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/mLb |
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
bNew data show normal variation by age. Level should be compared with age-related norms