HindawiPublishingCorporation DermatologyResearchandPractice Volume2010,ArticleID893080,13pages doi:10.1155/2010/893080 Review Article Acne Scars: Pathogenesis, Classification and Treatment GabriellaFabbrocini,M.C.Annunziata,V.D’Arco,V.DeVita,G.Lodi, M.C.Mauriello,F.Pastore,andG.Monfrecola DivisionofClinicalDermatology,DepartmentofSystematicPathology,UniversityofNaplesFedericoII, ViaSergioPansini5,80133Napoli,Italy CorrespondenceshouldbeaddressedtoGabriellaFabbrocini,[email protected] Received17March2010;Revised7September2010;Accepted28September2010 AcademicEditor:DanielBerg Copyright©2010GabriellaFabbrocinietal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Acne has a prevalence of over 90% among adolescents and persists into adulthood in approximately 12%–14% of cases with psychologicalandsocialimplications.Possibleoutcomesoftheinflammatoryacnelesionsareacnescarswhich,althoughtheycan betreatedinanumberofways,mayhaveanegativepsychologicalimpactonsociallifeandrelationships.Themaintypesofacne scarsareatrophicandhypertrophicscars.Thepathogenesisofacnescarringisstillnotfullyunderstood,butseveralhypotheses havebeenproposed.Therearenumeroustreatments:chemicalpeels,dermabrasion/microdermabrasion,lasertreatment,punch techniques, dermal grafting, needling and combined therapies for atrophic scars: silicone gels, intralesional steroid therapy, cryotherapy,andsurgeryforhypertrophicandkeloidallesions.Thispapersummarizesacnescarpathogenesis,classificationand treatmentoptions. 1.Introduction the quality of sebum lipids, androgen activity, proliferation ofPropionibacteriumacnes(P.acnes)withinthefollicleand Acne has a prevalence of over 90% among adolescents [1] follicularhyperkeratinization[6].Increasedsebumexcretion and persists into adulthood in approximately 12%–14% contributes to the development of acne. Neutral and polar of cases with psychological and social implications of high lipidsproducedbysebaceousglandsserveavarietyofrolesin gravity[2,3]. signal transduction and are involved in biological pathways Allbodyareaswithhighconcentrationsofpilosebaceous [7]. Additionally, fatty acids act as ligands of nuclear glandsareinvolved,butinparticulartheface,backandchest. receptors such as PPARs. Sebaceous gland lipids exhibit Inflammatory acne lesions can result in permanent scars, direct pro- and anti-inflammatory properties, whereas the theseverityofwhichmaydependondelaysintreatingacne inductionof5-lipoxygenaseandcyclooxygenase-2pathways patients.Theprevalenceandseverityofacnescarringinthe in sebocytes leads to the production of proinflammatory populationhasnotbeenwellstudied,althoughtheavailable lipids [8]. Furthermore, hormones like androgens control literature is usually correlated to the severity of acne [4]. sebaceous gland size and sebum secretion. In cell culture, 2133 volunteers aged 18 to 70 from the general population androgens only promote sebocyte proliferation, whereas showed that nearly 1% of people had acne scars, although PPARligandsarerequiredfortheinductionofdifferentiation only 1 in 7 of these were considered to have “disfiguring andlipogenicactivity[9].Ontheotherhand,keratinocytes scars”[5].Severescarringcausedbyacneisassociatedwith and sebocytes may be activated by P. acnes via TLR, CD14, substantialphysicalandpsychologicaldistress,particularlyin and CD1 molecules [10]. Pilosebaceous follicles in acne adolescents. lesions are surrounded by macrophages expressing TLR2 on their surface. TLR2 activation leads to a triggering of 2.Pathogenesis the transcription nuclear factor and thus the production of cytokines/chemokines,phenomenaobservedinacnelesions. Thepathogenesisofacneiscurrentlyattributedtomultiple Furthermore, P. acnes induces IL-8 and IL-12 release from factors, such as increased sebum production, alteration of TLR2positivemonocytes[11]. 2 DermatologyResearchandPractice All these events stimulate the infrainfundibular inflam- matoryprocess,follicularrupture,andperifollicularabscess Acnescarssubtypes formation, which stimulate the wound healing process. Injurytotheskininitiatesacascadeofwoundhealingevents. Woundhealingisoneofthemostcomplexbiologicalprocess Icepick Rolling Boxcar Skin surface andinvolvessolublechemicalmediators,extracellularmatrix components, parenchymal resident cells as keratinocytes, fibroblasts, endothelial cells, nerve cells, and infiltrating blood cells like lymphocytes, monocytes, and neutrophils, collectively known as immunoinflammatory cells. Scars SMAS originateinthesiteoftissueinjuryandmaybeatrophicor hypertrophic.Thewoundhealingprocessprogressesthrough 3stages:(1)inflammation,(2)granulationtissueformation, Figure1:Acnescarssubtypes. and(3)matrixremodeling[12,13]. (1)Inflammation. Blanching occurs secondary to vaso- constriction for hemostasis. After the blood flow has been stopped, vasodilatation and resultant ery- thema replace vasoconstriction. Melanogenesis may also be stimulated. This step plays an important role in the development of postacne erythema and hyperpigmentation. A variety of blood cells, including granulocytes, macrophages, neutrophils lymphocytes, fibroblasts, and platelets, are activated and release inflammatory mediators, which ready the site for granulation tissue formation [14]. By examiningbiopsyspecimensofacnelesionsfromthe Figure2:Icepickscars. backofpatientswithseverescarsandwithoutscars, Hollandetal.foundthattheinflammatoryreaction at the pilosebaceous gland was stronger and had a longer duration in patients with scars versus those for ECM remodeling [18]. As a consequence, an without;inaddition,theinflammatoryreactionwas imbalance in the ratio of MMPs to tissue inhibitors slower in those with scars versus patients who did of MMPs results in the development of atrophic notdevelopscars.Theyshowedastrongrelationship or hypertrophic scars. Inadequate response results between severity and duration of inflammation and in diminished deposition of collagen factors and thedevelopmentofscarring,suggestingthattreating formation of an atrophic scar while, if the healing early inflammation in acne lesions may be the best responseistooexuberant,araisednoduleoffibrotic approachtopreventacnescarring[15]. tissueformshypertrophicscars[19]. (2)Granulation Tissue Formation. Damaged tissues are repaired and new capillaries are formed. Neu- 3.Morphology,Histology,andClassification trophils are replaced by monocytes that change intomacrophagesandreleaseseveralgrowthfactors Scarringcanoccurasaresultofdamagetotheskin during including platelet-derived growth factor, fibroblast thehealingofactiveacne.Therearetwobasictypesofscar growthfactor,andtransforminggrowthfactorsαand dependingonwhetherthereisanetlossorgainofcollagen β, which stimulate the migration and proliferation (atrophic and hypertrophic scars). Eighty to ninety percent of fibroblasts [16]. New production of collagen by ofpeoplewithacnescarshavescarsassociatedwithalossof fibroblastsbeginsapproximately3to5daysafterthe collagen(atrophicscars)comparedtoaminoritywhoshow woundiscreated.Earlyon,thenewskincomposition hypertrophicscarsandkeloids. is dominated by type III collagen, with a small percentage (20%) of type I collagen. However, the 3.1. Atrophic Scars. Atrophic acne scars are more common balance of collagen types shifts in mature scars than keloids and hypertrophic scars with a ratio 3:1. They to be similar to that of unwounded skin, with havebeensubclassifiedintoicepick,boxcar,androllingscars approximately80%oftypeIcollagen[17]. (Figure1andTable1).Withatrophicscars,theicepicktype (3)Matrix Remodelling. Fibroblasts and keratinocytes represents 60%–70% of total scars, the boxcar 20%–30%, produceenzymesincludingthosethatdeterminethe androllingscars15%–25%[20]. architecture of the extracellular matrix metallopro- Icepick:narrow(2mm),punctiform,anddeepscarsare teinases (MMPs) and tissue inhibitors of MMPs. known as icepick scars. With this type of scar, the opening MMPs are extracellular matrix (ECM) degrading istypicallywiderthanthedeeperinfundibulum(forminga enzymes that interact and form a lytic cascade “V”shape)(Figure2). DermatologyResearchandPractice 3 Table1:Acnescarmorphologicalclassification(adaptedfrom[20]). AcneScarsSubtype ClinicalFeatures Icepickscarsarenarrow(<2mm),deep,sharplymarginatedepithelialtractsthatextendvertically Icepick tothedeepdermisorsubcutaneoustissue. Rollingscarsoccurfromdermaltetheringofotherwiserelativelynormal-appearingskinandare Rolling usuallywiderthan4to5mm.Abnormalfibrousanchoringofthedermistothesubcutisleadsto superficialshadowingandarollingorundulatingappearancetotheoverlyingskin. Boxcar Boxcarscarsareroundtoovaldepressionswithsharplydemarcatedverticaledges,similarto Shallow varicellascars.Theyareclinicallywideratthesurfacethanicepickscarsanddonottapertoa <3mmdiameter pointatthebase. >3mmdiameter Deep Theymaybeshallow(0.1–0.5mm)ordeep(≥0.5mm)andaremostoften1.5to4.0mmin <3mmdiameter diameter. >3mmdiameter tool [22] based on the type of scar and the number of scars.Thissystemassignsfewerpointstomacularandmild atrophicscoresthantomoderateandsevereatrophicscores (macularormildlyatrophic:1point;moderatelyatrophic:2 points;punchedoutorlinear-troughedseverescars:3points; hyperplastic papular scars: 4 points). The multiplication factorfortheselesiontypesisbasedonthenumericalrange whereby,foronetotenscars,themultiplieris1;for11–20it is2;formorethan20itis3. The ECCA (Echelle d’Evaluation clinique des Cicatrices d’acne´) for facial acne scarring is also a quantitative scale, designed for use in clinical practice with the aim of Figure3:Boxcarscars. standardizing discussion on scar treatment and it is based onthesumofindividualtypesofscarsandtheirnumerical extent. Scar types considered to be more visibly disfiguring Rolling: dermal tethering of the dermis to the subcutis were weighted more heavily. Specific scar types and their characterizesrollingscars,whichareusuallywiderthan4to associated weighting factors were the following: atrophic 5mm.Thesescarsgivearollingorundulatingappearanceto scars with diameter less than 2mm: 15; U-shaped atrophic theskin(“M”shape).Boxcar:roundorovalscarswithwell- scars with a diameter of 2–4mm: 20; M-shaped atrophic established vertical edges are known as boxcar scars. These scarswithdiametergreaterthan4mm:25;superficialelastol- scars tend to be wider at the surface than an icepick scar ysis:30;hypertrophicscarswithalessthan2-yearduration: and do not have the tapering V shape. Instead, they can be 40; hypertrophic scars of greater than 2-year duration: 50. visualizedasa“U”shapewithawidebase.Boxcarscarscan A semiquantitative assessment of the number of each of beshallowordeep(Figure3). thesescartypeswasthendeterminedwithafour-pointscale, Sometimes the 3 different types of atrophic scars can in which 0 indicates no scars, 1 indicates less than five be observed in the same patients and it can be very scars, 2 indicates between five and 20 scars, and 3 indicates difficult to differentiate between them. For this reason morethan20scars.Withthismethod,therelativeextentof severalclassificationsandscaleshavebeenproposedbyother scarring for each scar type was calculated. The total score authors. Goodman and Baron proposed a qualitative scale can vary from 0 to 540. In recent studies on the reliability and then presented a quantitative scale [21, 22]. Dreno et of this scale, seven dermatologists underwent a 30-min al.introducedtheECCAscale(Echelled’EvaluationClinique trainingsessionpriortotheevaluationoftenacnepatients. desCicatricesd’Acne´)[23]. Therewasnostatisticaldifferenceinscoregradingbetween The qualitative scarring grading system proposed by participating dermatologists. The global scores, however, GoodmanandBaron[9]issimpleanduniversallyapplicable. varied from a minimum of 15 to a maximum of 145. Accordingtothisclassification,fourdifferentgradescanbe Unfortunately,astatisticalestimateofreliabilitywithinand used to identify an acne scar, as shown in Table2. Often between raters was not provided. The potential advantages (especiallyinthoseaffectedwithmildacne)thepatternand of this system include independent accounting of specific grading is easy to achieve but, in the observation of severe scar types, thereby providing for separate atrophic and cases,differentpatternsaresimultaneouslypresentandmay hypertrophicsubscoresinadditiontototalscores.Potential bedifficulttodifferentiate.Thestandardapproachadopted shortcomingsincluderestrictiontofacialinvolvement,time by Goodman and Baron describes a grading pattern and intensity,andundeterminedclinicalrelevanceofscoreranges theydevelopedaquantitativeglobalacnescarringassessment [21]. 4 DermatologyResearchandPractice Table2:Qualitativescarringgradingsystem(adaptedfrom[21]). GradesofPost Levelofdisease Clinicalfeatures AcneScarring Thesescarscanbeerythematous,hyper-orhypopigmentedflatmarks. 1 Macular Theydonotrepresentaproblemofcontourlikeotherscargradesbutof color. Mildatrophyorhypertrophyscarsthatmaynotbeobviousatsocial distancesof50cmorgreaterandmaybecoveredadequatelybymakeupor 2 Mild thenormalshadowofshavedbeardhairinmenornormalbodyhairif extrafacial. Moderateatrophicorhypertrophicscarringthatisobviousatsocial distancesof50cmorgreaterandisnotcoveredeasilybymakeuporthe 3 Moderate normalshadowofshavedbeardhairinmenorbodyhairifextrafacial,but isstillabletobeflattenedbymanualstretchingoftheskin(ifatrophic). Severeatrophicorhypertrophicscarringthatisevidentatsocialdistances greaterthan50cmandisnotcoveredeasilybymakeuporthenormal 4 Severe shadowofshavedbeardhairinmenorbodyhairifextrafacialandisnot abletobeflattenedbymanualstretchingoftheskin. 3.2. Hypertrophic and Keloidal Scars. Hypertrophic and scars are the major clinical indications for facial chemical keloidal scars are associated with excess collagen deposi- peeling[26,27]. tion and decreased collagenase activity. Hypertrophic scars As regards acne scars, the best results are achieved in are typically pink, raised, and firm, with thick hyalinized macular scars. Icepick and rolling scars cannot disappear collagen bundles that remain within the borders of the completelyandneedsequentialpeelingstogetherwithhome- original site of injury. The histology of hypertrophic scars caretreatmentwithtopicalretinoidsandalphahydroxyacids is similar to that of other dermal scars. In contrast, keloids [28, 29]. The level of improvement expected is extremely formasreddish-purplepapulesandnodulesthatproliferate variable in different diseases and patients. For example, ice beyond the borders of the original wound; histologically, pickacnescarsinapatientwithhyperkeratoticskinareonly theyarecharacterizedbythickbundlesofhyalinizedacellular mildly improved even if skin texture is remodeled. On the collagenarrangedinwhorls.Hypertrophicandkeloidalscars other hand, a patient with isolated box scars can obtain a aremorecommonindarker-skinnedindividualsandoccur significantimprovementbyapplicationofTCAat50%–90% predominantlyonthetrunk. onthesinglescars. Severalhydroxyacidscanbeused. 4.Treatment (A) Glycolic Acid. Glycolic acid is an alpha-hydroxy acid, soluble in alcohol,derived fromfruit and milk sugars.Gly- Newacquisitionsbytheliteraturehaveshowedthatpreven- colicacidactsbythinningthestratumcorneum,promoting tionisthemainstepinavoidingtheappearanceofpost-acne epidermolysisanddispersingbasallayermelanin.Itincreases scars.Geneticfactorsandthecapacitytorespondtotrauma dermal hyaluronic acid and collagen gene expression by are the main factors influencing scar formation [24]. A increasingsecretion ofIL-6[30].Theprocedureiswelltol- numberoftreatmentsareavailabletoreducetheappearance eratedandpatientcomplianceisexcellent,butglycolicacid ofscars.First,itisimportanttoreduceasfaraspossiblethe peels are contraindicated in contact dermatitis, pregnancy, duration and intensity of the inflammation, thus stressing and in patients with glycolate hypersensitivity. Side effects, the importance of the acne treatment. The use of topical such as temporary hyperpigmentation or irritation, are not retinoids is useful in the prevention of acne scars but more very significant [31]. Some studies showed that the level of thananyothermeasure,theuseofsiliconegelhasaproven skindamagewithglycolicacidpeelincreasesinadose-and efficacyinthepreventionofscars,especiallyforhypertrophic time-dependent manner. The acid at the higher concentra- scarsandkeloids. tion(70%)createdmoretissuedamagethantheacidatthe lowerconcentration(50%)comparedtosolutionswithfree 4.1.AtrophicScars acid.Anincreaseinthetransmembranepermeabilitycoeffi- cientisobservedwithadecreaseinpH,providingapossible 4.1.1. Chemical Peels. By chemical peeling we mean the explanationfortheeffectivenessofglycolicacidinskintreat- processofapplyingchemicalstotheskintodestroytheouter ment[32].Thebestresultsachievedforacnescarsregardfive damagedlayersandacceleratetherepairprocess[25]. sequentialsessionsof70%glycolicacidevery2weeks. Chemicalpeelingisusedforthereversalofsignsofskin aging and for the treatment of skin lesions as well as scars, (B) Jessner’s Solution. Formulated by Dr. Max Jessner, this particularly acne scars. Dyschromias, wrinkles, and acne combination of salicylic acid, resorcinol, and lactic acid DermatologyResearchandPractice 5 in 95% ethanol is an excellent superficial peeling agent. a light superficial peel with diffusion encompassing the full Resorcinolisstructurallyandchemicallysimilartophenol.It thicknessoftheepidermis;40%–50%canproduceinjuryto disruptstheweakhydrogenbondsofkeratinandenhances- the papillary dermis; and finally, greater than 50% results penetration of other agents [33]. Lactic acid is an alpha in injury extending to the reticular dermis. Unfortunately hydroxy acid which causes corneocyte detachment and theuseofTCAconcentrationsabove35%TCAcanproduce subsequent desquamation of the stratum corneum [34]. unpredictable results such as scarring. Consequently, the As with other superficial peeling agents, Jessner’s peels medium depth chemical peel should only be obtained with are well tolerated. General contraindications include active the combination of 35% TCA. The use of TCA in con- inflammation, dermatitis or infection of the area to be centrations greater than 35%, should be avoided. It can be treated, isotretinoin therapy within 6 months of peeling preferredinsomecasesofisolatedlesionsorfortreatmentof and delayed or abnormal wound healing. Allergic contact isolatedicepickscars(TCACROSS)[49].Whenperformed dermatitis and systemic allergic reactions to resorcinol are properly,peelingwithTCAcanbeoneofthemostsatisfying rareandneedtobeconsideredasabsolutecontraindications procedures in acne scar treatment but it is not indicated [35,36]. fordarkskinbecauseofthehighriskofhyperpigmentation [50]. (C) Pyruvic Acid. Pyruvic acid is an alpha-ketoacid and an effective peeling agent [37]. It presents keratolytic, (F)TCACross. InourexperiencetheTCACROSStechnique antimicrobialandsebostaticpropertiesaswellastheability has shown high efficacy in the case of few isolated scars to stimulate new collagen production and the formation of on healthy skin. CROSS stands for chemical reconstruction elastic fibers [38]. The use of 40%–70% pyruvic acid has of skin scars method and involves local serial application been proposed for the treatment of moderate acne scars of high concentration TCA to skin scars with wooden [39,40].Sideeffectsincludedesquamation,crustinginareas applicators sized via a number 10 blade to a dull point to of thinner skin, intense stinging, and a burning sensation approximate the shape of the scar. No local anesthesia or during treatment. Pyruvic acid has stinging and irritating sedation is needed to perform this technique [51]. Unlike vaporsfortheupperrespiratorymucosa,anditisadvisable the reports found in the literature, in which 90% TCA is toensureadequateventilationduringapplication. suggested, our experiences have shown that a lower TCA concentration (50%) has similar results and much less (D) Salicylic Acid. Salicylic acid is one of the best peeling adverse reactions [52]. TCA is applied for a few seconds agentsforthetreatmentofacnescars[41].Itisabetahydroxy untilthescardisplaysawhitefrosting.Emollientsthenneeds acid agent which removes intercellular lipids that are cova- to be prescribed for the following 7 days and high photo- lentlylinkedtothecornifiedenvelopesurroundingcornified protectionisrequired.Theprocedureshouldberepeatedat epithelioidcells.Themostefficaciousconcentrationforacne 4-week intervals, and each patient receives a total of three scarsis30%inmultiplesessions,3–5times,every3-4weeks treatments. Our experiences have shown that, compared [42–44].Thesideeffectsofsalicylicacidpeelingaremildand with other procedures, this technique can avoid scarring transient. These include erythema and dryness. Persistent and reduce the risk of hypopigmentation by sparing the postinflammatory hyperpigmentation or scarring are very adjacentnormalskinandadnexalstructures[53](Figures4 rare and for this reason it is used to treat dark skin [45]. and5). Rapidbreathing,tinnitus,hearingloss,dizziness,abdominal cramps, and central nervous system symptoms characterize 4.1.2. Dermabrasion/Microdermabrasion. Dermabrasion salicylism or salicylic acid toxicity. This has been observed and microdermabrasion are facial resurfacing techniques with 20% salicylic acid applied to 50% of the body surface thatmechanicallyablatedamagedskininordertopromote [46]. Grimes has peeled more than 1,000 patients with the reepithelialisation. Although the act of physical abrasion of current20and30%marketedethanolformulationsandhas theskiniscommontobothprocedures,dermabrasion,and observednocasesofsalicylism[47]. microdermabrasion employ different instruments with a differenttechnicalexecution[54].Dermabrasioncompletely (E) Trichloroacetic Acid. The use of trichloroacetic acid removes the epidermis and penetrates to the level of the (TCA)asapeelingagentwasfirstdescribedbyP.G.Unna,a papillary or reticular dermis, inducing remodeling of the Germandermatologist,in1882.TCAapplicationtotheskin skin’s structural proteins. Microdermabrasion, a more causesproteindenaturation,theso-calledkeratocoagulation, superficial variation of dermabrasion, only removes the resulting in a readily observed white frost [48]. For the outerlayeroftheepidermis,acceleratingthenaturalprocess purposes of chemical peeling, it is mixed with 100mL of exfoliation [55, 56]. Both techniques are particularly of distilled water to create the desired concentration. The effective in the treatment of scars and produce clinically degree of tissue penetration and injury by a TCA solution significantimprovementsinskinappearance.Dermabrasion is dependent on several factors, including percentage of isperformedunderlocalorgeneralanaesthesia.Amotorized TCA used, anatomic site, and skin preparation. Selection handpiecerotatesawirebrushoradiamondfraise.Several of appropriate TCA-concentrated solutions is critical when decadesago,thehandpiecewasmadeofaluminumoxideor performingapeel.TCAinapercentageof10%–20%results sodiumbicarbonatecrystals,whereasnowdiamondtipshave inaverylightsuperficialpeelwithnopenetrationbelowthe replacedthesehandpiecestoincreaseaccuracyanddecrease stratumgranulosum;aconcentrationof25%–35%produces irritation.Thereisoftenasmallpinpointbleedingoftheraw 6 DermatologyResearchandPractice beneath. Nonablative lasers do not remove the tissue, but stimulate new collagen formation and cause tightening of the skin resulting in the scar being raised to the surface. Amongthenonablativelasersthemostcommonlyusedare theNdYAGandDiodelasers[61]. Theablativelasersaretechnologieswithahighselectivity for water. Therefore, their action takes place mainly on the surfacebutthedepthofactioniscertainlytobecorrelatedto the intensity of the emitted energy and the diameter of the spot used. Among the ablative lasers, Erbium technologies aresoselectiveforwaterthattheiractionisalmostexclusively ablative.CO lasers,whichpresentlowerselectivityforwater, 2 besides causing ablation are also capable of determining Figure4:TCACross:patientbeforethetreatment. a denaturation in the tissues surrounding the ablation and a thermal stimulus not coagulated for dermal protein. CO lasers have a double effect: they promote the wound 2 healing process and arouse an amplified production of myofibroblasts and matrix proteins such as hyaluronic acid [62]. Clinical and histopathologic studies have previously demonstrated the efficacy of CO laser resurfacing in the 2 improvement of facial atrophic acne scars, with a 50%– 80% improvement typically seen. The differences in results reported with apparently similar laser techniques may be due to variations in the types of scar treated. Candidates mustpresentaskindiseasewithacneoffforatleast1year; theyshouldhavestoppedtakingoralisotretinoinforatleast 1 year; they should not have presented skin infections by Figure5:TCACross:patientafterthetreatment. herpesvirusduringthesixmonthspriortotreatment;they mustnothaveahistoryofkeloidsorhypertrophicscarring. Patients with a high skin type phototype are exposed to woundthatsubsideswithappropriatewoundcare.Patients a higher risk of hyperpigmentation after treatment than with darker skin may experience permanent skin discol- patientswithlowphototype. orationorblotchiness.Asregardsthetechniqueofmicroder- All ablative lasers showed high risk of complications mabrasion,avarietyofmicrodermabradersareavailable.All and side effects. Adverse reactions to the first generation of microdermabradersincludeapumpthatgeneratesastream ablative lasers can be classified into short-term (bacterial, of aluminum oxide or salt crystals with a hand piece and herpeticorfungalinfections)andlong-term(persistentery- vacuum to remove the crystals and exfoliate the skin [57]. thema,hyperpigmentation,scarring)[63,64].Inparticular, Unlike dermabrasion, microdermabrasion can be repeated scarring after CO laser therapy may be due to the over 2 at short intervals, is painless, does not require anesthesia treatment of the areas (including excessive energy, density, and is associated with less severe and rare complications, orboth),lackoftechnicalaspects,infection,oridiopathic.It but it also has a lesser effect and does not treat deep scars isnecessarytotakeintoaccounttheseaspectswhensensitive [58,59]. areassuchastheeyelids,upperneck,andespeciallythelower Itisessentialtoconductathoroughinvestigationofthe neckandchestaretreated[65,66]. patient’s pharmacological history to ensure that the patient Nonablative skin remodeling systems have become has not taken isotretinoin in the previous 6–12 months. increasingly popular for the treatment of facial rhytides As noted by some studies [60], the use of tretinoin causes and acne scars because they decrease the risk of side delayedreepithelializationanddevelopmentofhypertrophic effects and the need for postoperative care. Nonablative scars. technologyusinglong-pulseinfrared(1.450nmdiode,1320 and1064nmneodymium-dopedyttriumaluminumgarnet 4.1.3. Laser Treatment. All patients with box-car scars (Nd:YAG), and 1540nm erbium glass) was developed as (superficialordeep)orrollingscarsarecandidatesforlaser a safe alternative to ablative technology for inducing a treatment.Differenttypesoflaser,includingthenonablative controlled thermal injury to the dermis, with subsequent and ablative lasers are very useful in treating acne scars. neocollagenesisandremodelingofscarredskin[67–72]. Ablative lasers achieve removal of the damaged scar tissue Althoughimprovementwasnotedwiththesenonablative through melting, evaporation, or vaporization. Carbon lasers, the results obtained were not as impressive as the dioxidelaserandErbiumYAGlaserarethemostcommonly resultsfromthoseusinglaserresurfacing[71]. used ablative lasers for the treatment of acne scars. These For this reason, a new concept in skin laser therapy, abrade the surface and also help tighten the collagen fibers called fractional photothermolysis, has been designed to DermatologyResearchandPractice 7 createmicroscopicthermalwoundstoachievehomogeneous 4.1.5.DermalGrafting. Acnescarsmaybetreatedsurgically thermal damage at a particular depth within the skin, using procedures such as dermabrasion and/or simple scar a method that differs from chemical peeling and laser excision,scarpunchelevation,orpunchgrafting[85]. resurfacing.Prior studies using fractionalphotothermolysis The useful modalities available are dermal punch graft- havedemonstrateditseffectivenessinthetreatmentofacne ing, excision, and facelifting. The selection of these tech- scars [73] with particular attention for dark skin to avoid niques is dependent on the above classification and the postinflammatoryhyperpigmentation[74]. patient’sdesireforimprovement[86]. Newer modalities using the principles of fractional Split-thicknessorfull-thicknessgrafts“take”onabedof photothermolysis devices (FP) to create patterns of tiny scartissueordermisfollowingtheremovaloftheepidermis. microscopic wounds surrounded by undamaged tissues are The technique is useful in repairing unstable scars from new devices that are preferred for these treatments. These chroniclegulcersorX-rayscars.Itcanalsocamouflageacne devices produce more modest results in many cases than scars,extensivenevipigmentosus,andtattoos[87,88].Itis traditional carbon dioxide lasers but have few side effects prepackaged dermal graft material that is easy to use, safe, and short recovery periods [75]. Many fractional lasers andeffective[89]. are available with different types of source. A great deal of experience with nonablative 1550nm erbium doped 4.1.6. Tissue Augmenting Agents. Fat transplantation. Fat is fractional photothermolysis has shown that the system can easily available and it has low incidence of side effects[90]. bewidelyusedforclinicalpurposes. The technique consists of two phases: procurement of the Anablative30WCO laserdeviceusesablativefractional 2 graft and placement of the graft. The injection phase with resurfacing (AFR) and combines CO ablation with an FP 2 smallparcelsoffatimplantedinmultipletunnelsallowsthe system. By depositing a pixilated pattern of microscopic fatgraftmaximalaccesstoitsavailablebloodysupply.Thefat ablative wounds surrounded by healthy tissue in a manner injectedwillnormalizethecontourexceptedwhereresidual similar to that of FP [76], AFR combines the increased efficacy of ablative techniques with the safety and reduced scarattachmentsimpedethis. downtimeassociatedwithFP. Topographic analysis performed by some authors has 4.1.7. Other Tissue Augmenting Agents. There are many shown that the depth of acneiform scars has quantifiable new and older autologous, nonautologous biologic, and objective improvement ranging from 43% to 80% with nonbiologictissueaugmentationagentsthathavebeenused a mean level of 66.8% [77]. The different experiences in the past for atrophic scars, such as autologous collagen, of numerous authors in this field have shown that, by bovine collagen, isolagen, alloderm, hyaluronic acid, fibrel, combiningablativetechnologywithFP,AFRtreatmentscon- artecoll, and silicon, but nowadays, because of the high stituteasafeandeffectivetreatmentmodalityforacneiform incidence of side effects, the recommended material to use scarring. Compared to conventional ablative CO devices ishyaluronicacid[91]. 2 the side effects profile is greatly improved and, as with FP, rapid reepithelization from surrounding undamaged 4.1.8. Needling. Skin needling is a recently proposed tech- tissue is believed to be responsible for the comparatively nique that involves using a sterile roller comprised of a rapid recovery and reduced downtime noted with AFR series of fine, sharp needles to puncture the skin. At first, [78–80]. facial skin must be disinfected, then a topical anesthetic is Pigmentationabnormalitiesfollowinglasertreatmentis applied,leftfor60minutes.Theskinneedlingprocedureis always a concern. Alster and West reported 36% incidence achievedbyrollingaperformedtoolonthecutaneousareas of hyperpigmentation when using conventional CO resur- affectedbyacnescars(Figure6),backwardandforwardwith 2 facingcomparedtoaminorityofpatientstreatedwithAFR some pressure in various directions. The needles penetrate treatments,probablylinkedtoshortenedperiodofrecovery about 1.5 to 2mm into the dermis. As expected, the skin and posttreatment erythema [81]. The treatment strategy bleeds for a short time, but that soon stops. The skin is linked to establishing the optimal energy, the interval develops multiple microbruises in the dermis that initiate betweensessions,andalongerfollow-upperiodtooptimize the complex cascade of growth factors that finally results treatmentparameters. in collagen production. Histology shows thickening of skin and a dramatic increase in new collagen and elastin fibers. 4.1.4. Punch Techniques. Atrophic scarring is the more Results generally start to be seen after about 6 weeks but commontypeofscarringencounteredafteracne.Autologous the full effects can take at least three months to occur and, and nonautologous tissue augmentation, and the use of as the deposition of new collagen takes place slowly, the punchreplacementtechniqueshasaddedmoreprecisionand skin texture will continue to improve over a 12 month efficacytothetreatmentofthesescars[82]. period.Clinicalresultsvarybetweenpatients,butallpatients The laser punch-out method is better than even depth achievesomeimprovements(Figures7and8).Thenumber resurfacingforimprovingdeepacnescarsandcanbecom- of treatments required varies depending on the individual binedwiththeshouldertechniqueorevendepthresurfacing collagenresponse,ontheconditionofthetissueandonthe accordingtothetypeofacnescar[83]. desired results. Most patients require around 3 treatments Laserskinresurfacingwiththeconcurrentuseofpunch approximately 4 weeks apart. Skin needling can be safely excisionimprovesfacialacnescarring[84]. performed on all skin colours and types: there is a lower 8 DermatologyResearchandPractice Figure6:Needling:theprocedure. Figure8:Needling:patientafterthetreatment. 4.2.HypertrophicScars 4.2.1.SiliconeGel. Silicone-basedproductsrepresentoneof themostcommonandeffectivesolutionsinpreventingand alsointhetreatmentofhypertrophicacnescars.Thesilicone gel was introduced in the treatment of hypertrophic acne scarstoovercomethe difficulties in themanagementof sil- iconesheets.Indeed,thesiliconegelhasseveraladvantages: it is transparent, quick drying, nonirritating and does not induce skin maceration, it can be used to treat extensive scarsandunevenareasofskin.Themechanismofactionis not fully understood but several hypotheses [95] have been advanced: (1) the increase in hydration; (2) the increase in temperature;(3)protectionofthescar;(4)increasedtension Figure7:Needling:patientbeforethetreatment. ofO2;(5)actionontheimmunesystem.Thereis,currently, only one observational open label study, conducted on 57 patients. In this study, the gel was applied on the scars 2 risk of postinflammatory hyperpigmentation than other times daily for 8 weeks with an average improvement in procedures, such as dermabrasion, chemical peelings, and thethicknessestimatedbetween40%and50%comparedto laser resurfacing. Skin needling is contraindicated in the baseline. presence of anticoagulant therapies, active skin infections, Asregardsthetreatmentofalreadyformedhypertrophic collageninjections,andotherinjectablefillersintheprevious scars,thegelshouldbeappliedinsmallamounts,twicedaily sixmonths,personalorfamiliarhistoryofhypertrophicand foratleast8weekstoachieveasatisfactoryaestheticresult. keloidalscars[92,93]. Whereasforthepurposesofprevention,thesamedosageis recommendedforatleast12–16weeks;thetreatmentshould be started as soon as possible after the risk of a patient 4.1.9. Combined Therapy. There is a new combination developinghypertrophicacnescarshasbeenidentified. therapy for the treatment of acne scars. The first therapy Treatmentwithsiliconegelcanbeusedinpatientsofany consists of peeling with trichloroacetic acid, then followed age and women of childbearing age. Moreover, the silicone bysubcision,theprocessbywhichthereisseparationofthe gelcanbeusedthroughouttheyear,includingsummer. acnescarfromtheunderlyingskinandintheendfractional laserirradiation.Theefficacyandsafetyofthismethodwas investigated for the treatment of acne scars. The duration 4.2.2. Intralesional Steroid Therapy. Intralesional injection of this therapy is 12 months. Dot peeling and subcision of steroids is one of the most common treatments for wereperformedtwice2-3monthsapartandfractionallaser keloids and hypertrophic scars. It can be used alone or irradiation was performed every 3-4 weeks. There were no as part of multiple therapeutic approaches. Corticosteroids significant complications at the treatment sites. It would mayreducethevolume,thickness,andtextureofscars,and appear that triple combination therapy is a safe and very they can relieve symptoms such as itching and discomfort effective combination treatment modality for a variety of [96]. The mechanisms of action have not been completely atrophicacnescars[94]. clarified: in addition to their anti-inflammatory properties, DermatologyResearchandPractice 9 it has been suggested that steroids exert a vasoconstrictor had only variable success in the past due to the minimal and an antimitotic activity. It is believed that steroids improvementinahighpercentofpatients[106–108]. arrestpathologicalcollagenproductionthroughtwodistinct On the contrary, the use of pulsed dye laser (PDL) has mechanisms: the reduction of oxygen and nutrients to the provided encouraging results in the treatment of hyper- scar with inhibition of the proliferation of keratinocytes trophic/keloidalscarsoverthepast10years.Severalstudies andfibroblasts[96];thestimulationofdigestionofcollagen have been conducted to investigate how the PDL works on deposition through block of a collagenase-inhibitor, the hypertrophic/keloidal scars. They have revealed that PDL alpha-2-microglobulin[97].Duringtheinjectionthesyringe decreases the number and proliferation of fibroblasts and needleshouldbekeptupright[24].Itisalwayspreferablefor collagenfibersappearlooserandlesscoarse[109].Moreover, theinjectionstobeprecededbytheapplicationofanesthetic PDL also produces an increase in MMP-I3 (collagenese- creamsorbeassociatedwithinjectionsoflidocaine[97]. 3) activity and a decrease in collagen type III deposition Intralesionalsteroidtherapymaybeprecededbyalight [110]. As a consequence, PDL flattens and decreases the cryotherapy with liquid nitrogen, 10–15 minutes before volume of hypertrophic scars [111, 112], improves texture injection, to improve the dispersion of the drug in scar [113],andincreaseselasticity[114],usuallyaftertwotothree tissueandminimizethedepositioninthesubcutaneousand treatments[115].Additionally,pruritisandpainwithinthe perilesional tissue [98]. The steroid that is currently most scarsaresignificantlyimproved[116].Besides,norecurrence frequently used in the treatment of hypertrophic scars and or worsening of PDL-treated scars occurs during the 4- keloidsistriamcinoloneacetonide(10–40mg/mL)[99].The year followup after cessation of treatment [116]. The most mostcommonadversereactionsarehypopigmentation,skin common side effect of the PDL is purpura which can last atrophy, telangiectasia, and infections [100]. As for injuries as long as 7–10 days. Blistering can also occur as well as totheface,theuseofintralesionalsteroidsisrecommended hypo-andhyperpigmentationwhichismorelikelyindarker for the treatment of individual elements which are skinned individuals [117]. Therefore, the ideal candidates particularly bulky and refractory to previous less invasive for PDL are patients with lighter skin types (Fitzpatrick methods. TypesI–III)becauselessmelaninispresenttocompetewith hemoglobinlaserenergyabsorption[118,119]. 4.2.3. Cryotherapy. Cryotherapy with liquid nitrogen can 4.2.5. Surgery. For the correction of large facial scars, W- significantlyimprovetheclinicalappearanceofhypertrophic plastyseemstobeoptimal[12].Thistherapeuticprocedure scarsandkeloidsandalsodeterminetheircompleteregres- causes a disruption of the scar which makes the lesion sion. less conspicuous. Especially in facial surgery, autologous The low temperatures reached during cryotherapy ses- skin transplants, namely, full thickness skin transplant or sionscauseaslowingofbloodflowandcausetheformation composite fat-skin graft, are another valuable alternative of intraluminal thrombus hesitant to anoxia and tissue for achieving wound closure with minimal tension. The necrosis[101].Ageandsizeofthescarareimportantfactors preferreddonorsitesforskingraftusedforfacialdefectsare conditioning the outcome of this technique: younger and theretro-andpreauricularsitesaswellastheneck[120]. smaller scars are most responsive to cryotherapy [102]. Compared with intralesional injections of corticosteroids, cryosurgery is significantly more effective than alternative 4.2.6.OtherApproaches. Othertreatmentoptionsforhyper- methodsforrichlyvascularizedinjuries12monthsyounger trophic acne scars and keloids that can be taken into [103]. During each session of cryotherapy the patient is account include elastic compression, intralesional injection usually subjected to 2-3 cycles, each lasting less than 25 of 5-fluorouracil, imiquimod, interferon, radiotherapy, and seconds. Cryotherapy can also be used before each cycle bleomycin.Alltheseapproaches,however,aremoreeffective of intralesional injections of steroids to reduce the pain of for the treatment of hypertrophic scars not caused by acne injectiontherapyandtofacilitatetheinjectionofcortisone, andtheiruseisnotrecommendedduetotheirimpracticality generatingasmallareaofedemaatthelevelofthescartissue (elastic compression), the lack of clinical experience in the tobetreated[98].Possibleadversereactionsarerepresented literature (5 FU, interferon, radiotherapy, bleomycin) the by hypo- and hyperpigmentation, skin atrophy, and pain lackofefficacy(imiquimod),andthehighcosts(interferon). [102]. With regard to localized lesions to the face, the possibleoutcomesoffreezingrestricttheuseofcryotherapy 5.Conclusion in these areas, especially in cases where the scars are numerous or for dark phenotypes. Therefore, cryotherapy There are no general guidelines available to optimize acne can be taken into consideration especially for scars located scar treatment. There are several multiple management onthetrunkorforparticularlybulkyscarsontheface. options,bothmedicalandsurgical,andlaserdevicesareuse- ful in obtaining significant improvement. Further primary 4.2.4. Pulsed Dye Laser. The use of lasers for hypertrophic research such as randomized controlled trials is needed in scars and keloids was first proposed by Apfelberg et al. order to quantify the benefits and to establish the duration [104] and Castro et al. 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