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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;

Annual Review of Medicine
|October 13, 2022
PubMed
Summary

Cytokine storm syndrome (CSS) involves dangerous hyperinflammation. New anticytokine therapies offer safer alternatives to traditional treatments for conditions like hemophagocytic lymphohistiocytosis (HLH).

Keywords:
cytokine release syndromecytokine storm syndromecytolysishemophagocytic lymphohistiocytosishyperinflammationmacrophage activation syndrome

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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.