Macrophage Activation Syndrome

Macrophage Activation Syndrome

Abridged from http://www.humpath.com/macrophage-activation-syndrome on 2/9/09.
All links lead to humpath.org

severe and acute clinical event; life threatening
due to uncontrolled phagocytosis of blood cells and precursors.
inappropriate stimulation of macrophages in bone marrow and lymphoid organs, leading to phagocytosis of blood cells (and precursors) and production of high amounts of pro-inflammatory cytokines. The result is a hemophagocytic syndrome.
non-specific clinical signs

fever, cachexia, hepatomegaly, enlargement of spleen and lymph nodes

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
erythro phagocytosis
lymphocyto phagocytosis
hemo phagocytosis
Etiologies
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)

viral infections (VAHS virus-associated hemophagocytic syndrome)

EBV infection (EBV-associated hemophagocytic syndrome) (12481907, 12467966, 11456362, 8389318)

abnormal response to EBV infection (fatal infectious mononucleosis)(8892735, 8241498)
chronic active Epstein-Barr virus infection (1850588)

Cytomegalovirus CMV (11868605)
Parvovirus B19 (8741323)
HIV (14704039)
Human Herpesvirus-6 (HHV6) (8607365)
Human Herpesvirus-8 (HHV8)
adenovirus (2291998)
Dengue
hepatitis A, B and C (10367794, 7771394)
Herpes simplex
Influenza A (H1N1), Parainfluenza type III
measles (7787329)
rubela (11475151)
varicella (11475151)
Hantaan virus hemorrhagic fever (11897077)

bacterial infections

severe sepsis
spirochetoses

leptospirosis (Leptospira sp.) (9398130)
Borreliose (Borrelia burgdorferi)
Syphilis (Treponema pallidum)

brucellosis (Brucella melitensis) (8213671)
typhoïd fever (Salmonella typhi)

mycobactérioses (mycobacteremia)

tuberculosis with mycobacteremia (Mycobacterium tuberculosis) (12374364, 3779613, 16271925)
Mycobacterium avium intracellulare (12729056)

Chromobacterium violaceum
psitaccosis (Chlamydia psitacci)
Coxiella burnetti
erlichiosis (Ehrlichia canis) (1951324)
Mycoplasma pneumoniae (11483400)
rickettsioses, mediterranean spotted fever (Richettsia conorii)(7824495, 2592187)
Orientia tsutsugamushi
scrub typhus (tsutsugamushi disease) (10879646)
acute Q fever (8645795)

fungal infections

Apergillose
Candidose
Cryptococcose
histoplasmosis (11888034)
Penicillium marneffei
Trichophyton beigelii

parasitic infections

protozooses

visceral leishmaniasis (Kala-azar) (Leishmania sp.) (12240858, 11764103, 11205842, 8241681)
malaria(Plasmodium falciparum) (12458577, 8923789)
babesiosis (Babesia microti) (8781622, 7668227, 3946448)
toxoplasmosis

helminthiases

Strongyloidiase (Strongylides stercoralis)

metabolic diseases

lysinuric protein intolerance (9931537)
lipid rich parenteral nutrition

dysimmunity - autoimmunity (11407091)

systemic erythematosus lupus (11868605, 9678692)
Still disease (12737332, 9263166)
allogeneic peripheral blood stem cell transplantation (12040480, 11372742, 11039676)
visceral allograft (9771844)
vasculitis

Kawasaki disease (12886898, 10845231)
systemic erythematosus lupus (11868605, 9678692)

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)

Leukemias

T-cell acute lymphoblastic leukemia (T-ALL) with t(11;14)(p15;q11) (3024802)
NK cell leukemia (8854571, 1746541)

histiocytoses

Langerhans cell histiocytosis (LCH) (11910507, 7626381, 7626381)
systemic juvenile janthogranuloma (systemic XLG) (16047346, 15022067, 9025843)
Erdheim-Chester disease (ECD) (15679446)

Miscellaneous
deletion of 22q11 (10588839)
fulminant ulcerative colitis (9772064)
Web. CDC.
References
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) hemo phagocytosis: 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;