Study on Risk Factors for Severe Hand, Foot and Mouth Disease in China

BACKGROUND Epidemics of HFMD are elevated every year globally, especially in mainland China. The disease now presents as an increasing threat to public health worldwide. METHODS Five hundred and seventy-one EV71-infected HFMD patients in Beijing You'an Hospital were grouped by disease severity: Mild (no severe complication) (n=221), and Severe group (complicated with brainstem encephalitis (BE), and/or pulmonary edema (PE) (n=350)). Clinical and laboratory findings and levels of 7 serum cytokines were analyzed. RESULTS Univariate analysis showed that (RR)>26/min (p<0.001), age<4 yo (p=0.001), GLU>8.3 mmol/L (p=0.008), CL<98 mmol/L (p=0.026), and WBC>1.2 × 10(9)/L (p=0.040) were associated with severe cases. Results of multivariate analysis indicated five independent risk factors (RR>26/min (p<0.001), Age<4 yo (p<0.001), GLU>8.3 mmol/L (p=0.011), LYM>40% (p=0.010), and ALT>40 U/L (p=0.045)). In addition to single-factor analysis, we further analyzed the use of different combinations of risk factors. "GLU>8.3 and CL<98 and RR>26" (confidence ration (CR)=100%) is the top indicator, followed by "ALT>40 and LYM>40% and RR>26 and Age<4 yo" (CR=92.9%). Serum levels of IL-2, IL-4, IL-10, IFNγ, GM-CSF, and TNFα were higher in severe cases than in mild cases. A new evaluation scoring system by scoring each risk factor 1 and independent risk factor 2 was developed for early identification of severe HFMD cases. CONCLUSIONS Five independent risk factors, along with indicative combinations of risk factors, for severe cases were identified, and a scoring system was created to facilitate the use of indicators for early medical intervention.