HLH- Haemophagocytic LymphoHistiocytosis

Question 1

Definition

Answer 1

• Definition:
  A condition of pathologic immune activation involving excessive activation of macrophages and T-cells, leading to a cytokine storm and tissue damage.

Question 2

Describe Pathophysiology of HLH

Answer 2

Pathophysiology:
* Uncontrolled macrophage and T-cell activation
* Excessive cytokine release causes multiorgan damage
* NK cell cytotoxicity is typically deficient

Question 3

Causes

Answer 3

Acquired HLH:

*	Viral infections (CMV, EBV, HIV, HSV)
*	Lymphoma, especially T-cell/NK-cell (more common in NHL and Hodgkin lymphoma)
*	Malignancy, immune deficiencies, rheumatological disorders (e.g., SLE)
*	Sepsis

*	Familial forms (e.g., Chediak-Higashi syndrome)

Question 4

Clinical Features:

Answer 4

• High fevers, hepatosplenomegaly
  
  • Lymphadenopathy
  • Jaundice, respiratory distress
  • Neurological symptoms (seizures, altered GCS)
  • Multiorgan failure

Question 5

Laboratory Findings:

Answer 5

• Cytopenias (anemia, neutropenia, thrombocytopenia)
  
  • Hyperferritinemia (>500 µg/L)
  • Hypertriglyceridemia
  • Hypofibrinogenemia
  • Raised LFTs, LDH
  • Bone marrow shows haemophagocytosis
  • Decreased/absent NK cell activity
  • ↑ soluble CD25 (IL-2 receptor)

Question 6

Diagnostic Criteria
(Need ≥5 of 8):

Answer 6

1. Fever >38.3°C >7 days
   
   2. Splenomegaly
   3. Cytopenias affecting ≥2 cell lines
   4. Hypertriglyceridemia or hypofibrinogenemia
   5. Haemophagocytosis in bone marrow, spleen, or LN
   6. Low/absent NK cell activity
   7. Ferritin >500 µg/L
   8. ↑ soluble CD25 (sIL-2 receptor)

Question 7

Management:

Answer 7

• Treat underlying cause (e.g., infection, malignancy)
  
  • Immunosuppression: Dexamethasone, Etoposide, Empalumab
  • Antibiotics/antivirals as needed
  • Consider Bone Marrow Transplant when stable