Table 1 Revised diagnostic guidelines for hemophagocytic lymphohistiocytosis [24]

The diagnosis HLH can be established if one of either 1 or 2 below is fulfilled:

(1) A molecular diagnosis consistent with HLH

(2) Diagnostic criteria for HLH fulfilled (5/8 criteria below)

(A) Initial diagnostic criteria (to be evaluated in all patients with HLH)

1. Fever

2. Splenomegaly

3. Cytopenias (affecting 2 of 3 lineages in the peripheral blood):

Hemoglobin < 9 g/dL (in infants < 4 weeks: Hb < 10 g/dL); Platelets < 100,000/mm³; Neutrophils < 1000/mm³

4. Hypertriglyceridemia and/or hypofibrinogenemia:

Fasting triglycerides 3.0 mmol/L (i.e., 265 mg/dl); Fibrinogen ≤ 1.5 g/L

5. Hemophagocytosis in bone marrow or spleen or lymph nodes

No evidence of malignancy

(B) New diagnostic criteria

6. Low or absent NK-cell activity (according to local laboratory reference)

7. Ferritin ≥ 500 mg/L

8. Soluble CD25 (i.e., soluble IL-2 receptor) ≥ 2400 U/ml

Comments:

(1) In cases where hemophagocytic activity is not initially evident, it is recommended to conduct further investigations to confirm its presence. If the examination of bone marrow samples yields inconclusive results, samples from alternative organs may be sought. Additionally, serial marrow aspirates over a period of time could offer valuable insights

(2) The following observations may strongly support the diagnosis: (a) presence of pleocytosis (mononuclear cells) and/or elevated protein levels in cerebrospinal fluid, (b) hepatic histology resembling that of chronic persistent hepatitis as observed in liver biopsies

(3) Additional clinical and laboratory abnormalities consistent with the diagnosis include: symptoms related to the central nervous system and meninges, enlargement of lymph nodes, jaundice, edema, and skin rash. Abnormalities in hepatic enzymes, hypoproteinemia, hyponatremia, elevated VLDL, and decreased HDL may also be present