PMC8282902_01
Effect of immune modulation on biomarkers, organ dysfunction, and cytokine levels during HSV-associated secondary HLH. The time course of clinical laboratory values of serum C-reactive protein (CRP), creatinine (Cr), and INR levels (A), ferritin levels (B), as well as the timing of the administration of the immune suppressive agents is shown (C). While IL-6 and TRAIL levels fell precipitously after admission, CXCL9 and IL-18 levels fell more gradually (D) (*Actual INR resulted as >15.7).
fped-09-681055-g0001.jpg
PMC8282902_01_fped-09-681055-g0001.jpg
F1
Further laboratory investigation demonstrated a severe coagulopathy with INR > 15.7 (Figure 1A) and fibrinogen <60 mg/dL. Inflammatory biomarkers revealed a slightly elevated C-reactive protein (CRP) of 5.18 mg/dL (Figure 1A) and procalcitonin of 0.65 ng/mL. Given the degree of fulminant hepatic failure, the medical team suspected hemophagocytic lymphohistiocytosis (HLH) and a ferritin level sent 6 h after admission measured 191,420 mug/L (Figure 1B). Immune modulation with dexamethasone was begun 8 h after admission (Figure 1C). Unfortunately, MODS progressed as evidenced by anuria and a rising serum creatinine (Figure 1A), as well as coagulopathy relatively refractory to the administration of fresh frozen plasma (Figure 1A), presumably due to loss of liver synthetic function and ongoing disseminated intravascular coagulation. IL-6 levels, as they fell precipitously from 11,713 to 289 pg/mL following the initiation of dexamethasone and etoposide (Figures 1C,D). In contrast, IL-18, which has been associated with macrophage activation syndrome, remained modestly elevated and relatively unaffected (Figures 1C,D). CXCL9, a serum biomarker of IFN-gamma activity, was markedly elevated at 39,184 pg/mL, then gradually decreased with immunosuppressive therapy (Figures 1C,D). TNF-related apoptosis-inducing ligand (TRAIL) as a marker of immune response to viral infection. TRAIL levels were elevated at 948 pg/mL and demonstrated a robust decrease similar to IL-6 after suppressive therapy (Figures 1C,D).