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

Abstract

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 remains 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.

Clinical Utility of Extracorporeal Cytokine Hemoadsorption Therapy: A Literature Review

“…Its use in this context persisted until 1996 when Aikawa used the term in the context of post-surgical sepsis and MODS [15]. At present, "cytokine storm" encompasses a heterogeneous group of disorders characterized by life-threatening hyper-inflammation [16]. Many cytokine storm syndromes are triggered by infection, and sepsis remains the largest catch-all term used to categorize these conditions [16].…”

“…At present, "cytokine storm" encompasses a heterogeneous group of disorders characterized by life-threatening hyper-inflammation [16]. Many cytokine storm syndromes are triggered by infection, and sepsis remains the largest catch-all term used to categorize these conditions [16]. Noninfectious conditions that may trigger a cytokine storm include active rheumatic diseases (e.g., macrophage activation syndrome) and certain malignancies (e.g., malignancy-associated syndrome of hyper-inflammation) [16,17].…”

“…Many cytokine storm syndromes are triggered by infection, and sepsis remains the largest catch-all term used to categorize these conditions [16]. Noninfectious conditions that may trigger a cytokine storm include active rheumatic diseases (e.g., macrophage activation syndrome) and certain malignancies (e.g., malignancy-associated syndrome of hyper-inflammation) [16,17]. Clinical manifestations of a cytokine storm may include refractory fevers, cytopenias, coagulopathy, MODS, and death [17].…”

Combining multiple biomarkers differentiates between active SJIA, SJIA-MAS and EBV-HLH

“…Patients with systemic juvenile idiopathic arthritis (SJIA) have the highest predisposition to the development of MAS, as 10-30% of all SJIA patients will develop MAS at some point in their disease [1,2]. For example, high-dose, pulse steroids are used as first-line therapy for the treatment of SJIA-associated MAS followed by anakinra and/or cyclosporin for refractory disease [4]. However, a proportion of SJIA patients present with MAS at diagnosis, making it clinically important to differentiate between SJIA-associated MAS and other types of cytokine storm syndromes.…”

“…Recent expert consensus was used to generate diagnostic criteria to help identify MAS in patients known to have SJIA [3]. The approach to treating sepsis and haemophagocytic lymphohistiocytosis (HLH) is altogether different, and includes administration of antibiotics, fluids and supportive care for sepsis and dexamethasone and etoposide for HLH [4]. The ability to make an accurate clinical diagnosis is critical for rapid initiation of life-saving therapies, as treatment strategies for different cytokine storm syndromes vary dramatically.…”