What establishes the diagnosis of a cytokine storm?

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Last updated: June 18, 2025View editorial policy

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From the Guidelines

The diagnosis of a cytokine storm is established through a combination of clinical presentation and laboratory findings, including fever, widespread inflammation, organ dysfunction, and rapid deterioration, with laboratory diagnosis relying on elevated inflammatory markers such as high levels of cytokines, ferritin, C-reactive protein, and D-dimer, as outlined in recent studies 1.

Key Diagnostic Features

The clinical presentation of a cytokine storm typically includes:

  • Fever
  • Widespread inflammation
  • Organ dysfunction
  • Rapid deterioration Laboratory findings that support the diagnosis of a cytokine storm include:
  • Elevated inflammatory markers, such as:
    • High levels of cytokines (particularly IL-6, TNF-alpha, IL-1)
    • Ferritin above 500 ng/mL
    • C-reactive protein above 100 mg/L
    • Elevated D-dimer
  • Cytopenias (particularly lymphopenia)
  • Elevated liver enzymes
  • Lactate dehydrogenase (LDH)
  • Triglycerides

Diagnostic Criteria

The H-Score or HLH-2004 criteria can help assess the probability of hemophagocytic lymphohistiocytosis, a condition often associated with cytokine storms 1.

Exclusion of Other Causes

Diagnosis requires excluding other causes of systemic inflammation, such as sepsis or malignancy, as these conditions can also present with similar laboratory findings 1.

Treatment

Prompt recognition is critical, as cytokine storms can rapidly progress to multi-organ failure, with treatment typically involving immunomodulatory agents like corticosteroids, IL-6 inhibitors (tocilizumab), or JAK inhibitors, depending on the underlying cause and clinical context 1.

From the FDA Drug Label

ACTEMRA® (tocilizumab) is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of: ... Cytokine Release Syndrome (CRS) (1. 6) Adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome.

The diagnosis of a cytokine storm, also known as Cytokine Release Syndrome (CRS), is established by the presence of severe or life-threatening symptoms induced by an overactive immune response, such as those seen in CAR T cell-induced CRS. However, the FDA drug label for tocilizumab does not provide specific diagnostic criteria for cytokine storm. Key points:

  • The label mentions CAR T cell-induced severe or life-threatening cytokine release syndrome as an indication for tocilizumab treatment.
  • It does not provide a definition or diagnostic criteria for cytokine storm. 2

From the Research

Diagnosis of Cytokine Storm

The diagnosis of a cytokine storm is established by a combination of clinical and biochemical criteria.

  • Clinical criteria include the worsening of symptoms, such as respiratory distress, and the alteration of biological parameters on days 8-12 of the disease 3.
  • Biochemical criteria include elevated levels of inflammatory markers, such as:
    • C-reactive protein (CRP) > 30 mg/dL 4
    • Ferritin > 700 ng/mL 4
    • Lactate dehydrogenase (LDH) > 300 U/L 4
    • D-dimer elevation 4

Laboratory Tests

Laboratory tests, such as CRP, LDH, and ferritin, are used to monitor the severity of the cytokine storm and the response to treatment 3, 4.

  • These tests can help identify patients who are at high risk for severe disease and may benefit from immunomodulatory therapy.

Clinical Considerations

Clinical considerations, such as the presence of sepsis and respiratory failure, can also influence the diagnosis and treatment of cytokine storm 5.

  • Patients who meet the criteria for cytokine storm should be closely monitored and treated promptly with anti-cytokine agents, such as anakinra or tocilizumab, and corticosteroids 3, 4, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab.

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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