Hemophagocytic

Lymphohistiocytosis
• Primary
– Familial Hemophagocytic
Lymphohistiocytosis (FHL)
– AR
– Onset during infancy or early childhood
– Fatal if untreated (median 2mo survival)

• Secondary
– Strong immunologic activation
• Infections (viral, bacterial, fungal, parasite)
• Collagen-vascular disease
• Malignancy (particularly T-cell lymphoma)
• Other
 Pathophysiology (for dummies)

• Activated macrophages (histiocytes)

engulf erythrocytes, leukocytes, and
platelets
– T-helper cells produce high levels of cytokines
(IFN-, IL2R, TNF-, IL1, IL6) that promotes
macrophage activation
– Cytokine storm causes defective apoptosis of
activated lymphocytes

• Takes place in the marrow, spleen, liver,

lymph nodes, ad occasionally the CNS.
Pathophysiology (for dummies)
Pathophysiology
 Diagnostic Criteria (five criteria)

• Fever (>38.5 for 7+ days)

• Splenomegaly
• Cytopenia (involving 2+ cell lines)
• Hypertriglyceridemia and/or
hypofibrinogenemia
• Hemophagocytosis
• Low/absent NK cell activity
• Ferritin >500
• Soluble CD25 (IL-2 receptor) >2400
 Additional Features

• Hepatomegaly/Hepatitis
• Jaundice and hyperbilirubinemia (hemolysis)
• Lymphadenopathy
• Rash
• Encephalopathy/seizures
• Elevated LDH
• DIC
 Associated Illness

• Infections
– EBV, CMV, Parvovirus, HHV8, HIV, HSV,
VZV, measles, H1N1
– Brucella, TB
– Leishmaniasis
• Auto-immune Conditions
– SLE, RA, Stills, Polyarteritis nodosa
• Other
– Leukemia and lympomay
– After initiation of HAART therapy
 Treatment

• Dexamethasone, Etoposide, Cyclosporine

• Intrathecal Methotrexate

• Pulses of Dexamethasone and Etoposide

for up to 1 year

• Most reach clinical remission by 10th week

of therapy

• Bone marrow transplant for non-responders

 References

• Henter J, et al. HLH-2004: Diagnostic and

Therapeutic Guildlines for Hemphagocytic
Lymphohistiocytosis. Pediatr Blood Cancer
2007;48:124-131.
• Allen CE, et al. Highly elevated ferritin
levels and the dianosis of hemophagocytic
lymphohistiocytosis. Pediatr Blood Cancer
2008;50:1227-35
• Fisman, D. Hemophagocytic Syndrome and
Infection. CDC 2000, Vol 6.
• Uptodate.com