Weathering the Storm: Improving Therapeutic Interventions for Cytokine Storm Syndromes by Targeting Disease Pathogenesis

Pediatric Rheumatology (M Becker and J Harris, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Pediatric Rheumatology

Opinion statement

Cytokine storm syndromes require rapid diagnosis and treatment to limit the morbidity and mortality caused by the hyperinflammatory state that characterizes these devastating conditions. Herein, we discuss the current knowledge that guides our therapeutic decision-making and personalization of treatment for patients with cytokine storm syndromes. Firstly, ICU-level supportive care is often required to stabilize patients with fulminant disease while additional diagnostic evaluations proceed to determine the underlying cause of cytokine storm. Pharmacologic interventions should be focused on removing the inciting trigger of inflammation and initiation of an individualized immunosuppressive regimen when immune activation is central to the underlying disease pathophysiology. Monitoring for a clinical response is required to ensure that changes in the therapeutic regimen can be made as clinically warranted. Escalation of immunosuppression may be required if patients respond poorly to the initial therapeutic interventions, while a slow wean of immunosuppression in patients who improve can limit medication-related toxicities. In certain scenarios, a decision must be made whether an individual patient requires hematopoietic cell transplantation to prevent recurrence of disease. Despite these interventions, significant morbidity and mortality remain for cytokine storm patients. Therefore, we use this review to propose a clinical schema to guide current and future attempts to design rational therapeutic interventions for patients suffering from these devastating conditions, which we believe speeds the diagnosis of disease, limits medication-related toxicities, and improves clinical outcomes by targeting the heterogeneous and dynamic mechanisms driving disease in each individual patient.

Keywords

Hyperinflammation Macrophage activation syndrome Hemophagocytic lymphohistiocytosis Personalized medicine Cytokine storm 

Notes

Compliance with Ethical Standards

Conflict of Interest

Lehn K. Weaver declares no conflicts of interest.

Dr. Behrens reports personal fees from AB2Bio, during the conduct of the study. In addition, Dr. Behrens has a patent compositions and methods for treating hemophagocytic lymphohistiocytosis pending to The Children’s Hospital of Philadelphia.

Human and Animal Rights and Informed Consent

With regard to the authors’ research cited in this paper, all procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. In addition, all applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Division of Pediatric RheumatologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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