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macrophage activation syndrome

Tuesday 21 October 2003

Definition: Macrophagic activation syndrome is a severe and acute clinical event occurring with fever, hepatosplenomegaly, and pancytopenia due to uncontrolled phagocytosis of blood cells and precursors.

Hemophagocytic syndrome results from a inappropriate stimulation of macrophages in bone marrow and lymphoid organs, leading to phagocytosis of blood cells and production of high amounts of pro-inflammatory cytokines.

This life-threatening disease combines non-specific clinical signs (fever, cachexia, hepatomegaly, enlargement of spleen and lymph nodes) as well as typical laboratory findings (bi- or pancytopenia, abnormal hepatic tests, hypofibrinemia, elevation of serum LDH, ferritinemia and triglyceride levels). Diagnosis is confirmed by cytological or pathological examination of bone marrow or tissue specimens.

Microscopical synopsis

- erythrophagocytosis
- lymphocytophagocytosis
- hemophagocytosis


Primary - Constitutional Immune deficiency

- familial hemophagocytic lymphohistiocytosis

  • FHL1 (unknown gene at 9q21-q22) (MIM.267700)
  • FHL2 (PRF1 mutations at 10q22) (MIM.603553)
  • FHL3 (UNC13D mutations at 17q25) (MIM.608898)
  • FHL4 (STX11 mutations at 6q24) (MIM.603552)

- Griscelli syndrome (Grsicelli disease)

  • GS1 (MYO5A mutations at 15q21) (MIM.214450)
  • GS2 (RAB27A mutations at 15q21) (MIM.607624)
  • GS3 ( (MLPH mutations at 2q37) (MIM.609227)

- X-linked EBV associated lymphoproliferative disease

  • XLP1 (SH2D1A or BIRC3 mutations at Xq25) (MIM.308240)
  • XLP2 (XIAP mutations at Xq25) (MIM.300635)

- Chediak-Higashi disease (LYST mutations at 1q42) (MIM.214500) (2165746)

- Ommen disease (MIM.603554)

  • RAG1 mutations at 11p13 (MIM.179615)
  • RAG2 mutations at 11p13 (MIM.179616)
  • DCLRE1C (Artemis) at 10p (MIM.605988)

- Abnormal response to EBV

Secondary (reactive hemophagocytic syndrome)

- infections (IAHS Infection Associated Hemophagocytic Syndrome)(11076718)

- fungal infections

- parasitic infections

  • helminthiases
    • Strongyloidiase (Strongylides stercoralis)

- metabolic diseases

- dysimmunity - autoimmunity (11407091)

- tumoral diseases (Tumors)

  • Lymphomas (11420457)
    • T lymphoma (10824495, 8590855, 8080885), nasal T-cell lymphoma (2423228)
    • CD30+ anaplastic large-cell lymphoma (ALCL) (11426532, 9575683)
    • subcutaneous panniculitic T-cell lymphoma (cytophagic histiocytic panniculitis) (8621826)
    • B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS)(11579948, 10965786)
    • hepatosplenic B-cell lymphoma (10642947)
    • hepato-splenic gammadelta T-cell lymphoma (9883807)
    • intravascular B-cell lymphoma (intravascular lymphomatosis, angiotropic large B-cell lymphoma)(10342574, 7808970)

- histiocytoses


- deletion of 22q11 (10588839)
- fulminant ulcerative colitis (9772064)

- Web. CDC.


- Gaffey MJ, Frierson HF Jr, Medeiros LJ, Weiss LM. The relationship of Epstein-Barr virus to infection-related (sporadic) and familial hemophagocytic syndrome and secondary (lymphoma-related) hemophagocytosis: an in situ hybridization study. Hum Pathol. 1993 Jun;24(6):657-67. PMID: 8389318

- Favara BE. Hemophagocytic lymphohistiocytosis: a hemophagocytic syndrome. Semin Diagn Pathol. 1992 9:63-74. PMID: 1561489; UI: 92221172

- Arya S, Hong R, Gilbert EF. Reactive hemophagocytic syndrome. Pediatr Pathol. 1985;3(2-4):129-41. PMID: 4095022;