Severe Dengue Associated With Hemophagocytic Lymphohistiocytosis (HLH) in an Adult ICU

Abstract

Background: Dengue virus infection is a growing global health concern, especially in tropical and subtropical regions. Dengue fever is commonly self-limiting, but sometimes, rare complications such as hemophagocytic lymphohistiocytosis (HLH) may occur, leading to fatal outcomes. HLH is a rare, hyperinflammatory syndrome marked by excessive immune activation, which can result in multiorgan failure and death. The relationship between dengue and HLH, particularly in adults, is not well understood, and early diagnosis and treatment remain critical for improving outcomes.

Method: A total of 15 adult patients with severe dengue were admitted to a tertiary care ICU setting in North India from September to December 2023. Out of 15 patients, seven were diagnosed with dengue-associated HLH based on H-Score, and bone marrow aspiration was done in six patients. In this retrospective case series, we reviewed their clinical characteristics, laboratory findings, treatment regimens, and outcomes.

Results: The median age of patients was 34 years, with female predominance. The Acute Physiology and Chronic Health Evaluation (APACHE) II score upon admission had a median value of 18, while the Sequential Organ Failure Assessment (SOFA) score at the time of HLH diagnosis had a median value of 11. The median day of illness at the time of HLH diagnosis was 23 days. The H-Score had a median value of 241 at the time of HLH diagnosis, supported by bone marrow aspiration, indicating a >99% probability of HLH. The mortality rate was 50%. Aggressive treatment with corticosteroid therapy, intravenous immunoglobulin (IVIG), or a combination of both, along with other supportive care, was given to the patients.

Conclusion: Persistent fever, altered mental status, bicytopenia, elevated triglyceride levels, and markedly elevated serum ferritin levels are important to differentiate dengue-associated HLH from severe dengue. H-Score can assist in the early identification of HLH. Early recognition and timely initiation of HLH-targeted therapy are essential for improving survival rates.

Keywords: dengue-associated hemophagocytic lymphohistiocytosis (hlh); h-score; immunosuppressive therapy; multiorgan failure; severe dengue.

Figure 1. (A) Peripheral smear shows pancytopenia. (B) Bone marrow aspirate showing hypocellular marrow with increased histocytes with hemophagocytosis