Cytokine-release syndromes

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

CRS; Cytokine release syndrome; Cytokine Release Syndrome

Definition
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Cytokine-release syndrome, also known as cytokine-release syndrome, is an undesirable side effect(ADR) caused by the systemic application of various drugs or other therapeutic measures that induce massive cell decay.

Etiopathogenesis
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The cytokine-release syndrome is considered an "infusion reaction". The ADR is caused by a sudden release of cytokines such as TNF-alpha, IL-8, IL-6 (Barker CA et al. 2018), triggered by massive decay of immune or tumor cells. The cytokine IL-6 is believed to play a central role in this process.

The syndrome was described after application

  • of various biologicals such as rituximab, tocilizumab, alemtuzumab, basiliximab, muromonab-CD3 (Lichtenstein L et al. 2015)
  • after a CAR-T cell therapy
  • after versch. Chemotherapeutics
  • after radiotherapy - very rarely - (Barker CA et al. 2018)

Clinical features
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Clinically, this ADR is characterized by varying degrees of body reactions such as fever, nausea, chills, arterial hypotension, tachycardia, asthenia, headache, macular exanthema and dyspnoea (Vultaggio A et al. 2014). The clinical presentation may well correspond to an IgE-mediated immediate type response (Lee DW et al. 2015)

Massive reactions up to a cytokine storm often occur during the first treatment, especially in hematological diseases. They can be life-threatening.

The following degrees of severity can be distinguished (Porter D et al. 2018):

  • Grade 1 (only symptomatic therapy required)
  • Grade 2 (moderately intensive treatment necessary)
  • Grade 3 (aggressive therapy necessary)
  • Grade 4 (life-threatening)
  • Grade 5 (with death consequences)

Therapy
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The therapeutic ones are to be aligned according to the trigger and severity. For rheumatic diseases, antihistamines, glucocorticoids or NSAIDs can be given as a preventive measure. Depending on the severity of the disease, immunosuppression can be administered in varying degrees. For grade 4 and 5 reactions, intensive medical measures are necessary.

Literature
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  1. Barker CA et al (2018) Cytokine release syndrome after radiation therapy: case report and review of the literature. J Immunother Cancer 6:1.
  2. Lichtenstein L et al (2015) Infliximab-Related Infusion Reactions: Systematic Review. J Crohn's colitis 9:806-815.
  3. Porter D et al (2018) Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol 11: 35
  4. Vultaggio A et al (2014) Hypersensitivity reactions to biological agents. Immunol Allergy Clin North Am 34:615-632

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

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Last updated on: 29.10.2020