A case of atypical hand-foot-and-mouth disease caused by coxsackievirus A6: differential diagnosis from varicella in a pediatric intensive care unit.
A case of atypical hand-foot-and-mouth disease caused by coxsackievirus A6: differential diagnosis from varicella in a pediatric intensive care unit.
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DOI：
10.7883/yoken.66.564
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发表时间：
2013
影响因子：
2.2
通讯作者：
Y. Yasui;Tomohiko Makino;Nozomu Hanaoka;K. Owa;A. Horikoshi;A. Tanaka;Y. Suehiro;H. Shimizu;Kazuhiko Kanou;Masaaki Kobayashi;Masami Konagaya;T. Fujimoto
中科院分区：
文献类型：
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作者：
Y. Yasui;Tomohiko Makino;Nozomu Hanaoka;K. Owa;A. Horikoshi;A. Tanaka;Y. Suehiro;H. Shimizu;Kazuhiko Kanou;Masaaki Kobayashi;Masami Konagaya;T. Fujimoto
Kobayashi Pediatric Clinic, Fujieda 426-0067, JapanTakaji Wakita 通讯（2013 年 8 月 26 日接受）2011 年，日本和其他国家发生了由柯萨奇病毒 A6（CV-A6）引起的手足口病（HFMD）大流行。 CV-A6 相关手足口病 (CV-A6-HFMD) 的皮肤表现比经典手足口病更广泛、更多样化 (1-3)。由于其不寻常的临床特征，手足口病与水痘的鉴别诊断有时具有挑战性。例如，CV-A6-HFMD 的皮疹多向四肢和躯干扩散，这与典型手足口病的皮疹多局限于手和脚底不同(1,2)。一名 24 个月大的女孩于 2013 年 5 月 16 日（第 0 天前 23 天）因以下原因入住儿科重症监护病房 (PICU)：低氧血症。该患者的基本诊断为唐氏综合症，伴有室间隔缺损和肺动脉高压，但无水痘感染史，也无水痘疫苗接种史。2013年6月8日（第0天）出院前，她的臀部出现了淡红色丘疹，伴有一些水疱，迅速扩散到全身和面部； 2013 年 6 月 10 日（第 2 天），日本大阪的济生会中津医院感染控制小组 (ICT) 接到通知，该患者为 PICU 疑似鸡痘病例。该病例的评估很复杂，因为皮疹扩散到了她的上肢和下肢；然而，在她的躯干上也观察到了较小程度的变化，但在头部却没有。尽管丘疹的大小与水痘相当（约5毫米），但由于水疱比预期的水痘少，且皮疹既无结痂也无色素，因此认为手足口病的可能性更大。水痘带状疱疹病毒（VZV）和肠道病毒的感染控制政策和措施不同。 VZV 通过飞沫核传播，而肠道病毒通过直接接触胃肠道或上呼吸道排出的病毒在人与人之间传播。为了预防肠道病毒传播，手部卫生尤为重要（4）。虽然PICU内没有发现其他疑似水痘病例，但儿科担心水痘的高传染性，水痘是通过空气传播的。 ICT与儿科工作人员合作，立即在儿科病房启动了水痘感染控制工作，并对本病例的治疗进行了实验室诊断。 ICT 决定实施以下应对措施：（i）从 2013 年 6 月 10 日起立即将感染患者与 PICU 的其他儿童隔离； (ii) 自 2013 年 6 月 10 日起立即限制使用 PICU； （3）根据水痘带状疱疹病毒的实验室检查结果，制定对同室儿童进行水痘带状疱疹病毒广泛预防性抗病毒药物治疗的计划。治疗过程中除进行水痘带状疱疹病毒的具体实验室检查外，还采集咽拭子、水泡液和粪便标本，并进行实验室检查以诊断和治疗。本研究已获得患者监护人的知情同意，并对临床样本进行检测，以制定治疗计划和感染控制措施。2013年6月12日（第4天），VZV检测结果（包括IgM、IgG和特异性病毒抗原分析）均为阴性。同一天，采集标本（水泡液、鼻咽拭子和粪便），并进行逆转录（RT）-hyper PCR（5）筛查所有样本（第4天）中的肠道病毒。采用RT-hyper PCR是因为它比以前可用的PCR方法更快（5,6）。根据RT-hyper PCR获得的结果，ICT立即终止了水痘监测并停止对 PICU 使用和患者抗病毒治疗的限制。该团队还撤回了整个科室范围内更广泛的预防性抗病毒治疗，转而支持针对接触感染的预防措施。 2013 年 6 月 14 日（第 6 天），进行了 RT-PCR 以确定衣壳蛋白 VP1 编码区的部分核苷酸序列。设计了引物对
Kobayashi Pediatric Clinic, Fujieda 426-0067, JapanCommunicated by Takaji Wakita(Accepted August 26, 2013)In 2011, a large outbreak of hand-foot-and-mouthdisease (HFMD) caused by coxsackievirus A6 (CV-A6)occurred in Japan and other countries. The cutaneousmanifestations of CV-A6-associated HFMD (CV-A6-HFMD) are more extensive and variable than those ofclassic HFMD (1–3). Differential diagnosis of HFMDfrom chickenpox is occasionally challenging because ofits unusual clinical characteristics. For example, thespread of rashes in CV-A6-HFMD is more toward theextremities and body trunk, a manner different fromthat in typical HFMD in which the rashes are mostly lo-calized to the hands and soles of the feet (1,2).A 24-month-old girl was hospitalized in the pediatricintensive care unit (PICU) on May 16, 2013 (23 days be-fore day 0) due to hypoxemia. The patient had an un-derlying diagnosis of Down syndrome with a ventricularseptal defect and pulmonary hypertension but no histo-ry of varicella infection or vaccination against varicella.Before discharge on June 8, 2013 (day 0), she devel-oped a reddish papular rash with some vesicles on herhip, which rapidly spread throughout her entire bodyand face; she was afebrile.On June 10, 2013 (day 2), the Infection Control Team(ICT) of the Saiseikai Nakatsu Hospital (Osaka, Japan)was notified of this patient as a suspected case of chick-enpox in PICU. Assessment of this case was complicat-ed because the rash spread to her upper and lower ex-tremities; however, it was also observed to a lesserextent on her body trunk but not on the head. Althoughthe papules were comparable to varicella in terms oftheir size (approximately 5 mm), HFMD was consideredto be more likely because there were fewer vesicles thanthat expected for varicella, and the rash was neithercrusted nor pigmented.Infection control policies and measures for varicella-zoster virus (VZV) and enterovirus are different. VZV istransmitted via droplet nuclei, whereas enterovirus istransmitted from person to person via direct contactwith the virus shed from the gastrointestinal or upperrespiratory tract. To prevent enteroviral transmission,hand hygiene is particularly important (4). Althoughthere was no other case of suspected chickenpox inPICU, the Department of Pediatrics was concernedabout the high transmissibility of varicella, which is air-borne. ICT in collaboration with the pediatric staff im-mediately initiated varicella infection control in thepediatric ward and performed laboratory diagnosis fortreatment of the present case. ICT decided to implementthe following responses: (i) immediate isolation of theinfected patient from other children in PICU from June10, 2013; (ii) immediate restriction on PICU use fromJune 10, 2013; and (iii) drafting a plan of broadprophylactic administration of antivirals against VZVfor children who were housed in the same room depend-ing on the laboratory result for VZV.In addition to a specific laboratory examination forVZV, specimens of pharyngeal swabs, vesicular fluid,and feces were collected during the course of medicalcare, and laboratory tests were performed for diagnosisand treatment. Informed consent for this study was ob-tained from the patient’s guardian, and the clinicalsamples were tested to device a treatment plan and in-fection control measures.On June 12, 2013 (day 4), the results of VZV tests in-cluding analysis of IgM, IgG, and specific viral antigen,were negative. On the same day, specimens (vesiclefluid, nasopharyngeal swabs, and feces) were collected,and reverse transcription (RT)-hyper PCR (5) was per-formed to screen for enterovirus in all samples (day 4).RT-hyper PCR was employed because it is faster thanpreviously available PCR methods (5,6).Based on the results obtained by RT-hyper PCR, ICTimmediately terminated varicella surveillance and dis-continued the restriction on PICU use and antiviraltherapy to the patient. The team also withdrew thebroader prophylactic antiviral administration through-out the unit and instead endorsed precautions againstcontact infections.On June 14, 2013 (day 6), RT-PCR was performed todetermine the partial nucleotide sequence of the capsidprotein VP1 cording region. Primer pairs were designed