Table 2. 2004 Diagnostic Guidelines for HLH (16).

The diagnosis of HLH can be established if one of the following criteria (A or B) is fulfilled.

(A) Molecular diagnosis consistent with known genetic susceptibility for the development of HLH (PRF1, UNC13D, STX11, STXBP2, RAB27A, SH2D1A or XIAP)

or

(B) Presence of 5 of 8 of the following clinical criteria:

Fever

Splenomegaly

Cytopenias affecting ≥2/3 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, spleen, or lymph nodes

Low or absent natural killer cell activity (according to local laboratory reference)

Elevated ferritin ≥500 ug/L

Elevated soluble CD25 (i.e., soluble IL-2 receptor) ≥2400 U/mL

No evidence of malignancy

Comments:

1. Absence of hemophagocytosis does not exclude a diagnosis of HLH.
2. The following may provide strong supportive evidence for the diagnosis:

   1. spinal fluid pleocytosis (mononuclear cells) and/or elevated spinal fluid protein
   2. histological evidence resembling chronic persistent hepatitis by liver biopsy.
3. Other abnormal clinical and laboratory findings consistent with the diagnosis: Jaundice, hepatic enzyme abnormalities, coagulopathy, lymph node enlargement, edema, skin rash, hypoproteinemia, hyponatremia, VLDL increased, HDL decreased.