Aggressive Periodontitis | IntechOpen

Aggressive periodontitis (AgP) is a disease characterized by rapid loss of periodontal tissues affecting systemically healthy individuals under age of 30 ... Home>Books>PeriodontologyandDentalImplantologyOpenaccesspeer-reviewedchapterAggressivePeriodontitisWrittenByAysanLektemurAlpanSubmitted:February5th,2018Reviewed:March29th,2018Published:November5th,2018DOI:10.5772/intechopen.76878DOWNLOADFORFREEShareCiteCitethischapterTherearetwowaystocitethischapter:1.ChoosecitationstyleSelectstyleVancouverAPAHarvardIEEEMLAChicagoPlaceholderCopytoclipboard2.ChoosecitationstyleSelectformatBibtexRISDownloadcitationIntechOpenPeriodontologyandDentalImplantologyEditedbyJaneManakilFromtheEditedVolumePeriodontologyandDentalImplantologyEditedbyJaneManakilBookDetailsOrderPrintChaptermetricsoverview1,675ChapterDownloadsViewFullMetricsDOWNLOADFORFREEShareCiteCitethischapterTherearetwowaystocitethischapter:1.ChoosecitationstyleSelectstyleVancouverAPAHarvardIEEEMLAChicagoPlaceholderCopytoclipboard2.ChoosecitationstyleSelectformatBibtexRISDownloadcitationImpactofthischapterIntechOpenDownloads1,675TotalChapterDownloadsonintechopen.comAdvertisementAdvertisementAbstractAggressiveperiodontitis(AgP)isadiseasecharacterizedbyrapidlossofperiodontaltissuesaffectingsystemicallyhealthyindividualsunderageof30 years.AgPclassifiedintotwocategoriesnamedlocalizedandgeneralizedaggressiveperiodontitis.Itdiffersfromchronicperiodontitis(CP)dependingonageofonsetofthedisease,rateofprogressionofthedisease,structureandcompositionoftheassociatedsubgingivalmicroflora,changesinhostresponseandfamilialpredisposition.TissuedestructioninpatientswithAgPisnotdirectlyrelatedtobacterialdepositsalsopersonalimmuneresponseplaysamajorroleinseverityofdestruction.Surgicalandnon-surgicaltechniquescanbeappliedinthetreatmentofAgP. ItisimportanttotreatandobtainfrequentcontrolsofindividualswithAgP. Themainpurposeofthetreatmentistocreateaclinicalconditionthatcanholdthelargestnumberofteethinthemouth.Afterthetreatmentperformedandprovidedthehealthofperiodontaltissues,patientshouldbeincludedinthemaintenanceprogram.KeywordsaggressiveperiodontitisgeneralizedaggressiveperiodontitisgeneticsfamilialpredispositionlocalizedaggressiveperiodontitisAuthorInformationShow+AysanLektemurAlpan*FacultyofDentistry,DepartmentofPeriodontology,PamukkaleUniversity,Denizli,Turkey*Addressallcorrespondenceto:[email protected](AgP)isadiseasecharacterizedbyrapidlossofperiodontaltissuesaffectingsystemicallyhealthyindividualsduringadolescenceandadulthood,andformsagroupofperiodontaldiseases[1].Itdiffersfromchronicperiodontitis(CP)dependingonageofonsetofthedisease,rateofprogressionofthedisease,structureandcompositionoftheassociatedsubgingivalmicroflora,changesinhostresponseandfamilialpredisposition.AgPclassifiedintotwocategoriesnamedlocalizedandgeneralizedaggressiveperiodontitis[2]andtookplaceprepubertal,juvenile,rapidlyprogressiveperiodontitisinthegroupthatwasdefinedasearlyonsetperiodontitisin1999InternationalWorkshopforaClassificationofPeriodontalDiseaseandConditions[1].ThisreportdefinedsomecharacteristicfeaturesoftheAgP[2,3].Patientsareclinicallyhealthy,exceptforthepresenceofperiodontitis.Rapidattachmentlossandbonedestruction.Familialaggregation.Secondaryfeaturesthatareoften,butnotalways,presentincludethefollowing:Theamountsofmicrobialdepositsareinconsistentwiththeseverityofperiodontaltissuedestruction.ElevatedproportionsofActinobacillusactinomycetemcomitans(A.actinomycetemcomitans)whichisnowtermedAggregatibacteractinomycetemcomitans.ElevatedproportionsofPorphyromonasgingivalis(P.gingivalis)insomepopulations.Phagocyteabnormalities.Ahyper-responsivemacrophagephenotype,includingelevatedlevelsofprostaglandinE2andinterleukin-1β.Advertisement2.Localizedaggressiveperiodontitis(LAgP)2.1.ClinicalfeaturesLAgPstartsatamuchearlieragethanCP,butitisnotrighttogotoacertainagelimit.Theageofonsetofthediseasecanhelpusdiagnosethedisease[4].ThereisnosignificantsubgingivalandsupragingivalcalculusinpatientswithLAgP. Lesionsaremostlyassociatedwiththebiofilmlayer.IntheformofLAgPthereislittleornoinflammationofthegums[5,6].Duringthisperiodgingivalhyperplasiadependingondentalplaqueand/orcalculusrarelyappears[6].Itischaracterizedbyrapidbonelossinthefirstmolarandincisors[7].Inthisdisease,thereareatleasttwopermanentteethinvolvement,oneofthemmustbethefirstmolar,andinvolvingnomorethantwoteethotherthanfirstmolarsandincisors[8].Powerfulserumantibodyresponsetoinfectingagentsandcircumpubertalonsetareamongdiseasefeatures[3].Accordingtotheworkshopin1999,iftheinvolvementislessthan30%,thediseaseislocalized,ifitisnot,consideredasgeneralize[1].Duringthediseasebonelossinthefirstmolarregionissymmetric[9].PatientswithLAgPbetweentheagesof21–35arethosewhohavenotbeendiagnosedandtreatedbefore,dependingontheseverityofthediseaseandprevioustreatments,toothloss,bonedefectsandgingivalrecessionsareobserved[6,7].ThefollowingreasonshavebeenproposedregardingthelimitedlocalizationoflesionsinAgP[8].A.actinomycetemcomitansaffectsthehostresponseinmanywaysaftercolonizationinfirstmolarsandincisors:AactinomycetemcomitanssecretesafactorthatinhibitsPolymorphonuclearleukocytes(PMNL)chemotaxis.Aactinomycetemcomitanssecretessomefactorssuchasendotoxin,collagenaseandleukotoxintofacilitatethecolonizationofbacteriaintheperiodontalpocketandcausedestructionofperiodontaltissues.AntagonisticbacteriaagainsttoA.actinomycetemcomitans.ColonizetheperiodontaltissuesandpreventthecolonizationofA.actinomycetemcomitansinotherareasofthemouth.Thissituationleadsthelocalizationofinfectionandtissuedestruction.Forunknownreasons,A.actinomycetemcomitansmayloseitsabilitytoproduceleukotoxin.Inthiscase,thediseaseprogressionslowsdownandcolonizationofnewareasisprevented.Thepossibilitythatthecementformationisdefectiveandmayalsocausethelesionstobelocalized.ThehypoplasiaoraplasticcementformationwasseenintheexaminationsperformedonteethwithdrawnfrompatientswithLAgP.LAgPprogressesrapidlyandbonelossisthreetofourtimesgreaterthanCP. OtherclinicalfeaturesofLAgParedistolabialmigrationsoftheupperincisorteethandconsequentdiestemaformation,increasedmobilityinthefirstmolars,tendernessontheuncoveredrootsurfaces,deeppainspreadingineverydirectionduringchewingthatdoesnotlastsolong.Inthisphase,periodontalabscessandregionallymphadenopathymayoccur[8].2.2.RadiographicfeaturesTheclassicfeatureofLAgPistheverticalbonelossseeninalveolarboneinthefirstmolarandincisorteethinhealthyteenagers.Radiographicfindingmayincludeanarcshapedalveolarbonelossextendingfromthedistalsurfaceofthepremolartothemesialsurfaceofthesecondmolar.InthisdiseasebonelossusuallywiderthanCP[8](Figure1).Figure1.LAgPpatient;(a)-clinicalviewoftheLAgPpatient,(b)7 mmprobingdepthatdistaloftheincisortooth,(c)radiographicviewoftheLAgPpatient.Advertisement3.Generalizedaggressiveperiodontitis(GAgP)3.1.ClinicalfeaturesGAgP;ischaracterizedbydiffuseattachmentandbonelossaffectingatleastthreepermanentteethotherthanfirstmolarandincisorteeth,usuallyseeninyoungadults,wherepoorserumantibodyresponsestoinfectiousagentsoccur[10].TheGAgPmaybeginaslocalizedandbecomemoregeneralizedasmoreteethareaffectedovertime.Thediseaseremainedactiveandpassiveperiods.Therateofattachmentandbonelossisnotthesameatthesetimes.Darkredandulceratedareasarecharacterizedbysevereacuteinflammatorydiseasetableisdetectedduringtheactivephase.Theconditionisaccompaniedbybleedingwhichusuallyoccurswithlightstimulationanddischargeofthepus.Severeattachmentandbonelossoccurduringthisperiodofthedisease[10,11].GAgPsometimesaccompaniedbysystemicfindingssuchasweightloss,mentaldepressionandfatigue[12].Also,GAgPhasbeenimplicatedinthepathogenesisofsystemicdiseasessuchasuncontrolleddiabetesmellitus,AIDS,leukemia,neutropenia,histiocytosisX,syndromessuchasPapillon-LefevreorCheidak-Higashi,rareinheriteddiseasessuchashypophosphatasiaandintraoralsymptomofacquireddisorderssuchasgranulocytopenia[13].Inthepassiveperiod,theclinicalimageisespeciallysimilartothatofhealthyindividualsintermsofcolor,shapeandconsistency.However,deepperiodontalpocketsareencounteredintheprobing.IthasbeenstatedthatGram(−)microorganismsplayarolemostlyinmicrobialdentalplaque(MDP).Pathogenicmicroorganisms,especiallyP.gingivalisandTannerellaforsythensis(T.forsythensis)arerelatedtodiseaseprogression[10,11].PatientsalsohadincreasedantibodyresponseagainstA. Actinomycetemcomitans,Prevotellaintermedia(P.intermedia)andCampylobacterrectus(C.rectus)[14].3.2.RadiographicfeaturesTheradiographicimageofGAgP,characterizedbyseverehorizontalandverticalalveolarbonelossespeciallyinthefirstmolarandincisors.Thisseveredestructioncanaffectonlyafewteethaswellasthemajorityoftheteethinthemouth.Thediseasecanprogresssoquicklythattheaggressivenature,radiographstakenatdifferenttimes,bonelossiseasilyrecognizable[8].Pageet al.[12]reportedthatinpatientswithGAgP,thelossofalveolarboneinregionswhereperiodontaldestructionismoresevereisincreasedfrom25–60%over9 weeks(Figure2).Figure2.GAgPpatient;(a)clinicalviewoftheGAgPpatient,(b,c)increasedprobingdeptharoundtheteeth,(d)radiographicviewoftheGAgPpatient.Advertisement4.EpidemiologyofAgPTheprevalenceofAgPchangessignificantlydifferentbetweengeographicalregionsandbetweendifferentracial/ethnicorigins.Forthisreason,theprevalenceofthediseaseinagivenpopulationcanbedeterminedbythedistributionofthepopulationaccordingtothetypeandproportionoftheraceandethnicgroup.Inthestudies,themethodswhichhavebeenusedtodiagnosisofdiseasesuchas;whetherradiographiesistakenornot,differencesindiagnosticequipment,differentindexingsystemsetc.varies.AccordinganepidemiologicstudyperformedbySusinet al.[15]prevalenceofAgPinAfricaisbetween1–5%,inNorthandmid-EuropeCaucasians0.1%,inSouthEuropean~0.5%,inNorthAmerica~0.1–0.2%ofCaucasians,0.5–1.0%ofHispanicsand2.6%ofBlackpeople,inSouthAmerica0.3–2.0%,inAsia0.2–1.0%.Accordingtheseresults,AgPcanbeahealthprobleminsomepopulationsand/orraces.InanationalsurveywhichincludeUSschoolchildrenaged13–19 years,theprevalenceofAgPwasfound0.40%in13–15 years,0.80%in16–19 years,0.06%inwhites,2.60%inblacksand0.50%inHispanics[16].Haubeket al.[17]foundahighprevalenceofAgPas7.6%inMoroccanchildrenaged14–19 years.AlsoAlbandaret al.[18]foundAgPwithahighprevalence6.5%,inUganda.GiventheprevalenceofAgPinAsia;itfound1.8%inIraq,0.86%inIsrael,0.47%inJapanand0.42%inSaudiArabia[19].InSouthAmerica,theprevalenceofdiseasewasvaryamongthecountries:0.32–2.6%inBrazil,0.32%inChile[19].InEuropeithasrelativelylowprevalencebeenobserved;0.1%inDenmark,0.1%inFinland,0.5%inItaly,0.1–0.3%inNetherlands,0%inNorway,0.11–0.13%inSwitzerland,0.02–0.8%inUnitedKingdom[19].ThediseaseismostcommonlyseeninAfrican-Caribbean(80%)andleastNorwegian(0.2%)[20].Intermsoftheprevalenceofracialattachment,itwasfoundthatAgPwashigherinblackpeople(2.6%)thanwhitepeople(0.17%)[21].Moststudiesshowcomparablediseaseprevalenceinbothmaleandfemalepatients.GenderfactoranditsroleindevelopmentofAgPhavenotbecomeclear.InsomestudiesAgPwasfoundtobemorecommoninwomenthanmenwith3:1ratio[22,23,24,25].However,researchesarealsoavailablethatindicatesAgPmorecommoninmenthanwomen[18,21].Advertisement5.PathogenesisofAgPPeriodontaldestructioninAgPoccurspathogenicmicroorganismsandhostimmunesysteminteraction[14,26]andthisinteractionisinfluencedbymanylocalandsystemicfactors[27].FourbasicfactorsplayroleinthepathogenesisofAgP[26].Microbialfactors.Hostfactors.Environmentalfactors.Geneticfactors.5.1.MicrobialfactorsThepresenceofmicroorganismsisessentialfortheinitiationoftheinflammatoryprocessinperiodontaldiseasesandthefactorsrelatedtothehostareinvolvedintheprogressofthedisease.TheappearanceofseveretissuedestructionwithasmallamountofplaqueinAgPsuggeststhatmicroorganismswithhighvirulenceintheetiologyofthediseasemayplayarole.A.actinomycetemcomitansisconsideredtobethemosteffectiveetiologicagentinAgPforabout30 years[28].A.actinomycetemcomitans,short(0.4–1 μm),facultativeanaerobic,immobile,Gram(−)rod.Thevirulencefactorisserotypicallyvariableandsomeserotypesareknowntobeinvasiveepithelialcellsandgingivaltissue.TonettiandMombelli(1999)listedthefindingsofA.actinomycetemcomitansinrelationtoLAgP[11].Inareaswhereperiodontaltissuedestructionoccursinaggressiveperiodontitispatients,90%ofA.actinomycetemcomitansarefound.Intheareaswherethedestructionproceedsandcontinues,inhighamounts,A.actinomycetemcomitansweredetected.HighserumantibodylevelsagainstA.actinomycetemcomitanswereobservedinthemajorityoflocallyaggressiveperiodontitispatients.ClinicaltrialshaveshownthatimprovementinclinicalparameterswithtreatmentisassociatedwithadecreaseinthelevelofA.actinomycetemcomitansinsubgingivalfloras.ItisknownthatA.actinomycetemcomitanshasvirulencefactorsthatcanplayaroleinthedevelopmentofthediseasesuchasleukotoxin.A.actinomycetemcomitanshasbeensuggestedtoplayaroleintheonsetofAgPbyinteractingwithfacultativeanaerobicandcapnophilicspeciessuchasthelocallyusefulCapnocytophagaspeciesandEikenellacorrodens(E.corrodens)[29].Today,themicrobiologicalprofileofAgPhaschangedfromthepresenceofspecificmicroorganismstothepresenceofmorecomplexmicrobiota[30].Someofthebacteriafoundinperiodontalpocketsrelatedtogingivitis,whilesomearerelatedtoperiodontitis.Dentalplaquebiofilmisadynamicstructureandchangesovertime.Differentbacterialgroupsarecomplexedatdifferenttimesinbiofilm.Amongthese,orangecomplexbacteria:P.intermedia,Prevotellanigrescense(P.nigrescense),Parvimonasmicra(P.micra),Fusobacteriumnucleatum(F.nucleatum),C.rectus,Eubacteriumnodatum(E.nodatum)andCampylobactershowae(C.showae)buildabridgebetweenthepathogensseenintheearlyperiodofperiodontaldiseasenamedredcomplexbacteria.RedcomplexbacterianamedP.gingivalis,T.forsythiaandTreponemadenticola(T.denticola)wereassociatedwithperiodontaltissuedestruction[31].Insomestudies,P.gingivalisandT. ForsythiahavebeenshowntobeanetiologicalagentforAgP[10,11].PatientsalsohadincreasedantibodyresponseagainstA. Actinomycetemcomitans,P.intermediaandC.rectus[14].ElectronmicroscopicstudiesperformedonLAgPdemonstratesthatbacteriafoundintheconnectivetissuetotheextendingbonesurface.Whenexaminedbymoreadvancedtechniques,thepresenceofA. Actinomycetemcomitans,Capnocytophagasputigena(C.sputigena),mycoplasmastrainsandspirocheteshasbeendefined[8].IntheextractedteethaffectedbyLAgP,electronmicroscopicobservationsshowedthatinthebiofilmlayerontherootsurfaceformedGram(−)coccibacteriaandothermicroorganisms[5].Insomestudies,ithasbeenreportedthatspirochetesarerarelyornotpresentinLAgPlesions[32,33],incontrastsomeauthorsreportedthatthereisahighnumberofspirochetesinlesions[34,35].InastudyperformedinpopulationofChileanpatientswithGAgPandCP,P.gingivalis,P.micraandC.rectusisolatedfromsubgingivalplaqueandfoundtoberelatedtodiseaseprogression[36].InarecentstudyperformedwithpatientswhoaffectedbyGAgP,theauthorsconcludedthatexistenceofacomplexcooperativeinteractionpromotedbyHerpesSimplexVirusType-1(HSV-1)infection,involvingStaphylococcusaureus(S.aureus)andtheperiodontopathogensP.gingivalis,T.forsythia,andFusobacteriumperiodonticum(F.periodonticum),thatcouldpromoteanaccelerateprogressionoflesionsofGAgP[37].Doganet al.[38]comparedsubgingivalflorainLAgP,GAgP,CPandhealthycontrolsin69Turkishpeople.T.forsythensisandC.rectusfoundthelowestfrequencyinLAgP.A.actinomycetemcomitans,P.gingivalis,andC.rectuswerehigherinGAgPthaninhealthycontrols.Yeastsalsowerefoundinsamples.Leeet al.[39]foundthebacteriaindiseasedsitesinKoreanAgPpatients,descendingpercentages;Fusobacteriumsp.,P.gingivalis,Treponemasp.,T.forsythensis,P.intermediaandA.actinomycetemcomitans.TheyalsoconcludedP.intermediawasassociatedwithGAgP. InastudyredcomplexbacteriafoundinthatofGeneralizedCPandGAgP. Nosignificantdifferencesfoundintermof40bacteriaspeciesinGeneralizedCPandGAgP[40].Humancytomegalovirus,Epstein–Barrvirustype-1andHSV-1arealsoinvolvedintheprogressionofthedisease[41,42].Thesedifferencesmayberelatedtovariationsinthesocietieslivinginthevariousregionsoftheworld,aswellasthedifficultiesingroupingdiseases.5.2.HostfactorsAgPisadiseasethatshowssignificantdifferencesfromotherperiodontaldiseasesintermsofseverityofdestruction,rateofprogression,responsetotreatment,etiologicfactorsandgeneticsusceptibilitycriteria.Defectsofhostdefensesystemandcomplexfactorslikemicrobialfloraplayaroletogetherinhostilityanddiseaseformationaffectingseverityofdestruction,speedofdiseaseprogressandresponsetotreatment.Intheresponsetodentalplaqueaccumulation,whichleadstogingivitis,substantialevidencehasbeencollectedtoproposelargedifferencesbetweenindividuals.Inlinewiththisconcept,ithasbeenshownfromtheinitialresearchattemptsonearly-onsetperiodontitisformsthataffectedindividuals,sufferfrommetabolicimbalanceorhereditaryhostresponsedefects.Thefirststepofperiodontaldefenseisinflammationininnateimmuneresponsethatprovidedarespondtobacterialplaquebyneutrophils,macrophages,fibroblasts,epithelialanddendriticcells[43].Ifthisimmuneresponseisnotcapabletocontroltheinflammationprocess,complexinflammatorycascadesareactivated.Secondstagewhichiscalledadaptiveimmuneresponsethatresumedbyantigen-presentingcellsandpredominantlyB-celllesionscomposedinperiodontitis[43].TissuedestructioninpatientswithAgPisnotdirectlyrelatedtobacteriaaccumulationinrootsurface.Personalimmuneresponseplaysamajorroleinseverityofdestruction[44].PMNLisanimportantcomponentoftheimmunesystemandfoundingingivallesionsandinrootsurfacesofAgPcases[45].Someofneutrophilmalfunctionssuchasincreasedadhesion,reducedchemotaxis,increasedsuperoxideandnitricoxideproductionandreducedphagocytosiswerethoughttoberesponsiblefordiseaseprogression[46,47,48].Hyper-responsivemacrophagephenotypeincludingelevatedprostaglandinE2andinterleukin-1βlevelstookplaceamongthefeaturesofAgPinthe1999Workshop[49].AccordingtoKantarciet al.[50]LAgPhasbeenassociatedwithvariousabnormalitiesofhostcellfunctionsuchas;neutrophilabnormalities,reducedchemotaxis,increasedsuperoxideproduction,reducedreceptorexpression,reducedphagocytosisandkillingofA. Actinomycetemcomitans,impairedleukotrieneB4andsignaltransductionabnormalities.TheysuggestthePMNLisnothypofunctionalordeficient,butitishyperfunctionalandexcessedactivityisresponsibleofthetissuedamage.Aconstantlyuncontrolledperiodontalinfectionactivatesneutrophilsandmakethemmoreeffectivelystimulatedtocounteractmicrobialepisodes.Thus,differencesinneutrophilfunctionsinAgParethoughttobeacombinationofgeneticandacquiredpropertiesofperson[51].Humanleukocyteantigens(HLA)areantigensthatregulatetheimmuneresponse.HLA-9andHLA-15antigenshavebeenshowntobeassociatedwithAgP[8,52].AnotherstudyhasshownthatHLAclassI,HLAclassIIantigensareassociatedwithperiodontaldisease[53]butnosignificantassociationswerefoundbetweenHLAclassIIantigensandAgP. ThereisapositiveassociationwithHLA-A9andnegativerelationshipwithHLA-A2andHLA-B5haveshowninpatientswithAgP[54].HLAclassIIantigensarecapablebindpeptidesderivedfrombacterialantigensandpresentthemtoTcellswhileHLAclassIantigensgenerallypresentpeptidesderivedfromvirusesandself-antigenstocytotoxicTcells.Inatheory,viralpeptidebindingandpresentationtoTcellsviaHLA-A9orHLA-B15isnotsufficientforactivatingimmuneresponseproperlyresultingAgPwithsevereperiodontaldestruction[53].IgAplaysanimportantroleinthehostdefensesystemand,locallydominantinsaliva.IgAisimportantbecauseofitsantiinflammatoryfunctionandreducesinflammationbyinhibitingIgGandIgMproduction.StudieshaveshownthattheIgAratiodecreasessignificantlyinAgPsubjects[55].Hwanget al.providesevidenceagainstthe1999Workshop’sdecisionofweakserumantibodyresponseinAgP. Intheirstudy,serumIgGlevelstoA. ActinomycetemcomitansinGAgPpatientsisnotdifferfromLAgP,LocalizedCPandGeneralizedCPbutitissignificantlyincreasedtoseveralspecies,includingP.gingivalis,T.denticola,andC.rectus[56].CRPisanacutephaseresponsemoleculeandincreasesinaninflammatoryconditionsuchasheat,infection,hypoxiaandtissuedamage.Elevatedfibrinogenlevelscanactivatetheinflammatorycascades.Chandyet al.[57]investigatedthesetwomoleculesinAgPpatients.ElevatedCRPandfibrinogenlevelsfoundinCPpatientsnotinAgPandhealthycontrols.TheseresultsmayexplaintheseverityofthelesionsbydelayingtheimmunologicalresponseagainsttoAgP. InsomestudiesplateletsizeandfunctionfoundtodecreaseinGAgPpatientsduetotheconsumptionoflargeplateletsatsitesofperiodontalinflammation.PlateletsmayplayactiveroleinhostresponseinGAgPpatients[58,59].5.3.EnvironmentalfactorsEnvironmentalfactorssuchasoralhygiene/bacterialplaque,smoking,stressandsystemicfactorsmayexacerbatetheinflammationandplayanimportantroleintheperiodontitisprogression.StudieshaveshownthatthereisapositivecorrelationbetweenAgPandstress[60].InacontrolledstudypatientsintheGAgPgroupweresignificantlymoredepressedandlonelythanpatientsintheCPandcontrolgroups[60].Existingdentalplaqueisalsoveryimportanttodeveloptheperiodontaldisease.ApositivecorrelationfoundbetweentheamountofplaqueandGAgP,butnotinLAgP[61].SmokingisalsoariskfactorforAgP[54].InastudysmokingfoundtorelateddiseaseactivityandprogressioninGAgPbutitisnotassociatedwithLAgP[62].AlsosmokingaffectsthecytokineprofilesofpatientswithAgPanddisturbsthehost–parasiterelationship[63].AgPpatientswhoaresmokingshowedpoorclinicalrespondtheperiodontaltreatment[64].Accordingtothe1999workshop,themainfeatureindiagnosingofAgPisthattheindividualshouldbemedicallyhealthy[1].Howeversymptomsoftheguminsomesystemicdiseases/conditionsmayresembleAgP. Thisgroupofdiseasesincludes;neutropenia,hypophosphatasia,leukemias,Cheidak-Higashisyndrome,leukocyteadhesiondeficiency,Papillon-Lefevresyndrome,trisomy21,histiocytosisandagranulocytosis[1].5.4.GeneticfactorsAgPisamultifactorialdiseaseandmanyetiologicalfactorsarerequiredforclinicalpresentation.Bacterialcontentandhostdefenseclearlyplayanimportantroleinthedisease.Geneticvariationsmayaffectthehostresponsetothedisease.Oncediagnosed,thesiblingofthechildoradolescentmustalsobeinvestigatedfortheAgP. ThegeneticfactorsthatmaybeinvolvedinthepathogenesisofAgP,havebeeninvestigatedbyconsideringtheimmunesystemregulatedbygeneticfactorsandthatcertaingeneticpolymorphismsmaydisruptthedefensesystemagainsttheagentthatinfectstheimmunesystem.Interleukin-1(IL-1)isapotentpro-inflammatorymediatorthatismainlyreleasedbymonocytes,macrophagesanddendriticcellsandgeneticpolymorphismsofIL1havebeenstudiedinassociationwithAgP. ThreestudieshavereportednoassociationbetweenthecarriageratesoftheIL1A−889(+4845)C → TgeneandAgP[65,66,67],butonestudyhavefoundanassociationwiththisgeneandAgPinChinesePopulation[68].IL1B+3954(+3953)C → Tgenepolymorphismsandcarriagerateoftherare(R)alleleinCaucasiansfoundassociatedwithAgPinastudy[65].InstudiesinvolvingIL-4whichhaveanti-inflammatoryproperties,noassociationwasfoundbetweenAgPandgenotypeencodingthiscytokine[69].Inameta-analysisthatconductedtheevaluatingIL-6polymorphisms,therewasconcludedanassociatedwithAgPandIL-6polymorphisms[70].IL-10isananti-inflammatorycytokinewhichdown-regulatesthepro-inflammatoryimmuneresponseofmonocytesandmacrophages.TheresultsofthestudiesinvestigatingpolymorphismonthegenethatencodedIL-10werenotsignificant[71,72].IL-17playsanimportantroleinnaturalandacquiredimmuneresponse;thereisastudyinmicedemonstratingthatIL-17receptortriggerbonelossininfectiousconditions[73].Inarecentmetaanalysisauthorsconcludedthatthereisnosignificantassociationbetweenthepolymorphismsrs2275913andrs763780 ininterleukins17Aand17FgenesandCPandAgPintheallelicevaluation[74].IL-23isapro-inflammatorycytokineandfoundpositivelycorrelatedwithCPbutexistingstudieshowthatthereisnosignificantassociationofIL-23polymorphismswithAgP[75].IL-8isachemokineandplaysroleofchemoattractantfortheneutrophils.InsufficientstudiesexistthatcorrelateIL-8polymorphismswithAgP. ExistingstudiesinliteraturedemonstratedthatthereisnosignificantassociationbetweenIL-8polymorphismsandAgP[75].Tumornecrosisfactor(TNF)isapro-inflammatorycytokinewhichhasthepotentialtostimulatetheproductionofsecondarymediators,includingchemokinesorcyclo-oxygenaseproducts,amplifyingthedegreeofinflammation.NoassociationsbetweentheTNFApolymorphismsandAgPinameta-analysis[72].AnFcreceptorisaproteinfoundonthesurfaceofcertaincellsandpartofimmunoglobulin(FcγR)linkcellularandhumoralpartsoftheimmunesystemthatcontributetotheprotectivefunctionsoftheimmunesystem[76].AJapanesestudyreportedanassociationforacompositegenotypeoftheFccRIIIaNalleleandtheFccRIIIb+141RalleleinAgP[77]incontrastinastudperformedwithCaucasianpopulationthereisnoassociationfoundintermofthisgene[78].ThereislimitedinformationaboutpolymorphismofFcγRandAgP. ThevitaminDreceptorwasincludedvariousbiologicalprocessessuchasbonemetabolismandtheimmuneresponsetomicrobialinfections.Nibaliet al.[79]andParket al.[80]foundanassociationwithAgPbutBretet al.[65]couldnotfindanyaccociation.CD14andTolllikereceptors(TLRs)areextraandintracellularreceptorssuchasrecognizepathogen-associatedmoleculesonGram(+)andGram(−)bacteriaandmediatetheproductionofcytokinesrequiredforeffectiveimmuneresponse.InstudiesthatperformedtofindarelationshipCD14polymorphismandAgPreceivednoassociation[81,82].AboutTLRs,thereislimitedinformationandstudiesareavailable.Moststudiesperformedaboutpolymorphismswerelimitedbysamplesizeandhadvariationsincaseinclusioncriteria.Geneticstudiescanalsobelimitedbygeographicandethnicaldifferences.Tounderstandthepathogenesisofthiscomplexdiseasemulticenterstudiesandlargesamplesizesarerequired.Advertisement6.GeneraltreatmentstrategyAgPisacomplexperiodontaldiseasethatcausesrapiddestructionoftheperiodonticumandevencausestoothloss.ComplexpathogensareinvolvedintheetiologyofAgP. Therefore,itisimportantforclinicianstotreatthediseaseandmaintainperiodontalhealth[83].Thetreatmentprotocolsarebasedonstudiessofar.Physicianscanachieveveryeffectiveresultsiftheyareworkingwithmicrobialtestsduringandaftertreatment.Peoplewiththesameclinicalcharacteristicsmayhavedifferentbacterialflora,orpeoplewithdifferentclinicalcharacteristicsmayhavethesamebacterialflora.Inclinicaltrials,thesuccessoftreatmentisassessedbyconsideringtheprobingdepth(PD),clinicalattachmentlevel(CAL)andbleedingonprobing(BOP)usingconventionalperiodontalinstruments.Allparametersforthepatientsshouldbeassessedandthetreatmentdecisionshouldbegiven.Surgicalandnon-surgicaltechniquesareappliedinthetreatmentofAgP[84].ItisimportanttotreatandobtainfrequentcontrolsofindividualswithAgPwhichisseeninyoungerpatientscoexistentrapidattachmentandalveolarboneloss.Therearestudiesdemonstratedthatthepost-treatmentattachmentlevelcanbemaintaineddespitetheriskofrecurrenceofthedisease[85,86].Astudyof40-yearfollow-upsfrompatientswithGAgPshowsthateventhemostaggressiveandmostadvancedperiodontitiscasesaretreatable[87].Themotivationandadaptationofthepatientisveryimportantinordertocontrolthedisease.Inthisphase,thepatientshouldbeinformedbythedoctorabouttheroleofthepatient,theseverityoftheillnessandtheriskfactors.Themainpurposeofthetreatmentistocreateaclinicalconditionthatcanholdthelargestnumberofteethinthemouthforaslongaspossible.Periodontaltreatmentisconsideredinfourmainphases.Firstphase;initialtherapyornon-surgicalperiodontaltreatment.Thesecondperiodontaltreatmentphaseissurgicalperiodontaltreatment,thirdphaseprosthetictreatmentandfourthphasemaintenanceperiodontaltreatment.6.1.Non-surgicaltreatmentofAgPRemovalofagentscausingperiodontaldisease,providinggoodoralhygienetothepatient,andreducingpre-existinggingivalinflammationandperiodontalpocketdepthsinadvanceoffuturephasesareamongthegoalsofnon-surgicalperiodontaltreatment.Mechanicaltreatmentinvolvesremovalofplaqueanditsproductsfromdentalsurfaces(supra/subgingival),aswellasdentalandotherplaque-retaininglocalagentsbyhandorultrasonicinstruments.Rootplanningarealsoincluded.TheresponsesofpatientswithLAgPtoinitialperiodontalcarevaryinstudies.Ingeneral,theleastamountofworkonthisissueanditisnotlongtoobservethefinalresults.BasedontheliteratureGAgPrespondsgoodclinicalresultstoscalingandrootplanning(SRP)intheshortterm(upto6 months).However,after6 monthsdespitefrequentvisitstothephysicianandstrengtheningoralhygiene,relapsesanddiseaseprogressionhavebeenreported[88].Studieshaveshownthatthetotalsupragingivalandsubgingivalplaquemassisreducedbymechanicaltreatment.However,becausesomepathogenscaninvadeintothetissue,orbecauseperiodontalinstrumentsarenoteffectiveindeepandcomplexpockets,mechanicaltreatmentissometimesineffective[89].Thesuccessofperiodontaltreatmentdependsontheremovalofdentalplaqueandthereforepathogenicmicroorganismsinthedentalplaque.Theanti-infectivetreatmentsappliedinthiscontextdirectlyaffectthesuccessofthetreatment.Anti-infectivetreatmentincludesbothmechanicalandchemotherapeuticapproachesandaimstodestroyorreducethemicrobialdentalplaquebiofilmwhichisprimaryetiologicalagentofperiodontalinfections.Theuseoftherapeuticagentsespeciallysystemicantibioticshavebeenwidespreadtobeabletoobtainpredictabletreatmentresponsesduetoconventionalperiodontaltreatmentandtosupporttreatmentforthespecificmicrobialstructureofthedisease.Atthistimethereisaclearconsensusthatmechanicalinstrumentationshouldalwaysprecedeantimicrobialtherapy.ToachieveeffectivelevelsofthedrugonthedayofthecompletionofSRP[90].Thesubgingivalbacterialloadthatwillbeinhibitedbytheantimicrobialagentmustbereducedbymechanicaltreatment.Insufficientantimicrobialagentconcentrationsmaycausetheemergenceofresistantbacterialstrains[88].Thetetracyclinegroupisconsideredfirstinsystemictreatment.TetracyclineandSRPfoundtobemoreeffectiveintermofeliminationA.actinomycetemcomitans,CapnocytophagaandspirochetescomparingonlySRP[91].Tetracyclineisknowntohavebeneficialeffectsinwoundhealingregardingitsanticollagenaseactivity[92].Doxycyclineisasemisynthetictetracyclineandiseffectiveinthetreatmentofperiodontitis.Itiseasiertotakedoxycyclineatlowerdosesanduseitwithdailyfoods.Inastudy60patientsweredividedintoaplacebogroupandagroupthatreceivedsystemicdoxycycline(loadingdoseof200 mganddosesof100 mgdailyfor14 days)SRPwasperformedtoallgroupsoveran8-weekperiod,systemicantibioticorplacebowasonlyusedduringthefirst2 weeksoftheSRP. AttheendofthestudynosignificantdifferenceswerefoundintermofPD,BOP[93].Itwasdemonstratedinmanystudies,biofilmshowedhighlevelsofresistanceagainsttetracycline,minocycline,amoxicillin,doxycyclineandamoxicillin/clavulanate.Inaddition,high-degreeofantibiotictolerancehasbeendemonstratedinmaturebiofilms[94]whentetracyclinewasunabletosuppressA.actinomycetemcomitans,ithasbeenraisedacombineduseofantibioticsforthetreatmentofAgP. MetronidazoleisanitroimidazolederivativeantibioticwhichhasastrongbactericidaleffectonobligateanaerobGram(−)bacteria.ItishighlyeffectiveonperiodontopathogenicbacteriasuchasP.gingivalisandP.intermediawhichinthe“redcomplex”[95].Thecombinationof250 mgofmetronidazoleand375 mgofamoxicillin,threetimesadayfor7 days,asanadjuncttoSRP,wasfoundtobeveryeffectiveinsuppressingsubgingivalA.actinomycetemcomitansload[96].Guerreroet al.[97]evaluatedSRPplussystemicmetronidazoleandamoxicillininuseonclinicalparameters,intotalof41individualswithGAgP. Twentyrandomlyselectedpatientsweregiven500 mgmetronidazoleand500 mgamoxicillinthreetimesadayfor1 weekinadditiontomechanicaltreatment,andtheremaining21patientsweregivenplaceboinadditiontomechanicaltreatment.Twoandsixmonthsre-evaluationsweremade.Additionalmetronidazoleandamoxicillinmayprovideastatisticallysignificantimprovementinclinicalparametersintheshortterm.Xajigeorgiouet al.[84]investigatedmetronidazole+amoxicillin,doxycycline,metronidazoleefficacyin43GAgPpatientclinicallyandmicrobiologically.Patientswererandomlydividedinto4groups.FirstgroupwasreceivedSRPplus500 mgmetronidazole+500 mgamoxicillinthreetimesadayfor1 week,secondgroupwasreceived200 mgforthefirstdayloading,100 mgdoxycyclineforthefollowing14 days,thirdgroupwasreceived500 mgmetronidazolethreetimesadayfor1 week,andthefourthgroupwasevaluatedasthecontrolgroup.After6 weeksand6 monthspatientswerereevaluatedintermofCAL,BOP,PD. Additionalmetronidazole+amoxicillinormetronidazoleplusSRPhavebeeneffectivecomparingtheothergroups.Adjunctiveuseofmetronidazoleplusamoxicillin,metronidazolealoneorclindamycininpatientswithGAgPresultsinwellclinicalimprovementscomparingwiththeuseofdoxycyclineforasimilaramountoftimeorwithSRPalone[88].TheuseofazithromycininrecentyearshasbecomeanissueinAgPtreatment.Longhalf-lifeofanduseofonlyonceevery3 daysofazithromycin,providesadvantagesforthepatientandthephysician.InastudyclinicalefficacyoftheadjunctiveuseofazithromycinwithSRPwasinvestigatedinAgP. Twelvemonthsaftertreatment,approximately1 mmreductioninPDandhigherpercentageofteethwithattachmentgainwasobservedintestgroup[98].ThereisnocertainprotocolfortheuseofadjunctivesystemicantimicrobialswithSRP,butingeneralsuggeststhatantibioticintakeshouldstartonthedayofdebridementcompletion;debridementshouldbecompletedwithinashorttime(preferably<1 week)[94].Localantibioticapplicationsmayalsousedtocompletetheperiodontaltherapy.Severallocalantibioticapplicationshavebeendevelopedinadditiontoinitialperiodontaltherapy.Theseincludemetronidazole,chlorhexidine,minocycline,doxycyclineandtetracycline.TheuseofthissystemsinLAgPmaybemorebeneficialeffectintermofthenatureofthedisease.Toachievemaximumefficacy,drugsmustprovidesomecriteriasuchas;thedrugmustreachthetargetedsiteofaction,remainataneffectiveconcentrationandlastforanadequateperiodoftime[99].Inastudy,26patientswithLAgPdividedintoacontrolgroup,agroupreceiving1%chlorhexidinegelandagroupreceivinga40%tetracyclinegel.After12 weeks,eitheroftheseantimicrobialagentsprovidesignificantadditionalimprovementoftheclinicalparameters[100].Kaneret al.comparedlocalchlorhexidinechipandministrationandsystemicamoxicillinplusmetronidazolecombinationinadditiontoSRPonclinicalparametersinGAgPpatients.Systemicuseofamoxicillinplusmetronidazolecombinationfoundtobestatisticallysignificantclinicalimprovementscomparingthelocalchlorhexidinechip[101].InasimilarstudyPuruckeret al.[102]concludedthatadditionalappliedlocal(tetracyclinefibers)andsystemic(500 mgamoxicillin/clavulanicacid)antibioticsshowedequallybenefitsintermsofclinicalparameters.Inconclusion,localantimicrobialadjuvanteffectsreportedintheliteraturedonotappeartoimproveontheadjunctiveeffectofsystemicantibioticsinpatientswithAgP. Whenusingsuchsystems,cost-benefitandefficiencyshouldbeconsideredwell.6.2.SurgicaltreatmentofAgPSurgicaltreatmentmayrequirefortheremainingpocketsafterinitialperiodontaltreatmentofAgP. Thesurgicalapproachhastheadvantagessuchas;reachingdifficultanatomicalformationsoftheteeth,cleaningthepocketepitheliumfrominvadedA.actinomycetemcomitansandapplicationofregenerativeprocedures.Twenty-fiveperiodontallesionsinsevenpatientswithLAgPdividedintothreetreatmentgroups:SRP;SRPplussofttissuecurettage;SRPplusmodifiedWidmanflapsurgery.Themicrobiologicandclinicalmeasurementswereperformedupto16 weeks.AttheendofthestudySRPaloneunabletosuppressA.actinomycetemcomitansinperiodontallesions,incontrastSRPplussofttissuecurettageandmodifiedWidmanflapsurgerysucceeded[103].SystemicantibioticusecanpreferredwithvarioussurgicaltechniquesinthetreatmentofAgP. KornmanandRobertson[104]foundmodifiedWidmanflapsurgeryplustetracyclinewaseffectiveinareaswheretheblackpigmentedbacteroidesandA.actinomycetemcomitansloadwashigh.LindheandLiljenberg[105]treated16patientswithmodifiedWidmanflAgPsurgeryplustetracycline(14 days).Asaresultof5-yearfollow-up,successfulclinicalresultswereobtainedandradiologicalbonefillinangularbonydefects.InacaseseriesperformedbyBuchmannet al.[106],SRPandmodifiedWidmanflapsurgeryplussystemicamoxicillin/metronidazolecombinationprovideperiodontaltissuestabilizationatarate95%over5 years.Therearemanymethodstoregainboneinverticalbonedefectssuchasbonegrafting,guidedtissueregenerationbyusingmembranes,theuseofbiologicmodifiersandcombinationsoftheabove.Autograftsarethegoldstandardandhavebeenextensivelyusedbecauseofitsosseoinductive,osseoconductive,andosteogenicpropertiesbutithaslimitationslikemorbidityandmortalityhencedifferentgraftmaterialsareavailableinpractice.Allografts(e.g.freeze-driedboneallograft),xenografts(bovineorcorralderived)andalloplasticmaterials(e.g.bioactiveglass,hydroxyapatiteandbeta-tricalciumphosphate)arealternativelyusedinsteadofautograft[107].YuknaandSepe[108]demonstratedanaveragedefectfill(80%)in12LAgPpatientsusingfreeze-driedboneallografts.Inastudydifferentgraftmaterialswereevaluatedin10patientswithLAgP.4:1ratiocombinationofbeta-tricalciumphosphate/tetracycline,hydroxyapatite/tetracyclineorfreeze-driedboneallograft/tetracyclinewereappliedintothesegroups.Eachgraftmaterialshowedadecreaseindefectandpocketdepthalthoughnosignificantdifferencesbetweenthedifferentgraftingmaterialswerefoundintermsofhard-tissueorsoft-tissuechanges.Buthydroxyapatite/tetracyclineshowedagreaterpercentageofdefectfillwascomparingwithbeta-tricalciumphosphate/tetracycline[109].Membraneshavebeengroupedintotwomajorcategories:nonresorbable(high-densitypolytetrafluoroethylene(PTFE)membranesreinforcedornotwithatitaniumframework(e.g.Cytoplast®TXT-200;OsteogenicsBiomedical,Lubbock,Tex.,USA)andresorbablemembranes(polylacticacid(PLA)anditscopolymers,tissue-derivedcollagenmembranes)[110].Nonresorbablemembranesserveasaspacemaintenancewhichisneededfortissueregenerationandinertalsobiocompatible.Unfortunately,secondsurgeryforremovalormembraneexposuretakeplaceamongitsdisadvantages.Althoughresorbablemembranesshowlackofsufficientstrength,unpredictabledegradationrateandcauseagreaterinflammatoryresponse[110].UsageofnonresorbableorresorbablemembranesfortreatingintrabonydefectsinAgPhasbeenshowntobeeffectiveinmanystudies[86,111].6.3.OthertreatmentmodalitiesPhotodynamicantimicrobialtherapythatphotosensitizers(toluidineblue,methyleneblue,malachitegreen)areusedinsideperiodontalpocketsforincreasingthecytotoxicpotentialoflaserlighttopotentialperiodontalpathogens.InametaanalysisauthorsconcludedthatphotodynamicantimicrobialtherapycannotbesuggestedasroutinewithnonsurgicaltreatmentofpatientswithAgPaccordingtolackofevidencebasedontheliterature[112].Enamelmatrixproteins(amelogenin)whichprovidesnewcementumandtheformationofnewattachmentinperiodontaldefectsandgrowthfactors/differentiationfactors(platelet-derivedgrowthfactor,insulin-likegrowthfactor,fibroblastgrowthfactor,bonemorphogeneticprotein,transforminggrowthfactor-beta)whichplayanimportroleintissuedevelopmentandhealingaretoolsforgainingattachment.TheireffectivenessonperiodontiumweredemonstratedinmanystudieswithCPbutstudieswithAgP,mostlyexistascasereports[113,114].Yılmazet al.[115]treatedpatientswithGAgPwithatotalof12intrabonydefectswiththecombinationofplateletrichplasma+bovinederivedxenograftcombination.PD,marginalrecession,relativeattachment,probingboneandradiographicbonelevelsweremeasuredatthebeginningandat12 monthsreentry.TheresearchersnotedthatthecombinationofplateletrichplasmaandbovinederivedxenograftforthetreatmentofGAgP,providedsuccessfulclinicalresultsinlargeintrabonydefectsandthatprognosiswasaffectedpositivelyevenforteeththatwerethoughttohavehopelessprognosis.Dentalimplantsareawidelyusedtreatmentedentulismandprovidesfunctionalandestheticresolutions.SincetoothlossisfrequentlyseeninAgPpatients,dentalimplantapplicationscanbeapplied.However,marginalbonelossandimplantsurvivalratesinAgPpatientssignificantlyhigherthanthoseofCPandhealthysubjects[113,114].CareshouldbetakenwhenconsideringdentalimplantinAgPpatients.Frequentfollow-upsshouldnotbeneglectedinthesepatients.6.4.MaintenancetherapyAfterthetreatmentperformedandprovidedthehealthofperiodontaltissues,patientshouldbeincludedinthemaintenanceprogram.DuetotherecurrencenatureofAgP,maintenanceisgiventoforpreventionofadditionaltoothlossanddiseaserecurrence.Regularcontrolsareusefulforcontrollingtheprogressionofthedisease.Thesecontrolsshouldbelifelong,butthereisnodefinitiveprotocolforfrequency.Someresearcherssuggestedmonthlychecksduringthefirst6 monthsafterthetreatmentfinished.Someresearchersstatedthat3–4controlsperyearwouldsuffice.Ineverycontrolsession;PDandCALshouldbeassessed.Also,whennecessary,SRPshouldbeperformed.Radiographsshouldbetakenseparatelyfromeachtoothorareaaffectedbythediseaseonceayear.Localantibioticadministrationmaybepreferredtoriskyareas[116].TheprognosisofteeththataffectedAgPdependsonmanyfactorssuchastheamountofmissingbone,thepresenceorabsenceoffurcationregion,themorphologyofbonedefects,thedegreeofmobility,crown/rootratio,occlusalcontacts,oralhygieneandgeneralhealth.Treatmentshouldbeevaluatedaccordingtotheinitialcondition.Itisalsoimportanttoperformmicrobialtestingateverycontrolsessionwheneverpossible.Thus,thephysicianmaybeanideaabouttheactivationofthedisease.Advertisement7.ConclusionAgPisacomplexdiseaseandhasmultifactorialetiology.Whilebacterialplaqueisessentialforinitiationofdisease,itisgenerallyacceptedthatgeneticfactorsandhostimmuneresponseplayalargeroleinthediseasesusceptibility.Alsoenvironmentalandbehavioralfactorsdeterminethefinalclinicaloutcome.Theoutcomeofrapidandseverealveolarboneloss;gingivalrecession,pathologicalmigrationofteeth,mobilityandeventuallossofteethoccur.Becauseoftheclinicalresults,AgPpatientssuffersocialproblemsduetoesthetic,phoneticandnutritionalproblemsandtheirqualityoflifediminishes.Thetreatmentofthesepatientsisquitechallenging,duetotheabsenceofastandardtreatmentprotocolforthisdiseasewhichitsetiologyisnotfullyunderstood,butalsobecauseoftherapidprogression,severeperiodontaltissuelossandrecurrenceofthedisease.Non-surgicalandsurgicalperiodontaltreatmentscombinedwithsystemicantibioticsarerecommendedforthecompleteeradicationofdeepperiodontalpockets.Inlongterm,activeperiodontaltreatmentmustfollowedbymaintenanceperiodontaltreatmentforpreventingattachmentandtoothloss.References1.ArmitageGC. Developmentofaclassificationsystemforperiodontaldiseasesandconditions.AnnalsofPeriodontology.1999Dec;4(1):1-6.DOI:10.1902/annals.1999.4.1.12.LangNBP,CullinanM,JeffcoatM,MombelliA,MurakamiS,PageR,PapapanouP,TonettiM,VanDykeT. Consensusreport–aggressiveperiodontitis.AnnalsofPeriod-ontology.1999;4:53.DOI:10.1902/annals.1999.4.1.533.AlbandarJM. Aggressiveperiodontitis:Casedefinitionanddiagnosticcriteria.Period-ontology2000.Jun2014;65(1):13-26.DOI:10.1111/prd.120144.ArmitageGC,CullinanMP. Comparisonoftheclinicalfeaturesofchronicandagg-ressiveperiodontitis.Periodontology2000.Jun2010;53:12-27.DOI:10.1111/j.1600-0757.2010.00353.x5.ArmitageGC. Comparisonofthemicrobiologicalfeaturesofchronicandaggressiveperiodontitis.Periodontol2000.Jun2010;53:70-88.DOI:10.1111/j.1600-0757.2010.00357.x6.NevinsML,MelloningJT.PeriodontalTherapyVolume1:ClinicalApproachesandEvidenceofSuccess.Germany:QuintessencePublishing;1998.pp.101-116.ISBN978-0-86715-309-57.DörferCE. Antimicrobialsforthetreatmentofaggressiveperiodontitis.OralDiseases.2003;9(Suppl1):51-53.PMID:129745318.NewmanMG,TakeiH,CarranzaFA,KlokkevoldPR.Carranza’sClinicalPeriodontology.10thed.St.Louis,Missouri:SaundersElsevier;2006.pp.506-5129.MombelliA,MeierC. Onthesymmetryofperiodontaldisease.JournalofClinicalPeriodontology.Aug2001;28(8):741-745.PMID:1144273310.TrevilattoPC,TramontinaVA,MachadoMA,GoncalvesRB,SallumAW,LineSR. Clinical,geneticandmicrobiologicalfindingsinaBrazilianfamilywithaggressiveperiodontitis.JournalofClinicalPeriodontology.Mar2002;29(3):233-239.DOI:10.1034/j.1600-051x.2002.290309.x11.TonettiMS,MombelliA. Early-onsetperiodontitis.AnnalsofPeriodontology.Dec1999;4(1):39-53.DOI:10.1902/annals.1999.4.1.3912.PageRC,AltmanLC,EbersoleJL,VandesteenGE,DahlbergWH,WilliamsBL,et al.Rapidlyprogressiveperiodontitis.Adistinctclinicalcondition.JournalofPeriodontology.Apr1983;54(4):197-209.DOI:10.1902/jop.1983.54.4.19713.TonettiMS,MombelliA. Aggressiveperiodontitis.In:LindheJ,LangNP,KarringT,editors.ClinicalPeriodontologyandImplantDentistry.5thed.Oxford,Malden,Iowa,Copenhagen,Victoria,Berlin,Paris:BlackwellMunksgaardPublishingCo.;2008.pp. 428-45814.SchenkeinHA,VanDykeTE. Early-onsetperiodontitis:Systemicaspectsofetiologyandpathogenesis.Periodontology2000.Oct1994;6:7-25.DOI:10.1111/j.1600-0757.1994.tb00023.x15.SusinC,HaasAN,AlbandarJM. Epidemiologyanddemographicsofaggressiveperiodontitis.Periodontology2000.Jun2014;65(1):27-45.DOI:10.1111/prd.1201916.AlbandarJM,BrownLJ,LoeH. Clinicalfeaturesofearly-onsetperiodontitis.JournaloftheAmericanDentalAssociation(1939).Oct1997;128(10):1393-1399.DOI:10.14219/jada.archive.1997.005817.HaubekD,EnnibiOK,AbdellaouiL,BenzartiN,PoulsenS. AttachmentlossinMoroccanearlyonsetperiodontitispatientsandinfectionwiththeJP2-typeofActinobacillusactinomycetemcomitans.JournalofClinicalPeriodontology.Jul2002;29(7):657-660.DOI:10.1034/j.1600-051X.2002.290711.x18.AlbandarJM,MurangaMB,RamsTE. PrevalenceofaggressiveperiodontitisinschoolattendeesinUganda.JournalofClinicalPeriodontology.Sep2002;29(9):823-831.DOI:10.1034/j.1600-051X.2002.290906.x19.AlbandarJM,TinocoEM. Globalepidemiologyofperiodontaldiseasesinchildrenandyoungpersons.Periodontology2000.2002;29:153-176.DOI:10.1034/j.1600-0757.2002.290108.x20.RonderosMMB. Epidemiologyofperiodontaldiseasesandriskfactors.In:GencoRJ,CohenDW,editors.PeriodonticsMedicine,Surgery,andImplants.4thed.St.Louis:ElsevierMosby;2004.pp. 32-6921.LoeH,BrownLJ. EarlyonsetperiodontitisintheUnitedStatesofAmerica.JournalofPeriodontology.Oct1991;62(10):608-616.DOI:10.1902/jop.1991.62.10.60822.BaerPN. Thecaseforperiodontosisasaclinicalentity.JournalofPeriodontology.Aug1971;42(8):516-520.DOI:10.1902/jop.1971.42.8.51623.DaviesRM,SmithRG,PorterSR. Destructiveformsofperiodontaldiseaseinadolescentsandyoungadults.BritishDentalJournal.Jun22,1985;158(12):429-436.PMID:386022624.GencoRJ,ChristerssonLA,ZambonJJ. Juvenileperiodontitis.InternationalDentalJournal.Sep1986;36(3):168-176.PMID:353378925.HormandJ,FrandsenA. Juvenileperiodontitis.Localizationofbonelossinrelationtoage,sex,andteeth.JournalofClinicalPeriodontology.Dec1979;6(6):407-416.DOI:10.1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