HSV Hepatitis, HLH, or Both?

Artistic rendition of Herpes Simplex Virus

Artistic rendition of Herpes Simplex Virus

1.  Very high ferritin levels have a short ddx:
   -Malignancy
   -Still's disease
   -Hemophagocytic Lymphohistiocytosis (HLH)
   -Iron overload disorders or states

2.  HLH is diagnosed based on the presence of 5 out of 8 criteria:
•Fever ≥38.5°C
•Splenomegaly
•Peripheral blood cytopenia, with at least two of the following: Hb<9 g/dL; plts <100,000/microL; ANC <1000/microL
•Hypertriglyceridemia (fasting triglycerides >265 mg/dL) and/or hypofibrinogenemia (fibrinogen <150 mg/dL)
•Hemophagocytosis in bone marrow, spleen, lymph node, or liver
•Low or absent NK cell activity (ie flow cytometry)
•Ferritin >500 ng/mL (ferritin >3000 ng/mL as more indicative of HLH)
•Elevated soluble CD25 (soluble IL-2 receptor alpha) two standard deviations above age-adjusted laboratory-specific norms

3.  Considering that some of these criteria require specialized studies/biopsies which are not always readily available, a predictive calculator exists or this alternative criteria based diagnosis:
  •3 of 4 clinical findings (fever, splenomegaly, cytopenias, hepatitis) + 1 of 4 immune markers (hemophagocytosis, increased ferritin, hypofibrinogenemia, absent or very decreased NK cell function)