Clinical And Etiological Characteristics Of Atypical Hand-Foot-And-Mouth Disease In Children From Chongqing, China

Objective:To investigate the clinical and etiological characteristics of atypical hand-foot-and-mouth disease (HFMD) in children from Chongqing, in order to provide significant evidence for avoiding misdiagnosis and inappropriate treatment of this disease.Methods:Epidemiological data of 887 inpatients with HFMD admitted to Children’s Hospital of Chongqing Medical University from September 2013 to August 2014 were collected. Among these children,64 children with atypical HFMD were enrolled, stools were collected, and reverse transcription-nested PCR (RT-nested PCR) was performed for detecting viral VP1. After sequencing of VP1, the phylogenetic tree was constructed. Then, the clinical and etiological characteristics were investigated and summarized, and sequelae and complications were monitored by follow-up interviews.Results:1. A total of 887 hospitalized children were diagnosed with HFMD, of whom 7.2% were atypical HFMD. There were two peaks in its prevalence.The proportion of atypical HFMD varied over time and ranged from 1.9% to 30.4%. The proportion was the highest from January to March, a season transiting from winter to spring, in which atypical HFMD accounted for 30.4%,17.6% and 12.5%, of total HFMD in the same month, respectively. The second peak was found between August and October, a season transiting from summer to autumn, in which the atypical HFMD accounted for 12.1%,7.8% and 5.3%, respectively, of total HFMD in the same month.2. The patients with atypical HFMD had male-to-female ratio of 1.67: 1. In addition,93.8% was children younger than 3 years, and 54.7% younger than 1 year; 62.5% was found in city. The majority patients involved were at home (79.7%) and in the nursery care (15.6%).3. (1)Of the atypical HFMD,10 children (15.6%) had manifestations of neurologic involvement, of whom 4 (6.3%) were diagnosed with severe HFMD and 1 with critically severe HFMD, but all recovered smoothly. (2) Rashes of atypical HFMD were distributed not only in typical sites but also in other sites,such as lower limbs (56.3%), faces (53.1%), trunks (42.2%), upper limbs(29.7%), and externalia(14.1%). In respect of rash morphology, papula-dominant rashes were found in 44 patients (68.8%) and vesicle-dominant rashes in 41 children (64.1%), among which 20.3% showed large vesicles and 3.1% had erosions. (3) Onychomadesis and desquamation were found in 14 patients (21.9%) and 15 patients (23.4%), respectively. In addition, both occurred mainly at 4-5 weeks after the acute phase.4. Among these 64 patients with atypical HFMD, RT-nested PCR showed all the samples were positive for EV-U, and the most common pathogen was CA6 (67.2%), followed by non-typable enterovirus, EV71 and CA16 which were found in 26.6%,4.7% and 1.5% of patients, respectively.5. Phylogenetic analysis showed the strains in Chongqing shared most commonality with strains from Spain, and were also close to those circulating in Finland, Japan and Taiwan.Conclusions:Atypical HFMD had its seasonal prevalence, frequently occurred in the transiting from winter to spring and from summer to autumn. The percentage of males was higher than females, frequently occurred in young children (usually<1 year), and was often found in city. The manifestations of neurologic involvement in atypical HFMD are mild and usually have a good prognosis. However, atypical HFMD may even cause severe or critically severe HFMD. The children presented with widespread distribution and morphological diversity of skin lesions, accompanied by high rate of onychomadesis and desquamation.CA6 was a major pathogen causing atypical HFMD, but not a major pathogen in Chongqing, China. Phylogenetic analysis showed the CA6 strains in Chongqing were close to those circulating in Finland, Japan and Taiwan etc. It indicated that the CA6 strains may have some evolutionary relationship with these strains.