Even before the recent development of biological agents文档格式.docx

Even before the recent development of biological agents文档格式.docx

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localisedareassuchastheelbowsorknees.Forthese

patients,topicaltherapymayremainpartoftheirtherapeutic

regimenwhetherornottheyrequireadditionaltreatments

forpsoriaticarthritis.Eventhosetreatedwithphototherapy

orsystemictherapies,includingbiologicals,haveresidual

lesionsthatmayrequiretopicalremedies.

Topicalcorticosteroidsremainthemostwidelyprescribed

medicationsforplaquepsoriasis.Theserangeinstrength

fromweak,over-the-countersteroidssuchas1%hydrocortisone

tosuperpotentcorticosteroids,suchasclobetasol

propionate,halobetasolpropionate,betamethasonedipropionate

inoptimisedbase,anddiflorasonediacetatein

augmentedbase（table2）.TheStoughton–Cornellclassificaclassification

ranksthepotencyoftopicalcorticosteroidsontheir

abilitytoinducevasoconstriction.3Topicalcorticosteroidsare

availableinnumerousvehiclesincludingpowders,sprays,

lotions,solutions,creams,emollientcreams,ointments,gels,

andtape.Recently,clobetasolpropionateandbetamethasone

valeratehavebothbeenintroducedinfoamvehiclesthatare

cosmeticallyelegantandshouldimprovecompliance.

Differentvehiclesareusedondifferentbodysites.For

example,thescalpandotherhairbearingareasaremost

easilytreatedwithfoams,solutions,andgels.Creamsare

mostusefulfordaytimeuse,andointments,whichareoften

moreeffectivebutlessappealingcosmetically,canbeapplied

atnight.Twopossibleexceptionsarethenewerfoam

vehicles,whichhavecomparableclinicalefficacytoointments.

45

Sideeffectsoftopicalcorticosteroids,especiallythosethat

carrythesuperpotentcategorisation,includecutaneous

atrophy,developmentofstriae,formationoftelangiectasia,

andahostofotherlocalcutaneouseffectssuchasthe

formationofanacneiformeruptionknownasperioral

dermatitisontheface.67Hypothalamic–pituitary–adrenal

（HPA）axissuppressioncanoccurwithprolongeduseof

excessivequantitiesoftopicalcorticosteroids,particularlyiftheyareoccludedorifsuperpotentcorticosteroidsareused

continuouslyoverlargeareasofthebody.However,the

cutaneoussideeffectsaremorecommonlyproblematicthan

significantHPAaxissuppression,whichisseldomanissue.8

Oneofthemosttroublingfeaturesoftopicalcorticosteroids

isthatpatientsdeveloptachyphylaxis,aphenomenon

wherebymedicationsthatarehighlyeffectiveinitially,lose

efficacywithprolongeduse.Toavoidtachyphylaxisandthe

othersideeffectsoftopicalcorticosteroids,regimenshave

beendevelopedinwhichsuperpotentcorticosteroidsare

appliedtwicedailyfortwoweeks,afterwhichtheyare

appliedonweekendsonly.Strongtopicalcorticosteroids

shouldalsobeavoidedonthefaceandintertriginoussites,

areasthataremorepronetosteroidsideeffects.Thequantity

ofstrongtopicalcorticosteroidsappliedshouldbelimitedto

50or60gperweek,andocclusionshouldbeavoidedexcept

onthescalp,palms,andsoles.Strongcorticosteroidsshould

beavoidedorusedcautiouslyinchildren.

Thesecondmostcommonlyusedgroupofmedications

consistsofthevitaminDanalogues.IntheUSA,calcipotriene

isavailableinointment,cream,andsolutionformulations.

Thisagentisappliedtwicedailyandismostoftenusedin

conjunctionwithtopicalcorticosteroids.Itscommonestside

effectisirritation,primarilyonthefaceandintertriginous

sites.Iflargequantitiesofcalcipotrieneareapplied,absorption

ofthisvitaminDanaloguecanresultinhypercalcaemia.9

Consequently,lessthan120gshouldbeusedweekly.Topical

calcitriolisavailableinotherpartsoftheworldandmaybe

lessirritatingonthefaceandinintertriginoussites.Other

vitaminDanaloguessuchastacalcitolarealsobeingusedfor

psoriasis.SomevitaminDanaloguesareunstable,andconsequently,theyshouldonlybecombinedwithother

medicationsthathavebeendemonstratednottoaffecttheir

stability.10PhototherapymayinactivatevitaminDanalogues

and,conversely,vitaminDanaloguesmayblockthe

therapeuticcomponentofultravioletlight;

thusthesetopical

agentsshouldbeappliedafterphototherapy,notbefore.11

Tazarotenegel,arecentlydevelopedtopicalretinoidfor

psoriasis,isavailablein0.05%and0.1%gelsandcreams.

Topicalretinoidsmayreversesomeofthecutaneousatrophy

causedbytopicalcorticosteroids12butareassociatedwith

localcutaneousirritation.Thus,theyareoftenprescribedin

combinationwithtopicalcorticosteroids.13

Oldertopicalremediesofpsoriasissuchasanthralinand

coaltararestillinuse.Becausetheyaresomewhat

unpleasanttouse,especiallyduetoodour,productmigration,

andlocalirritation,theyarelesscommonlyprescribedthan

theaforementionedtopicalmedications.Keratolyticpreparations

suchasthosecontainingsalicylicacidandemollients

arealsoeffectiveforremovingtheexcessscalethattroubles

manypatientswithpsoriasis.

LIGHTTHERAPY

Severalformsoflighttherapyhavebeenusedtotreat

psoriasisforhundredsofyears.Inthe1920s,William

GoeckermancombinedtheuseofultravioletB（UVB）

phototherapywithtopicalapplicationoftars.14Thisinpatient

psoriasisregimen,knownastheGoeckermanregimen,isstill

occasionallyused,butoutpatientregimensusingUVB

phototherapywithemollientshavelargelyreplacedthe

inpatientregimens.

BroadbandUVBphototherapyhasalsobeeninusesince

the1920s.Ithasnotbeenassociatedwiththedevelopmentof

skincancersdespitetheconcomitantapplicationoftars,

whichareconsideredcarcinogenic.15Thistherapyremains

oneofthesafesttreatmentsforcutaneouspsoriasis,but

requirestreatmentsatleastthreetimesperweekforseveral

monthstobeeffective.

ThemosteffectivewavelengthsofUVBlightusedforthe

treatmentofpsoriasisfallinaverynarrowrange,311–

313nm.1617Thishasledtothedevelopmentofnarrowbandphototherapy.16InthefewyearsthatnarrowbandUVB

phototherapyhasbeenused,noincreaseincutaneous

malignancieshasbeenreported.Moreexperiencewillbe

neededtofirmlyestablishthesafetyofnarrowbandUVB

phototherapy.Theexcimerlaserisapowerfulbeamof

308nmlight（anotherformofnarrowbandultravioletlight）

thathasbeenusedsuccessfullytotreatlocalisedplaquesof

psoriasisincludingthoseonthepalmsandsoles.18

Inthe1970s,apowerfulnewtreatmentofpsoriasisknown

asPUVAwasintroduced.PUVAinvolvestheingestionor

topicalapplicationofaphotosensitisingmedication,usually

8-methoxypsoralen.PatientsarethenexposedtoUVA,which

activatesthe8-methoxypsoralen.Onceactivated,thisdrug

crosslinksDNAstrandspreventingreplicationofkeratinocytes

andinducesdeathofactivatedTcellsinskin.19Bath

PUVA,atopicalphotosensitisingmethod,involvesimmersion

ofeitherlocalisedareas（suchasthehandsorfeet）orthe

wholebodyinwatercontainingdissolved8-methoxypsoralen

capsulespriortoUVAexposure.Thetopicaluseofthisagent

isnotassociatedwithadversesystemicsymptomssuchas

nausea.PsoriasisclearsinmostpatientstreatedwithPUVA.

PUVAmayalsobenefitpsoriaticarthritisinsomepatients.20

Foroptimaleffect,patientsaretypicallytreatedtwotothree

timesperweekforseveralmonths.PUVAissignificantly

moreeffectivethanbroadbandUVB,butitisassociatedwith

thedevelopmentofsquamouscellcarcinomasoftheskin.

Theriskofnon-melanomacutaneousmalignanciesincreases

withthenumberoftreatmentsbutarerareindarkskinned

patients.21Mostrecently,therehavebeenunconfirmed

reportsofanincreasedriskofmalignantmelanomasthat

correlateswiththenumberoftreatmentsandtimeoffollow

up,theincreasedriskbeingnoted15yearsafterstartiPUVA.22

Climatotherapy,theoldestformofphototherapyinvolving

exposuretosunlight,iswellestablishedatanumberof

clinicsaroundtheworld.Perhapsthemostsuccessfulisthe

psoriasistreatmentcentreattheDeadSea.23At300mbelow

sealevel,theDeadSeaisthelowestpointonearth.Its

mineralcontentisgreaterthanthatofanyothernaturally

occurringbodyofwateronearth.Theextra300mthrough

whichsunlighthastopass,combinedwiththemineralhaze

overtheDeadSea,resultsinlightexposurethathasproved

highlybeneficialforpsoriasis.Resultsarecomparablewith

thoseobtainedwithbroadbandUVBphototherapy.24

SYSTEMICTHERAPY

Thethreeapprovedsystemictreatmentsforpsoriasisare:

methotrexate,acitretin,andciclosporin.Theiruse,advantages,

anddisadvantages,arediscussedbelow.

Methotrexate

Methotrexate,theoldestsystemictherapyforpsoriasis,

remainsoneofthemosteffectivetreatmentsforpsoriasis

andpsoriaticarthritis.Ithasanumberofshorttermside

effectsincludingbonemarrowtoxicit