Effects of Plasma Exchange (PE) Therapy in a Severe Fever with Thrombocytopenia Syndrome (SFTS) Patient with High Virus Quantities

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by the SFTS bunyavirus, which is carried by ticks, and presents various symptoms such as fever, fatigue, digestive symptoms, and hemophagocytic lymphhistiocytosis (HLH). Since the first case was reported from China in 2011, there has been a rapid increase of newly diagnosed patients in Japan. Because the mortality rate has remained high (10-30%), there is an urgent need to establish a management strategy for SFTS.

Method: We retrospectively reviewed two newly-diagnosed cases of severe SFTS in our hospital from April 2015 to July 2015. Diagnosis of SFTS was confirmed rapidly using a conventional one-step RT-PCR (cvPCR) method, and the quantity of SFTS virus in each serum was determined with a quantitative one-step RT-PCR (qPCR) method described by Yoshikawa et al. (JCM2014, 52, 3325-33). Virus titer is indicated in units of log10 copies/ml.

Results: Case 1 was an 87-year-old female and Case 2 was an 81-year-old male. They showed similar severe clinical symptoms including disturbance of consciousness and a variety of abnormal laboratory findings. Both cases were quickly confirmed as SFTS using cvPCR on the next day after blood sampling. Bone marrow (BM) aspiration was performed at diagnosis, and confirmed HLH in both cases.

[Case 1]

Although methylprednisolone (mPSL) 250 mg was administrated to control HLH on day 3, the data indicated that HLH had become worse on day 4. To control HLH, mPSL pulse therapy (1000 mg/day) was administrated from day four to day six. However, multiple organ failure proceeded rapidly, and she expired on day eight. Serum virus quantities increased markedly from 6.99 (day 3) to 9.05 (day 6). In this case, the virus level at diagnosis was extremely high compared to previously reported cases and it was possible that the high-dose mPSL therapy suppressed anti-virus immunity.

[Case 2]

Although mPSL 500 mg was administrated from day two, organ damage progressed on day three. In this case, instead of increasing the dosage of mPSL, plasma exchange (PE) was performed from day four to day six, and organ damage was relieved and the patient recovered in good condition. The serum virus quantities decreased slowly from 6.62 (day 4) to 6.48 (day 7) after PE.

Discussion: Yoshikawa et al. reported that virus level at diagnosis correlated to the outcomes of SFTS patients and that in most fatal cases virus quantities at diagnosis were over 5.0. In our cases, the patients had higher virus quantities at diagnosis and presented with severe symptoms. In the first case of fatality, the virus quantities remarkably increased shortly after mPSL therapy. As most SFTS patients are over the age of 50 and the mortality rate is higher in the elderly, lowered immunity in elderly patients might be the cause of SFTS progression. Moreover, immunosuppression therapy, including high dose mPSL therapy for HLH, might enhance the accelerated proliferation of SFTS virus. Although mPSL therapy is effective in some cases, immunosuppressive therapy for a SFTS patient is still controversial. In the second case, after PE therapy the virus level didn't increase and symptoms were improved. PE therapy does not suppress humoral and cellular immunity, which is different from mPSL therapy. As such, PE therapy might be effective in serious cases of SFTS with high virus quantities. In these cases, treatment plans were developed without information on virus quantities, and we obtained qPCR results afterwards. In the future, if qPCR can be performed as quickly as cvPCR, then data on the virus level at diagnosis may be the most important information for planning treatment.