Table 2.

List of diagnostic criteria for HLH that were used in the Histiocyte Society HLH-2004 study

(A) Genetic defect consistent with HLH or (B) 5 out of 8 clinical and laboratory criteria fulfilled

Fever

Splenomegaly

Cytopenia in ≥2 cell lineages

Hemoglobin <9 g/dL, in neonates <10 g/dL

Platelet count <100 × 103/mL

Neutrophil count <1 × 103/mL

Hypertriglyceridemia (>265 mg/dL) or hypofibrinogenemia (<150 mg/dL)

Hyperferritinemia (>500 ng/mL)

Soluble CD25 >2400 U/mL (or elevated compared with laboratory-defined normal ranges)

Hemophagocytosis in bone marrow, spleen, lymph nodes, or liver

Low or absent NK-cell cytotoxicity

According to the revised diagnostic criteria guideline of the HLH-2004 protocol, HLH is assumed if either a genetic diagnosis consistent with HLH is present (A) or if 5 out of 8 criteria are fulfilled (B). The finding of a genetic defect does not mean that a patient has acute hyperinflammatory HLH, only that they have a predisposition to the syndrome of HLH.¹⁰