Higher Fatality for Severe Fever with Thrombocytopenia Syndrome Complicated by Hemophagocytic Lymphohistiocytosis

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious zoonosis caused by the SFTS virus. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome associated with excessive immune activation. Cytokine storms are often seen in both SFTS and HLH, resulting in rapid disease progression and poor prognosis. The aim of this study was to identify whether SFTS cases complicated by HLH are related to higher rates of mortality. Descriptive analysis of the frequency of clinical and laboratory data, complications, treatment outcomes, and HLH-2004 criteria was performed. Cases presenting with five or more clinical or laboratory findings corresponding to the HLH-2004 diagnostic criteria were defined as SFTS cases complicated by HLH. Eighteen cases of SFTS were identified during a 2-year study period, with a case-fatality proportion of 22.2% (4 among 18 cases, 95% confidence interval 9%–45.2%). SFTS cases complicated by HLH were identified in 33.3% (6 among 18 cases). A mortality rate of 75% (3 among 4 cases) was recorded among SFTS cases complicated by HLH. Although there were no statistically significant differences in outcomes, fatal cases exhibited more frequent correlation with HLH-2004 criteria than non-fatal cases [3/14 (21.4%) vs. 3/4 (75%), p =0.083]. In conclusion, the present study suggests the possibility that SFTS cases complicated by HLH are at higher risk of poor prognosis.

Risk Factors and Clinical Characteristics of Severe Fever with Thrombocytopenia Syndrome

“… 4 Jung et al suggested SFTS cases complicated by HLH have a worse prognosis. 27 In our data, bone marrow aspirate was performed in 23 patients. Heteromorphic lymphocyte can be found in more than half of surviving patients.…”

Single-cell landscape of peripheral immune responses to fatal SFTS

“…The underlying mechanism had been posed from other viruses such as influenza virus or HIV, where infected monocytes could initiate hyper-coagulation and severely decrease the clotting time (Bouwman et al, 2002;Wilson et al, 2014). It is strongly postulated that SFTSV-activated monocytes in part trigger systemic inflammatory response syndrome (SIRS) in severe/fatal cases, and they play a critical role in inducing coagulation abnormalities, even hemophagocytic lymphohistiocytosis (HLH), the complication of which had been disclosed from autopsy pathology of fatal SFTS and clinical series (Jung et al, 2019).…”

Severe fever with thrombocytopenia syndrome virus: emerging novel phlebovirus and their control strategy

“…Apart from the advanced age of the affected patient, hemophagocytic lymphohistiocytosis (HLH) and central nervous symptoms have also been found to be associated with fatal outcomes. Further, an association between fatal cases of SFTS and HLH was described in another study 54 , 55 , although only a small number of cases were reported. HLH is an immune-mediated life-threatening syndrome associated with excessive immune activation 56 .…”