ToenailOnychomycosis–ACanadianApproachwithaNewTransungalTreatment–aPodiatristPerspective

AlanDBoroditsky,DPM1,AnnekeAndriessen,PHD2 1.VancouverGeneralHospital,DepartmentofPodiatry,Vancouver,BC,Canada

2.MaldenandUMCStRadboudNijmegen,TheNetherlands Introduction Onychomycosisindiabeticpatientsincreasestheriskforotherfootdisordersandlimbamputationandisincludedindiabeticfootulcerguidelinesasoneoftheriskfactorsforseriouscomplicationsthatshouldbescreenedfor.Eventhoughfootexaminationindiabetespatientsiscommonpractice,onychomycosiseithergoesunnoticedorisleftuntreatedandremainsunresolved.Earlytreatmentandinterventionincludingdiabeticfootcareandeducationisadvisableowingtotheprogressivenatureoffungalinfectionsandthehigh-riskdiabeticfoot.Treatmentwithtransungualefinaconazole10%solutionisaneffectiveandsafeoptionformanyofthesepatients.Arecentlypublishedclinicalpathwayfortoeonychomycosis1isusedasthebasisforthemanagementstrategypresentedhere,andfollowsapathwayreflectiveofthetherapeuticoptionsavailableinCanada. Background

• Onychomycosisaccountsforabouthalfofallnailabnormalitiesandcomprisesathirdoffungalskininfections.2

• Theprevalenceofonychomycosisbecomesmorecommonaspeopleageandconditionssuchasdiabetes,peripheralvasculardisease,psoriasisandimmunosuppression(HIVinfectionorimmunosuppressivetherapy)increaseinourpopulations.

• Fungalnaildiseasecancoexistwithothernaildisorders.2,3,6 • Theprevalenceofonychomycosisinpatientswithdiabeteshasbeenreportedtobe

26%.3-5• Diabeticsappearalmostthreetimesaslikelytohaveonychomycosisasnon-diabetic

individuals.3-5• Althoughtherearenostudiesaddressingtherelationshipbetweenonychomycosisand

diabeticfootulcers,itispossiblethatonecouldpredisposetotheother.4• Otherfactorsenhancingtheriskforonychomycosisaresmoking;avidsports

participation;theuseofcommercialswimmingpools;wearingocclusive,tightfootwear;useofcommon,hot,humidclimates;andfrequenttraveltoendemicareas.2

• Thiscommonnailinfectionoftenresultsinnailplatedamage,deformityandtoenaildystrophythatcaninterferewithwalking.2

• Itisalsoassociatedwithdetrimentalpsychosocialeffects.7 ToeOnychomycosis

• Onychomycosisismostfrequentlycausedbydermatophytes(approximately90%oftoenailinfections)andnon-dermatophytemolds(approximately6%)thatmainlyaffecttoenails(Fig1).8,9

• Onychomycosismaypresentwithfourpatternsofinvolvement.1Mostcommonisadistalsubungalpattern,whereproximalsubungalpresentationisrareandoftenindicatesimmunodeficiency.1Yeastinfectionsmaypresentasasuperficialwhitepatternandcanbetreatedtopically.1Inadvanceddiseasethewholenailplatemaybeinvolved,makingtheconditionlessresponsivetotherapy.1

Fig1:Toeonychomycosis:Mild-distal-lateralsubungual

• Onychomycosisisaseriousconditioninpeoplewithdiabetesandincreasestheirriskforotherfootdisordersandlimbamputation(Fig2aand2b).11,12,15,16,20

• Onychomycosiswilloftenresultinthickenedanddystrophicnailsthataredifficulttomanageformanypatientsbecauseoftentheycan’treach,see,feelorhavethestrengthordexteritytocuttheirnails.12Theresultisthatthenailsgounmanagedandprovideasignificantandoftenoverlookedareaofriskforlowerextremityinfectionandlimbloss.11,12

• Manydiabeticpatientshavelossofprotectivesensationthatwillresultintheirinabilitytofeelanyofthewarningsignsofinfectionintheirfeet.

• Advancedperipheralneuropathywillalsoleadtomotorneuropathyresultinginanimbalanceofthestabilizingmusclesofthefootcausingdeformitysuchasdigitaloverlapandhammertoes,assignificantprecursorstofungalinfectionsandulcerations.12,15,16

• Asimpleingrownnailoralessertoedeformitythatcausesthenailtorubintotheadjacenttoecaneasilyandtoooftencausecellulitisorosteomyelitisoftheunderlyingbone.12

• Brokenskinprovidesaportalforbacteriaandoftenwillstartthecascadeofdiabeticfootcomplications.12

• Earlytreatmentandinterventionincludingdiabeticprophylacticfootcareeducationisadvisableowingtotheprogressivenatureoffungalinfectionsandthehighriskdiabeticfoot.12,15,16

• Thelongcourseoftreatmentforonychomycosis,togetherwiththeexistingpolypharmacyindiabeticpatientsmayleadtomonetarychallengesandpotentialsideeffects.

Fig2a:Prevalenceoftoeonychomycosis20 Fig2b:HigherIncidenceofsecondaryinfectionsinpatientswithdiabetes Assessment

• Diagnosisofonychomycosisisbasedonclinicalpresentationandtestresults.1Astherearemanydisordersthatcausenailchanges,objectiveassessmentmayhelpclarifytheaetiology.

• Apracticalapproachmaybetotreattopicallybeforetestingorwhilewaitingfortestresults.1Inclinicalpractice,treatmentisoftenbegunwithoutconfirmationoftestresults.Apositivepotassiumhydroxidemicroscopicorcultureforfungusshouldbeperformedbeforeconsideringusingsystemicantifungaltherapy.1,8-9,14

• Fungalinfectionmayalsoexistwithotherdisorders(e.g.psoriasis/pincernails)andsuccessfultreatmentofthefunguswillnotcleartheco-existingdisorder.1

Thefollowing1maybereviewedwhenapatientpresentswithonychomycosis:

• Investigatepatienthistoryandwhattreatmenthasbeenutilized.• Checkifthereisanincidentalfindingofonychomycosis.• Establishthepatient’spastmedicalhistoryincludingage(isthepatientelderly),

comorbiditiessuchasdiabetes,cancerandrenaldisease.

• Checkifthepatientisimmuno-suppressedorhasaninflammatoryskindiseasesuchaspsoriasis.

• Establishifthereisahistoryoffunguselsewhere,e.g.Tineapedis.• Discusstherecreationalhabitsofthepatientincludingtheirhygiene,environment

andathleticwear.• Establishthepatient’sfootcaremaintenanceincludingspa’s,self-debridementor

pedicures.• Patientpsychologicalwelfareisanotherimportantareaforassessment,with

concernsaroundhowthediseaseimpactstheirlifestyle.Askpatientsiftheyareembarrassedabouttheircondition,ifthevisittotheclinicwastheirowninitiative,andiftheyareengagedandinformedintheirhealthcarechoices.

• Beforeconsideringtreatment,itisimportanttodiscusspatientexpectationsoftreatmentoutcomes.1Thephysicianmustbeabletodiscussalloptionsandroadblocksthatarecommonwithonychomycosistreatment.

TreatmentforToeOnychomycosis

• Arecentlypublishedclinicalpathwayforthepreventionandtreatmentoftoeonychomycosis1wasmodifiedforusebypodiatristsandchiropodistsandaddressesthefollowingsteps:aetiologyanddifferentialdiagnosis,prevention,treatment,evaluationandmaintenancestrategies(Fig3).

• Beforeinitiatingtreatment,patientsshouldbeinformedaboutstepstheycantaketocontaintheinfectionandpreventrecurrence,suchas.foothygiene,useofshowersandalsandregularmedicalpedicures.1

• Oftenpatientspresentwithalonghistoryoftryingamyriadofhomeremedies.Whenrecommendingtreatment

• t,prosandconsofvariousavailableoptionsmaybediscussed.1• PatientsmayhavesearchedtheInternetforinformationandoftenhaveconcerns

regardingtreatmentstheyhavereadabout,suchasoralantifungalandhepaticinvolvement,andvariousdrug-interactions.

• Patientsmayhaveheardaboutlasertreatmentsandmaybeconcernedaboutcost,sideeffects,efficacyandthepossibilityofinfectionreoccurrence.

• Ifthepatientdoesnotrespondtotreatment,microscopicorcultureconfirmationisneededbeforeproceedingtooraltherapy.1,8-9,14

SystemicTreatment • Oraltreatmentisthegoldstandardfortoeonychomycosiswithmorethan60%nail

plateinvolvement.8,13ThetwooptionsavailableareItraconazole(Sporanoxitraconazole),JanssenPharmaceuticalsInc,Titusville,NJ)andterbinafine(Lamisil(terbinafineHCl),NovartisPharmaceuticalsCorporation,EastHanover,NJ).

• Thereareissuestobeconsideredwhenprescribingsystemictreatment,suchasdruginteractions,hepatotoxicity,safetyconcernsandtheneedformonitoring.8

• Studiesoforaltreatmentthatevaluatedmycologiccureatweek48,definedasnegativeKOHandnegativeculture,8showedterbinafineHCltobemoreeffective,witha70%

healingrateversus54%withitraconazole.Forcompletecurerates,terbinafinewasequallymoreeffective,with38%completecureversus14%foritraconazole.8

• Fig3:PathwaytothePreventionandTreatmentofToeOnychomycosis TopicalTreatment

• Topicalnailpreparationsareindicatedfordistalsubungalandsuperficialwhitepatternsofnailonychomycosis.1,10

• Sometopicalantifungalagentsactasalacquerappliedtothenailsurface(e.g.Penlaclacquerwiththeantifungalciclopirox).8,19Thisspecifictopicaltreatmentshouldbecombinedwithselectivedebridementofthenail,toenablepenetration.19

• Newertopicalortransungalagentshavetheabilitytopenetratenailkeratin.10• Thenon-laquertransungaltreatmentcontainingefinaconazole10%solutionhas

demonstratedclinicaleffectivenesswhenappliedasmonotherapyinpatientswithmild-to-moderatetoeonychomycosis.10Theprimaryefficacyendpoints(completeclinicalcureandmycologiccure)weresignificantlygreaterthanvehicleatweek52(p<0.001)andclinicalimprovementcontinuedaftertreatmentwasstopped(week48).10

LaserTreatment • Lasermaybeusedforthetreatmentofonychomycosiswithanemphasisonclinical

improvementofthenail.17,18• Protocolsincludedebridementofthenail,followedbylasertherapy5-7times,with

morepasses(notincreasingjoules)todisruptfungussepsis.17,18• Treatmentwithlasermaytake3-4monthsormore.17,18• Theefficacyoflasertherapyisasubjectofdebateandcurrentlyresearchhasnot

demonstratedsustainedefficacy.18• Ithasbecomecommonpracticetoadoptauniversalfootcareapproachforthe

utilizationoflasertherapy,whichincludesaddressingconcomitantTineapedisinfections,hygiene,shoegearandsockchanges,andhabitchangesincludingawarenessofenvironmentalfactorssuchasgymorlockerroomfloorcontamination.

• Thepatientmustbeeducatedaboutfootcareduetothehighchanceofrecurrenceandmustnotrelysolelyononetreatmentmodality.

Conclusion

• Alargepopulationofonychomycosispatientsareseeninpodiatristandchiropodistsoffices,1,15andtheincidenceisincreasingparticularlyamongyoung,elderlyanddiabeticpatients.2,4

• Diabeticfootulcerguidelinesidentifyonychomycosisasahigh-riskfactorforcomplications,evenamputation.12Earlydiabeticfootexaminationshouldincludescreeningforonychomycosis.

• Adiabeticfootexamwillincludeadermatologicalevaluation,vascularassessment,neurologicalevaluationandbiomechanicalreview11,12,15,16toidentifytheassociatedriskfactorsandenableaccuratecategorizationofthepatient’scondition(e.g.low,mediumorhigh-riskstatus).12

• Eventhoughfootexaminationindiabeticpatientsiscommonpractice,onychomycosiseithergoesunnoticedorisleftuntreatedandremainsunresolvedinmanypatients.Itisimperativethatpatientsbeengagedindiabeticfooteducation.

• Theinformationobtainedenablesthephysiciantodevelopaneffectiveplanforpreventionandtreatment.

• Thegoalofmanagementistoeducatethepatient,assessriskfactorsandmanagethoserisksinaprophylacticmanner.12,15

• Healthcareprovidersmustbeawareofpatientbarriersregardingtreatmentandfootcare.Tothatend,itisquitecommontoincludethefamilyorcaregiversinconversationsconcerningriskfactorsandfootcareforinpatientswithdiabetes.

• Efinaconazolesolutioniseffectiveinpatientsthathavemildtomoderateonychomycosis1wherethenailislessthan60%involvedandlessthan3nailsintotalareinvolved.Moreover,itisagoodoptionwhensystemiconychomycosistreatmentiscontraindicated.1

• Transungualonychomycosistreatmenthasbenefitsoversystemictreatmentasbothpatientsandcliniciansprefertoavoidsystemicsideeffectsandtheneedformonitoring.17

• Whenusingatopicalagent,thepropertiesofnailplate–thicknessandtherelativecompactstructureofthenail–mustbeaddressed.

• Alimitationassociatedwithusingtopicallacquertreatmentsisthenecessityoffrequentnaildebridementtoenabletreatmentpenetration.19

• Efinaconazole10%solutionisanon-lacqueralcohol-basedformulationthathasalowmolecularweightandbindswithkeratin.10Theproductiseasytoadminister,withaplasticsqueezebottlewithaflow-throughbrushusedforapplication.1,10

• Althoughthetransungualefinaconazole10%solutiondoesnotrequiredebridementtobeeffectiveinindividualswithonychomycosis,high-riskdiabeticfootpatientsdorequireassessment,dailyobservationandpossiblynaildebridement.12

• Treatmentthatcanbetopicallyappliedshouldbeoffered.12,15• Whenonychomycosisistreatedearlywithefinaconazolesolution,complicationsmaybe

avoided,includingtheseriousandcostlyoutcomeoflimbsalvage.10,12• Itisimperativethatpreventionmeasuresbetakentoreducetheriskof

recurrence.Thesemeasuresinclude,butarenotlimitedtolifestylemodifications(avoidbeingbarefootinhighareasofcontagion),sanitizationofshoesandsocks,regularfollowupandperiodicfootexams,treattineapedisandtreattoenailspreviouslyinfectedorreinfectedwithtopicalmedication.

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