Table 1 Histiocyte Society HLH-2004 diagnostic criteria [2, 3]

The diagnosis HLH requires that either 1 or 2 below are fulfilled:

(1) A molecular diagnosis consistent with HLH: Pathological mutations of PRF1, UNC13D, STXBP1, RAB27A, STX11, SH2D1A, or XIAP

OR

(2) Diagnostic criteria for HLH fulfilled (5 out of the 8 criteria below):^a

 (A) Initial diagnostic criteria

  • Fever 38·5 °C or more

  • Splenomegaly

  • Cytopenias (affecting at least 2 of 3 cell lineages in the peripheral blood):

   ○ Hemoglobin < 90 g/L (in infants < 4 weeks: hemoglobin < 100 g/L)

   ○ Platelets < 100 × 10⁹/L

   ○ Neutrophils < 1.0 × 10⁹/L

  • Hypertriglyceridemia and/or hypofibrinogenemia:

   ○ Fasting triglycerides ≥3.0 mmol/L (i.e., ≥ 265 mg/dL)

   ○ Fibrinogen ≤1.5 g/L

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

 (B) New diagnostic criteria

  • Low or absent NK-cell activity

  • Ferritin ≥500 mg/L

  • Soluble CD25 (i.e., soluble IL-2 receptor) ≥ 2400 U/mL^b