What are the Histiocyte Society HLH-2004 criteria for diagnosis of hemophagocytic lymphohistiocytosis (HLH)?

By William Aird

Clinical criteria for predicting the diagnosis of hemophagocytic lymphohistiocytosis (HLH):

  • In 1991, the Histiocyte Society proposed a standardized set of 5 diagnostic criteria for HLH used for the prospective HLH-94 clinical trial.
  • These criteria were revised for HLH-2004: individuals needed to meet 5 or more of 8 diagnostic criteria.
    • Fever
    • Splenomegaly
    • Hypertriglyceridemia or hypofibrinogenemia
    • Hemophagocytosis in bone marrow, spleen, or lymph nodes
    • Low or absent NK-cell activity
    • Ferritin ≥ 500 mcg/L
    • Elevated soluble interleukin-2 receptor.
  • The HLH-2004 criteria, developed for children, are not validated formally for adults and remain based on expert opinion.

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