Prevalence and mortality of haemophagocytic lymphohistiocytosis in dengue fever: a systematic review and meta-analysis

Trans R Soc Trop Med Hyg. 2024 May 9:trae032. doi: 10.1093/trstmh/trae032. Online ahead of print.

Abstract

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare complication of dengue fever with potentially life-threatening consequences and high mortality. Therefore, this study aims to investigate the prevalence, management and outcome of HLH in dengue fever.

Methods: The major electronic databases, including PubMed, ScienceDirect and Ovid SP, were searched from inception until 31 January 2024 to identify relevant studies. Pooled prevalence and mortality were calculated using the random-effects generic inverse variance model with a 95% CI. All the statistical analysis was conducted using R programming.

Results: A total of nine studies with 157 patients with HLH, 576 patients with severe dengue and 5081 patients with dengue fever were included in this meta-analysis. The prevalence of HLH in severe dengue (22.1%, 95% CI 8.07 to 48.0%) was significantly higher than the prevalence in dengue fever (3.12%, 95% CI 0.37 to 21.9%). The prevalence of HLH in severe dengue was higher in the paediatric population (22.8%, 95% CI 3.9 to 68.4%) compared with the adult population (19.0%, 95% CI 3.0 to 63.9%). The overall mortality rate was 20.2% (95% CI 9.7 to 37.2%).

Conclusion: The prevalence of dengue-associated HLH was low in patients with dengue fever but is significantly higher in patients with severe dengue and a high mortality rate.

Keywords: dengue; haemophagocytic lymphohistiocytosis; mortality; prevalence; treatment outcome.