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14
Psoriasis
ShellyR.Schneider
LearningObjectives
1.Thelearner will discusstreatmentoptionsthatincludetopical, oral,andinjectable pharmacologic
agents.
2.Thelearnerwilldistinguishbetweenfirst-,second-,andthird-lineagentswithregardtoseverityof
disease,sideeffects,andrisk-benefit.
3. The learner will be able to recognize factors in choosing biologic agents to treat psoriasis for
preventingsystemiccomplications,aswellastreatlocallesions.
INTRODUCTION
Psoriasis is a chronic debilitatingdisease characterized by recurrent exacerbations and remissions. It
affects between 2% and 3% of the U.S. population, with a higher incidence in whites and an equal
distributionbetweenthegenders.Approximately36%ofpatientswithpsoriasishavea positive family
history.Thecostofoutpatienttreatmentforpsoriasisaverages$1.6to$3.2billionannually.Thereappear
tobetwopeakagesofonset:betweenages16and22andbetweenages57and60.
Psoriatic lesions areassociatedwith physical discomfortincluding pain, itching, stinging, cracking,
and bleeding. In approximately 10% of patients with psoriasis, the disease develops into psoriatic
arthritis. Psoriasis affectsalmostallaspectsoflife,includingsexualrelationshipsandemotionalwellbeing.Inaddition,patientswithpsoriasisspendoneormorehoursadaycaringfortheirskin.Ofasurvey
groupofpatientswithpsoriasis,upto25%,atsomepointintheirlife,feltthattheywouldratherbedead
thanalivewithpsoriasis.
Psoriasis affects approximately 2.5% of whites and 1.3% of blacks in the United States, with
approximately150,000newlydiagnosedcaseseveryyear.Theincidenceofpsoriasisissomewhatlower
in Asians (0.4%). Generally, it is more commonin individuals living at higher latitudes or in colder
localesandlesscommoninindividualswhohavegreatersunexposure.
Thereseemstobeageneticfactorassociatedwithpsoriasis.Basedonpopulationstudies,theriskof
psoriasisinchildrenisestimatedtobe41%ifbothparentsareaffected,14%ifoneparentisaffected,
and6%ifonesiblingisaffected,andafamilyhistorycanbefoundin5%to10%ofpatientswhohave
psoriasis.
CAUSES
A definitive cause for psoriasis is unknown, although there are several possible etiologic factors:
abnormal epidermal cell cycle, hereditary factors, and triggers, including trauma, infection,endocrine
imbalance,climate,andemotionalstress. Physical trauma, suchasrubbing,scratching,or sunburn,isa
majorexacerbatingfactorinpsoriasis,whichresultsinareactionknownasKoebnerphenomenon.Stress
playsaroleinasmanyas40%ofpsoriasisflaresinadultsandchildren.Exacerbationsofpsoriasismay
developfromtheuseofcertaindrugs(Box14.1).
PATHOPHYSIOLOGY
PsoriasisisaTcell–mediateddiseaseinvolvingadysregulationoftheinflammatoryprocess,aswellas
skin barrier dysfunction.Believed to be multifaceted,insults to the body due to genetic influences in
additiontostress,infection,ordrugscanelicitthealteredanddisruptiveinflammatoryprocessexhibited
in the skin as plaques. Any immunologic or environmental trauma may trigger an abnormal immune
response,resultinginacascadeofevents,notfullyunderstood.Hallmarksoftheconditionincludehyperproliferation and abnormal differentiation of epidermal keratinocytes with infiltrative T lymphocytes.
Epidermalthickeningandremodelingoccursexternallywhilepro inflammatorysubstancesarereleased
intosystemiccirculation.Thismayaccountforchronichealthissuesandjointinvolvementlaterinthe
diseaseprocess.
Box14.1 DrugsKnowntoExacerbatePsoriasis
Systemiccorticosteroids(whendoseisdecreasedorstopped)
Lithiumcarbonate
Antimalarials
Betablockers
Systemicinterferon
Alcohol
Researchshowsanassociationwithepidermaldefensegenes,sixofwhicharelocatedonchromosome
8p23.Tumornecrosis factoralpha(TNF-alpha),interleukin(IL)-23, andIL-17havebeenshowntobe
elevated in patients with psoriasis. These cytokines act to attract and activate neutrophils which are
responsible for much of the inflammation seen in the skin. In addition, IL-17 A downregulates the
expression of filaggrin which binds to keratin fibers in epithelial cells causing disruption in the skin
barrier.Intercellular adhesionmoleculeisalteredalongwithTNF-alphaandlymphocyticantigencells,
which initiate inflammatory cytokines IL-7 and IL-6 and pro-inflammatory transcription factor. High
levelsofIL-6suppressTregulatoryactivity,whichresultsinunopposedactivityofpathogenicTcells.
IncreasedIL-22leadstoepidermalacanthusesandabnormaldifferentiationofkeratinocytes.Activation
of these cells can occur through specific interactions with antigen-presenting cells (APCs) or via
nonspecific super antigen reaction (i.e., guttate psoriasis is triggered by streptococcal antigens). This
becomesacontinuousfeedbackloopofinflammation.
ActivationoftheseTcellscanoccurthroughspecificinteractionswithAPCsorvianonspecificsuper
antigeninteractions(i.e.,guttatepsoriasisistriggeredbystreptococcalantigens).APCactivationrequires
co-stimulatorysignals. Threemainpathways, TNF-alpha,IL-23,andIL-17,havebeenshowntoaffect
those withpsoriasis.These cytokines act toattractandactivateneutrophils which are responsiblefor
muchoftheinflammationseeninpsoriasis.
DIAGNOSTICCRITERIA
Clinical presentationof the plaque type of psoriasis consistsofsharp, well-demarcated,erythematous
papulesorplaquessurroundedbysilvery-whitescales.Thelesionsaresymmetric,andmanyarefoundon
theextensorsurfaces—elbowsandknees.Othercommonareasaffectedincludescalp,nails,anogenital,
intertriginous(inversepsoriasis),trunk,andears.Theplaquetypeisthemostcommonform.Otherforms
of psoriatic disease include guttate, erythrodermic, and pustular. The guttate type is characterized by
small,scattered,teardrop-shapedpapulesandplaques.Inmanycasespsoriasisbeginsastheguttateform
and may evolve into any of its other forms. The erythrodermic form is characterized by generalized
erythemaandsheddingwithscales.
Individualsareextremelyillandshouldbetreatedsimilartoburnvictims.Finally,thepustulartypehas
three additional forms: generalized, localized, and palmo-plantar. All these forms share a similar
characteristic:2-to3-mmsterilepustulesonspecificbodyregions.
Bleedingmayfollow removalofthescales(Auspitzsign).Pittinganddiscolorationofthenails are
also someofthecharacteristics ofpsoriasis.Insomecases,thenail mayseparatefromthenail bed—
referredtoasonycholysis.
INITIATINGDRUGTHERAPY
Beforebeginningdrugtherapy, thepatientisusuallycounseled toavoidprecipitatingfactors.Cigarette
smokingisdiscouragedsincethiscanexacerbatethecondition.
Therearethreetreatmentmodalitiesavailable:topical,phototherapy,andsystemicagents.Toselectthe
mostappropriatetreatment,onemustdeterminewhetherthepatienthaslocalizedorgeneralizedpsoriasis.
Patients with10% or less of bodyinvolvement can usuallybe successfully treated in a primary care
setting with topical agents, whereas those with greater body surface area (BSA) involvement usually
require treatment by a dermatologist with phototherapy or systemic therapy. In estimating BSA
involvement,theprescriberkeepsinmindthatthepalmrepresents1%BSA;thiscanbeusedasatoolto
estimatetotalBSAinvolvement.
GoalsofDrugTherapy
Thegoalsoftherapyarethefollowing:
•Decreasethesizeandthicknessoftheplaques.
•Decreasepruritus.
•Improveemotionalwell-beingandqualityoflife.
•Putthepatientinremission.
•Ensureminimalsideeffectsfromtreatment.
Itisimperativetouseamanagementstrategywiththeleastpossibletoxicitydeemedacceptabletothe
patient.Table14.1identifiestopicalandsystemicpreparationsusedinpsoriasistreatment.
TABLE14.1
OverviewofSelectedAgentsforPsoriasis
GI,gastrointestinal;IBS,irritablebowelsyndrome.
Emollients
Emollientsare usefulforall casesofpsoriasisas anadjuncttherapy. Theseagentshydratethestratum
corneum, decrease water evaporation, and soften the scales of the plaques. Multiple products are
availablecommerciallyinlotions,creams,andointments.Thethickerthepreparation,themoreeffective
itis. Inadditiontopreservingmoisture,emollientshaveamildantipruritic effect.Gentlecleansers are
encouraged.
TopicalCorticosteroids
The foundation of topical treatment is topical corticosteroids. They play an important role in treating
psoriasis bydecreasing erythema, pruritus, and scaling. Theypromote vasoconstriction. They are fast
actingbutnotintendedforlong-termuse.Topicalcorticosteroidsare classified intoseveralcategories
based onpotencyandvasoconstrictiveproperties.Low-potencycorticosteroidsaresafer forlong-term
useandforuseatthin-skinnedsitessuchasthefaceandgroin.Themosteffectivetopicaltreatmentisa
medium-orhigh-potencyagentusedforalimitedtime,followedbyalesspotentagentformaintenance.
Occlusion ofthearea where the topicalsteroid is applied is recommended. Saran wrap canbe used;
Cordrantapeisalsoeffectivebutquiteexpensive.
This method increases the absorption (hence the potency) of the topical preparation. Topical
corticosteroids maybe used twice daily for 2 weeks and then decreased to alternating days. Topical
corticosteroids have a rapid onset of action giving quick relief. For more information on topical
corticosteroids,seeChapter12.Intralesionalsteroidusemayalsobehelpfulforindividualplaques.
CoalTars
Coaltar(Cutar)containspolycyclichydrocarboncompoundsformedfrombituminouscoal.Itdepresses
deoxyribonucleic acid (DNA) synthesis and has antiinflammatory and antipruritic properties. Several
preparations are available over the counter (OTC), including ointments, gels, bath preparations, and
shampoos. Coaltar canbe usedas aninitial therapy, usuallywithadjuncttopical corticosteroids. The
emulsionisdissolvedinbathwater(15–25mL),andthepatientimmersestheaffectedareainthewater
for 10 to 20 minutes. Itis used for 30 to45 days, 3 to 7 times a week. The shampoopreparationis
massagedintoa wetscalp andrinsed. Itis applied a secondtimeandleftonthe scalpfor 5 minutes.
Disadvantages ofcoal tarincludetheunpleasantodor;stainingof clothes, skin,andfiberglass tubsor
sinks(evenwiththeclear preparation);andphotosensitivity. Thesedisadvantagestendtolead topoor
compliance.
Anthralin
Anthralin(Drithocreme,Micanol)isanothertopicaltreatmentforpsoriasis.Similartocutar,thisisacoal
tarderivative.
MechanismofAction
Therearetwopossiblemechanismsofaction:inhibitionofDNAsynthesisandadecreaseinepidermal
proliferation. Anthralin is a good alternative therapy if the patient has a limited number of lesions,
becauseitsuseistimeconsuming.
Dosage
Anthralinisappliedfor30minutesto1hourandthenremoved.Itshouldbeappliedonlytothelesions.
Treatmentstartswithalowstrengththatisgraduallyincreased.Stainingofthepsoriasisplaquessignifies
thattreatmentisdecreasingcellularproliferation.Treatmentistimeconsumingbutshortterm.
TimeFrameforResponse
Thereisaslowonsetofaction,andresponseisslowaswell.
Contraindications
Anthralintherapyiscontraindicatedinacutepsoriasisandinflammation.
AdverseEvents
Anthralin therapymaybe limitedbyirritationof the unaffectedskin.Themedication stains clothinga
brownishpurpleandpermanentlystainstowels,tubs,andsinks.
VitaminDAnalogs
Calcipotriene(Dovonex)andCalcipotriolarevitaminDanalogsfortreatingmildtomoderatepsoriasis.
Theyaresuppliedincreams,ointments,andtopicalfoams.
MechanismofAction
Its mechanism of action is a reduction of cell proliferation by binding to receptors in epidermal
keratinocytes.Thedrugisalsothoughttohaveanantiinflammatoryeffect.Itiseffectiveforlong-termuse
andmaintenancetherapyandisoftenusedasrotationaltherapywithtopicalcorticosteroids.
Dosage
Athinlayerisappliedtwicedailytoaffectedskinfor6to8weeks.Itmaybeusedasrotationaltherapy
orbypulsedosing(off-and-ontherapy)inwhichthepatientfollowsthetherapeuticregimenfor2weeks,
followedby1weekoff.Usewithapotenttopicalcorticosteroidismosteffective.
TimeFrameforResponse
Someimprovementisusuallyseenin2to4weeks,althoughtherapyisrecommendedfor6to8weeks.An
advantage of calcipotriene is its efficacy similar to that of medium- to high-potency topical
corticosteroids. Unlike corticosteroids, however, calcipotriene does not cause skin atrophy or
hypothalamus–pituitary–adrenalaxissuppression.However,itisanirritantandshouldnotbeusedonthe
face.
Contraindications
ItiscontraindicatedinpatientswithhypercalcemiaandvitaminDtoxicity.
AdverseEvents
The most common adverse effects of calcipotriene are mild and include dry skin, peeling, and rash.
HypercalcemiamaybecausedbyvitaminD ingestionbutis rareifthepatientuseslessthan100 gof
calcipotrieneperweek.
Retinoid(VitaminADerivative)
Tazarotene(Tazorac)isatopicalretinoidusedformildtomoderatepsoriasis.
MechanismofAction
This drug normalizes epidermal differentiation, decreases hyperproliferation, and diminishes
inflammationofthecellsintheskin.Useoftazarotenepromoteslongerremissionofpsoriasis.
Dosage
Itcomesinaclear,nonstaininggel,incream(0.05%and0.1%),andinfoam(Fabior)preparationsandis
appliedinathinlayeronceadayatbedtime.Skinmustbeairdriedandthearealeftun-occluded.The
preparationcanbeusedforthebody,scalp,hairline,andfacebutnotonthegenitalia,ontheintertriginous
areas,oraroundtheeyes.
TimeFrameforResponse
After1weekoftherapy,diminishedscalingisnoted.Clearingisseeninapproximately8weeks.
Contraindications
Tazarotenecancausefetalharm,soitisstartedinwomenduringthemenstrualcycle.Womenusingthis
agentshouldensurethattheydonotgetpregnantduringtherapy.
AdverseEvents
Adverseeffectsoftazaroteneincludepruritus,erythema,andmildtomoderateburning.Theuseoftopical
corticosteroidscounteracts these effects. The patient mustbe warnedthatthepsoriasismaygetworse
beforeitimproves.
Interactions
VitaminAingestionistobeavoided,andtazaroteneistobeusedwithcautionwithotherphotosensitizers
suchastetracyclinesandwithothertopicalirritantssuchasabrasives,depilatories,orpermanentwave
solutions.
CombinationProducts
Newertherapiesincludetopicalsteroidsincombinationwithkeratolyticagents:betamethasone0.064%
andcalcipotriene0.005% gel andointment(Taclonex), foam(Enstilar), halobetasol propriante 0.01%,
andtazoratene0.045%lotion(Duobrii).
MechanismofAction
Themechanismissameasthatdescribedpreviouslyforindividualproducts.
Dosage
Thedosageissameasthatdescribedpreviouslyforindividualproducts.
Contraindications
Thecontraindicationsaresameasthosedescribedpreviouslyforindividualproducts.
AdverseEvents
Combination products may reduce theirritating side effects due to decreased dosage of each product
whilemaximizingresults.
Interactions
Theinteractionsarethesameasthosedescribedpreviouslyforindividualproducts.
SystemicRetinoids
Acitretin(Soriatane)isasystemicretinoidusedforlong-termpsoriasistherapy.
MechanismofAction
Acitretin normalizes epidermal differentiation and diminishes hyperproliferation and inflammation of
cells in the skin. Prior to initiation of drug therapy, complete blood count (CBC) with differential
diagnosis,comprehensivemetabolicpanel(CMP),andlipidprofileshouldbeobtained.
Dosage
Initially,acitretin10mgoncedailyandthenupto50mgoncedailymustbetakenwiththemainmealuntil
thelesionsclear,whichoccursgradually.
Contraindications
Acitretinis contraindicatedinpregnancyandlactationandwiththeuseofalcohol.Itcannotbeusedin
patients withsevere renal impairment andincreased lipid levels. Thepatient cannot donate bloodfor
threeyearsaftertherapy.Cautionisexercisedifthepatienthasahistoryofdepression,obesity,oralcohol
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