Abstract

Background
Globally approximately 500,000 people with severe dengue (SD) require hospitalization yearly; about 12,500 (2.5%) die. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially fatal hyperinflammatory condition for which HLH-directed therapy (as etoposide and dexamethasone) can be life-saving. Prompted by the high mortality in SD and the increasing awareness that patients with SD may develop sHLH, our objectives were to i) determine the frequency of dengue-HLH in SD, ii) describe clinical features of dengue-HLH, iii) assess mortality rate in SD and dengue-HLH, and iv). identify mortality-associated risk factors in SD.
Methods
A 5-year retrospective single-center study on all adult patients with SD admitted to a tertiary ICU in Malaysia.
Results
Thirty-nine/180 (22%) patients with SD died. Twenty-one/180 (12%) had HLH defined as HLH-probability ≥70% according to HScore; nine (43%) died. Similarly, 12/31 (39%) fulfilling ≥4 and 7/9 (78%) fulfilling ≥5 HLH-2004 diagnostic criteria died. Peak values of AST, ALT, LDH, and creatinine correlated to fatality (OR=2.9, 3.4, 5.8, and 31.9; all p<0.0001), as did peak ferritin (OR=2.5, p=0.0028), nadir platelets (OR=1.9, p=0.00068), hepatomegaly (OR=2.9, p=0.012), and increasing age (OR=1.2, p=0.0043). Multivariable logistic regression revealed peak AST (OR=2.8, p=0.0019), peak creatinine (OR=7.3, p=0.0065), and SOFA score (OR=1.4, p=0.0051) as independent risk factors of death.
Conclusions
Be observant of dengue-HLH due to its high mortality. A prospective study is suggested on prompt HLH-directed therapy in SD patients with hyperinflammation and evolving multi-organ failure at risk of developing dengue-HLH.
Dengue infection, hemophagocytic lymphohistiocytosis, corticosteroids, etoposide, multi-organ failure
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Author notes

Authors LHT and JIH contributed equally to this manuscript
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Supplementary data

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