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Review
. 2024 Apr;52(2):471-482.
doi: 10.1007/s15010-023-02104-w. Epub 2023 Oct 24.

Hemophagocytic lymphohistiocytosis-how common and how severe is it as a complication of malaria? Retrospective case series and review of the literature

Hans Martin Orth  1 , Dorothea Wiemer  2 , Sophie Schneitler  3 , Andreas Schönfeld  4 , Martha Charlotte Holtfreter  5 , Smaranda Gliga  5 , Andre Fuchs  6 , Frieder Pfäfflin  7 , Claudia Maria Denkinger  8   9 , Sven Kalbitz  10 , Carlos Fritzsche  11 , Marc P Hübner  12   13 , Janina Trauth  14 , Björn-Erik Ole Jensen  5 , Tom Luedde  5 , Torsten Feldt  5
Affiliations
Review

Hemophagocytic lymphohistiocytosis-how common and how severe is it as a complication of malaria? Retrospective case series and review of the literature

Hans Martin Orth et al. Infection. 2024 Apr.

Abstract

Background: Infection-associated secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially life-threatening hyperinflammatory condition caused by various infectious diseases. Malaria has rarely been described as trigger. The aim of this study is to collect data on frequency, clinical spectrum, and outcome of sHLH induced by malaria.

Methods: We collected case numbers on malaria and malaria-associated sHLH from specialized centers in Germany from 2015 to 2022. In addition, we conducted a literature search on published cases of malaria-associated sHLH and systematically analyzed the literature regarding clinical and diagnostic criteria.

Results: We obtained data from 13 centers treating 1461 malaria cases with different Plasmodium species, of which 5 patients (0.34%) also were diagnosed with sHLH. The literature search revealed detailed case reports from further 51 patients and case series comprising the description of further 24 patients with malaria-associated sHLH. Most cases (48/80; 60%) were reported from Asia. The median time interval between onset of malaria symptoms and hospital admission was 7 days. Severe complications of sHLH were documented in 36% (20/56) of patients, including two patients with multiple organ failure in our case series. Only 41% (23/56) of patients received specific treatment for sHLH, nevertheless the mortality rate (CFR) of 5% is lower compared to the CFR reported for sHLH triggered by other infectious diseases (e.g., 25% in sHLH due to EBV infection).

Conclusion: Malaria-associated sHLH appears to have a comparatively good prognosis but may still represent an underdiagnosed and potentially fatal complication of malaria, especially in resource-poor settings.

Keywords: Plasmodium; HLH; HScore; Malaria.

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Conflict of interest statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Calculation of HScore for the diagnosis of reactive hemophagocytic lymphohistiocytosis. The HScore is formed from the sum of the values of the individual criteria. Hgb hemoglobin, WBC white blood count, AST aspartate aminotransferase
Fig. 2
Fig. 2
HLH-2004 criteria for the diagnosis of hemophagocytic lymphohistiocytosis. The diagnosis is confirmed if five or more criteria are fulfilled. Hgb hemoglobin, sIL2 soluble interleukin-2, CSF cerebrospinal fluid
See this image and copyright information in PMC

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