It is thought to be closely related and pathophysiologically very similar to reactive (secondary) hemophagocytic lymphohistiocytosis (HLH).
[1] The incidence of MAS is unknown as there is a wide spectrum of clinical manifestations, and episodes may remain unrecognized.
The hallmark clinical and laboratory features include high fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, liver dysfunction, disseminated intravascular coagulation, hypofibrinogenemia, hyperferritinemia, and hypertriglyceridemia.
Despite marked systemic inflammation, the erythrocyte sedimentation rate (ESR) is paradoxically depressed, caused by low fibrinogen levels.
[2] There is uncontrolled activation and proliferation of macrophages, and T lymphocytes, with a marked increase in circulating cytokines, such as IFN-gamma, and GM-CSF.