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Letters to the Editor

Serial Changes of Serum Cytokine in a Pediatric Patient with Severe Fever with Thrombocytopenia Syndrome

Kawase, Mayumi MD; Hoshina, Takayuki MD, PhD; Nakamoto, Takato MD; Asai, Hiroshi MD; Ishii, Masahiro MD; Kusuhara, Koichi MD, PhD

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The Pediatric Infectious Disease Journal: March 2016 - Volume 35 - Issue 3 - p 359-360
doi: 10.1097/INF.0000000000001005
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To the Editors,

Severe fever with thrombocytopenia syndrome (SFTS) is an acute self-limited illness with various grades of severity. A few pediatric cases with mild clinical course have been reported.1 We report a Japanese pediatric SFTS patient in whom serial measurements of serum cytokines were performed.

A previously healthy 5-year-old girl was admitted to our hospital on the fourth day of illness for the evaluation of possible tick-borne diseases. The patient had gone to a mountain for hiking 7 days before admission and developed lymph node swelling in the left postauricular region 3 days before admission. The day before admission, her mother found a tick on her left parietal region. The tick was removed together with the skin lesion by a dermatologist. Fever over 38°C appeared on the admission day. On admission, the febrile girl also showed redness of the left bulbar conjunctiva. Leukocyte and platelet counts were normal (4.7 × 109/L and 209 × 109/L, respectively). Biochemistries and coagulation studies were also unremarkable. The diagnosis of SFTS was based on the detection of SFTS virus (SFTSV) nucleoprotein gene in a blood sample by reverse-transcription polymerase chain reaction. Leukopenia and thrombocytopenia continued during high continuous fever (minimal leukocyte count of 2.3 × 109/L on the sixth day of illness and minimal platelet count of 71 × 109/L on the seventh day of illness), but all abnormal data spontaneously returned to normal after the defervescence on the eighth day of illness. Serum interferon (IFN)-γ and interleukin (IL)-10 were slightly elevated during the acute phase (79.8 and 83.3 pg/mL, respectively) and varied in reverse proportion to peripheral leukocyte and platelet counts (Table 1).

Serial Changes of Clinical and Laboratory Findings

In a previous study, none of SFTS patient younger than 20 years died.2 All pediatric patients whose clinical courses were described in detail improved spontaneously.1 The severity of Crimean–Congo hemorrhagic fever, caused by a virus classified in the same family as SFTSV, is milder in children than in adults.3 The excessive immune responses in adults contribute to the more severe clinical course of the disease.3 Serum IFN-γ was associated with disease severity of adult SFTS patients.4 Slight elevation of serum IFN-γ in the present patient may be associated with mild clinical course of SFTS. As with Crimean–Congo hemorrhagic fever, the immune response to SFTSV in children may be different from that in adults.

Serum IFN-γ and IL-10 varied in reverse proportion to leukocyte and platelet counts in the present case. Th1 and Th2 cytokines may be important markers for not only the prediction of disease severity but may also reflect disease activity. However, serum IFN-γ and IL-10 levels did not correlate with leukocyte and platelet counts in adult SFTS patients.5 This discrepancy may result from the difference of immune responses between adults and children.


We thank Dr. Masayuki Saijo and Dr. Masayuki Shimojima, Special Pathogens Laboratory, Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan, for analyzing a blood sample for diagnosis of SFTS.

Mayumi Kawase, MD

Takayuki Hoshina, MD, PhD

Takato Nakamoto, MD

Hiroshi Asai, MD

Masahiro Ishii, MD

Koichi Kusuhara, MD, PhD

Department of Pediatrics School of Medicine University of Occupational and Environmental Health Japan Kitakyushu, Japan


1. Wang LY, Cui N, Lu QB, et al. Severe fever with thrombocytopenia syndrome in children: a case report. BMC Infect Dis. 2014;14:366
2. Liu W, Lu QB, Cui N, et al. Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome. Clin Infect Dis. 2013;57:1292–1299
3. Arasli M, Ozsurekci Y, Elaldi N, et al. Elevated chemokine levels during adult but not pediatric Crimean-Congo hemorrhagic fever. J Clin Virol. 2015;66:76–82
4. Deng B, Zhang S, Geng Y, et al. Cytokine and chemokine levels in patients with severe fever with thrombocytopenia syndrome virus. PLoS One. 2012;7:e41365
5. Sun Y, Jin C, Zhan F, et al. Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome. J Infect Dis. 2012;206:1085–1094
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