Onychomadesis following hand, foot, and mouth disease

甲脱落手足口病

Casereport

Onychomadesisfollowinghand,foot,andmouthdisease:acasereportfromItalyandreviewoftheliterature

VincenzoBettoli,MD,StefaniaZauli,MD,GiuliaToni,MD,andAnnarosaVirgili,MD

DermatologySection,DepartmentofClinicalandExperimentalMedicine,HospitalSant’Anna,UniversityofFerrara,Italy

CorrespondenceVincenzoBettoli,MDDermatologySection

DepartmentofClinicalandExperimentalMedicineAziendaOspedalieraUniversitariadiFerrara

ArcispedaleSant’Anna,FerraraCorsoGiovecca20344100FerraraItaly

E-mails:vincenzo.bettoli@fastwebnet.it,stefania.zauli@libero.itCon ictsofinterest:none.

Hand,foot,andmouthdisease(HFMD)isarelativelycommonandhighlycontagiousenteroviralinfectionthatoccursinsmallepidemics,usuallyinautumnorspring.Theillnessprimarilyaffectsyoungchildrenandisclini-callycharacterizedbyvesicularanderosivestomatitisincombinationwithvesiculareruptionofthepalmsandsoles,and,sometimes,amaculopapularrash.OutbreaksofHFMDhavebeencausedmainlybycoxsackievirus(CV)A16andenterovirus71,butCVstrainsA5,A7,A9,A10,B1,B2,B3andB5havealsobeenassociatedwiththeillness.1WereporttwocasesofHFMD-relatedony-chomadesisinItalyandreviewthepublisheddatacon-cerningthisemergentcondition.Casereport

Twobrothers,2and5yearsofage,wereevaluatedforchangesintheirnailsthathadoccurredduringtheweekpriortopresentation.Onexamination,thetwochildrendidnotshowanysystemicdiseaseorchronicdermatitis,andhadnohistoryoftraumaorperiungualerythema.Theirmotherreportedtheoccurrence,aboutamonthpreviously,ofamaculopapularvesiculareruptiononthe728

hands,feet,andbuttocks.Thiswasassociatedwithsmall

InternationalJournalofDermatology2013,52,728–730

aphthoidulcerationsoftheoralmucosawhichhadoccurredinbothbrothers,beginningintheolderboyandappearing3dayslaterintheyoungerbrother.Thecuta-neousrashhadbeenprecededbylow-gradefeverofabout8–12hoursinduration,whichhadbeentreatedwithonetabletofparacetamolineachchild.Apediatri-cianhaddiagnosedHFMDinbothchildren.

Atthedermatologyconsultation,examinationofthe5-year-oldpatientrevealednailplatesheddingonthe rstandsecond ngersofbothhands(Fig.1);thetoenailsinthispatientwerenormal.Intheyoungerpatient,involve-mentwasapparentinatotalof ve ngernailsand vetoenails(Fig.2).

Noparonychiaorcuticularalterationsandnohairlossordentalabnormalitieswereapparent;skinandgingivaehadcompletelyhealed.Directmicroscopicexaminationofnailfragmentswasnegativeforfungi.Aboutsixweekslater,themotherreportedthatcompleteresolutionhadoccurredspontaneouslyinbothchildren.Discussion

Onychomadesisisde nedasproximalnailplatesepara-tionfromthenailmatrixandthenailbed,andmay

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甲脱落手足口病

Bettolietal.(a)

(b)

Figure1Nailplatesheddingintheolderbrotheron(a)

the rsttoeoftherightfootand(b)thefourthand fth ngersofthelefthand

representanextremeformofBeau’slineswithinvolve-mentoftheentirethicknessofthenailandsubsequentseparation.BothBeau’slinesandonychomadesisarecausedbyatemporaryarrestintheactivityofthenailmatrix,andbotharereversibleuponcessationoftheincitingagentorresolutionofthesystemicupset.Differ-

Figure2Nailplatesheddingintheyoungerbrotheronthe

rstandsecond ngersofthelefthand

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Onychomadesisandhand,foot,andmouthdiseaseCasereport729

entconditions,suchasseveresystemicdiseases,nutri-tionalde ciencies,trauma,fever,periungualdermatitis,chemotherapyadministrationorotherdrugintake,andinfectionsarereportedinassociationwithBeau’slines.Themechanismofnailmatrixarrestsecondarytoinfec-tionisunknown.

Hand,foot,andmouthdiseasehasalreadybeenassoci-atedwithBeau’slinesandonychomadesis(Table1).Clementzetal.1reportedthe rst vecases,allfromtheChicagometropolitanarea,andsuggestedthatallpatientshadbeeninfectedwiththesameviralstrain,butdidnotidentifythevirusresponsible.Bernieretal.2describedanotherfourcasesfromFranceandBelgiumandproposedthatmanyviralstrainsmaybeimplicatedinthenailmatrixarrest.Morerecentstudieshavesupportedthisassumption.Differentviruseshavebeenidenti edinSpanishoutbreaksofHFMD-relatedonychomadesisas,respectively:CV10andCV16inValencia;CVB1inMadrid,andCVB1,CVB2andanunidenti ednon-polioenterovirusinSaragozza.3–5InthereportfromValencia,HFMDwassuggestedtorepresentthepathologicalback-groundin134of221(61%)casesofonychomadesis.5

Bycontrast,Osterbacketal.6detectedCV6asapri-marypathogenassociatedwithanationwideoutbreakofHFMDinFinland.Unfortunately,thisstudy,whichfocusedonHFMDepidemiology,reportedtheoccurrenceofHFMD-relatedonychomadesiswithoutspecifyingitsincidence.6

Thesedatasuggestthatspeci cstrainsofenterovirusandnewgeneticvariantsofthem,inwhichmolecularandbiologicalactivityshowmodi cation,areseeminglyresponsibleforoutbreaksofHFMD-inducedonychoma-desis.7TheabsenceofonychomadesisinHFMDepidem-icscausedbyotherviralstrainssupportsthishypothesis.Forexample,enterovirus71hasbeenfoundfrequentlyinHFMDepidemicsinSoutheastAsiainrecentyears,butonychomadesishasnotbeenreportedasacomplication.8

Withregardtothetwocasesreportedhere,itwashypothesizedthatnailmatrixarrestmayhaveresultedfromaviralinfectionthathadoccurredaboutamonthearlier.Infact,feverwaslowgradeandpresentonlyforafewhours.Thus,fever-inducedmatrixarrestseemsimplausible.Anumberofdrugsarereportedtoinducenailchanges,butparacetamolisnotamongthem.9Furthermore,thebrothersconsumedonlyonetabletofparacetamoleachanddidnottakeanyotherdrug;hencedrug-inducedmatrixarresthasbeenexcluded.

AcausalrelationshipbetweenHFMDandonychoma-desisisstronglysuggestedby:(i)thetemporallatencyofapproximatelyonemonthbetweenthetwoconditions,widelyreportedintheliterature;(ii)theabsenceofotherpathologicalconditionsrecognizedaspossiblecausesofonychomadesis,and(iii)thesimultaneouspresence

of

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甲脱落手足口病

730CasereportOnychomadesisandhand,foot,andmouthdiseaseBettolietal.

Table1Previousreportsofonychomadesisidenti edintheliteraturereview

Reference

Clementzetal.(2000)1Bernieretal.(2001)2

RedondoGranadoetal.(2009)11Osterbacketal.(2009)6Cabrerizoetal.(2010)3Daviaetal.(2010)4

Guimbaoetal.(2010)5

Location

Chicago,IL,USAFranceandBelgiumValladolid,SpainFinland

Madrid,SpainValencia,SpainSaragozza,Spain

Cases,n549N/A1213424

1–6,11

Meanage,years2.681.661.5–3.0N/A1.8

Selected,<6years1.75

Meanlatency,weeks4.4N/A64–85–105.65.7

N/A,notavailable.

onychomadesisinbothbrothers,whowereassumedtohavebeeninfectedbythesameviralstrain.

Whetherenterovirusescanbeconsideredasthedirectcauseofonychomadesisandwhyallthenailsarenotaffectedremainsunanswered.In ammationaroundthenailmatrixcanbehypothesizedasapossiblealternativemechanism.10Thisin ammation,secondarytoviralinfec-tion,maybeinduceddirectlybythevirusorindirectlybyvirus-speci cimmunocomplexesandconsequentdistalembolism.Eitherway,thearrestofnailgrowthmustbesuf cientlyprolongedtoresultinonychomadesis.

OnlyafewcasesofHFMD-inducedonychomadesisinwhichaspeci ccoxsackievirus(CV6)wasdetectedinshednailshavebeenreportedintheliterature.3Thissup-portsthesuggestionthatvirusreplicationdirectlydam-agesthenailmatrix,butfurtherstudiesofthemolecularcharacterizationofenterovirusesinnailspecimensshouldbeperformed.

Thefrequencyofdiagnosisofthisconditionmaybeunderestimatedasaconsequenceofthelongintervalbetweentheacuteviralprocessandtheappearanceofnailshedding(about40days),thenormallylowmorbidityofnaildisorders,andthelimitednumberofnailsinvolvedbyonychomadesis.Thiscontemporaryoccurrenceintwobrotherssuggestseitherageneticpredispositionortheinvolvementofavirusstrainthatisparticularlypronetoinducingonychomadesis.GiventhatthesestrainsarealreadywidelydiffusedinEurope,itisreasonabletoexpectfurtheroutbreaksofHFMD-inducedonychomadesisinItaly.References

1ClementzGC,ManciniAJ.Nailmatrixarrestfollowinghand-foot-mouthdisease:areportof vechildren.PediatrDermatol2000;17:7–11.

2BernierV,LabrèzeC,BuryF,etal.Nailmatrixarrestinthecourseofhand,footandmouthdisease.EurJPediatr2001;160:649–651.

3CabrerizoM,DeMiguelT,ArmadaA,etal.

Onychomadesisafterahand,foot,andmouthdiseaseoutbreakinSpain,2009.EpidemiolInfect2010;138:1775–1778.

4DaviaJL,BelPH,NinetVZ,etal.OnychomadesisoutbreakinValencia,Spainassociatedwithhand,foot,andmouthdiseasecausedbyenteroviruses.PediatrDermatol2011;28:1–5.

5GuimbaoJ,RodrigoP,AlbertoMJ,etal.Onychomadesisoutbreaklinkedtohand,foot,andmouthdisease,Spain,July2008.EuroSurveill2010;15:19663.

6OsterbackR,VuorinenT,LinnaM,etal.CoxsackievirusA6andhand,foot,andmouthdisease,Finland.EmergInfectDis2009;15:1485–1488.

7BlomqvistS,KlemolaP,KaijalainenS,etal.Co-circulationofcoxsackievirusesA6andA10inhand,footandmouthdiseaseoutbreakinFinland.JClinVirol2010;48:49–54.

8ChanKP,GohKT,ChongCY,etal.Epidemichand,footandmouthdiseasecausedbyhumanenterovirus71,Singapore.EmergInfectDis2003;9:78–85.

9PiracciniBM,IorizzoM,StaraceM,etal.Drug-inducednaildiseases.DermatolClin2006;24:387–391.

10HanekeE.Onychomadesisandhand,footandmouth

disease–isthereaconnection?EuroSurveill2010;15:19664.

11RedondoGranadoMJ,TorresHinojalMC,Izquierdo

LópezB.Post-viralonychomadesisoutbreakinValladolid.AnPediatr(Barc)2009;71:436–439.

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