Cytokine Storm- A Comprehensive Review By NEJM
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The SARS-CoV-2 pandemic has reminded us of the critical role of an effective host immune response and the devastating effect of immune dysregulation. This year marks 10 years since the first description of a cytokine storm that developed after chimeric antigen receptor (CAR) T-cell therapy and 27 years since the term was first used in the literature to describe the engraftment syndrome of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation.

The term “cytokine release syndrome” was coined to describe a similar syndrome after infusion of muromonab-CD3 (OKT3). Cytokine storm and cytokine release syndrome are life-threatening systemic inflammatory syndromes involving elevated levels of circulating cytokines and immune-cell hyperactivation that can be triggered by various therapies, pathogens, cancers, autoimmune conditions, and monogenic disorders.

It is important for the clinician to recognize cytokine storm because it has prognostic and therapeutic implications. This review proposes a unifying definition of cytokine storm; discuss the pathophysiological features, clinical presentation, and management of the syndrome; and provide an overview of iatrogenic, pathogen-induced, neoplasia-induced, and monogenic causes.

The general treatment strategy for cytokine storm involves supportive care to maintain critical organ function, control of the underlying disease and elimination of triggers for abnormal immune system activation, and targeted immunomodulation or nonspecific immunosuppression to limit the collateral damage of the activated immune system. As noted in this review, a number of drugs are effective across multiple disorders under the cytokine storm umbrella and still more may be effective in multiple conditions that have not yet been studied.

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