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Cytokine Storm Syndrome
Randy Q Cron1,2, Gaurav Goyal3, W Winn Chatham2
1Department of Pediatrics, Division of Rheumatology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA;
Insights
Cytokine storm syndrome (CSS) involves dangerous hyperinflammation. New anticytokine therapies offer safer alternatives to traditional treatments for conditions like hemophagocytic lymphohistiocytosis (HLH).
Area of Science:
- Immunology
- Pathology
- Genetics
Background:
- Cytokine storm syndrome (CSS) is a severe, often fatal hyperinflammatory condition.
- CSS encompasses conditions like familial and secondary hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS).
- The COVID-19 pandemic has increased focus on CSS due to its frequent occurrence and severity.
Purpose of the Study:
- To review the classification, diagnosis, and treatment of Cytokine Storm Syndrome (CSS).
- To highlight the genetic underpinnings of familial HLH and immune cell dysfunction in secondary HLH/MAS.
- To discuss evolving therapeutic strategies for CSS, including targeted anticytokine approaches.
Main Methods:
- Review of existing literature on Cytokine Storm Syndrome (CSS) classification and diagnostics.
- Analysis of genetic defects in familial hemophagocytic lymphohistiocytosis (HLH) and immune cell dysfunction in related syndromes.
- Evaluation of current and emerging therapeutic interventions for CSS, HLH, and MAS.
Main Results:
- Familial HLH stems from genetic defects in cytotoxic pathways (perforin).
- NK cell dysfunction is common in secondary HLH and MAS.
- Standard treatments like etoposide and glucocorticoids are being complemented by targeted anticytokine therapies (anti-IL-1, anti-IL-6).
Conclusions:
- Cytokine storm syndrome (CSS) presents diverse hyperinflammatory conditions requiring precise diagnosis.
- Genetic factors play a crucial role in familial HLH and contribute to secondary forms.
- Targeted anticytokine therapies represent a promising, safer alternative for managing CSS and related disorders.
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.
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