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Pustularpsoriasis:Management
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Aug2015.|Thistopiclastupdated:May20,2015.
INTRODUCTIONPustularpsoriasisisanuncommonsubtypeofpsoriasisthatmaypresentasageneralizedor
localizedpustularskineruption.Thegoalsoftreatmentofgeneralizedpustularpsoriasis(GPP)aretoimproveskin
manifestations,toalleviateassociatedsystemicsymptoms,andtominimizeriskforlifethreateningsystemic
complications.Treatmentoflocalizedpustularpsoriasisisindicatedtominimizethedevelopmentofbothersomeor
disablingsymptoms.
Thetreatmentofgeneralizedandlocalizedpustularpsoriasiswillbereviewedhere.Theclinicalfeaturesof
pustularpsoriasis,themanagementofpustularpsoriasisinpregnantwomen(impetigoherpetiformis),andthe
managementofotherformsofpsoriasisarereviewedseparately.(See"Pustularpsoriasis:Pathogenesis,clinical
manifestations,anddiagnosis"and"Dermatosesofpregnancy"and"Treatmentofpsoriasis"and"Guttate
psoriasis".)
GENERALIZEDPUSTULARPSORIASISGeneralizedpustularpsoriasis(GPP)ischaracterizedbythe
developmentofawidespreaderuptionofpustulesanderythematousplaques(picture1AC).Aprecedinghistoryof
psoriasismayormaynotbepresent.Theacutevariant(alsoknownasgeneralizedpustularpsoriasisofvon
Zumbusch)ischaracterizedbysuddenonsetofthepustulareruptionaccompaniedbysystemicsymptomsof
feverandmalaise.Laboratoryabnormalities,suchasleukocytosis,anelevatederythrocytesedimentationrate,
hypocalcemiaandotherelectrolyteabnormalities,hypoalbuminemia,andelevatedliverenzymesarecommon.In
addition,seriouscomplications,includingsepsisandhepatic,respiratory,orrenaldysfunctioncanoccur[14].
(See"Pustularpsoriasis:Pathogenesis,clinicalmanifestations,anddiagnosis",sectionon'Generalizedpustular
psoriasis'.)
GPPmayalsopresentasalessacutedisorderinwhichpatientsdevelopwidespreadannularorfigurate
erythematousplaqueswithperipheralpustulesandscale(generalizedannularpustularpsoriasis)[4,5].Painand
fevermayaccompanythesecutaneousmanifestations.(See"Pustularpsoriasis:Pathogenesis,clinical
manifestations,anddiagnosis",sectionon'Clinicalmanifestations'.)
ThereisnocureforGPPandrecurrencesarecommon[4].Thus,longtermtreatmentoftenisrequiredtominimize
recurrencesofdisease.
IncreasingknowledgeaboutthepathogenesisofGPPassociatedwithIL36RNmutationsmayleadtonew
therapeuticoptionsforthisformofGPP.(See'IL36RNmutations'belowand"Pustularpsoriasis:Pathogenesis,
clinicalmanifestations,anddiagnosis",sectionon'Genetics'.)
ApproachtotherapyDeterminingtheoptimalapproachtothetreatmentofGPPiscomplicatedbythelackof
highqualitydataontheefficacyoftreatmentsforthisdisease.Dataontreatmentprimarilyconsistsoffindingsof
retrospectivestudies,casereports,andexpertopinion.Interpretationoftheavailabledataisfurthercompromised
bythelackofavalidatedgradingsystemfortheseverityofGPPandtheabsenceofastandardizedmethodof
assessingtheresponsetotreatment.Theapproachdescribedinthistopicreflectsourpreferredapproachbased
uponreviewoftheliteratureandclinicalexperienceotherapproachesalsomaybereasonable.
Ourapproachtotreatmentconsistsofthefollowingkeysteps:
DetermineneedforhospitalizationandsupportivecarePatientswithacuteGPPusuallyappear
systemicallyillandadmissiontothehospitaloftenisnecessarytoensureadequatesupportivecare.The
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decisiontohospitalizeapatientismadebaseduponglobalconsiderationoftheseverityofillness,vitalsign
stability,fluidandelectrolytestatus,andconcernforsystemicinfection.
SupportiveskincaremeasuresmayhelptosootheskinsymptomsinpatientswithGPP.Useof
moisturizers,wetwraps,and/oroatmealbathscanbebeneficialinpatientswiththisdisease[1].
Identifyanddiscontinuethecausativedrug(indruginducedcases)Thewithdrawaloradministration
ofavarietyofdrugshasbeenlinkedtoGPP.Systemicglucocorticoidsarecommonlycitedcontributors[4].
Ingeneral,acausativeagentshouldbediscontinuedprovidedthiscanbedonesafely.However,thereis
insufficientevidencetoconfirmthebestwaytodiscontinuesystemicglucocorticoidtherapywhenGPPis
precipitatedbysystemicglucocorticoidwithdrawal.Optionsincludemaintainingtheglucocorticoiddoseuntil
diseasecontrolisachievedwithothertherapiesandcontinuingtotaperthesystemicglucocorticoidduring
theinitiationofGPPtherapy.(See"Pustularpsoriasis:Pathogenesis,clinicalmanifestations,anddiagnosis",
sectionon'Precipitatingfactors'.)
InitiatetreatmenttocontrolskindiseaseMedicaltreatmentoptionsforGPPconsistofsystemic
therapies,topicaltherapies,andphototherapy.Wetypicallyusesystemictreatmentfortheinitial
managementofadultswithGPPbecausephototherapytendstohaveadelayedonsetofactionandtopical
therapiesareimpracticalforthetreatmentofwidespreaddisease.
Inadditiontolimitingfactorssuchasdrugavailabilityandpatientspecificcontraindications,theselectionof
aninitialsystemictherapyforGPPisbasedupontheacuityandseverityofdisease.Whereasadultswith
slowlyprogressing,relativelystableeruptionscanbemanagedwithagentssuchasacitretinormethotrexate,
patientswithacute,severediseaserequiringrapidimprovementmaybenefitfrominitialtreatmentwithfaster
actingtherapies,suchascyclosporineorinfliximab[6,7].
Topicaltherapies,includingtopicalcorticosteroids,topicalvitaminDanalogs,andtopicaltacrolimus,
primarilyserveasadjunctstosystemictherapyinadultswithGPP.Wetypicallyfocustopicaltherapyon
areasofpersistentorrecalcitrantskininvolvement[6,8].Phototherapyisasecondlinetreatmenttypically
reservedforpatientswhohavealreadyachievedcontrolofacutedisease.
ManageextracutaneouscomplicationsExtracutaneouscomplicationssuchassepsisorinternalorgan
dysfunctionshouldbemanagedappropriately.(See"Pustularpsoriasis:Pathogenesis,clinical
manifestations,anddiagnosis",sectionon'Clinicalcourse'.)
TheapproachtotreatmentreviewedbelowfocusesonnonpregnantadultswithGPP.Thetreatmentofpregnant
womenandchildrenwithGPPisreviewedseparately.(See"Dermatosesofpregnancy",sectionon'Pustular
psoriasisofpregnancy'and'Children'below.)
FirstlinetherapyOurselectionofacitretin,methotrexate,infliximab,andcyclosporineasfirstlinetherapeutic
optionsforadultonsetGPPisinagreementwitha2012consensusstatementfromthetaskforceoftheNational
PsoriasisFoundationMedicalBoard[6].
Acitretinandmethotrexatearegenerallywelltolerateddrugsthatcanbeusedforlongtermtreatment.However,
asnotedabove,thetimetotreatmentefficacyforacitretinandmethotrexatetendstobelongerthanforinfliximab
andcyclosporine.Thus,forourpatientswithsevere,acutediseasethatwarrantsrapidstabilizationand
improvement,thefasteractingdrugsinfliximabandcyclosporineareourpreferredinitialagents.Oncecontrolof
acutediseaseisachieved,patientsmaybetransitionedtoacitretin,methotrexate,orothertherapies.
Inadditiontorapidityofonset,otherpatientspecificfactorscaninfluencetreatmentselection.Asanexample,the
requirementthatwomenabstainfrompregnancyforthreeyearsafteracitretintreatmentgivesacitretinarelative
contraindicationforuseinwomenofchildbearingage.
PatientswithrelativelystablediseaseAcitretinisourtreatmentofchoicefortheinitialmanagementof
adultswithrelativelystableGPP.Methotrexateisanalternativefirstlinetreatment.Wealsousethesedrugsfor
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longtermtreatmentofGPPfollowingcontrolofsevereacutedisease.
OralretinoidsOralretinoids(etretinate,acitretin)arewellacceptedandwidelyusedtreatmentsfor
GPP.EtretinatewaswithdrawnfromtheUSmarketin1998andreplacedbyitsmetaboliteacitretinbecauseof
concernabouttheprolongedeliminationhalflifeofetretinate.
EfficacyAlthoughoralretinoidsareconsideredastandardtreatmentforGPP,evidencetosupporttheiruse
islimited.SomesupportfortheuseoforalretinoidsstemsfromaJapanesestudythatanalyzedtreatment
datafrom385patientswithacuteGPPobtainedthroughquestionnaireresponsesfrommultiplecommunity
centerhospitals[9].Thestudyfoundthatamong188patientstreatedwithretinoids,treatmentwasreported
aseffectivein84percent.Retinoidtreatmentregimenswerenotstandardizedtypically,treatmentwaswith
etretinate(1mg/kgperdayandtaperedastolerated).Manypatientsreceivedretinoidsincombinationwith
othertherapies.
Aseparateretrospectivestudyof63patientshospitalizedatMayoClinicaffiliatedhospitalsbetween1961
and1989alsosuggestsefficacyoforalretinoidtherapy.Goodresponseswererecordedinallofsixpatients
treatedwithetretinateforacuteGPPandbothoftwopatientsgiventhedrugforannularpustularpsoriasis
[10].
Thereissomeevidencetosuggestthatisotretinoin,whichisnotconsideredeffectiveforchronicplaque
psoriasis,maybeofbenefitinGPP.Inaseriesof11adultswithGPP,isotretinointherapyseemed
beneficialforimprovingpustuleformationin10patients,althoughmonotherapywiththedrugdidnotseemto
beeffectiveforclearingalllesions[11].Isotretinoinalsoappearedusefulinanadolescentfemalewhofailed
torespondadequatelytotopicalcorticosteroidsandmethotrexate[12].
AdministrationAcitretinisourpreferredoralretinoidforGPPbecauseclinicalexperiencewithisotretinoin
forthisindicationismorelimitedandetretinateisnotavailableintheUnitedStates.Ourusualstartingdose
foracitretinis0.75to1mg/kgperday.Japaneseauthorshavesuggestedaninitialdoseofetretinateof0.5
to1mg/kgperday[13].
ImprovementinGPP(ie,cessationofnewpustuleformationandinitialimprovementinotherclinicalsigns)is
usuallynotedwithin7to10daysoforalretinoidtherapy.Afterdiseasecontrolisachieved,thedoseof
acitretincanbetaperedslowlytothelowestdosenecessarytomaintaintheresponse.Itisimpossibleto
predictforindividualpatientsbutacompleteresponseoftenrequirestwotothreemonthstoachieve.
Examplesofadverseeffectsoforalretinoidsincludexerosis,cheilitis,drymucousmembranes,
hypertriglyceridemia,hairloss,liverfunctiontestabnormalities,bonechanges,andvisualchanges.Oral
retinoidsareteratogenicandpregnancyshouldbeavoidedforthreeyearsfollowingacitretintherapy.
Therefore,thedrughasarelativecontraindicationforwomenofchildbearingage.Incontrast,pregnancyis
contraindicatedforonlyonemonthfollowingisotretinointherapy.(See"Oralisotretinointherapyforacne
vulgaris",sectionon'Isotretinoinsafety'.)
MethotrexateOralmethotrexateappearstobeeffectiveforGPPandisanalternativetoacitretintherapy
[6].
EfficacyDataontheefficacyofmethotrexateforGPParelimited.InamulticenterstudyinJapaninwhich
communityhospitalsweresentquestionnairesaboutpatientswithGPP,efficacyofmethotrexatewas
documentedfor76percentof41patientsgiventhistherapyaloneorinconjunctionwithothertherapies[9].
Inaddition,inaretrospectivestudyof63patientshospitalizedforGPPatMayoClinicaffiliatedhospitals
between1961and1989,goodresponsestomethotrexatewerereportedforthreeofeightpatientswithacute
GPPandbothoftwopatientswithannularpustularpsoriasis[10].
AdministrationAtypicaldoseofmethotrexateforadultswithGPPis15mgperweek,withamaximum
doseof25mgperweek.Methotrexateisnotgivendaily.Absorptionoforalmethotrexatemaybereducedat
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higherdoses[14,15].Thus,whendoseshigherthan15mgperweekarerequired,weoftenuse
subcutaneousorintramuscularadministration.
Myelosuppressionisapotentialseriousadverseeffectofmethotrexatetherapythatwarrantscareful
administrationoftreatmentandlaboratoryfollowup.Theamountofmethotrexateusedfortheinitialdose
variesamongexperts,withsomeexpertsinitiatingwithasmalltestdose(eg,5mgperweek)followedby
upwardtitrationofthedoseandothersinitiatingathigherdoses(eg,15mgperweek)[16].Whentreating
olderadultpatientsorpatientswithrenalinsufficiency,theinitialdoseshouldnotexceed10mgperweek.
Additionaladverseeffectsofmethotrexateincludegastrointestinaldistress,hepatotoxicity,pulmonary
toxicity,andteratogenicity.Methotrexateshouldbecombinedwithfolicacidsupplementation(eg,1mgof
folicacidperday)todecreasehematologicandgastrointestinaltoxicity[17].(See"Majorsideeffectsoflow
dosemethotrexate".)
Monitoringprotocolsformethotrexatetreatmentvaryingeneral,acompletebloodcountwithdifferentialand
plateletsshouldbeperformedatbaselineandsoonaftertheinitiationofmethotrexateandfollowingdose
increases.Whilesomecliniciansperformhematologictestingapproximatelyoneweekafterdoseinitiationor
changes,others(includingtheauthor)performtestsaftertwotofourweeksprovidedthepatientisnotan
olderadultindividualanddoesnothaverenalinsufficiency.Hematologictestingisrepeatedeverytwotofour
weeksduringthefirstfewmonthsoftreatmentandissubsequentlytaperedtoeveryonetothreemonths.
Periodiclaboratorymonitoringofkidneyandliverfunctionisalsoindicatedduringmethotrexatetherapy.
TopicaltherapyBecauseofthewidespreadnatureofGPP,topicalmedicationsareprimarilyreserved
foradjunctivetherapy.Topicaltherapiesthathaveseemedusefulforadjunctivetherapyincasereportsaresimilar
tothoseusedinchronicplaquepsoriasis,andincludetopicalcorticosteroids[18],combinationtherapywitha
topicalcorticosteroidandtopicalvitaminDanalog[19],andtopicaltacrolimus[20].Topicalcorticosteroidsarethe
topicalagentsweusemostfrequentlyinpatientsforwhomcorticosteroidsarenottheprecipitatingfactorforthe
episodeofGPP.ThedevelopmentofGPPinassociationwithuseoftopicalcorticosteroids[2123]andtopical
vitaminDanalogs[21,24,25]hasbeenreported.
Wetypicallylimituseoftopicalagentstolocalizedareasofrecalcitrantskininvolvement.However,apatientin
whomGPPappearedtorespondtototalbodyapplicationoftopicaltacrolimusastheprimarytreatmenthasbeen
reported[26].
PatientswithsevereacutediseaseCyclosporineandinfliximabareourtreatmentsofchoicefortheinitial
managementofsevereacuteGPP.
CyclosporineOralcyclosporinehasalonghistoryofuseforpsoriasisandcaninducerapid
improvementofGPP.
EfficacyDespitethecommonuseofcyclosporineforsevereacuteGPP,dataontheefficacyofthedrug
arelimited.Abeneficialeffectofcyclosporineissupportedbyretrospectivedataobtainedfromhospitalsin
Japanthatsuggestedtreatmentefficacyin60to70percentofpatientstreatedwithcyclosporinealoneorin
conjunctionwithothertherapies[9,13].Markedimprovementoftenoccurswithinthefirstfewdaysof
treatment[1,27,28].
AdministrationEffectivedosesofcyclosporineforadultswithGPPhaverangedfrom2.5to5mg/kgper
day[6].WetypicallytreatsevereacuteGPPwith4to5mg/kg(idealbodyweight)perday.Becauseside
effectsoftreatmentwithcyclosporineareaconcern,oncediseasecontrolisachieved,weattempttotaper
thedoseoverthecourseoftwotothreemonths.
Potentialadverseeffectsofcyclosporineincludehypertension,renaltoxicity,andincreasedriskfor
infectionsandmalignancy.Laboratorytestsaswellasbloodpressureshouldbemonitoredcloselyduring
therapy.Adverseeffectsofcyclosporinearediscussedingreaterdetailseparately.(See"Pharmacologyand
sideeffectsofcyclosporineandtacrolimus",sectionon'Sideeffects'and"Pharmacologyandsideeffectsof
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cyclosporineandtacrolimus",sectionon'Strategiestominimizetoxicityinrheumaticdiseases'.)
InfliximabComparedwithotherfirstlinetreatments,infliximabisanewertreatmentoptionforadults
withGPP.
EfficacyTheuseofinfliximabforGPPisbaseduponcasereportsandaretrospectivestudythatsuggest
efficacyofthistreatment[7,2936].Among10patientsinwhomflaresofacuteGPPweretreatedwith
infliximabinaFrenchmulticenterretrospectivestudy,clinicalremissionwasachievedby8patients(80
percent).Thefastonsetofinfliximabwasevidentinthetimerequiredtoachieveclearanceofpustules
pustulesclearedinamedianoftwodays(rangeonetoeightdays)[7].
AdministrationStandarddosingforinfliximabforpsoriasisis5mg/kgatweekszero,two,andsix,and
everysixtoeightweeksthereafter.Treatmentwithinfliximabmaybecontinuedforlongtermmanagementof
GPP.Alternatively,patientscanbetransitionedtoothertherapiesaftercontrolofacutediseaseisachieved.
Thepossibilitythatasingledoseofinfliximabmaybesufficientissuggestedbyacasereportdocumenting
dramaticimprovementinacuteGPPwithin24hoursfollowingasingledoseofinfliximabfollowedbythe
initiationofmethotrexate[29].Infliximabhasalsobeensuccessfullyusedincombinationwithacitretinforthe
inductionofrapidimprovementwhileawaitingtheonsetofactionofacitretin[37].
PatientsshouldbeevaluatedforlatenttuberculosisandhepatitisBpriortoinitiatingtherapy.Potential
adverseeffectsofinfliximabincludeinfusionreactionsandincreasedriskforinfection,malignancy,heart
failure,anddemyelinatingdisease.Therearealsoreportsofinfliximabinducingpsoriaticeruptions,including
GPP[38].Theadverseeffectsofinfliximabarereviewedseparately.(See"Tumornecrosisfactoralpha
inhibitors:Anoverviewofadverseeffects".)
SecondlinetherapyPatientswhodonotrespondtoorcannottoleratefirstlinetherapiesforGPPmaybenefit
fromotherapproachestotherapy,suchasphotochemotherapy,additionalbiologicTNFalphainhibitors,and
combinationtherapy.
PsoralenplusUVA(PUVA)photochemotherapyPUVAphototherapyinvolvestheadministrationof
photosensitizingpsoralenorallyortopicallypriortoexposuretoaUVAlightsource.Inanuncontrolled
prospectivestudyofeightpatientswithacuteGPP,oralPUVAphotochemotherapy(fourtimesweekly)was
associatedwithcompleteclearingofGPPinallpatientswithinameanof13.510treatmentsessions[39].
Maintenancetherapy(twiceweeklyPUVAtreatmentstaperedtodiscontinuationiftolerated)wasgivenupon
completeremission,andsevenpatientsremainedincompleteremissionduringfollowupperiodsofupto1.5
years.ThefrequentclinicvisitsrequiredforPUVAphotochemotherapymaymakethisalessfavorable
treatmentoptionforsomepatients.
OtherbiologicTNFalphainhibitorsSuccessfulcontrolofGPPduringadalimumaboretanercepttherapy
hasbeenreportedinsmallnumbersofpatients[7,4044].Inoneretrospectivestudy,twoofthreeGPPflares
treatedwithadalimumabprogressedtoclinicalremissionsandclearanceofpustulesoccurredwithin7and
28days[7].Ofnote,therearereportsofGPPinducingpsoriaticeruptionsincludingGPP[38].
CombinationtherapySeveralcasereportsdemonstrateefficacyinrecalcitrantGPPwhentwoormore
classesoftherapeuticagentsareusedincombination.Examplesincludeetanerceptandcyclosporine[28],
infliximabandmethotrexate[36],adalimumabandacitretin[45],infliximabandacitretin[37],and
cyclosporineandPUVAphotochemotherapy[27].Inaddition,childrenhaverespondedtocombination
therapywithnarrowbandUVBandsystemictherapies[46,47].
OthertherapiesAvarietyofothertherapieshavebeenusedforGPP,althoughconcernforsideeffectsor
limitedexperienceprecludesarecommendationfortheroutineuseofthesetherapies.
AlthoughsystemicglucocorticoidtherapycanleadtorapidimprovementinGPP[13],thetreatmentmustbeused
withcautionbecausesystemicglucocorticoidsareimplicatedaspotentialincitingfactorsforGPP[6].Inaddition,
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thereisconcernfortheserioussideeffectsfromlongtermglucocorticoidtherapy.Thus,wedonottypicallyuse
systemicglucocorticoidsinthetreatmentofGPP.Intheeventthatsystemicglucocorticoidtreatmentisgivento
obtaininitialcontrolofGPP,wesuggestalsoinitiatingasecondtherapyinanattempttoreducethelikelihoodofa
diseaseflareduringtaperinganddiscontinuationofthesystemicglucocorticoid.However,evidencetosupportthis
approachislacking.Theadverseeffectsofsystemicglucocorticoidsarereviewedseparately.(See"Majorside
effectsofsystemicglucocorticoids".)
Severalcasereportsdocumentthesuccessfuluseofgranulocyteandmonocyteapheresisforthetreatmentof
refractoryGPP[4852].OthertreatmentsthathavebeenreportedtobeeffectiveforGPPincasereportsinclude
anakinra[51,53,54],ustekinumab[55],mycophenolatemofetil[56],andoralzinc[57].Itremainstobeseen
whetheranakinraisprimarilyeffectiveforGPPassociatedwithdeficiencyoftheinterleukin36receptorantagonist
(DITRA).Inaddition,theonsetorworseningofpustularpsoriasisfollowingustekinumabtreatmenthasbeen
reported[58,59].(See'IL36RNmutations'below.)
Specialpopulations
ChildrenChildhoodGPPisrare,contributingtoapaucityofdataontheefficacyandsafetyoftreatments
forGPPinchildren.WeagreewiththefollowingfirstlinetreatmentapproachforacuteGPPasoutlinedbythe
taskforceoftheNationalPsoriasisFoundationMedicalBoard[6]:
Firstlinetherapy
Acitretin(<1mg/kgperday)
Cyclosporine(1to3mg/kgperday)
Methotrexate(0.2to0.4mg/kgperweek)
Etanercept(0.4mg/kgperday)
NorandomizedtrialshavebeenperformedtoconfirmtheefficacyoftheseagentsinthetreatmentofacuteGPPin
children.Theselectionofanoralretinoid[8,12,60,61],cyclosporine[47,6265],methotrexate[61,66,67],and
etanercept[68]isprimarilybasedoncasereportsthatsuggestefficacyofthesedrugsinchildrenwithGPPand
experiencewiththeseagentsforotherformsofpsoriasisinchildren.Inparticular,randomizedtrialshave
supportedtheefficacyandsafetyofetanerceptformoderatetosevereplaquepsoriasisinchildren[69,70].
However,evidenceforefficacyofetanerceptinGPPisverylimited[68].
Giventhecontraindicationforpregnancyduringacitretintreatmentandforthreeyearsafterdrugdiscontinuation,
theuseofacitretiningirlsmustbeconsideredcarefully.Successfultreatmentwithisotretinoininplaceofacitretin
hasbeenreportedinanadolescentfemale[12].Aslightriskforskeletaltoxicityhasbeenobservedinchildren
treatedwithhighdosesoforalretinoidsfordisordersofkeratinization[71].
AdditionaltherapiesthatmaybeusefulinthetreatmentofpediatricacuteGPPbaseduponcasereportsinclude
narrowbandUVBphototherapyinconjunctionwithsystemictherapy[46,47],adalimumab[40],andinfliximab[68].
Also,aninfantwithGPPassociatedwithIL36receptorantagonistdeficiencyhasrespondedtoanakinra[72].
Topicalcorticosteroidtherapymaybeeffectiveforthetreatmentofchildrenwithannularpustularpsoriasis,which
exhibitslessseveremanifestationsthanacuteGPP[5].Inaddition,topicalcompresses,wetwraps,oroatmeal
bathsmaybehelpfulforsoothingtheskinlesions[5,73].
Topicaltherapyforannularpustularpsoriasisislesspracticalwhenalargeproportionofthebodysurfaceis
affected.Patientswhocannotbemanagedonlywithtopicaltherapycanbetreatedwithsystemicagents.Case
reportssuggestthatoralretinoids,oraldapsone,andmethotrexatecanbeeffectiveforthisvariant[5].
PregnantwomenThemanagementofpustularpsoriasisinpregnancy(impetigoherpetiformis)isreviewed
separately.(See"Dermatosesofpregnancy",sectionon'Pustularpsoriasisofpregnancy'.)
IL36RNmutationsGrowingunderstandingofthemolecularbasisofGPPassociatedwithIL36RN
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mutationsmayaidintherapeuticdecisionsforpatientswiththistypeofGPP.Evidencesuggeststhatsomecases
ofGPP(oracutegeneralizedexanthematouspustulosis[AGEP])mayactuallyrepresentanewgenetic
autoinflammatorydiseasebasedonmutationsintheIL36RNgene,whichencodestheIL36receptorantagonist.
Thisdiseaseisknownasthedeficiencyofinterleukin36receptorantagonist(DITRA).(See"Pustularpsoriasis:
Pathogenesis,clinicalmanifestations,anddiagnosis".)
PatientswithIL36RNmutationsupregulateIL1inresponsetoIL36stimulation.Casereportsdocumenting
successfultreatmentofGPPinpatientswithIL36RNmutationswithanakinra,anIL1receptorantagonist,support
theimportanceofthispathway[54,72].Inaddition,preliminaryfindingsofclinicaltrialssuggestthattreatmentwith
IL1antagonistscanimproveGPP(picture2).Asmoredataaccumulate,IL1blockademaybecomethetreatment
ofchoiceforpatientswhoharborthegeneticmutation.
LOCALIZEDPUSTULARPSORIASISTheapproachtothetreatmentofpustularpsoriasisdiffersfrom
generalizedpustularpsoriasis(GPP).Localtreatmentgenerallyisusedasfirstlinetreatment,withsystemic
therapiesreservedforpatientswhofailtorespondwelltolocaltherapy.
AcrodermatitiscontinuaofHallopeauAcrodermatitiscontinuaofHallopeau(ACH)isarare,chronic,
localizedformofpustularpsoriasisthatprimarilyinvolvesoneormoreextremitydigits(picture3).ACHisoften
poorlyresponsivetotherapy.
AvarietyoftopicalandsystemictherapieshavebeenutilizedforACHwithvariableresults.Dataontreatmentof
thisrarediseaseareprimarilylimitedtocasereports.Topicalcorticosteroids,topicaltacrolimus,topicalcalcipotriol
(aloneorincombinationwithtopicalcorticosteroidsortopicaltacrolimus),topicalmechlorethaminehydrochloride,
topicalfluorouracil,PUVAphotochemotherapy,andnarrowbandUVBphototherapyareamongthelocaltreatments
documentedaseffectiveinindividualpatientswithACH[74].Systemictherapieshaveincludedoralretinoids,
methotrexate,cyclosporine,systemicglucocorticoids,methotrexateandpropylthiouracil,infliximab,adalimumab,
etanercept,andanakinra[7478].Theefficaciesoftheseinterventionshavenotbeencomparedandthebest
approachtotreatmentisunclear.
OurinitialchoicefortreatmentofACHistypicallyasuperpotenttopicalcorticosteroid(eg,halobetasolor
clobetasol),whichweinstructthepatienttoapplytotheaffectedareasoncetotwicedailyfortwotofourweeks
(table1).Preferably,thepatientshouldapplythemedicationunderanocclusivedressingatnight,particularly
duringthefirstweekoftherapy.Plasticwrapiscommonlyusedasanocclusivedressing.Alternatively,occlusion
canbeappliedusingdampclothcoveredbydrycloth.
Ifagoodresponsetotreatmentoccurs,thefrequencyofapplicationcanbetaperedastoleratedtoafrequencyas
lowasonceortwiceperweek.Alternatively,weprescribeatopicalvitaminDanalog(eg,topicalcalcitriolor
calcipotriene)inconjunctionwiththesuperpotenttopicalcorticosteroidandinstructthepatienttoapplythetopical
corticosteroidfollowedimmediatelybythevitaminDanalogoncetotwicedailyfortwotofourweeks.Once
sufficientimprovementisachieved,wetaperthetopicalcorticosteroidastoleratedandcontinuetreatmentwiththe
vitaminDanalog.Acommercialproductcontainingbothbetamethasonedipropionateandcalcipotrieneis
available.
Whenpatientsfailtorespondadequatelytotopicaltherapy,weproceedtolocalphototherapyorsystemictherapy,
althoughweusuallycontinuetousetopicalcorticosteroidsasadjunctivetherapy.BothpsoralenplusUVA(PUVA)
photochemotherapyandnarrowbandUVBhaveappearedeffectiveforACHincasereports[74].Weoftenuse
acitretin(0.5to1mg/kgperday)asourfirstlinesystemictreatment,withmethotrexateandcyclosporineas
alternatives.Ifapatientfailstoimprovewiththesetraditionalsystemictherapies,wemayattempttreatmentwith
abiologicTNFalphainhibitor,suchasadalimumab,infliximab,oretanercept.
PalmoplantarpustulosisPalmoplantarpustulosisisachronicconditioncharacterizedbythedevelopmentof
yellowtobrownpustules,scale,andpatchyerythemaonthepalmsorsoles.Itiscontroversialwhether
palmoplantarpustulosisisalocalizedvariantofpustularpsoriasis(palmoplantarpustularpsoriasis)oraseparate
entity.Thetreatmentofpalmoplantarpustulosisisreviewedseparately.(See"Palmoplantarpustulosis:
http://www.uptodate.com.ezproxy.ugm.ac.id/contents/pustularpsoriasismanagement?topicKey=DERM%2F93554&elapsedTimeMs=4&source=see_link&vie 7/23
9/5/2015 Pustularpsoriasis:Management
Treatment".)
SUMMARYANDRECOMMENDATIONS
Generalizedpustularpsoriasis(GPP)isanuncommonformofpsoriasischaracterizedbythedevelopmentof
widespreadpustulesanderythematousplaquesontheskin.Thegoalsoftreatmentaretoimproveskin
manifestations,alleviatesystemicsymptoms,andpreventseriousorlifethreateningcomplicationsofthis
disease.(See'Generalizedpustularpsoriasis'above.)
TreatmentoptionsforadultswithGPPincludetopicaltherapies,systemictherapies,andphototherapy.Most
patientsrequiresystemictherapy.Topicaltherapiesareprimarilyusedasadjunctstosystemictherapy.(See
'Approachtotherapy'above.)
AspartoftheinitialmanagementofpatientswithGPP,theneedforhospitalizationshouldbeassessed.In
addition,thepatientsmedicalhistoryshouldbereviewedfordrugsthatmaycontributetothedevelopmentof
GPP.(See'Approachtotherapy'above.)
TheapproachtothetreatmentofGPPisinfluencedbytheacuityandseverityofsymptoms.Foradult
patientswithrelativelystabledisease,wesuggestacitretinasinitialtherapy(Grade2C).Methotrexateisan
alternativefirstlinetreatment.ForadultpatientswithsevereacuteGPP,wesuggestinitialtherapywithfast
actingtherapiessuchascyclosporineorinfliximab(Grade2C).(See'Firstlinetherapy'above.)
OthertherapeuticagentsthatmaybeeffectiveinadultswithGPPincludepsoralenplusUVA(PUVA)
photochemotherapy,adalimumab,andetanercept.Combinationtherapywithmorethanonetreatmentcan
alsobeattempted.(See'Secondlinetherapy'above.)
SystemicglucocorticoidscaninducerapidimprovementinGPP,buthavebeenidentifiedaspotentialinciting
factorsforthisdisease.WedonotusuallyusesystemicglucocorticoidsforthetreatmentofGPP.(See
'Othertherapies'above.)
DataonthetreatmentofacuteGPPinchildrenareverylimited.Optionsforfirstlinetherapyincludeacitretin,
cyclosporine,methotrexate,andetanercept.Somechildrenwithannularpustularpsoriasiscanbemanaged
withtopicaltreatment.(See'Children'above.)
IncreasingknowledgeaboutthepathogenesisofGPPassociatedwithIL36RNmutationsmayleadtonew
therapeuticoptionsforthisformofGPP.(See'IL36RNmutations'above.)
AcrodermatitiscontinuaofHallopeau(ACH)isarareformoflocalizedpustularpsoriasisthatprimarily
affectstheextremitydigitsandisoftenrefractorytotreatment.DataontreatmentsforACHarelimitedto
casereports.Wesuggestasuperpotenttopicalcorticosteroidasinitialtreatment(Grade2C).(See
'AcrodermatitiscontinuaofHallopeau'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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Topic93554Version3.0
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GRAPHICS
Generalizedpustularpsoriasis
Pustules,erythema,andscaleingeneralizedpustularpsoriasis.
Reproducedwithpermissionfrom:www.visualdx.com.CopyrightLogicalImages,Inc.
Graphic94789Version1.0
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Pustularpsoriasis
Widespreaderythematouspatches,desquamation,andpustulesinpustularpsoriasis.
Reproducedwithpermissionfrom:www.visualdx.com.CopyrightLogicalImages,Inc.
Graphic94790Version1.0
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Generalizedpustularpsoriasis
Diffuseerythema,numerouspustules,andscale.
Reproducedwithpermissionfrom:www.visualdx.com.CopyrightLogicalImages,Inc.
Graphic95194Version1.0
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ResponseofgeneralizedpustularpsoriasistotreatmentwithanIL1antagon
DramaticresponseofseveregeneralizedacutepustularpsoriasistotreatmentwithanIL1antagonist.
Reproducedwithpermission.ImagecourtesyofXOMA(US),LLC.Copyright2014.
Graphic95263Version3.0
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AcrodermatitiscontinuaofHallopeau
Pustules,erythema,scale,andnaildystrophyinvolvingthedistalfingers.
Reproducedwithpermissionfrom:www.visualdx.com.CopyrightLogicalImages,Inc.
Graphic94791Version1.0
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Comparisonofrepresentativetopicalcorticosteroidpreparations
(classifiedaccordingtotheUSAsystem)
Available
Trade strength(s), Generic
Potency Vehicle
Corticosteroid names percent available
group* type/form
(US) (exceptas inUS
noted)
Super Betamethasone Ointment, Diprolene 0.05 Yes
high dipropionate, optimized
potency augmented
Lotion Diprolene 0.05 Yes
(group1)
Gel Diprolene 0.05 Yes
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SarnolHC,
Cortizone
10
%:percent.
*ListedbypotencyaccordingtotheUSAclassificationsystem:group1isthemostpotent,group7is
theleastpotent.Othercountriesuseadifferentclassificationsystemwithonlyfourorfivegroups.
Vehicleandbaseingredient(s)forgenericproducts,insomecases,maynotbeidenticaltotrade
version.
InactiveUStradenameforspecificproductbrandmaybeavailableoutsideUS.
48%refinedpeanutoil.
Datafrom:LexicompOnline.Copyright19782015Lexicomp,Inc.AllRightsReservedandTadicherla
S,RossK,ShenefeltD,TopicalcorticosteroidsindermatologyJournalofDrugsinDermatology2009
12:1093.
Graphic62402Version27.0
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Disclosures
Disclosures:RobertEKalb,MDGrant/Research/ClinicalTrialSupport:AbbVie[Psoriasis
(Adalimumab)]Amgen[Psoriasis(Etanercept)]Janssen[Psoriasis(Adalimumab)]LEOPharma
[Psoriasis(Taclonex)]Merck[Psoriasis].Consultant/AdvisoryBoards:AbbVie[Psoriasis(Adalimumab)]
CelgeneCorporation[Psoriasis]Janssen[Psoriasis(Adalimumab)]LEOParma[Psoriasis(Taclonex)]
Novartis[Psoriasis]Pfizer[Psoriasis]Ranbaxy[Psoriasis]TaroPharm[Psoriasis].KristinaCallis
Duffin,MDGrant/Research/ClinicalTrialSupport:Amgen[Psoriasis(Etanercept,brodalumab)]Pfizer
[Psoriasis(tofacitinib)]BristolMyersSquibb[Psoriasis(abatacept)]EliLilly[Psoriasis(ixekizumab)]
AbbVie[Psoriasis(Adalimumab)]Janssen[Psoriasis(Ustekinumab,guselkumab,infliximab)Novartis
[psoriasis(secukinumab)]Celgene[psoriasis(apremilast)]SteifelXenoport[psoriasis(calcipotriene)].
Consultant/AdvisoryBoards:Amgen[Psoriasis(Etanercept,brodalumab)]Pfizer[Psoriasis(tofacitinib)]
BristolMyersSquibb[Psoriasis(abatacept)]EliLilly[Psoriasis(ixekizumab)]AbbVie[Psoriasis
(Adalimumab)]Janssen[Psoriasis(Ustekinumab,guselkumab,infliximab)Novartis[psoriasis
(secukinumab)]Celgene[psoriasis(apremilast)]SteifelXenoport[psoriasis(calcipotriene)].AbenaO
Ofori,MDNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmust
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