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Annual Review of Medicine

Volume 74, 2023

Cytokine Storm Syndrome

Abstract

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.

Keyword(s): cytokine release syndrome, cytokine storm syndrome, cytolysis, hemophagocytic lymphohistiocytosis, hyperinflammation, macrophage activation syndrome
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2023-01-27
2024-04-28
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Cytokine Storm Syndrome
Annual Review of Medicine 74, 321 (2023); https://doi.org/10.1146/annurev-med-042921-112837
/content/journals/10.1146/annurev-med-042921-112837
/content/journals/10.1146/annurev-med-042921-112837
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