Criteria for the diagnosis of HLH:
(1) familial disease
(2) molecular marker diagnostic for HLH
(3) 5 or more out of 8 diagnostic markers (see below)
Diagnostic markers:
(1) fever
(2) splenomegaly
(3) cytopenia affecting at least 2 out of 3 hematologic lineages (hemoglobin, platelet count, neutrophils)
(4) fasting hypertriglyceridemia (>= 265 mg/dL) OR hypofibrinogenemia (<= 150 mg/dL)
(5) hemophagoctyosis on biopsy of bone marrow, spleen, or lymph node AND no evidence of malignancy
(6) absent or low natural killer (NK) cell activity
(7) serum ferritin >= 500 µg/L
(8) soluble IL-2 receptor (CD25) >= 2,400 U/mL
where:
• Items 6, 7 and 8 are the new criteria.
• Cytopenia criteria for infants < 4 weeks old: hemoglobin < 10 g/dL, platelet count < 100,000 per µL, neutrophil count < 1,000 per µL
• Cytopenia criteria for noninfant: hemoglobin < 9 g/dL, platelet count < 100,000 per µL, neutrophil count < 1,000 per µL
• The serum ferritin may not be a useful criteria in a patient with hemochromatosis. The method and reference range for measuring ferritin was not listed.
• The method and reference range for measuring soluble IL-2 receptor was not given.
Additional findings which may be supportive of the diagnosis:
(1) CSF mononuclear pleocytosis
(2) elevated CSF protein
(3) liver biopsy showing chronic persistent hepatitis
(4) cerebromeningeal symptoms
(5) lymphadenopathy
(6) jaundice
(7) edema
(8) skin rash
(9) elevated liver enzymes
(10) hypoproteinemia
(11) hyponatremia
(12) decreased HDL
(13) increased VLDL
