Is Severe Dengue a Cytokine Storm Syndrome?

The immunopathogenesis of dengue severity remains an enigma. There is a growing body of evidence pointing towards a transient hyperinflammatory hypercytokinemic state responsible for the development of severe dengue including dengue hemorrhagic fever that coincides with the onset of thrombocytopenia, capillary leak, multiorgan dysfunction and hyperferritinemia. There are several reports of dengue associated hemophagocytic lymphohistiocytosis (HLH). However, the cytokine storm in dengue as well as in other infections may not conform to the classic HLH 2004 diagnostic criteria. Following the recent COVID-19 pandemic, there has been a paradigm shift in the understanding of infection-associated cytokine storms. There is a need to explore timely short-course immunotherapy for the management of selected patients with dengue spiraling into the critical phase.