Role of anakinra in the management of children with severe dengue.

Abstract

Severe dengue in children may present with a hyperinflammatory phenotype resembling cytokine storm or secondary haemophagocytic lymphohistiocytosis, characterised by refractory shock, hepatic dysfunction and multiorgan failure. We evaluated the use of interleukin 1 receptor antagonist therapy (anakinra) in children with severe dengue. We conducted a retrospective study of children admitted to a tertiary paediatric intensive care unit in India between May 2021 and December 2023 with confirmed severe dengue who received anakinra. Cytokine storm was suspected based on clinical and laboratory criteria including elevated ferritin levels and hepatic dysfunction. Anakinra was administered intravenously and titrated according to clinical response. Adjunctive therapies included corticosteroids, intravenous immunoglobulin and plasmapheresis. The primary outcome was survival and is summarised descriptively. Of 49 children with severe dengue, 45 met the inclusion criteria. The median age was 48 months; median ferritin level was 16 433 ng/mL; peak levels exceeded 100 000 ng/mL in four children. Anakinra was used as monotherapy in 49%, and in combination with other immunomodulators in the remainder. Overall survival was 73% (36/49); when the four children who died within 24 hours of admission were excluded, survival was 80% (36/45). Improvement in fluid requirements, ferritin levels and hepatic transaminases was noted following anakinra initiation. Mortality was 100% in those with ferritin levels >100 000 ng/mL. Anakinra may represent a valuable adjunct in the management of severe dengue with hyperinflammation. Prospective, controlled studies are warranted to establish its efficacy, timing and optimal dosing.