Hyperferritinemia in Severe Dengue Infection: Single-Center Retrospective Cohort Study

OBJECTIVES: Hyperferritinemia in the critical phase of dengue infections may correlate with severe dengue ( sd ) disease, and our primary objective was to examine the association between ferritin level on day 1 of PICU admission and 2009 World Health Organization (WHO) criteria for sd . Our secondary objective was outcome in relation to care. It is unclear whether immunomodulatory therapy during the critical phase may restore immune homeostasis and mitigate disease severity.

DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of children with dengue 1 month to 16 years old with admission ferritin greater than or equal to 500 ng/mL requiring PICU admission. Demographics, clinical, and laboratory parameters, presence of the 2009 WHO sd criteria and outcomes were analyzed. Immunomodulatory therapy was used when there was persistent hyperinflammation beyond the critical phase of plasma leakage.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Fifty-five patients were admitted in the critical phase of dengue with median (interquartile range) ferritin levels of 8,105 ng/mL (2,350-15,765 ng/mL). Patients with at least one WHO sd category had higher ferritin levels compared to those without any sd criteria, with the highest levels in eight patients with all three sd categories. In our cohort of 55, 52 patients (94%) recovered with standard supportive therapy. Recovery was associated with decreased ferritin levels that occurred in parallel with improved circulation and platelet counts; this included 22 of 24 patients with admission ferritin levels greater than or equal to 10,000 ng/mL and two with ferritin greater than 1,00,000 ng/mL. Immunomodulation was used in three patients with unremitting fever, persistent hyperferritinemia, and progressive multiple organ dysfunction beyond the critical phase, of whom two died.

CONCLUSIONS: Hyperferritinemia in the critical phase of sd is associated with the number of 2009 WHO sd criteria present. Our data also indicate that many patients with sd recover well with supportive care.