Cytokine Storm Syndrome

Cytokine storm syndrome (CSS), which is frequently fatal, has garnered increased attention with the ongoing coronavirus pandemic. A variety of hyperinflammatory conditions associated with multiorgan system failure can be lumped under the CSS umbrella, including familial hemophagocytic lymphohistiocytosis (HLH) and secondary HLH associated with infections, hematologic malignancies, and autoimmune and autoinflammatory disorders, in which case CSS is termed macrophage activation syndrome (MAS). Various classification and diagnostic CSS criteria exist and include clinical, laboratory, pathologic, and genetic features. Familial HLH results from cytolytic homozygous genetic defects in the perforin pathway employed by cytotoxic CD8 T lymphocytes and natural killer (NK) cells. Similarly, NK cell dysfunction is often present in secondary HLH and MAS, and heterozygous mutations in familial HLH genes are frequently present. Targeting overly active lymphocytes and macrophages with etoposide and glucocorticoids is the standard for treating HLH; however, more targeted and safer anticytokine (e.g., anti-interleukin-1, -6) approaches are gaining traction as effective alternatives.

Automated summary

Cytokine storm syndrome (CSS) is a frequently fatal hyperinflammatory condition that has gained attention during the ongoing coronavirus pandemic. It encompasses various hyperinflammatory disorders associated with multiorgan system failure, including familial hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). Familial HLH is caused by genetic defects in the perforin pathway, while secondary HLH and MAS often involve NK cell dysfunction. Treatment for HLH involves targeting overactive lymphocytes and macrophages with etoposide and glucocorticoids, but more targeted and safer anticytokine approaches are becoming popular.