治疗色素沉着Approach to the patient with hyperpigmentation disorders.docx
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治疗色素沉着Approachtothepatientwithhyperpigmentationdisorders
Approachtothepatientwithhyperpigmentationdisorders
Authors
NeelamVashi,MD
RoopalKundu,MD
SectionEditor
ErikStratman,MD
DeputyEditor
RosamariaCorona,MD,DSc
Disclosures:
NeelamVashi,MDConsultant/AdvisoryBoards:
L'Oreal[Hyperpigmentation].RoopalKundu,MDNothingtodisclose.ErikStratman,MDNothingtodisclose.RosamariaCorona,MD,DScNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamulti-levelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:
Jul2015.|Thistopiclastupdated:
Jan19,2015.
INTRODUCTION — Hyperpigmentationisthedarkeningorincreaseinthenaturalcoloroftheskinusuallyduetoanincreaseddepositionofmelanin(hypermelanosis)intheepidermisand/ordermis.Lessfrequently,itmaybecausedbythedepositioninthedermisofendogenousorexogenouspigments,suchashemosiderin,iron,orheavymetals.
Hyperpigmentationisafeatureofamultitudeofclinicalconditions,rangingfromnormalvariationsofskincolortoacquiredandinheritedsyndromes,andisoneofthemostcommonreasonsfordermatologicconsultation,particularlyinpatientswithdarkerskintypes[1-3].Althoughhyperpigmentationisnotharmful,itcancausesignificantcosmeticdisfigurementandbecomeapersistentpsychosocialburdenforthepatient,duetothelimitedefficacyoftheavailabletreatments.
Thistopicwillreviewtheapproachtothepatientwithhyperpigmentationdisorders.Melasmaisdiscussedseparately.Benignandmalignantmelanocytictumorsarediscussedseparately.
●(See"Melasma".)
●(See"Benignpigmentedskinlesionsotherthanmelanocyticnevi(moles)".)
●(See"Acquiredmelanocyticnevi(moles)".)
●(See"Skinexaminationandclinicalfeaturesofmelanoma".)
PATHOPHYSIOLOGY
Determinantsofskincolor — Thecolorofhumanskinismainlydeterminedbythetwotypesofmelanin,theblack-browneumelaninandtheyellow-redpheomelanin.Othersignificantdeterminantsarethecapillarybloodflow,chromophoressuchascaroteneorlycopene,andthecollagencontentofthedermis.
Eumelaninandpheomelaninarepresentinindividualofallskincolors,buttheirratioishighlyvariableanddeterminesthehueoftheskin[4].Differencesinthenumber,size,andaggregationofmelanosomeswithinthemelanocytesandkeratinocytes,butnotintheoverallnumberofmelanocytes,contributetoethnicdifferencesinskincolor[5,6].Darkerskintypeshaveahighercontentofmelanin,highereumelanin-to-pheomelaninratio,nonaggregatedandlargermelanosomes,andslowermelanosomedegradationwithinthekeratinocytes[7].
Melanin — Melaninisproducedbymelanocytes,specializedcellsofneuralcrestoriginthatresideinthebasallayeroftheepidermis.Thebiosynthesisofmelaninoccursinlysosome-likeorganellescalledmelanosomes,whicharetransportedtothecellperipheryandtransferredfromthedendritictipsofthemelanocytestothesurroundingkeratinocytes[8].Eachmelanocyteisassociatedwithapproximately36basalkeratinocytestoformtheso-calledepidermalmelaninunit.
MelaninsynthesisistriggeredbythehydroxylationofL-phenylalaninetoL-tyrosineordirectlyfromL-tyrosine.TyrosinasehydroxylatesL-tyrosineto3,4-L-dihydroxyphenylalanine(L-DOPA),whichfurtherundergoesoxidationtodopaquinone.Thereafter,twomainpathwaysdiverge,leadingtoproductionofblack-browneumelaninandyellow-redpheomelanin.Melaninsynthesisisregulatedbymultiplecomplexsignalingpathways,includingmelanocyte-stimulatinghormones(MSH)/cAMPandKIT[8].
Geneticmutationsaffectingthepathwaysthatregulatethedifferentiationandmigrationofmelanocyteprecursorsintheneuralcrestortheproliferationandactivityofmaturemelanocytesmaybeinvolvedinthepathogenesisofhyperpigmentationassociatedwithinheritedsyndromes[8].
Hypermelanosis — Skinhyperpigmentationisinmostcasescausedbyincreasedbiosynthesisanddepositionofmelaninintheepidermisand/ordermis.Epidermalhypermelanosisresultsfromanexcessofmelanininthebasalandsuprabasallayersoftheskinduetoincreasedmelaninproductioneitherbyanabnormallyhighnumberofmelanocytesorbyanormalmelanocytepopulation.Theseabnormalitiesmaybeduetobothacquiredandgeneticfactors.
Thenormaldermisdoesnotcontainmelanin.Dermalhypermelanosismaydevelopthroughseveralmechanisms:
●Transferofmelaninfromtheepidermistothedermisandaccumulationwithinmelanophages("pigmentaryincontinence").Thisprocessiscommonlyobservedininflammatoryskindiseasesthatinvolveadamageofthebasallayerand/orthedermoepidermaljunction.
●Productionofmelaninbyectopicdermalmelanocytes.ExamplesofdermalmelanocytosisarethenevusofOtaandnevusofIto.
●Bindingofmelanintoexogenouspigmentsdepositedinthedermis.
Otherpigments — Cutaneoushyperpigmentationcanbecausedbythedepositioninthedermisofendogenousorexogenouspigments,suchashemosiderin,iron,orheavymetals.Recurrentextravasationofredbloodcellsinthedermisleadstodepositionofhemosiderin,resultinginared-browndiscolorationoftheskin.Dermalhyperpigmentationmimickingdermalhypermelanosiscanbecausedbytopicalorsystemicexposuretoheavymetals(eg,silver,gold,mercury).Somemetals,suchasiron,mayalsostimulatemelanogenesis,asobservedinpatientswithhemochromatosis.
PATIENTEVALUATION — Thediagnosisofhyperpigmentationdisordersmaybechallenging.Inmostcases,theinitialpatientevaluationinvolvesadetailedfamilyandpersonalmedicalhistoryandacompletephysicalexamination,whichshouldincludeacarefulsearchforadditionalcutaneousandextracutaneoussignsandsymptoms.
Questionsthatmaybeusefulfortheevaluationofpatientswithhyperpigmentationdisordersinclude[9]:
●Isthedisordercongenitaloracquired?
●Isthedisorderisolatedorpartofasyndrome?
●Isthepigmentationlocalizedordiffuse?
●Isthepigmentationwellcircumscribedorill-defined?
●Doesthepigmentationhaveapattern(eg,linear,reticular)?
●Isthepigmentationassociatedwithinflammationand/orpriorcutaneousinjury?
●Isthepigmentationstable,progressing,orregressing?
●Doesthepatienthaveconcomitantsystemicdiseases?
●Doesthepatienthaveahistoryofexposuretoanewmedication?
History — Adetailedmedicalhistoryshouldbeobtainedfromthepatienttodetermineifthehyperpigmentationisrelatedtoanunderlyingdisease.Thepossibilityofdrug-inducedpigmentationmustbekeptinmind.Patientsshouldalsobequestionedaboutoccupationalandorhobby-relatedexposuretochemicalsthatmaycausehyperpigmentation.
Investigationofthefamilyhistorymaybehelpfultodeterminewhetherthedisorderisacquiredorinherited,and,inthelattercase,whatistheprobableinheritancepattern[10].However,althoughcongenitalorinheritedhyperpigmentationdisordersareoftenpresentatbirth,historymaybemisleading,sinceparentsmaynothavenoteditformonthsorlonger.
Thecourseofthedisorderisalsoausefulparameterintheclinicaldiagnosisofhyperpigmentationdisorders.Inheritedhyperpigmentationsareoftenstable,whereasmostacquiredformsshowprogressionorregression.
Skinexamination — Inallpatientswithhyperpigmentationdisorders,acompleteskinexaminationshouldbeperformedundervisiblelightandWood'slight.Importantclinicalparametersinclude:
●Extentofthepigmentaryabnormality(localizedversusdiffuse)
●Colorhue(shadesofbrown/black,slate-gray/blue)
●Morphologyofindividuallesions
●Distribution(eg,sun-exposedareas,areaspreviouslyinvolvedbyinflammatoryprocesses)
●Pattern(eg,linear,reticular,nonfigurate)
Acarefulsearchforassociatedcutaneousandextracutaneoussignsandsymptomsmayprovideimportantcluestothediagnosis,particularlyinpatientswithhyperpigmentationdisordersassociatedwithsystemicdiseasesorgeneticsyndromes.
Wood'slightexamination — Wood'slight,alsoknownas"blacklight,"isultravioletAlightwithapeakemissionat365nm[11].Thepatientisexaminedinadarkenedroomwiththelightsourceheldat10to15cmfromtheskin.Wood'slightishelpfulindeterminingwhetherthepigmentdepositionispredominantlyepidermal,dermal,ormixed[12].
●Epidermalhypermelanosis–Undernaturallight,epidermalhypermelanosisappearslightbrowntodarkbrownincolor.Thepigmentation,aswellasthecontrastbetweeninvolvedanduninvolvedskin,isenhancedwhenviewedunderaWood'slamp.
●Dermalhypermelanosis–Undernaturallight,dermalhypermelanosishasabluishorashengrayhuewithmarginslessdefinedthanepidermalhypermelanosis.ThepigmentationisnotaccentuatedbytheWood'slight.
●Mixedhypermelanosis–Mixedhypermelanosisappearslighttodarkbrownundernaturallight,whereasWood'slightexaminationwillshowenhancementinsomeareasandnoneinothers.
Reflectanceconfocalmicroscopy — Invivoreflectanceconfocalmicroscopyisatechniquethatallowsnoninvasiveimagingoftheepidermisandpapillarydermisathistologicresolution[13].Theconfocalmicroscopeemitsanear-infraredlightfromadiodelasersourcefocusedonamicroscopicskintarget.Asthislightpenetratescellularstructureswithdifferentrefractionindexes,itisnatural