Macrophage Activation Syndrome

  • Esraa M. Eloseily
  • Randy Q. CronEmail author


Hemophagocytic lymphohistiocytosis (HLH), or termed macrophage activation syndrome (MAS) when associated with rheumatic disorders, is a frequently fatal complication of infections, rheumatic disorders, and hematopoietic malignancies. Clinically, HLH/MAS is a life-threatening condition that is usually diagnosed among febrile hospitalized patients (children and adults) who commonly present with unremitting fever and a shock-like multiorgan dysfunction scenario. Laboratory studies reveal pancytopenia, elevated liver enzymes, elevated markers of inflammation (ESR, CRP), hyperferritinemia, and features of coagulopathy. In about 60% of cases, excess hemophagocytosis (macrophages/histiocytes engulfing other hematopoietic cell types) is noted on biopsy specimens from the bone marrow, liver, lymph nodes, and other organs. HLH/MAS has been hypothesized to occur when a threshold level of inflammation has been achieved, and genetic and environmental risk factors are believed to contribute to the hyperinflammatory state. A broad variety of infections, from viruses to fungi to bacteria, have been identified as triggers of HLH/MAS, either in isolation or in addition to an underlying inflammatory disease state. Certain infections, particularly by members of the herpesvirus family, are the most notorious triggers of HLH/MAS. Treatment for infection-triggered MAS requires therapy for both the underlying infection and dampening of the hyperactive immune response.


Cytokine storm Epstein-Barr virus Hemophagocytic lymphohistiocytosis Interleukin-1 Macrophage activation syndrome 



Acquired immunodeficiency syndrome


Antigen-presenting cell


Cyclosporine A


Cytotoxic T lymphocyte


Cytotoxic T-lymphocyte-associated protein 4


Disseminated intravascular coagulopathy


Epstein-Barr virus


Familial hemophagocytic lymphohistiocytosis


Follistatin-like 1


Granulocyte colony-stimulating factor


Granulocyte-macrophage colony-stimulating factor


Hepatitis A virus


Hepatitis B virus


Hepatitis C virus


Human immunodeficiency virus


Hemophagocytic lymphohistiocytosis




Hematopoietic stem cell transplant


Intensive care unit






Interleukin-18-binding protein


Interleukin-1 receptor antagonist


Intravenous immunoglobulin


Macrophage activation syndrome

NK cell

Natural killer cell


Soluble haptoglobin receptor


Soluble interleukin-2 receptor alpha chain


Secondary hemophagocytic lymphohistiocytosis


Systemic juvenile idiopathic arthritis


Systemic lupus erythematosus


T-helper 1


Toll-like receptor


Tumor necrosis factor


United States of America


X-linked lymphoproliferative disease


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Assiut University Children’s HospitalAssiutEgypt
  2. 2.University of Alabama at BirminghamBirminghamUSA

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