Hemophagocytic lymphohistiocytosis

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For the protein structural motif, see Basic-helix-loop-helix.

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Hemophagocytic lymphohistiocytosis Classification and external resources
ICD-10	D 76.1
ICD-9	288.4
OMIM	267700 603552
DiseasesDB	31418
eMedicine	ped/745
MeSH	D051359

Hemophagocytic lymphohistiocytosis (HLH) is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis. This is phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues.

Light microscopic image of bone marrow showing stromal macrophages containing numerous red blood cells in their cytoplasm

HLH may be associated with malignant, genetic, or autoimmune diseases. It is also prominently linked with Epstein-Barr virus (EBV) infection, however it can also be associated with other viruses as well as fungal infections.

Hyperproduction of cytokines, including interferon-g and tumor necrosis factor-a, by EBV-infected T lymphocytes may play a role in the pathogenesis of HLH. EBV-associated HLH may mimic T-cell lymphoma and is treated with cytotoxic chemotherapy. In contrast, hemophagocytic syndromes associated with nonviral pathogens often respond to treatment of the underlying infection.

HLH comprises familial (primary) hemophagocytic lymphohistiocytosis (FHL) and secondary HLH (SHLH), both clinically characterized by the features described above, in particular fever, hepatosplenomegaly, and cytopenia.

[edit] Familial forms

Familial hemophagocytic lymphohistiocytosis has an autosomal recessive pattern of inheritance.

FHL, an autosomal recessive disorder, is invariably fatal when untreated. It is associated with defective triggering of apoptosis and reduced cytotoxic activity, resulting in a widespread accumulation of T lymphocytes and activated macrophages.

There are four types, and each is associated with a specific gene:

FHL1 - HPLH1
FHL2 - PRF1
FHL3 - UNC13D
FHL4 - STX11

[edit] References

Fisman DN (2000). "Hemophagocytic syndromes and infection". Emerging Infect. Dis. 6 (6): 601–608. PMID 11076718.

Henter JI, Samuelsson-Horne A, Aricò M, et al (2002). "Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation". Blood 100 (7): 2367–2373. doi:10.1182/blood-2002-01-0172. PMID 12239144.

[edit] External links

v • d • e Pathology: hematology, hematologic disease (primarily D50-D77, 280-289)

RBCs/anemia/ hemoglobinopathy (Myeloid)	nutritional anemia: Iron deficiency anemia, Plummer-Vinson syndrome, Megaloblastic anemia (Pernicious anemia) hereditary hemolytic anemia: enzyme disorders (G6PD Deficiency, Pyruvate kinase deficiency,Triosephosphate isomerase deficiency), Thalassemia, Sickle-cell disease/trait, Hereditary spherocytosis, Hereditary elliptocytosis, Hereditary stomatocytosis acquired hemolytic anemia: Autoimmune (Warm), HUS, MAHA, PNH, PCH aplastic anemia: Acquired PRCA, Diamond-Blackfan anemia, Fanconi anemia • Sideroblastic anemia Polycythemia - Methemoglobinemia

Coagulation/platelets (Myeloid)	coagulopathy: DIC (Congenital afibrinogenemia, Purpura fulminans) • Hemophilia (A/VII, B/IX, C/XI, XIII) • Von Willebrand disease • Hypoprothrombinemia Purpura: Henoch-Schönlein, ITP (Evans syndrome), TTP primary hypercoagulable state: Protein C deficiency - Protein S deficiency - Antithrombin III deficiency - Factor V Leiden - Activated protein C resistance - Antiphospholipid syndrome other hemorrhagic conditions: Bernard-Soulier syndrome - Glanzmann's thrombasthenia - Grey platelet syndrome - May Hegglin anomaly - Pelger-Huet anomaly Essential thrombocytosis - Thrombocytopenia

Monocytes/Macrophages (Myeloid)	WHO-I histiocytosis (Langerhans cell histiocytosis) WHO-II/non-Langerhans-cell histiocytosis (Juvenile xanthogranuloma, Hemophagocytic lymphohistiocytosis) WHO-III/malignant histiocytic disorders (Acute monocytic leukemia, Malignant histiocytosis, Erdheim-Chester disease) -cytosis: Monocytosis -penia: Monocytopenia

Granulocytes (Myeloid)	-cytosis: granulocytosis (Neutrophilia, Eosinophilia, Basophilia) -penia: Granulocytopenia/agranulocytosis (Neutropenia, Kostmann syndrome)

Other/general myeloid	Chronic granulomatous disease

Lymphoid	-cytosis: Lymphocytosis -penia: Lymphopenia

Other	Splenic disease (Asplenia/hyposplenism, Wandering spleen) - Pancytopenia

See also hematological malignancy and immune disorders