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

From: Hemophagocytic lymphohistiocytosis with immunotherapy: brief review and case report

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/mLb
  1. aSupportive criteria include neurologic symptoms, cerebrospinal pleocytosis, conjugated hyperbilirubinemia and transaminitis, hypoalbuminemia, hyponatremia, elevated D-dimers, and lactate dehydrogenase. The absence of hemophagocytosis (in the bone marrow) does not exclude a diagnosis of HLH
  2. bNew data show normal variation by age. Level should be compared with age-related norms