Download PDF
J Pediatr Infect Dis 2020; 15(04): 176-183
DOI: 10.1055/s-0040-1708053
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Diagnostic and Prognostic Values of Blood Test Parameters in Hand, Foot, and Mouth Disease: A Meta-analysis

Boqiu Zhang
1   Pediatrics Department, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China
,
Youcheng Huang
1   Pediatrics Department, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China
,
Rongrong Yang
1   Pediatrics Department, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China
,
Liu Yang
2   Unimed Scientific Inc., Wuxi, China
› Author Affiliations
Further Information

Publication History

04 September 2019

08 February 2020

Publication Date:
04 March 2020 (online)

   Permissions and Reprints

Abstract

Objective The present meta-analysis was conducted to identify the diagnostic and prognostic significance of routine blood test parameters in patients with hand, foot, and mouth disease (HFMD), in particular for white blood cell (WBC) count, platelet level, C-reactive protein (CRP), interleukin-8 (IL-8) level, fasting blood glucose level, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, etc.

Methods PubMed, Web of Science, Embase, Cochrane Library were searched to identify relevant articles. The potential risk factors were analyzed when patients were divided into groups using different standards.

The meta-analyses were performed using the RevMan software. After screening, data from the 26 papers were used for meta-analysis.

Results Some factors with potential diagnostic and prognostic value, and others with no value, were identified. Specifically, WBC counts had an association with later survival; CRP and platelet levels had limited indicative roles; higher plasma glucose levels were associated with more serious complications and poorer survival; fatal progression was correlated with increased IL-8 and NT-proBNP levels. There was great heterogenicity between studies.

Conclusion Blood factors, especially WBC counts, plasma glucose level, IL-8, and NTproBNP levels are associated with the severity and outcome of HFMD.

Keywords

HFMD - meta-analysis - NT-proBNP - IL-8 - blood glucose
 

  • References

  • 1 Koh WM, Bogich T, Siegel K. , et al. The epidemiology of hand, foot and mouth disease in Asia: a systematic review and analysis. Pediatr Infect Dis J 2016; 35 (10) e285-e300
    CrossrefPubMedGoogle Scholar
  • 2 Kaminska K, Martinetti G, Lucchini R, Kaya G, Mainetti C. Coxsackievirus A6 and hand, foot and mouth disease: three case reports of familial child-to-immunocompetent adult transmission and a literature review. Case Rep Dermatol 2013; 5 (02) 203-209
    CrossrefPubMedGoogle Scholar
  • 3 Omaña-Cepeda C, Martínez-Valverde A, del Mar Sabater-Recolons M, Jané-Salas E, Marí-Roig A, López-López J. A literature review and case report of hand, foot and mouth disease in an immunocompetent adult. BMC Res Notes 2016; 9: 165
    CrossrefPubMedGoogle Scholar
  • 4 Chang LY, Hsia SH, Wu CT. , et al. Outcome of enterovirus 71 infections with or without stage-based management: 1998 to 2002. Pediatr Infect Dis J 2004; 23 (04) 327-332
    CrossrefPubMedGoogle Scholar
  • 5 Chen S, Yang Y, Yan X, Chen J, Yu H, Wang W. Influence of vitamin A status on the antiviral immunity of children with hand, foot and mouth disease. Clin Nutr 2012; 31 (04) 543-548
    CrossrefPubMedGoogle Scholar
  • 6 Cui L, Qi Y, Li H. , et al. Serum microRNA expression profile distinguishes enterovirus 71 and coxsackievirus 16 infections in patients with hand-foot-and-mouth disease. PLoS One 2011; 6 (11) e27071
    CrossrefPubMedGoogle Scholar
  • 7 Deng HL, Zhang YF, Li YP. , et al. N-terminal pro-brain natriuretic peptide levels associated with severe hand, foot and mouth disease. BMC Infect Dis 2016; 16 (01) 585
    CrossrefPubMedGoogle Scholar
  • 8 Duan G, Yang H, Shi L. , et al. Serum inflammatory cytokine levels correlate with hand-foot-mouth disease severity: a nested serial case-control study. PLoS One 2014; 9 (11) e112676
    CrossrefPubMedGoogle Scholar
  • 9 Hao J, Li P, Tian Y. , et al. Crosstalk between toll-like receptor 3 and notch signaling contributes to CD14+ monocytes activity in enterovirus 71 infected hand, foot, and mouth disease. Int Immunopharmacol 2018; 60: 26-33
    CrossrefPubMedGoogle Scholar
  • 10 Huang M, Du W, Liu J. , et al. Interleukin-27 as a novel biomarker for early cardiopulmonary failure in enterovirus 71-infected children with central nervous system involvement. Mediators Inflamm 2016; 2016: 4025167
    PubMedGoogle Scholar
  • 11 Huang YF, Chiu PC, Chen CC. , et al. Cardiac troponin I: a reliable marker and early myocardial involvement with meningoencephalitis after fatal enterovirus-71 infection. J Infect 2003; 46 (04) 238-243
    CrossrefPubMedGoogle Scholar
  • 12 Kim SJ, Kim JH, Kang JH. , et al; Enteroviruses Complications Working Group. Risk factors for neurologic complications of hand, foot and mouth disease in the Republic of Korea, 2009. J Korean Med Sci 2013; 28 (01) 120-127
    PubMedGoogle Scholar
  • 13 Lee CC, Lu X, Xiao Z, Yang M, Zhu Y. Prognostic value of B-type natriuretic peptide, leukocytosis, and hyperglycemia in children with severe hand, foot, and mouth disease. Shock 2016; 45 (06) 620-625
    CrossrefPubMedGoogle Scholar
  • 14 Li CC, Yang MY, Chen RF. , et al. Clinical manifestations and laboratory assessment in an enterovirus 71 outbreak in southern Taiwan. Scand J Infect Dis 2002; 34 (02) 104-109
    CrossrefPubMedGoogle Scholar
  • 15 Li S, Cai C, Feng J. , et al. Peripheral T lymphocyte subset imbalances in children with enterovirus 71-induced hand, foot and mouth disease. Virus Res 2014; 180: 84-91
    CrossrefPubMedGoogle Scholar
  • 16 Li W, Teng G, Tong H. , et al. Study on risk factors for severe hand, foot and mouth disease in China. PLoS One 2014; 9 (01) e87603
    CrossrefPubMedGoogle Scholar
  • 17 Li X, Li Q, Li J. , et al. Elevated levels of circulating histones indicate disease activity in patients with hand, foot, and mouth disease (HFMD). Scand J Infect Dis 2014; 46 (12) 818-824
    CrossrefPubMedGoogle Scholar
  • 18 Liu J, Huang P, He Y. , et al. Serum amyloid A and clusterin as potential predictive biomarkers for severe hand, foot and mouth disease by 2D-DIGE proteomics analysis. PLoS One 2014; 9 (09) e108816
    CrossrefPubMedGoogle Scholar
  • 19 Liu JT, Peng D, Guan XH, Zou DD, Zhao DC. Clinical characteristics and treatment assessments of severe enterovirus 71 infected children [in Chinese]. Zhonghua Er Ke Za Zhi 2010; 48 (01) 24-28
    PubMedGoogle Scholar
  • 20 Ou JB, Zhang CM, Fu SM, Huang X, Huang LH. Relationship between G6PD deficiency and hand-foot-mouth disease induced by enterovirus 71 [in Chinese]. Zhongguo Dang Dai Er Ke Za Zhi 2013; 15 (09) 751-755
    PubMedGoogle Scholar
  • 21 Van Pham H, Hoang TNA, Duong HT. , et al. Clinical characteristics of hand, foot and mouth disease in Daklak Province, Vietnam and associated factors of severe cases. Virusdisease 2017; 28 (04) 430-433
    CrossrefPubMedGoogle Scholar
  • 22 Wang W, Li W, Yang X. , et al. Interleukin-8 is elevated in severe hand, foot, and mouth disease. J Infect Dev Ctries 2014; 8 (01) 94-100
    CrossrefPubMedGoogle Scholar
  • 23 Wu J, Cui D, Yang X. , et al. Increased frequency of circulating follicular helper T cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection. J Immunol Res 2014; 2014: 651872
    PubMedGoogle Scholar
  • 24 Zeng M, Zheng X, Wei R. , et al. The cytokine and chemokine profiles in patients with hand, foot and mouth disease of different severities in Shanghai, China, 2010. PLoS Negl Trop Dis 2013; 7 (12) e2599
    CrossrefPubMedGoogle Scholar
  • 25 Zhang A, Yang L, Guo P. , et al. B-type brain natriuretic peptide as a measure of the severity of hand-foot-mouth disease: a case-control study. BMC Infect Dis 2017; 17 (01) 651
    CrossrefPubMedGoogle Scholar
  • 26 Zhang C, Chen S, Zhou G. , et al. Involvement of the renin-angiotensin system in the progression of severe hand-foot-and-mouth disease. PLoS One 2018; 13 (05) e0197861
    CrossrefPubMedGoogle Scholar
  • 27 Zhang SL, Song CF. Dynamic changes in plasma D-dimer level and its prognostic value in children with severe hand-foot- mouth disease [in Chinese]. Zhongguo Dang Dai Er Ke Za Zhi 2013; 15 (12) 1119-1122
    PubMedGoogle Scholar
  • 28 Zhao N, Chen HL, Chen ZZ, Li J, Chen ZB. IL-10-592 polymorphism is associated with IL-10 expression and severity of enterovirus 71 infection in Chinese children. J Clin Virol 2017; 95: 42-46
    CrossrefPubMedGoogle Scholar
  • 29 Zhao ZX, Lu JH, Mei ZQ. , et al. The level of peripheral circular DNA in patients with hand foot and mouth disease [in Chinese]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2011; 25 (06) 483-485
    PubMedGoogle Scholar
  • 30 Zheng G, Cao J, Yu J, Zhang Z, Liu Q, Chen J. Risk factors for death in children with critical and severe hand-foot-and-mouth disease in Chongqing, China: an observational study. Medicine (Baltimore) 2017; 96 (49) e8934
    PubMedGoogle Scholar
  • 31 Tan Y, Yang T, Liu P. , et al. Association of the OAS3 rs1859330 G/A genetic polymorphism with severity of enterovirus-71 infection in Chinese Han children. Arch Virol 2017; 162 (08) 2305-2313
    CrossrefPubMedGoogle Scholar
  • 32 Zhang J, Weng Z, Du H. , et al. Development and evaluation of rapid point-of-care tests for detection of Enterovirus 71 and Coxsackievirus A16 specific immunoglobulin M antibodies. J Virol Methods 2016; 231: 44-47
    CrossrefPubMedGoogle Scholar
  • 33 Zhang A, Xiu B, Zhang H, Li N. Protein microarray-mediated detection of antienterovirus antibodies in serum. J Int Med Res 2016; 44 (02) 287-296
    PubMedGoogle Scholar
  • 34 Coates SJ, Davis MDP, Andersen LK. Temperature and humidity affect the incidence of hand, foot, and mouth disease: a systematic review of the literature—a report from the International Society of Dermatology Climate Change Committee. Int J Dermatol 2019; 58 (04) 388-399
    CrossrefPubMedGoogle Scholar
  • 35 Chen SM, Du JW, Jin YM. , et al. Risk factors for severe hand-foot-mouth disease in children in Hainan, China, 2011-2012. Asia Pac J Public Health 2015; 27 (07) 715-722
    CrossrefPubMedGoogle Scholar
  • 36 Long L, Gao LD, Hu SX. , et al. Risk factors for death in children with severe hand, foot, and mouth disease in Hunan, China. Infect Dis (Lond) 2016; 48 (10) 744-748
    CrossrefPubMedGoogle Scholar
  • 37 Toya M, Endo Y, Tanizaki H, Fujisawa A, Tanioka M, Miyachi Y. An adult case of severe hand-foot-mouth disease accompanying persistent fever and systemic arthritis. Dermatol Online J 2012; 18 (08) 14
    PubMedGoogle Scholar
  • 38 Han FX, Gao JH, Gai JH. Clinical significance of combined liver function and high-sensitivity C-reactive protein measurement in children with hand-foot-mouth disease. Genet Mol Res 2016 15. (03):
    PubMedGoogle Scholar
  • 39 Qiu J, Lu X, Liu X. , et al. Derivation and validation of a mortality risk score for severe hand, foot and mouth disease in China. Sci Rep 2017; 7 (01) 3371
    CrossrefPubMedGoogle Scholar
  • 40 Han J, Wang Y, Gan X, Song J, Sun P, Dong XP. Serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease. J Med Virol 2014; 86 (08) 1377-1385
    CrossrefPubMedGoogle Scholar
  • 41 Shang W, Qian S, Fang L, Han Y, Zheng C. Association study of inflammatory cytokine and chemokine expression in hand foot and mouth disease. Oncotarget 2017; 8 (45) 79425-79432
    CrossrefPubMedGoogle Scholar
  • 42 Shao P, Wu X, Li H, Wu Z, Yang Z, Yao H. Clinical significance of inflammatory cytokine and chemokine expression in hand, foot and mouth disease. Mol Med Rep 2017; 15 (05) 2859-2866
    CrossrefPubMedGoogle Scholar