Macrophage Activation Syndrome

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.