Criteria for diagnosis of HLH: all of the following:
(1) fever
(2) splenomegaly
(3) cytopenias not cause by a hypocellular or dysplastic bone marrow
(4) hypertriglyceridemia and/or hypofibrinogenemia
(5) hemophagocytosis on histologic examination of bone marrow, spleen or lymph nodes
(6) no histopathologic evidence of malignancy
Criteria for Familial HLH:
(1) all of the above criteria
(2) history
(a) family history of HLH: diagnostic
(b) parental consanguinity: suggestive
where:
• Fever: peak temperature >= 38.5°C for >= 7 days. The fever may be intermittent and may spontaneously resolve.
• Splenomegaly: extends >= 3 cm below the costal arch
• Cytopenias involves at least of the following: hemoglobin < 9.0 g/dL; platelets < 100,000 per µL; absolute neutrophil count < 1,000 per µL
• Hypertriglyceridemia: fasting triglycerides >= 2 mmol/L (177 mg/dL), or >= 3 standard deviations above the mean for the normal range for age.
• Hypofibrinogenemia: <= 150 mg/dL or <= 3 standard deviations below the mean of the normal range for age.
• If the initial histopathologic examination fails to demonstrate hemophagocytosis, then either serial bone marrow aspirates or biopsy of other sites (such as lymph nodes, spleen) may be diagnostic.
Additional findings that are supportive for the diagnosis:
(1) CSF pleocytosis, predominantly mononuclear cells, usually < 50 cells per µL
(2) Liver biopsy showing a histologic appearance resembling chronic persistent hepatitis.
(3) Low natural killer cell activity.
Additional findings that may be encountered:
(1) lymphadenopathy
(2) skin rash
(3) cerebro-meningeal symptoms
(4) jaundice
(5) edema, especially periorbital
(6) increased CSF protein
(7) elevated serum transaminases
(8) hypoproteinemia
(9) hyponatremia
(10) increased VLDL and decreased HDL
(11) increased serum ferritin
(12) increased number of soluble interleukin-2 receptors
