Hemophagocytic lymphohistiocytosis: Difference between revisions

Revision as of 14:00, 22 January 2021

Etiologies

Infection
- Viral
  - EBV (most common)
  - CMV, parvovirus, HSV, VZV, measles, HHV-8, H1N1 influenza virus, parechovirus, and HIV
  - SARS-CoV-2, possibly
- After anti-TNF therapy: tuberculosis, CMV, EBV, or histoplasmosis
- Rare: Brucella, gram-negative bacilli, tuberculosis, Leishmaniasis, malaria, and fungal infections
Malignancy, most commonly lymphoid cancers and leukemias, but also solid cancers
Rheumatologic disease
- Systemic juvenile idiopathic arthritis (Still disease)
- Rheumatoid arthritis, dermatomyositis, systemic sclerosis, mixed connective tissue disease, antiphospholipid syndrome, Sjogren syndrome, ankylosing spondylitis, vasculitis, and sarcoidosis
Immunodeficiency
- Primary immunodeficiency
- HIV/AIDS, stem cell transplant, kidney transplant, liver transplant

Differential Diagnosis

Macrophage activation syndrome
Severe sepsis
Liver failure
Multiple organ dysfunction syndrome
Encephalitis
Autoimmune lymphoproliferative syndrome
Drug reaction with eosinophilia and systemic symptoms (DRESS)
Kawasaki disease
Cytophagic histiocytic panniculitis
TTP/HUS/DITMA
Transfusion-associated graft-versus-host disease

Diagnostic Criteria (HLH-2004)

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

A molecular diagnosis consistent with HLH is made.
Diagnostic criteria for HLH are fulfilled (5 of the 8 criteria below):*
- Fever
- Splenomegaly
- Cytopenias (affecting ≥ 2-3 lineages in the peripheral blood):
  - hemoglobin < 90 g/L (in infants < 4 weeks of age, hemoglobin < 100 g/L)
  - platelets < 100x10^9^/L
  - neutrophils < 1.0x10^9^/L
- Hypertriglyceridemia and/or hypofibrinogenemia:
  - fasting triglycerides ≥ 3.0 mmol/L (ie, ≥ 265 mg/dL)
  - fibrinogen ≤ 1.5 g/L
- Hemophagocytosis in BM, spleen, or lymph nodes
- Low or absent NK-cell activity (according to local laboratory reference)
- Ferritin ≥ 500 g/L
- Soluble CD25 (ie, sIL2r) 2400 U/mL†

Supportive criteria include neurologic symptoms, cerebrospinal fluid pleocytosis, conjugated hyperbilirubinemia and transaminitis, hypoalbuminemia, hyponatremia, elevated D-dimers, and lactate dehydrogenase (see text for details). The absence of hemophagocytosis in the BM does not exclude a diagnosis of HLH.

† New data show normal variation by age. Level should be compared with age-related norms.

@@ Line 1: / Line 1: @@
+== Etiologies ==
-== Diagnostic Criteria (HLH-2004) ==
+* Infection
+** Viral
+*** EBV (most common)
+*** CMV, parvovirus, HSV, VZV, measles, HHV-8, H1N1 influenza virus, parechovirus, and HIV
+*** SARS-CoV-2, possibly
+** After anti-TNF therapy: tuberculosis, CMV, EBV, or histoplasmosis
+** Rare: Brucella, gram-negative bacilli, tuberculosis, Leishmaniasis, malaria, and fungal infections
+* Malignancy, most commonly lymphoid cancers and leukemias, but also solid cancers
+* Rheumatologic disease
+** Systemic juvenile idiopathic arthritis (Still disease)
+** Rheumatoid arthritis, dermatomyositis, systemic sclerosis, mixed connective tissue disease, antiphospholipid syndrome, Sjogren syndrome, ankylosing spondylitis, vasculitis, and sarcoidosis
+* Immunodeficiency
+** [[Primary immunodeficiency]]
+** HIV/AIDS, stem cell transplant, kidney transplant, liver transplant
+== Differential Diagnosis ==
+* Macrophage activation syndrome
+* Severe sepsis
+* Liver failure
+* Multiple organ dysfunction syndrome
+* [[Encephalitis]]
+* Autoimmune lymphoproliferative syndrome
+* [[Drug reaction with eosinophilia and systemic symptoms]] (DRESS)
+* [[Kawasaki disease]]
+* [[Cytophagic histiocytic panniculitis]]
+* [[TTP]]/[[HUS]]/[[DITMA]]
+* Transfusion-associated graft-versus-host disease
+==Diagnostic Criteria (HLH-2004)==
 The diagnosis of HLH can be established if one of either 1 or 2 below is fulfilled:
-# A molecular diagnosis consistent with HLH is made.
+#A molecular diagnosis consistent with HLH is made.
-# Diagnostic criteria for HLH are fulfilled (5 of the 8 criteria below):*
+#Diagnostic criteria for HLH are fulfilled (5 of the 8 criteria below):*
-#* Fever
+#*Fever
-#* Splenomegaly
+#*Splenomegaly
-#* Cytopenias (affecting ≥ 2-3 lineages in the peripheral blood):
+#*Cytopenias (affecting ≥ 2-3 lineages in the peripheral blood):
-#** hemoglobin &lt; 90 g/L (in infants &lt; 4 weeks of age, hemoglobin &lt; 100 g/L)
+#**hemoglobin &lt; 90 g/L (in infants &lt; 4 weeks of age, hemoglobin &lt; 100 g/L)
-#** platelets &lt; 100x10^9^/L
+#**platelets &lt; 100x10^9^/L
-#** neutrophils &lt; 1.0x10^9^/L
+#**neutrophils &lt; 1.0x10^9^/L
-#* Hypertriglyceridemia and/or hypofibrinogenemia:
+#*Hypertriglyceridemia and/or hypofibrinogenemia:
-#** fasting triglycerides ≥ 3.0 mmol/L (ie, ≥ 265 mg/dL)
+#**fasting triglycerides ≥ 3.0 mmol/L (ie, ≥ 265 mg/dL)
-#** fibrinogen ≤ 1.5 g/L
+#**fibrinogen ≤ 1.5 g/L
-#* Hemophagocytosis in BM, spleen, or lymph nodes
+#*Hemophagocytosis in BM, spleen, or lymph nodes
-#* Low or absent NK-cell activity (according to local laboratory reference)
+#*Low or absent NK-cell activity (according to local laboratory reference)
-#* Ferritin ≥ 500 g/L
+#*Ferritin ≥ 500 g/L
-#* Soluble CD25 (ie, sIL2r)  2400 U/mL†
+#*Soluble CD25 (ie, sIL2r)  2400 U/mL†
-* Supportive criteria include neurologic symptoms, cerebrospinal fluid pleocytosis, conjugated hyperbilirubinemia and transaminitis, hypoalbuminemia, hyponatremia, elevated D-dimers, and lactate dehydrogenase (see text for details). The absence of hemophagocytosis in the BM does not exclude a diagnosis of HLH.
+*Supportive criteria include neurologic symptoms, cerebrospinal fluid pleocytosis, conjugated hyperbilirubinemia and transaminitis, hypoalbuminemia, hyponatremia, elevated D-dimers, and lactate dehydrogenase (see text for details). The absence of hemophagocytosis in the BM does not exclude a diagnosis of HLH.
-† New data show normal variation by age. Level should be compared with agerelated norms.
+† New data show normal variation by age. Level should be compared with age-related norms.
 [[Category:Hematology]]