From the Guidelines
The diagnosis of Hemophagocytic Lymphohistiocytosis (HLH) can be established if a molecular diagnosis consistent with HLH is made or if 5 of the 8 diagnostic criteria are fulfilled, as outlined in the 2019 Blood journal study 1. The diagnostic criteria for HLH include:
- Fever
- Splenomegaly
- Cytopenias affecting at least two cell lines (hemoglobin < 90 g/L, platelets < 100 × 10^9/L, or neutrophils < 1.0 × 10^9/L)
- Hypertriglyceridemia and/or hypofibrinogenemia (fasting triglycerides ≥ 3.0 mmol/L or fibrinogen ≤ 1.5 g/L)
- Hemophagocytosis in bone marrow or spleen or lymph nodes
- Low or no NK cell activity
- Ferritin ≥ 500 mg/L
- Soluble CD25 (IL-2 receptor) ≥ 2400 U/mL According to the study 1, soluble interleukin-2 (IL-2) receptor has been reported as a good to excellent low-cost diagnostic test for adult HLH, with an area under the curve of 0.90. Key points to consider in the diagnosis of HLH include:
- The HLH-2004 criteria, although developed for children, have been used in adults, but are not formally validated for this population 1.
- The diagnosis of HLH requires a comprehensive approach, including clinical evaluation, laboratory tests, and histological examination of bone marrow or other affected organs 1.
- A high index of suspicion is necessary to diagnose HLH, as the clinical presentation can be non-specific and similar to other conditions 1.
From the Research
Diagnostic Criteria for HLH
The diagnostic criteria for Hemophagocytic Lymphohistiocytosis (HLH) include:
- Fever, cytopenias, coagulopathy, and hepatosplenomegaly as hallmark findings 2
- Anemia, thrombocytopenia, neutropenia, elevated ferritin, hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis (in bone marrow, spleen, or lymph nodes), low or absent natural killer cells, and elevated soluble interleukin 2 receptor assay as diagnostic features 2
- The HLH-2004 protocol, which includes criteria such as:
- Molecular diagnosis consistent with HLH 3
- Fever 3
- Splenomegaly 3
- Cytopenias (affecting at least 2 of 3 lineages in the peripheral blood) 3
- Hemophagocytosis in bone marrow, spleen, or lymph nodes 3
- Low or absent natural killer cell activity 3
- Ferritin level ≥ 500 ng/mL 3
- Elevated soluble CD25 (soluble interleukin-2 receptor) level 3
Early Parameters and Scoring Systems
Early parameters that can predict the risk of HLH include:
- Anemia (hemoglobin < 10 g/dL) 4
- Thrombocytopenia (platelet count < 100 × 10^3 /μL) 4
- Leukoerythroblastosis 4
- Hyperbilirubinemia (total bilirubin > 2 × upper normal limit) 4
- Hyperferritinemia (ferritin > 1000 ng/mL) 4
- Splenomegaly 4 A bone marrow (BM) score can also be used as an independent predictor of HLH, with a cutoff of 10 points having a sensitivity of 95% and specificity of 75% 4
Clinical Features and Diagnosis
HLH can present with diverse clinical manifestations, making diagnosis challenging 5, 3, 6 The diagnosis of HLH is often delayed due to its rarity and similarity to other conditions, such as sepsis 6 Prompt recognition and diagnosis are critical for treatment and improving outcomes 2