Table 2.

HLH-2004 diagnostic criteria

The diagnosis of HLH can be established if Criterion 1 or 2 is fulfilled.
1. A molecular diagnosis consistent with HLH
2. Diagnostic criteria for HLH fulfilled (5 of the 8 criteria below)
 Fever
 Splenomegaly
 Cytopenias (affecting ≥2 of 3 lineages in the peripheral blood)
  Hemoglobin <90 g/L (hemoglobin <100 g/L in infants <4 wk)
  Platelets <100 × 109/L
  Neutrophils <1.0 × 109/L
 Hypertriglyceridemia and/or hypofibrinogenemia
  Fasting triglycerides ≥3.0 mmol/L (ie, ≥265 mg/dL)
  Fibrinogen ≤1.5 g/L
 Hemophagocytosis in bone marrow or spleen or lymph nodes. No evidence of malignancy.
 Low or no NK cell activity (according to local laboratory reference)
 Ferritin ≥500 μg/L
 sCD25 (ie, soluble IL-2 receptor) ≥2400 U/mL
  • If hemophagocytic activity is not proven at the time of presentation, further search for hemophagocytic activity is encouraged. If the bone marrow specimen is not conclusive, material may be obtained from other organs. Serial marrow aspirates over time may also be helpful. The following findings may provide strong supportive evidence for the diagnosis: spinal fluid pleocytosis (mononuclear cells) and/or elevated spinal fluid protein and histological picture in the liver resembling chronic persistent hepatitis (biopsy). Other abnormal clinical and laboratory findings consistent with the diagnosis are cerebromeningeal symptoms, lymph node enlargement, jaundice, edema, skin rash, hepatic enzyme abnormalities, hypoproteinemia, hyponatremia, and elevated very low-density lipoprotein (VLDL↑)/low high-density lipoprotein (HDL↓).