than ACE (54%) and 1,25-OH vitamin D3 (51%) but lower specificity (55.8% vs 75.7% and 81.1%). The combination of sIL2R and 1,25-OH vitamin D3 increased specificity to 94.6% and positive predictive value to 91.3%. sIL2R is a sensitive and relevant biomarker for sarcoidosis activity assessment. Combined with 1,25-OH vitamin D3, it enhances diagnostic specificity and may guide disease monitoring.