Hemophagocytic lymphohistiocytosis: Difference between revisions

Latest revision as of 12:28, 7 June 2023

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, Sjögren syndrome, ankylosing spondylitis, vasculitis, and sarcoidosis
Immunodeficiency
- Primary immunodeficiency
- HIV, stem cell transplant, kidney transplant, liver transplant

Differential Diagnosis

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]], [[Sjögren syndrome]], [[ankylosing spondylitis]], [[vasculitis]], and [[sarcoidosis]]
+* Immunodeficiency
+** [[Primary immunodeficiency]]
+** [[HIV]], [[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]]