Description: A life-threatening syndrome of severe, uncontrolled immune activation resulting in a massive cytokine storm and widespread tissue damage. It is characterized by the accumulation of activated macrophages and lymphocytes in the reticuloendothelial system.

Classification:
- Familial (Primary) HLH: Inherited disorder most commonly presenting during infancy.
- Secondary (Acquired) HLH: Triggered by an underlying condition in patients of any age.

Diagnostic Criteria: Diagnosis requires either an established molecular/genetic defect OR meeting at least 5 of the following 8 criteria:

Fever
Splenomegaly
Cytopenias involving 2 or 3 lineages
Hypertriglyceridemia and/or hypofibrinogenemia
Hemophagocytosis in bone marrow, spleen, lymph nodes, or liver
Low or absent natural killer (NK) cell activity
Ferritin >500 µg/L
Elevated soluble CD25 (soluble IL-2 receptor)

Clinical Pearl: Prompt initiation of immunochemotherapy is vital for survival, but treatment is often complicated by a dynamic clinical course, treatment-related morbidity, and high recurrence risk.

Hematopathology

Pathologies