Review
Porcine ear necrosis
Mateusz Malik
a,*, Koen Chiers
b, Filip Boyen
b, Siska Croubels
c, Dominiek Maes
aaDepartmentofReproduction,ObstetricsandHerdHealth,FacultyofVeterinaryMedicine,GhentUniversity,Merelbeke9820,Belgium
bDepartmentofPathology,BacteriologyandAvianDiseases,FacultyofVeterinaryMedicine,GhentUniversity,Merelbeke9820,Belgium
cDepartmentofPharmacology,ToxicologyandBiochemistry,FacultyofVeterinaryMedicine,GhentUniversity,Merelbeke9820,Belgium
ARTICLE INFO
Keywords:
Animals Detoxifier Earnecrosis Mycotoxins Pigs
ABSTRACT
Porcineearnecrosis(PEN)isaconditionthatmainlyoccursinintensivepigproductionsystemsand mostlyaffectspigletsafterweaning.Thesyndromemanifestsitselfwithlesionsonthepinna,whichcan healorbecomemoresevereresultinginpartiallossoftheear.Thepathogenesisoftheconditionisnot fullyknown.ThreedifferenthypothesesforthedevelopmentofPENaredescribedinthisreview:(1) damageoftheepidermisduetoStaphylococcalexfoliativetoxins;(2)occlusionofsmallbloodvessels;
and(3)ear bitingwithsubsequentβ-hemolyticstreptococcalinfection. Risk factorshavenotbeen completelyelucidated,butviralandbacterialinfections,andhusbandryfactorssuchasenvironment, housingconditionsandmanagement,havebeensuggested.Itisalsopossiblethatsomecasesareduetoa combinationofthesefactors.Theroleofparasiticinfestationshasbeennotinvestigated.Duetobacterial involvement,severelyaffectedpigscanbetreatedwithantimicrobials.Controlandpreventivemeasures should focus on reducing potential risk factors by implementing herd immunization, as well as improvement of sanitary conditions, feed quality (with respect to mycotoxin contamination), management(appropriate stockingdensity),andenvironmentalconditions(e.g.numberofdrinkers andfeedersand/oroptimalventilation).Furtherresearchisneededtobetterunderstandtheprecise etiologyandpathogenesisofPEN, sothatriskfactorscanbe identifiedandmoretargeted control measurescanbeimplemented.
©2021ElsevierLtd.Allrightsreserved.
Introduction
Porcineearnecrosis(PEN),alsoknownaseartipnecrosis,ear necrosis syndrome, ulcerative spirochetosis of the ear, or Streptococcalauriculardermatitis,ischaracterizedbynecrotizing ulcerativelesionsonthepinna(Richardsonetal.,1984).Trauma andbleedingmayalsobepresent,whichisoftenassociatedwith traumaand/orearbitingaccompanyingthenecrosis(Park,2011;
Cameron,2012).Lossofapartoftheearortheentireearispossible after healing. This is an increasing problem in countries with intensive pig farming (Papatsiros, 2011), but PEN remains a mysteriousandunexploredprobleminpigproduction.Thisreview aims tosummarize and discuss the current knowledge and to elucidateavenuesforfutureresearch.Thepublishedliteratureon this topicislimited andmust becarefullyinterpreted,assome papers mentionearlesionsanddo notspecifythecauseasear necrosisorearbiting.Inpreparingthisreview,electronicsearches wereperformedinGoogleScholar,PubMed,NCBI,ResearchGate,
BioMed Central, and Web of Science,using thekeywords ‘pig’,
‘swine’,‘porcine’,‘piglets’,‘ear’,‘lesions’,and‘necrosis’. Prevalence
OneDanishstudyof90herdsandover150,000finisherpigs reportedtheprevalenceofallclinicalsignsofillnessoccurringon pigfarms.Earnecrosiswasbyfarthemostfrequentlyobserved clinicalsignat30%.The prevalenceofotherconditions suchas lameness,otherskindiseases (superficialabscesses,woundson theflank),respiratorysigns(coughing,forcedrespiration)ortail bitelesionsdidnotexceed15% (Petersenet al.,2008).Another Danishstudy(Buschetal.,2008)reportedthattheprevalenceof PENwas46%.VanStaaverenetal.(2018)reportedthatearandtail lesionswereamongthemostcommonproblems(prevalence,9%) inaninvestigationofanimalwelfareoutcomeson31Irishfarms, representing12%ofthepigfarmsinIreland.Pringleetal.(2009) foundthehighestprevalenceofPENduringthewinter(50–70%)in twoorganicfatteningfarmsthatweremonitored overa 2-year period.Thisindicatesthatprevalencemayvarybetweencountries, betweenfarms,andalsoovertimewithinafarm.Visiblelesionsof PENstarttoappearmostlyinweanedpigletsbetweenthe6thand 8th weekof life(Papatsiros,2011; Malik et al.,2020)and may
*Correspondingauthor.
E-mailaddress:Mateusz.Malik@UGent.be(M.Malik).
http://dx.doi.org/10.1016/j.tvjl.2021.105655 1090-0233/©2021ElsevierLtd.Allrightsreserved.
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The Veterinary Journal
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remainvisibleuntil14–16weeksofage(Park,2011).Theaverage ageatwhichlesionsoccuris7weeks,andinitialmildlesionsmay becomesevereoveranaverageof4weeks(Parketal.,2013).
Diagnosisandscoringofseverityoflesions
Diagnosis is based mostly onthepresence of lesionsof the affected ears; histologic examination may help to distinguish necrosis fromtrauma. Identification of thepossiblecause inan individualherdcanbedifficultandtime-consuming.Byminimiz- ing or eliminating potential risk factors,subsequent effects on prevalence and/or severity of PEN can be monitored. Lesion severitycanbe scoredand classified(Pejsak etal., 2011; Malik etal.,2020).Maliketal.(2020)usedthefollowingscore:score1, small crust on ear tip; score 2, small wound on ear tip with reddeningaround; and score 3, bloody,necrotic wound onear edge;score4,partiallackofauriclewithnecroticedge.Pejsaketal.
(2011)scoredseverityaccordingtotheaffectedsurfaceoftheear asfollows:weakchangescoveringlessthan5%oftheearsurface;
mild lesions covering 5–10% of the ear; and serious lesions coveringmorethan10%oftheear.However,auniversalscoring methodhasnotyetbeenestablished.Scoringmethodstodescribe diseaseseverityoftenusenumericalvaluestofacilitatesubsequent dataanalyses.Thesescoresmaynotalwaysreflectpreciselythe severityofthediseaseorlesion,especiallywhenassessmentisby visualappraisaland/orperformedbyaninexperiencedperson.A binaryscore(lesionpresentornot)istheeasiestandpotentially theleastbiasedmethod,buttheseverityofthelesionsisnottaken into account, failing to capture important information. More complex scoring systems are more difficult to implement in practice.Otherconditionsthatcanchangetheappearanceofthe pinnashouldalsobeconsiderede.g.frostbiteduetoexposureto lowambienttemperatures,bluediscolorationoftheearcausedby systemicinfectionswithpathogenssuchasporcinereproductive and respiratorysyndromevirus(PRRSV),Erysipelothrixrhusiopa- thiae, Salmonella species (spp), and bovine viral diarrhea virus (BVDV).
Pathogenesis
The pathogenesis of PEN is not fullyelucidated (Richardson etal., 1984)andhasnotyetbeenreproducedexperimentally.Three hypotheseshavebeensuggested.
Accordingtothefirsthypothesis,necrosisstartsontheouter surface of the injured skin and is caused by exfoliative staphylococcal toxins that damage the epidermis (Park et al.,
2013)bydamagingdesmosomalcadherins(Bukowskietal.,2010).
Fudabaet al.(2005) demonstratedthat when exfoliativetoxins (ExhA,ExhB,ExhCandExhD),whichcodingsequencesarepresent inthegenomeofStaphylococcushyicus(S.hyicus)wereinjected intoporcineskin,theycausedsuperficialformationofcrustsand blisters, and digested porcine desmoglein 1 (Dsg1). Dsg1 is a desmosome component that binds vertebrate epithelial cells.
SimilartoS.hyicustoxins(Exh),exfoliativetoxinsA,BandD(ETA, ETB,ETD)producedbyStaphylococcusaureus(S.aureus)belongto serine proteases, but cleave bonds in human Dsg1, causing complexskininfectionswithblisterformationsuchasstaphylo- coccal scales skin syndrome (SSSS) or bullous impetigo (BI;
Nishifujietal.,2008).
A second hypothesis states that ear necrosis is due to the occlusionofsmallbloodvessels.Pejsaketal.(2011)suggestedthat Mycoplasmasuis(M.suis)infectioncanleadtotheproductionof cold agglutinins which act as autoantibodies against antigens presentonthe erythrocytesurface. Together witherythrocytes, theyformimmunecomplexeswhichoccludecirculation(Hoelzle etal.,2006).Astheeartipsaresuppliedbysmallvessels,theyare particularly vulnerable to vascular occlusion and subsequent necrosis(Park,2011).Septicvasculitisleadingtonecrosislocalized tothepinnahasbeendescribedindogsandcats,butnotyetinpigs (LeeGrossetal.,2005).
The third hypothesis states that trauma e.g. ear biting or environmentalfactors,istheprimarytrigger.Theinjuredeartip becomes infected withβ-hemolytic streptococci present in the mouthsofbitingpigsandmaycausecellulitisandnecrosis(Park etal.,2013).ItisimportanttorealizethatbacteriasuchasS.hyicus orStreptococcusspp.arepartoftheporcineskinmicrobiota,and thereforetheirpresenceontheearwillnotnecessarilyleadtoPEN.
However,ifthereisskintraumaortissuedamage,thesebacteria couldmultiplyandexacerbatethelesions.
Clinicalsigns
Porcineearnecrosislesionsvarygreatly,rangingfrommildto severe(Fig.1).Mildlesionsconsistofanencrustedsore,localized ontheeartiporventralmarginoftheear.Itisunclearwhyinsome casestheeartipisaffected,whereasinothersmainlytheventral marginoftheearis affected.Based ontheauthors’experience, mildcasesdonotrequiretreatmentandcanheal.Lesionscanalso progresstothesevereformwithepidermalulcerationandnecrotic lesions (Richardson et al., 1984). Affected parts of the pinna becomedark-red,moistandcrusted.Thelesionscanbepresenton oneorbothears.Theeffectsonpigperformancearelow,although
Fig.1.Graphicpresentationofporcineearnecrosis(PEN)lesions:mildlesion(A),severelesion(B).PhotographstakenbyDriesDonkers.
severelesionsmightdecreaseperformanceandimpedethesaleof piglets (Park et al., 2013).The most frequent histopathological findingsinthemildformarehyperkeratosis,acanthosisandintra- epidermalabscesses.Theepidermismaybecoveredbyalayerof necrotic cells, degenerated neutrophils, and exudate. Vacuolar degeneration and necrosis of basal cells, with subsequent formationofintra-epidermalvesicles,islesscommon.Mononu- clearcellinfiltratesoftensurrounddermalcapillaries(Richardson et al.,1984).Histologically, mild PEN is characterized by intra- epidermal abscesses,intracellularedemaofkeratinocytes, para- keratotichyperkeratosisofthestratumcorneum,and/orinfiltra- tion of neutrophils (Mirt,1999). These findings agree withthe definition of skinnecrosis.1 Reiner et al. (2019) also described inflammationandcrustsontheearbaseofsucklingpiglets,which didnotresembletypicalPEN.However,apossibleassociationwith PEN, which usually occurs later, in weaned pigs, is worthy of investigation.
Riskfactors
BecausethepreciseetiologyandpathogenesisofPENislargely unknown, many potential risk factors have been suggested to explainlesionprevalenceand/orseverity.Itisgenerallyaccepted thatPENisamultifactorialconditioninwhichinfectiousandnon- infectiousfactorsmayplayanimportantrole(Park,2011).Table1 presentsanoverviewofreportedriskfactors.
Infectiousfactors
Infectious factorsthat mayincrease therisk for PENmainly includeviralandbacterialinfections.Virusespotentiallyinvolved includeporcinecircovirustype2(PCV2)andPRRSV.Bothviruses are thought to exert immunosuppressive effects, potentially associatedwithPEN(Pejsaketal.,2011).Tomasini(2015)reported thatinimmunosuppressedhumans,suchaspatientstreatedwith high-dose corticosteroids,organtransplantrecipientsorhuman immunodeficiency virus infected patients, avirulent or low- virulence bacterial infections can causeseptic vasculitis, which
cantheoreticallyleadtoskinnecrosis.However,thisimmunosup- pressionislikelytobemuchmorepronouncedthanthatcausedby PCV2 or PRRSV in pigs. The most common PCV2-associated syndromes are postweaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS). Systemic necrotizing vasculitis, as observed in PDNS, can also lead tonecrotic skinlesions; however, thesevascular lesionscanbealsoobservedinthekidneys,spleenormesenterium (Segalésetal.,2005).Theunderlyingmechanismisthoughttobe associatedwithTypeIIIhypersensitivityanddepositionofantigen- antibodyaggregates (Drolet,2012).Pejsak et al.(2011) demon- stratedthat vaccination of sowsagainst PCV2beforefarrowing decreased theprevalenceof PENin weanedpiglets onaPCV2- positivefarm.Lesionprevalencedecreasedfrom13.1%to5.9%and lesion severity was reduced. When the vaccination protocol ceased,thenumberofaffectedpigletsrosebacktopre-vaccination levels(11.6%)within3months.Thepercentageofmildandsevere lesionswas3–4timeshigherinpigsfromunvaccinatedsowsthan vaccinatedsows.Thisstudyindirectlyshowedtheimportanceof PCV2inthedevelopmentofPENonthatindividualfarm.Tothe authors’knowledge,nosimilarstudies havebeenpublishedfor PRRSV.ThepossibleroleofPRRSVinPENisbasedonthefrequent prevalenceofthevirusinweanedpigsandtheimmunosuppres- sive characteristics of the virus (Drew, 2000). Therefore, viral causedimmunosuppressioncouldallownormalskinmicrobiotato multiplyandcausedamage.Riskfactorsshouldbedistinguished from etiologic factors, as their presence increase the risk for disease,butdonotnecessarilyinducethediseaseinaspecificfarm (ThrusfieldandChristley,2018).Forinstance,onPCV2-freefarms, PCV2infectionsdonotcontributetotheproblem;similarly,PCV2 vaccination regimens also reduce the likelihood that PCV2 is involvedinPEN.
S.hyicusisthemostfrequentlyisolatedbacteriumfromeartip necrosis lesions and can produce toxins that damage the skin (Tanabeetal.,1996).S.hyicusispresentattheearlystageofeartip necrosis, but streptococci can alsobe foundin more advanced lesions.Bacterial colonization of the lesionsis consideredas a crucial step in the breakdown of the epidermis and lesion deterioration (Richardson et al., 1984). Similar to S. hyicus, S.
aureusisalsocommonlyfoundontheskinsurfaceofhealthypigs andcanproducetoxinsthatcoulddamagetheskin.Therefore,the possibleinvolvementofS.aureusinPENhasbeensuggested(Park, 2011). Parket al. (2013) investigatedthecausative potential of Table1
Overviewofdifferentinfectiousandnon-infectiousriskfactorsforporcineearnecrosis(PEN).
Riskfactors Relatedto
hypothesisa
References Prevention Possibleeffecton
PEN Infectious
factors
Immunosuppressioncausedby PCV2andPRRSV
1,3 Pejsaketal.(2011) Vaccination Indirect
Staphylococcushyicus 1 Richardsonetal.(1984) Adequatepenhygiene Direct
Staphylococcusaureus 1 Park(2011) Direct
Mycoplasmasuis 2 Truszczynskiand
Pejsak(2009)
Quickdiagnosisandtreatment;nocommercial vaccineavailable
Direct
Non-infectious factors
Highhumidity/poorairqualityin thepen
3 Smuldersetal.(2008) Adequateventilation Indirect
Fullyslattedfloorwithoutstraw 3 Adequatependesign,andadditionalstraw Indirect
Lowavailabilityofdrinkersand feeders
3 Indirect
Highstockingdensity 3 Parketal.(2013) Appropriatestockingdensity Indirect
Mycotoxincontamination 1 Non-contaminatedfeed;mycotoxinbinderand/
ordetoxifiers
Direct
Highenvironmentaltemperature 3 Appropriatetemperatureadjustment/
ventilation
Indirect
PCV2,Porcinecircovirustype2;PRRSV,Porcinereproductiveandrespiratorysyndromevirus.
aThreehypotheses,asdescribedinthetext:(1)skindamageviatoxins;(2)occlusionofbloodvesselsinear;and(3)earbiting.
1See: National Toxicology Program, US Department of Healthand Human Service,NTPNonneoplasticLesionAtlas,Skin-Necrosis.https://ntp.niehs.nih.gov/
nnl/integumentary/skin/necrosis/skin-necrosis_508.pdf(Accessed12March2021).
staphylococci. The recovery rate ofS. hyicusfrom96 ear tissue biopsies originating from 11 different farms was 66% and the recoveryrateofS.aureuswas91%,indicatingtheirhighprevalence.
Otherbacteriamentionedintheliteratureinassociationwith PENarespirochetesofthegenusTreponema.Thesearecommonly foundinskinlesionsandmouthmicrobiotaofseveralspeciessuch pigs,cats,dogsandhumans.Treponemaspp.isolatedfromporcine gingival and ear lesions are closely related but not identical (Pringle et al., 2009), which brings into question connections betweenTreponemaspp.andearbitinglesions.Parketal.(2013) demonstrated sparsenumbersof spirochetes in PENlesionson histological examination, but could not culture the bacteria.
Treponemapedis(T.pedis)isacommonspeciesfoundinporcineear lesionsandshoulder ulcers.Karlssonetal.(2013)reportedthat spirocheteswerefoundin73%ofshoulderulcers,in53%ofPEN casesandin9.7%ofgingiva.However,experimentalintradermal inoculationofT.pedisdidnotresultinPEN(Karlssonetal.,2017).
ThismaysuggestthatTreponemamightactassecondaryagents, but thepaper doesnotrule outtheirimportance asa primary agent.
M.suisisanotheragentthathasbeenassociatedwithPEN.This bacteriumdestroyserythrocytes,leadingtoanemiaandbilirubi- nemia.A subsequentautoimmuneresponseis consideredtobe important in the pathogenesis in PEN, as cold agglutinins (autoantibodies)canbeproduced,targetingantigenspresenton red blood cells surface (Truszczynski and Pejsak, 2009).When body temperature drops, IgM antibodies lead to erythrocyte agglutination (Schmidt etal.,1992).Thiscan takeplaceonthe pinna,occludingsmallvesselsandconsequentlycausingischemia andnecrosisofthesurroundingtissues.TruszczynskiandPejsak (2009) reportedthatM.suis infectionmayalsocauseimmuno- suppressionintheacutephase,renderingpigsmoresusceptibleto other infections. A positive clinical response to appropriate antibiotictherapyconfirmstheroleofbacteriainthedevelopment and/orprogressofthelesions(Richardsonetal.,1984),but this doesnotprovethatbacteriaaretheprimarycause.Alternatively, non-responsetoantimicrobialtherapycannotexcludeaninfec- tious cause, as acquired antimicrobial resistance to commonly usedantibioticscanoccur(Park,2011),orinappropriateantimi- crobial choices could have been made. The role of parasitic infestationshasbeennotbeeninvestigated,howeverMirt(1999) mentionedscabiesasapossiblefactor.
Non-infectiousfactors
Non-infectious factors potentially involved in PEN include environmentalfactorssuchasafullyslattedfloorwithnostraw, poorairqualityandhighpenhumidity(Parketal.,2013),aswellas management factors such as high stocking density and early weaning,inadequateavailabilityofdrinkersandfeedersperpig, andmycotoxincontaminationofthefeed(Parketal.,2013).Park et al. (2013) alsosuggested fighting and ear bitingas possible factors. Smulders et al. (2008) described four factors which increasedearand tailbiting:(1) inadequatenumber offeeding places;(2)highstabletemperature;(3)highratioofslattedareas;
and(4)dryfeeding.Camerlinketal.(2015)suggestedgeneticsas animportantfactorinfluencingthebehaviorandbitingfrequency ofpigs.Allofthesefactorsmaygreatlyinfluenceanimalwelfare.
Diana et al. (2019) showed alsothat management factorsmay impactthedevelopmentofear,tail,orskinlesions.
Regarding feed quality, special attention has been paid to mycotoxins. Although there is no publishedevidence of direct involvementofmycotoxinsinPEN,sometoxinsareconsidereda risk factor because of their potential immunosuppressive and dermonecrotic effects (Osweiler, 2006). Immunosuppressive effects of aflatoxins, ochratoxins, or trichothecenes have been
demonstratedinvitroandinvivo,andcanresultfromdepressedT/
Blymphocyteactivity,suppressedproductionofimmunoglobulins andantibodies,ordecreasedcomplementactivity(Corrier,1991).
Weissenbacher-Lang et al. (2012) demonstrated a correlation betweenhighdeoxynivalenolconcentrations(0.251mg/kg)inthe feedandmicroscopicalternationsinearlyPENi.e.focalepidermal necrosis, histiocyte infiltration, or bacterial growth in the superficialcelldebris.Othermicroscopiclesions,suchascollagen lysis, acute vasculitis, granulation tissue, hyperkeratosis, or histiocyteinfiltrationhavebeenassociatedwithhigherconcen- trationsoftheergotalkaloidmycotoxinsergotamine,ergocryptine andergocristine.Gangrenousergotismcausedbyergotalkaloidsis usuallyaresultofvasoconstrictionandendothelialdamage,which leadstoischemiaandfinallydrygangrene(Osweiler,2006).
Othernon-infectiousfactorsbesidesfeedcontaminationwith mycotoxinscould havean indirecteffect onPEN by increasing stresslevelsand/oraggressivebehaviorsuchasearbiting.Inthis sense,theyfitwithinthethirdhypothesisofPENpathogenesis.
Furtherinformationaboutpossiblecausesofaggressionandbiting inpigscanbefoundintheappropriateinwelfarerelatedliterature.
Treatmentandprevention
Severelyaffectedpigsshouldbeseparatedfromthepenmates andhousedinahospitalpen,inordertopreventbitingbyother animals.Administrationofantimicrobialscanslowlesionprogres- sion, but severely affected necrotic tissue will not heal using antimicrobialtreatment alone, and usually dies. Bacteriological cultureshouldbeperformedfromthelesionsandantimicrobial susceptibilitytestingshouldberequested.Skinsamplesshouldbe taken from the transition between healthy and affected tissue beneath crusts, or deep swabs of the lesions. Pejsak and Truszczynski(2009) suggestedthattheentireagegroupshould bemedicated for 2 weeks withamoxicillinor amoxicillinwith clavulanicacid.However,oralmedicationforanextendedperiod does not align with current policy for the prudent use of antimicrobialsandreducingthespreadofantimicrobialresistance inveterinarymedicine(Magnussonetal.,2019).HansenandBusch (2008)isolatedS.hyicusinoneDanishherdaffectedbyPEN.After antimicrobialsusceptibilitytestingwasperformed,affectedpigs wereinjected with sulfadoxine (200mg/mL) and trimethoprim (40mg/mL)for5days.Thetreatmentincreasedtheaveragedaily bodyweightgainby12%,butdidnotdecreaselesionprevalenceor severity.Theauthorsspeculatedthatahigherdoseorlongercourse oftreatmentmighthaveresultedinapositiveeffect.Dianaetal.
(2017)alsoreportedthatlongtermantimicrobialusedecreased PENseverity;however,pigsweretreatedfor 9weeks(sulfadia- zine-trimethoprim,14.4mg/kg/dfor5days/week).Extendedand prophylacticmedicationregimensarenotrecommendedandare prohibitedinsomecountriesbecausetheyriskthedevelopmentof antimicrobialresistance.
Onestudyreportedthatapproximately95%ofS.aureusisolates (n=87)inPENwereresistanttopenicillinGandampicillin,and 75%oftheisolateswerenotsusceptibletotetracycline(Parketal., 2013). Trimethoprim-sulfamethoxazole (0%), sulfonamide (5%) and tiamulin (15%) had the lowest prevalence of antimicrobial resistance. In thesame study, antimicrobialsusceptibility of S.
hyicus isolates was also performed (n=63). More than 80% of isolates demonstrated resistance topenicillinG, ampicillinand ceftiofur, but there was almost noresistanceto trimethoprim- sulfamethoxazole (0%) and sulphonamide (5%). In M. suis infections,affectedpigscouldbetreatedwithoxytetracycline.
VaccinationofpigletsagainstPCV2orPRRSVmayreducethe prevalence of ear necrosis. Sow vaccination mayalso enhance piglet immunity through antigen specific immunoglobulins or lymphocytesinthecolostrum(Joiseletal.,2008).
Reducingpotential riskfactorssuchasadequate pendesign, avoidingovercrowding,limitingmixingofpigs,optimalventilation andairquality,andgoodfeedquality2e.g.byaimingtoeliminate exposure to mycotoxins in the feed. Post-harvest mycotoxin mitigation strategies such as mycotoxin detoxifiers, including binders(Jouany,2007),andmodifierscontainingyeasts(Molnar etal.,2004),orspecificenzymes(Duvicketal.,1998),whichcanbe mixedin thefeedtoreduceexposure,couldbeconsidered.Ear biting and aggression between pen mates can be reduced by improvingsanitation,andpotentiallybydietarysupplementation withmethionine,threonineandtryptophan(Meeretal.,2017).
Conclusions
Despiteascarcityofdataandwidepotentialforfuturestudies, thepublishedliteratureandresearchonPENSislimited.PENSisa commondisorderinpigs worldwide,especiallyinnursery pigs.
The exact etiology and pathogenesis are not yet known; this hampers optimaltreatment.Itisunclearwhetherreductionsin antimicrobial use due to strict regulations will influence the prevalenceandseverityofPEN.Asthecurrentstateofknowledge doesnotallowcausativefactorstoberuledinorout,controland prevention measures should focus on reducing potential risk factors reportedin the publishedliterature, and increasingthe immune status of animals.Underfieldconditions, practitioners shouldcheckforpotentialriskfactorsandtoassesstheirroleinthe problem. Histopathological investigations can help to identify whetherassociated pathologyoriginatedontheskinsurface or systemically.Itispossiblethatmultiplepathogenicmechanisms couldbeinvolved,dependingonfarmconditions;necrosisonthe pinnacanbeaclinicalsignofseveralspecificunderlyingpathways.
Toidentifyandquantifytheimportanceofpotentialriskfactors, largemulti-farmobservationalstudiesarerequired.Astheexisting PENliteratureislimited,furtherresearchisrequired,inparticular studies investigating prevalence, etiology and pathogenesis, to elucidatefactorsthatmaydecreaserisk.
Conflictofintereststatement
Noneoftheauthorsof thispaperhasafinancialorpersonal relationship with other people or organisations that could inappropriatelyinfluenceorbiasthecontentofthepaper.
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