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See also Commentary , p . 303 CLINICAL REPORT ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Atypical Hand , Foot , and Mouth Disease Caused by Coxsackievirus A6 in Denmark : A Diagnostic Mimicker
Hans-Henrik HORSTEN 1 , Michael KEMP 2 , Thea K . FISCHER 3 , Kim H . LINDAHL 4 and Anette BYGUM 1
1
Department of Dermatology and Allergy Centre , Odense University Hospital , 2 Department of Clinical Microbiology , Odense University Hospital , University of Southern Denmark , 3 Virology Surveillance and Research Section , Department of Microbiological Diagnostics and Virology , Statens Serum Institut , Copenhagen , Denmark and University of Southern Denmark , Clinical Institute , and Center for Global Health , and
4
Department of Clinical Pathology , Odense University Hospital , Odense , Denmark
Since 2008 , outbreaks of atypical hand , foot , and mouth disease ( HFMD ) in children and adults have been reported worldwide . The majority of these outbreaks are caused by a new lineage of Coxsackie virus A6 ( CV-A6 ) presenting a more severe clinical phenotype than the classical childhood HFMD caused by CV- A16 . Between June 2014 and January 2016 , 23 cases of atypical HFMD disease presented at a Dermatology Department at a regional University Hospital in Denmark . Patients were referred by general practitioners and dermatologists with a variety of clinical diagnoses , including eczema herpeticum , vasculitis , syphilis , dermatophytid , erythema multiforme and Stevens-Johnson syndrome . Three adults and 3 children required hospitalization due to extensive skin involvement and fever . All reported patients had laboratory-confirmed enterovirus infection . This study demonstrated an upsurge in atypical HFMD caused by CV-A6 in the Region of Southern Denmark and that atypical HFMD can be difficult to diagnose clinically as it may mimic other severe skin diseases .
Key words : atypical hand , foot , and mouth disease ; Coxsackievirus A6 ; diagnostic mimicker .
Accepted Nov 24 , 2017 ; Epub ahead of print Nov 28 , 2017 Acta Derm Venereol 2018 ; 98 : 350 – 354 .
Corr : Hans-Henrik Horsten , Department of Dermatology and Allergy Centre , Odense University Hospital , DK-5000 Odense C , Denmark . E-mail : hans-henrik . horsten @ rsyd . dk
Hand , foot , and mouth disease ( HFMD ) is a common viral illness generally affecting children under 7 years of age ( 1 ). Classical HFMD is a self-limiting condition presenting with oropharyngeal blisters , papular vesicles on the palms and soles , and sometimes fever . Patients will rarely be referred to the hospital , as symptoms are mild and complications , such as encephalitis and myocarditis , are rare in Europe ( 2 – 4 ). Seasonal outbreaks occur , with incident peaks during the summer and early autumn . The major causative agents have been Coxsackievirus A16 ( CV-A16 ) and enterovirus ( EV ) -A71 within the species EV-A , members of the virus family Picornaviridae in the genus Enterovirus ( 5 ).
Since 2008 outbreaks of atypical HFMD caused by CV-A6 have been reported worldwide , mostly during the winter in temperate climates ( 6 , 7 ). An increasing number of reports indicate that this new lineage of CV-A6 is more virulent , causing a widespread vesicular skin eruption in children as well as adults ( 8 , 9 ). In atopic children , a clinical presentation resembling eczema herpeticum has been described and termed eczema coxsackium ( 10 , 11 ).
The histopathological findings are mainly in the epithelium and consist of widespread keratinocyte necrosis and spongiosis , often with formation of vesicles . Neutrophilic exocytosis and reticular degeneration of the basal cell layer also occur . In the papillary dermis there is often massive oedema and a variable inflammatory infiltrate dominated by lymphocytes . As opposed to common findings in other viral diseases , there are no multinucleate cells , inclusion bodies or koilocytes ( 12 , 13 ).
The aim of this study is to present the clinical and paraclinical features of atypical HFMD , in order to inform physicians about the new phenotype . Intrafamilial cases are also reported .
METHODS
The Department of Dermatology and Allergy Centre , Odense University Hospital see patients referred from primary care physicians , practicing dermatologists and other hospital departments in the Region of Southern Denmark , which covers a population of ~ 1.2 million people . Based on a clinical picture suspicious of atypical HFMD , specimens were taken as vesicle fluid swabs , oropharyngeal swabs , and / or stool samples . The initial testing for EV was performed at the local Department of Microbiology using an in-house real-time PCR method . EV-positive samples were sent to the National World Health Organization ( WHO ) Reference Center for Polio at Statens Serum Institut for further characterization . Here , EV-RNA was subjected to a multiplex 1-step real-time assay with semi-nested PCR , and subsequently sequenced using Sanger technique targeting the region encoding the VP1 and VP2 genes , whose sequence corresponds with antigenic serotype ( 14 ). In addition , all EV-RNA positive samples were routinely cultivated in 3 cell lines established as part of the poliovirus surveillance programme . For samples that might not have been characterized successfully during the first attempts , the typing procedure was repeated on cultivated material .
RESULTS
From June 2014 until January 2016 , a total of 26 patients with a clinical presentation suggesting possible atypical HFMD were tested for EV infection . Of these patients , 23 ( 88 %) tested EV-positive , including 15 adults and 8 doi : 10.2340 / 00015555-2853 Acta Derm Venereol 2018 ; 98 : 350 – 354
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2018 Acta Dermato-Venereologica .