Guidelines of Care for the Management of Psoriasis and Psoriatic Arthritis

151 Pages·2011·6.11 MB·English

A series of articles reprinted from

Guidelines of Care for the Management
of Psoriasis and Psoriatic Arthritis

Section 1. Overview of Psoriasis and Guidelines of Care for the
Treatment of Psoriasis with Biologics

Section 2. Psoriatic Arthritis: Overview and Guidelines of Care for
Treatment with an Emphasis on the Biologics

Section 3. Guidelines of Care for the Management and Treatment of
Psoriasis with Topic Therapies

Section 4. Guidelines of Care for the Management and Treatment of
Psoriasis with Traditional Systemic Agents

Section 5. Guidelines of Care for the Treatment of Psoriasis with
Phototherapy and Photochemotherapy

Section 6: Guidelines of Care for the Treatment of Psoriasis and
Psoriatic Arthritis: Case Based Presentations and Evidence Based
Conclusions
F
ROM THE ACADEMY
Guidelines of care for the management of
psoriasis and psoriatic arthritis
Section 1. Overview of psoriasis and guidelines of care
for the treatment of psoriasis with biologics
Work Group: Alan Menter, MD, Chair,a Alice Gottlieb, MD, PhD,b Steven R. Feldman, MD, PhD,c
Abby S. Van Voorhees, MD,d Craig L. Leonardi, MD,e Kenneth B. Gordon, MD,f Mark Lebwohl, MD,g
John Y. M. Koo, MD,h Craig A. Elmets, MD,i Neil J. Korman, MD, PhD,j Karl R. Beutner, MD, PhD,k
and Reva Bhushan, PhDl
Dallas, Texas; Boston, Massachusetts; Winston-Salem, North Carolina; Philadelphia, Pennsylvania;
Saint Louis, Missouri; Chicago and Schaumburg, Illinois; New York, New York; San Francisco
and Palo Alto, California; Birmingham, Alabama; and Cleveland, Ohio
Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint
manifestationsaffectingapproximately2%ofthepopulation.Inthisfirstof5sectionsoftheguidelinesof
careforpsoriasis,wediscusstheclassificationofpsoriasis;associatedcomorbiditiesincludingautoimmune
diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools
for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic
treatments used to treat patients with psoriasis. (J Am Acad Dermatol 2008;58:826-50.)
DISCLAIMER
Abbreviationsused:
Adherence to these guidelines will not ensure
AAD: AmericanAcademyofDermatology
successfultreatmentineverysituation.Furthermore,
BMI: bodymassindex
these guidelines do not purport to establish a legal BSA: bodysurfacearea
standardofcareandshouldnotbedeemedinclusive CHF: congestiveheartfailure
CyA: cyclosporine
ofallpropermethodsofcarenorexclusiveofother
FDA: FoodandDrugAdministration
methods of care reasonably directed to obtaining IL: interleukin
the same results. The ultimate judgment regarding LFA: lymphocytefunctionassociatedantigen
MS: multiplesclerosis
NB: narrowband
PASI: PsoriasisAreaandSeverityIndex
FromtheBaylorUniversityMedicalCenter,Dallasa;Departmentof PASI-75: 75%improvementinthePsoriasisArea
andSeverityIndexscore
Dermatology,Tufts-NewEnglandMedicalCenter,TuftsUniver-
PGA: PhysiciansGlobalAssessment
sitySchoolofMedicine,Bostonb;DepartmentofDermatology, PUVA: psoralenplusultravioletA
Wake Forest University School of Medicine, Winston-Salemc; QOL: qualityoflife
DepartmentofDermatology,UniversityofPennsylvaniad;Saint TB: tuberculosis
Louis Universitye; Division of Dermatology, Evanston North- TNF: tumornecrosisfactor
western Healthcare and Department of Dermatology, North- UV: ultraviolet
western University, Fienberg School of Medicine, Chicagof;
DepartmentofDermatology,MountSinaiSchoolofMedicine,
NewYorkg;DepartmentofDermatology,UniversityofCaliforniae the propriety of any specific therapy must be
San Franciscoh; Department of Dermatology, University of made by the physician and the patient in light of
Alabama at Birminghami; Murdough Family Center For Psori-
all the circumstances presented by the individual
asis, Department of Dermatology, University Hospitals Case
Medical Center, Clevelandj; Anacor Pharmaceuticals Inc, Palo patient.
Altok;andAmericanAcademyofDermatology,Schaumburg.l
Fundingsources:None.
The authors’ conflict of interest/disclosure statements appear at SCOPE
theendofthearticle. These guidelines address the treatment of both
Reprint requests: Reva Bhushan, PhD, 930 E Woodfield Rd, adultandchildhoodpsoriasisandpsoriaticarthritis.
Schaumburg,IL60173.E-mail:[email protected].
Thisdocumentwillincludethevarioustreatmentsof
0190-9622/$34.00
psoriasis including topical modalities, ultraviolet
ª2008bytheAmericanAcademyofDermatology,Inc.
doi:10.1016/j.jaad.2008.02.039 (UV) light therapies, systemic agents, and the
826
JAMACADDERMATOL Menter etal 827
VOLUME58,NUMBER5
TableI.Eightclinicalquestionsusedtostructuretheprimaryissuesindiagnosisandtreatmentofpatientswith
psoriasis
Guidelinesection Clinicalquestions
Section1 dHow ispsoriasis classified?
dWhat are the potentialcomorbidities ofpsoriasis?
dWhattoolsareusedtomeasurequalityoflifeinpsoriasisandhowarethesetoolsusedinthetreatment
ofpatients?
dWhat are the safety andefficacy ofbiologic therapies usedto treatpsoriasis?
Section2 dDiscusstheclassification,prognosis,assessmenttools,andsystemictherapiesusedinthetreatmentof
patients with psoriatic arthritis.
Section3 dWhat are the safety andefficacy oftopical therapies usedto treatpsoriasis?
Section4 dWhat are the safety andefficacy ofsystemic therapies and phototherapies used totreatpsoriasis?
Section5 dDescribeanoverallapproachtothetreatmentofpatientswithpsoriasiswithanemphasisondecision-
making criteria thatenable theclinician to individualizetherapy basedon disease type,extent,
response toprevious treatments,quality-of-life issues, and comorbidities.
biologictherapies.Inaddition,qualityoflife(QOL) Practice, andBMJUSA). This strategy was supported
parameters,thetypeofpsoriasis,andthepresenceof byadecisionoftheClinicalGuidelinesTaskForcein
comorbiditiessuchasobesityandotherassociations 2005 with some minor modifications for a consistent
of the metabolic syndrome will be reviewed. This approach to rating the strength of the evidence of
guideline will be subdivided into 5 separate docu- scientificstudies.1Evidencewasgradedusinga3-point
ments given the large breadth of material. The first scalebasedonthequalityofmethodologyasfollows:
section will give an overview of classification, co-
I. Good-quality patient-oriented evidence.
morbidities, and assessment tools and cover the
II. Limited-quality patient-oriented evidence.
biologictreatmentsforpsoriasis.Thesecondsection
III. Otherevidenceincludingconsensusguidelines,
will cover treatments for psoriatic arthritis with an
opinion, or case studies.
emphasis on the biologics; the third section will
covertopicaltherapies;thefourthsectionwillcover Clinical recommendations were developed on the
UVlighttherapyandsystemicnonbiologictherapies; best available evidence tabled in the guideline.
and the fifth section will be an overall approach to Thesearerankedasfollows:
the treatment of patients with psoriasis with an
A. Recommendationbasedonconsistentandgood-
emphasisondecision-makingcriteria.
quality patient-oriented evidence.
It is important, however, for dermatologists to
B. Recommendation based on inconsistent or lim-
addresspsoriasisinitsentirescopeofmanifestations.
ited-quality patient-oriented evidence.
This guideline will not cover the effectiveness of
C. Recommendation based on consensus, opinion,
treatmentsforthelesscommonsubtypesofpsoriasis,
or case studies.
suchasguttate,pustular,inverse,anderythrodermic.
Prior guidelines on psoriasis were also evalu-
METHOD ated.2,3Thisguidelinehasbeendevelopedinaccor-
Aworkgroupofrecognizedpsoriasisexpertswas dance with the American Academy of Dermatology
convened to determine the audience and scope of (AAD)/AADAssociation‘‘AdministrativeRegulations
the guideline, and identify clinical questions to for Evidence-based Clinical Practice Guidelines,’’
structure the primary issues in diagnosis and man- which includethe opportunityforreview and com-
agement(TableI).Workgroupmemberscompleted ment by the entire AAD membership and final
adisclosureofcommercialsupport. reviewandapprovalbytheAADBoardofDirectors.
Anevidence-basedmodelwasusedandevidence
was obtained using a search of the MEDLINE data- DEFINITION
base spanning the years 1990 through 2007. Only Psoriasisvulgarisisagenetic,systemic,inflamma-
English-languagepublicationswerereviewed. tory,chronicdisorder,whichcanbealteredbyenvi-
Theavailableevidencewasevaluatedusingauni- ronmental factors. It may be associated with other
fied system called the Strength of Recommendation inflammatory disorders such as psoriatic arthritis,
Taxonomy developed by editors of the US family inflammatory bowel disease, and coronary artery
medicine and primary care journals (ie, American disease. It is characterized by scaly, erythematous
FamilyPhysician,FamilyMedicine,JournalofFamily patches,papules,andplaquesthatareoftenpruritic.
828 Menter et al JAMACADDERMATOL
MAY2008
INTRODUCTION within plaques can occur when lesions are present
Psoriasis is a multisystem disease with predomi- over joint lines or on the palms and soles. Psoriatic
nantly skin and joint manifestations affecting ap- plaques typically have a dry, thin, silvery-white or
proximately 2% of the population. Psoriaticarthritis micaceous scale, often modified by regional ana-
is a member of the seronegative spondyloarthropa- tomic differences, and tend to be symmetrically
thies. Other conditions that may be associated with distributed over the body (Fig 1). Approximately
psoriasis, psoriatic arthritis, or both include autoim- 80% of those affected with psoriasis have mild to
munediseasessuchasinflammatoryboweldisease, moderate disease, with 20% having moderate to
components of the metabolic syndrome such as severepsoriasisaffectingmorethan5%ofthebody
diabetes, cardiovascular disease, and lymphoma. surface area (BSA) or affecting crucial body areas
As physicians who care for the large majority of suchasthehands,feet,face,orgenitals.5,6
patients with psoriasis, dermatologists play an im-
portantroleinidentifyingthemorbidityofallaspects Inverse
ofpsoriaticdisease. Inversepsoriasisischaracterizedbylesionsinthe
The major manifestation of psoriasis is chronic skinfolds.Becauseofthemoistnatureoftheseareas,
inflammation of the skin. It is characterized by the lesions tend to be erythematous plaques with
disfiguring, scaling, and erythematous plaques that minimal scale. Common locations include the axil-
may be painful or often severely pruritic and may lary, genital, perineal, intergluteal, and inframam-
cause significant QOL issues. Psoriasis is a chronic maryareas.Flexuralsurfacessuchastheantecubital
disease that waxes and wanes during a patient’s fossaecanexhibitsimilarlesions(Fig1,B).
lifetime,isoftenmodifiedbytreatmentinitiationand
cessationandhasfewspontaneousremissions. Erythrodermic
Erythrodermic psoriasis can develop gradually
from chronic plaque disease or acutely with little
CLASSIFICATION OF PSORIASIS
precedingpsoriasis.Generalizederythemacovering
The phenotyping of psoriasis has traditionally
nearlytheentireBSAwithvaryingdegreesofscaling
beenbasedonhistoricalmorphologicdescriptions.4
isseen(Fig1,E).Alteredthermoregulatoryproper-
Although this phenotyping is very useful for classi-
ties of erythrodermic skin may lead to chills and
fication purposes, clinical findings in individual
hypothermia,andfluidlossmayleadtodehydration.
patients frequently overlap in more than one
Feverandmalaisearecommon.
category.
Pustular
Plaque All forms of psoriasis may contain neutrophils in
Plaquepsoriasisisthemostcommonform,affect- the stratum corneum. When the collections of neu-
ing approximately 80% to 90% of patients. The vast trophilsarelargeenoughtobeapparentclinically,it
majority of all high-quality and regulatory clinical istermed‘‘pustularpsoriasis.’’Pustularpsoriasismay
trials in psoriasis have been conducted on patients be generalized or localized. The acute generalized
withthisformofpsoriasis.Plaquepsoriasismanifests variety (termed the ‘‘von Zumbusch variant’’) is an
as well-defined, sharply demarcated, erythematous uncommon, severe form of psoriasis accompanied
plaques varying in size from 1 cm to several centi- by fever and toxicity and consists of widespread
meters (Figs 1 and 2). These clinical findings are pustuleson an erythematous background (Fig 1, D,
mirrored histologically by psoriasiform epidermal and Fig 2, C). Cutaneous lesions characteristic of
hyperplasia,parakeratosis withintracornealneutro- psoriasisvulgaris may be present before, during, or
phils,hypogranulosis,spongiformpustules,aninfil- after an acute pustular episode. There is also a
trate of neutrophils and lymphocytes in the localized pustular variant of psoriasis involving the
epidermis and dermis, along with an expanded palmsandsoles,withorwithoutevidenceofclassic
dermal papillary vasculature. Patients may have plaque-typedisease.
involvement ranging from only a few plaques to
numerous lesions covering almost the entire body Guttate
surface. The plaques are irregular, round to oval in Guttate psoriasis is characterized by dew-drop-
shape, and most often located on the scalp, trunk, like,1-to10-mm,salmon-pinkpapules,usuallywith
buttocks,andlimbs,withapredilectionforextensor a fine scale. This variant of psoriasis, common in
surfaces such as the elbows and knees. Smaller individualsyoungerthan30years,isfoundprimarily
plaquesorpapulesmaycoalesceintolargerlesions, onthetrunkandtheproximalextremitiesandoccurs
especially on the legs and trunk. Painful fissuring inlessthan2%ofpatientswithpsoriasis.Ahistoryof
JAMACADDERMATOL Menter etal 829
VOLUME58,NUMBER5
Fig 1. Photographs of patients with psoriasis. A, Small plaque psoriasis. B, Localized thick
plaque type psoriasis. C, Large plaque psoriasis. D, Inflammatory localized psoriasis. E,
Erythrodermicpsoriasis.F,Psoriasisandpsoriaticarthritis.
upper respiratory infection with group A beta-he- (Fig3).Upto90%ofpatientswithpsoriaticarthritis
molyticstreptococcioftenprecedesguttatepsoriasis, may have nail changes. Psoriasis of the nails is a
especiallyinyoungerpatients,by2to3weeks.This significanttherapeuticchallenge.
suddenappearanceofpapularlesionsmaybeeither
the first manifestation of psoriasis in a previously
Psoriatic arthritis
unaffected individual or an acute exacerbation of
Psoriatic arthritis is an inflammatory arthropathy
long-standingplaquepsoriasis(Fig2,D).
associated with psoriasis that will be discussed at
lengthinSection2oftheguidelines(Fig1,F).
Nail disease (psoriatic onychodystrophy)
Nail psoriasis can occur in all psoriasis subtypes.
Fingernailsareinvolvedinapproximately50%ofall COMORBIDITIES ASSOCIATED WITH
patients who are psoriatic and toenails in 35% of PSORIASIS
patients.Thesechangesincludepitting,onycholysis, Althoughpsoriasishasbeenpreviouslythoughtto
subungual hyperkeratosis, and the oil-drop sign be a disease solely affecting primarily the skin and
830 Menter et al JAMACADDERMATOL
MAY2008
Fig2. Photographsofpatientswithpsoriasis.A,Thinplaquetypepsoriasis. B,Inversetype
psoriasis.C,Pustulartypepsoriasis.D,Guttatetypepsoriasis.
the joints, our understanding of the comorbidities MEDICAL COMORBIDITIES
that may be associated with this disease has grown Autoimmune diseases
significantly.Recentevidencehasevensuggestedan Some of the comorbidities associated with psori-
increased overall risk of mortality in patients with asishavebeenattributedtosharedorcloselylinked
severepsoriasis.7 genetic susceptibility traits. For example, the
JAMACADDERMATOL Menter etal 831
VOLUME58,NUMBER5
Fig3. Photographsofpatientswithnailpsoriasis.
incidenceofCrohn’sdiseaseandulcerativecolitisis play a role in the promotion of coronary heart
3.8to7.5timesgreaterinpatientswithpsoriasisthan disease. Preliminary studies suggest that therapy of
in the general population.8 Although individual both rheumatoid arthritis and psoriasis with metho-
susceptibility to all 3 of these diseases has been trexate18andrheumatoidarthritiswithtumornecro-
localized to a similar region of chromosome 16, sis factor (TNF) inhibitors19 can decrease the
multipleothergeneticlociarefoundineachcondi- cardiovascularmortality.
tion.9Otherstudiessuggestapossiblelinkbetween
multiple sclerosis (MS) and psoriasis as psoriasis Metabolic syndrome
occurs more commonly in families of patients with The combination of obesity, impaired glucose
MS compared with control subjects.10 Furthermore, regulation, hypertriglyceridemia, reduced high-den-
inthisstudy,familieswithmorethanonecaseofMS sity lipoprotein, and hypertension is known as the
had the highest likelihood of having a family mem- metabolicsyndrome.Patientswiththemetabolicsyn-
berwithpsoriasis,supportingageneticrelationship dromeareatasignificantlyincreasedriskofdevelop-
betweenthesetwodiseases.10 ingcardiovascularmorbidityandmortality.Although
the prevalence ofmetabolic syndromeiselevated in
Cardiovascular disease most westernizedcountries,a recentstudy of hospi-
Thereisanincreasedriskofcardiovasculardisease talized patients demonstrates that the prevalence of
inpatientswithpsoriasis.Severalfactorsarebelieved metabolic syndrome in hospitalized patients with
tocontributetotheincreasedriskforcardiovascular psoriasis is significantly elevated when compared
diseaseinthesepatients.11Patientswithpsoriasisare withhospitalizedpatientswhodonothavepsoriasis.20
morefrequentlyoverweight,haveanincreasedinci-
dence of diabetes, have an increased incidence of Lymphoma, melanoma, and nonmelanoma
hypertension, and have an atherogenic lipoprotein skin cancer
profile at the onset of psoriasis with significantly The question of whether patients with psoriasis
higher very low-density lipoprotein cholesterol areatgreaterriskofdevelopinglymphomathanthe
levels and high-density lipoprotein levels.11-16 general population is an area of ongoing contro-
Epidemiologic analysis of the United Kingdom versy. One study of more than 2700 patients with
General Practice Database, which contains data on psoriasis followed up for nearly 4 years showed an
morethan130,000patientswithpsoriasisaged20to almost 3-fold increased relative risk of developing
90years,hasdeterminedthatpatientswithpsoriasis any type of lymphoma compared with a control
have a higher than normal incidence of myocardial group,afteraccountingforsexandage.21Although
infarction.11 Even after correcting for the heart dis- medications with a known risk of lymphoma had
ease risk factors of smoking, diabetes, obesity, hy- onlybeenusedin1.55%ofpatientsinthisstudy,they
pertension, and hyperlipidemia, the probability of cannot be completely eliminated as a potential
myocardial infarction is higher in patients who are confounding factor. In addition, the patients in this
psoriaticthaninnonaffectedindividuals(therelative studywereallolderthan65years,anditisunknown
risk being particularly elevated in younger patients whether thesefindings would hold trueforayoun-
with more severe psoriasis). Patients with both ger cohort. A more recent retrospective study of
rheumatoidarthritisandsystemiclupuserythemato- 150,000patientsofallageswith psoriasisalsodem-
sus also have an increased incidence of coronary onstrates an increased risk of lymphoma, but sug-
heart disease,17 suggesting that the chronic inflam- geststhattherelativeriskforalllymphomasislower
matory process found in all of these diseases may at 1.34. In this study, there was a significantly
832 Menter et al JAMACADDERMATOL
MAY2008
increased risk of developing cutaneous T-cell lym- maynotreflectthedegreeofemotionalimpactofthe
phoma (relative risk of 10.75), or Hodgkin’s lym- disease, it is important that clinicians consider the
phoma(relativeriskof3.18)inpatientswith severe psychosocialaspectsofthisillness.
psoriasis.22
Although many23 but not all24 studies reveal that BEHAVIORSCONTRIBUTINGTOMEDICAL
theriskofmelanomaandnonmelanomaskincancer AND PSYCHIATRIC COMORBIDITIES
inpatientswith psoriasisisequivalenttothatofthe Smoking
general population, there are subpopulations in In 2004, the prevalence of smoking among US
which there is an increased risk of skin cancer. adults was 21%. Smoking increases the risk of
Caucasian individuals who have received more hypertension, peripheral vascular disease, stroke,
than 250 psoralen plus UVA (PUVA) treatments andmyocardialinfarction.
have a 14-fold higher risk of cutaneous squamous An increased prevalence of smoking among pa-
cell carcinoma than patients who have received tientswithpsoriasishasbeenobservedinnumerous
fewer treatments.25,26 There is also evidence that countries including Finland, Italy, the United
Caucasians with extensive PUVA exposure have an Kingdom,Norway,China,andtheUnitedStates.35-37
increased risk of melanoma, although this is not Data from the Utah Psoriasis Initiative, which in-
universallyacceptedandhasnotbeendemonstrated cluded more than 800 subjects, reveals that 37% of
inthenon-Caucasianpopulation.27,28 patients with psoriasis were smokers versus 13%
smokers in the general population. Among patients
PSYCHIATRIC/PSYCHOLOGIC with psoriasis who smoke, 78% started smoking
COMORBIDITIES beforetheonsetoftheirpsoriasisand22%ofpatients
Depression/suicide startingafteronset.12BoththeItalianstudiesandthe
Psoriasisisassociatedwithlackofself-esteemand NursesHealthStudyIIclearlyestablishsmokingasa
increased prevalence of mood disorders including risk factor for incident psoriasis.36,38 The increased
depression.29 The prevalence of depression in pa- prevalenceofsmokinginpatientswithpsoriasismay
tients with psoriasis may be as high as 60%.30 alsocontributetoanelevationincardiovascularrisk.
Depression may be severe enough that some pa-
tients will contemplate suicide. In one study of 217 Alcohol
patients with psoriasis, almost 10% reported a wish The prevalence of psoriasis is increased among
to be dead and 5% reported active suicidal idea- patients who abuse alcohol.39 However, conflicting
tion.31 Treatments for psoriasis may affect depres- evidence exists as to whether increased alcohol
sion. One study demonstrated that patients with intake in patients with psoriasis is a factor in the
psoriasis treated with etanercept had a significant pathogenesis or whether having a chronic disorder
decreaseintheirdepressionscoreswhencompared such as psoriasis leads to greater intake of alcohol.
withcontrolsubjects.However,clinicallydiagnosed Forexample,onestudyof144patientswithpsoriasis
depression was an exclusionary criterion for entry demonstrated that alcohol consumption in the pre-
into this study.32 Therefore, treatment of psoriasis vious12monthswaslinkedtotheonsetofpsoriasis.
withetanerceptlessenedsymptomsofdepressionin This study suggests that psoriasis may lead to
patients without overt clinical depression.32 sustained alcohol abuse and that alcohol intake
Increasedratesofdepressioninpatientswithpsori- may perpetuate psoriasis.40 In contrast, another
asis may be another factor leading to increased risk studyof55patientsshowednoassociationbetween
of cardiovascular disease. Although there is some alcohol consumption and the onset of psoriasis.41
suggestive evidence that treatment of depression Support of increasing alcohol abuse as a postdiag-
with selective serotonin reuptake inhibitors may nosisconditionwasfoundinacase-controlstudyof
reduce cardiovascular events, conclusive evidence 60 twins discordant for psoriasis. In this study, no
islacking.33 difference in alcohol consumption between discor-
dant twins, either monozygotic or dizygotic, was
Psychologicandemotionalburdenofpsoriasis discovered.42 In summary, alcohol consumption is
Psoriasis can have a substantial psychologic and moreprevalentinpatientswithpsoriasis,anditmay
emotional impact on an individual, which is not alsoincreasetheseverityofpsoriasis.
alwaysrelatedtotheextentofskindisease.Thereare
elevated rates of various psychopathologies among Obesity
patients with psoriasis including poor self-esteem, Obesity has become an epidemic within the
sexualdysfunction,anxiety,depression,andsuicidal United States. A body mass index (BMI) of more
ideation.34 Because the clinical severity of psoriasis than 30 is defined as obese with overweight being
JAMACADDERMATOL Menter etal 833
VOLUME58,NUMBER5
defined as a BMI between 25 and 30. In the United severityofaspecificskindiseasesuchaspsoriasis.53
States, 65% of people older than 20 years are either ThePsoriasisQOL12-item instrumentdiscriminates
overweight or obese. Obesity has serious health among patients with psoriasis and varying degrees
consequences including hypertension, vascular dis- of disease severity and reliably captures clinical
ease,andtype2diabetesmellitus.Psoriasiswasfirst changes from topical or systemic treatments.54-56
associated with obesity in several large, European Psoriasisclinicaltrialentrycriteriahavetraditionally
epidemiologicstudies.StudiesfromtheUnitedStates beenbasedpurelyontheextentandcharacterofthe
alsoshowanelevatedBMIinpatientswithpsoriasis. skinlesions.However,clinicaldecisionmakingmust
These analyses of BMI compared subjects with and incorporate the impact of the skin lesions on pa-
withoutpsoriasiswhilecontrollingforage,sex,and tients’ lives.57,58 This involves assessing both the
race. Analysis of data from the Utah Psoriasis burdenofdiseaseandtheseverityoftheskinlesions.
Initiative revealed that patients with psoriasis had a An instrument incorporating the Psoriasis QOL
significantly higherBMIthan control subjects inthe 12-item instrument with the physician’s rating of
generalUtahpopulation.12TheNursesHealthStudy severity by BSA measurement, the Koo-Menter
II, which contains prospective data from 78,626 Psoriasis Instrument, was designed to help physi-
women followed up during a 14-year period, indi- cians perform a comprehensive and quantitative
cates that obesity and weight gain are strong risk evaluationofpatientswithpsoriasisincludingphys-
factorsforthedevelopmentofpsoriasisinwomen.43 icalseverity,QOLimpact,andarthritisissues,tohelp
Inthisstudy,multiplemeasuresofobesity,including the physician properly characterize all relevant as-
BMI, waist and hip circumference, waist-hip ratio, pectsofdiseaseseverity.57Anothertoolthatattempts
and change in adiposity as assessed by weight gain to capture several relevant aspects of psoriatic dis-
sincetheageof18years,weresubstantialriskfactors ease severity is the Salford index.59 Treatments that
for the development of psoriasis. Multivariate anal- are effective for psoriasis skin lesions also improve
ysisdemonstratedthattherelativeriskofdeveloping patients’ QOL.60-66 The specific characteristics of
psoriasiswashighestinthosewiththehighestBMIs. psoriasis treatments may directly impact patients’
In contrast, a low BMI (\21) was associated with a QOL, requiring treatment to be tailored to the spe-
lower risk of psoriasis, further supporting these cific patient’s situation and preferences.67 The QOL
findings. Furthermore, the average weights of pa- impactofpsoriasismaybelargeeveninpatientswith
tients with psoriasis in the large clinical trials of the small areas of involvement.6,68 For example, psori-
biologicagentshavebeeninthe90-to95-kgrange44-47 asisofthepalmsandsolestendstohavemoreimpact
(although these clinical trials all enrolled more men than far more extensive involvement on the
than women) whereas the average body weight for trunk.69,70Thus,patientswiththesetypesofpsoriasis
the US population from the NHANES database from may be considered candidates for systemic
1999 to 2002 was 86 kg.48 An association between treatment.58,71
psoriasisandelevatedBMIappearstobeyetanother
factor that predisposes individuals with psoriasis to PATHOGENESIS
cardiovasculardisease.49 Psoriasisisacomplexgeneticdiseaseofdysregu-
lated inflammation, although the mechanism of in-
QOL heritancehasnotbeencompletelydefined.Todate,
Psoriasiscausespsychosocialmorbidityanddec- atleast8chromosomallocihavebeenidentifiedfor
rementinoccupationalfunction.50,51Inalargestudy whichstatisticallysignificantevidenceforlinkageto
of more than 300 university-based patients with psoriasishasbeenobserved(theselociareknownas
psoriasis, the physical and mental disability experi- PSORS I-VIII). Detailed genetic mapping studies
encedbypatientswithpsoriasiswascomparableor demonstrate that the HLA-Cw6 allele, also known
inexcessofthatfoundinpatientswithotherchronic as PSORS1, is the major susceptibility gene for
illnessessuchascancer,arthritis,hypertension,heart psoriasis.72 In addition, a number of environmental
disease,diabetes,anddepressionasmeasuredbythe factorsplayanimportantroleinthepathogenesisof
SF-36 Health Survey Form.52 QOL measures are an psoriasis including drugs, skin trauma (Koebner’s
important adjunct to skin lesion assessments to phenomenon),infection,andstress.
properly assess the full effect of an illness such as Evidence suggesting that psoriasis involves
psoriasis that is not life-threatening. Dermatology- immunologic mechanisms includes the efficacy of
specific,butnotpsoriasis-specific,instrumentssuch immunosuppressive drugs such as methotrexate,
as the Dermatology Life Quality Index or SKINDEX cyclosporine (CyA), immune-targeting biologic
areveryusefultoassesstheQOLimpactofpsoriasis, agents, immunotoxins (denileukin diftitox), and
but may have a limited correlation with the actual TNF-blocking biologics in treating psoriasis, and
834 Menter et al JAMACADDERMATOL
MAY2008
exacerbation of psoriasis by certain cytokine thera- withpercentofBSAinvolvementareothercommonly
pies such as interferons alfa, beta, and gamma; used assessment tools for patients, particularly for
interleukin (IL)-2; granulocyte colony-stimulating thosewithmilderdisease.AfterPASI,thePGAisthe
factor; and bacterial superantigens such as strepto- tool most often used to measure psoriasis severity.
coccalantigens.Resolutionofpsoriasisisassociated WhenusingthePGA,theinvestigatorassignsasingle
withdecreasedlesionalinfiltrationofTcells,dermal estimate of the patients overall severity of disease;
dendritic cells, Langerhans cells, and neutrophils, usually a 7-point scale from clear to severe is used.
and decreased expression of TNF-a-, interferon-Y-, Efforts to improve quantitative psoriasis assessment
andIL-12/23-dependentgenes.Inaddition,thereare continue, eg, the Lattice System-PGA, where 1% of
altered levels of chemokines and integrins affecting BSA is approximately equal to the patient’s open
migration of T cells, dermal dendritic cells, macro- handprint(fromwristtotipsoffingers)withfingers
phages, and neutrophils into the plaques. Thus, tuckedtogetherandthethumbtuckedtotheside.74
psoriasis is an immune-mediated organ-specific In clinical practice, the physician generally uses
(skin, and/or joints) inflammatory disease in which subjectivequalitativeassessmentoftheseverityofa
intralesional inflammation primes basal stem kerat- patient’spsoriasisbycombiningobjectiveassessment
inocytes to hyperproliferate and perpetuate the oftheBSAinvolvement,diseaselocation,thickness,
diseaseprocess. and symptoms, presence or absence of psoriatic
arthritis with the subjective assessment of the phys-
EVALUATION OF PSORIASIS TREATMENT ical,financial,andemotionalimpactofthediseaseon
Assessment tools used to evaluate psoriasis thepatient’slife.
Mostlargedouble-blind,placebo-controlledclin-
icaltrialsofpsoriasistreatmentsincludepatientswith
chronicstableplaquepsoriasisbutexcludeotherless GENERAL RECOMMENDATIONS FOR THE
commontypesofpsoriasisincludingthoseinvolving TREATMENT OF PSORIASIS
the palms and soles,scalp,and intertriginousareas. (Points 1-6 will be discussed in detail in future
Similarly,erythrodermicandpustularpsoriasishave sections of the guidelines and point 7 will be
been excluded. These areas of involvement and discussedindetailbelow[Fig4].)
typesofpsoriasisshouldbeconsideredinevaluating 1.Topicaltreatmentsareappropriateforpatients
severityofdiseasebecausetheimpactofthesetypes whoarecandidatesforlocalizedtherapybutmaynot
ofpsoriasismaybequitesubstantial. be practical as monotherapy for most patients who
are candidates for systemic and/or phototherapy,75
The Psoriasis Area and Severity Index where traditional systemic treatments, including
The Psoriasis Area and Severity Index (PASI) is a methotrexate, CyA, narrowband (NB) and broad-
measure of overall psoriasis severity and coverage band UVB, PUVA, oral retinoids, and the newer
that assesses BSA and erythema, induration, and biologicagentsareprescribed.
scaling.73 It is commonly used in clinical trials for 2. UVB is safe, effective, and cost-effective. NB
psoriasis treatments but is rarely used in clinical UVBismoreeffectivethanbroadbandUVB.Upto20
practice. Typically, the PASI score is calculated be- to25NBUVBtreatments,given2to3timesaweek,
fore,during,andafteratreatmenttodeterminehow are usually required for significant improvement.
wellpsoriasisrespondstothetreatmentundertest.A Treatment can be offered in the office or at home;
decreaseinthePASIscoresupportsclaimsofefficacy. home UVB reduces the inconvenience of patients
The vast majority of clinical trials of biologics com- havingtotravelalongdistancefortreatment.Other
parethestudydrugwithaplaceboratherthanother formsofUVexposure,includingsunexposure,may
effectivetreatmentsmakingitdifficulttocomparethe offerbenefitinselectpatients.
efficacy of the various systemic and biologic treat- 3. PUVA therapy is very effective in the majority
mentsforpsoriasis.A75%improvementinthePASI of patients, with potential for long remissions.
score (PASI-75) is predominantly used to document However, long-term PUVA treatment in Caucasians
the effectiveness of individual therapies in clinical isassociatedwithanincreasedriskofsquamouscell
trialsofpatientswithextensivepsoriasis.ThePASIis carcinomaandpossiblymalignantmelanoma.PUVA
considered by the authors to be less sensitive in induces photoaging and other skin changes includ-
patientswithlowerBSAinvolvement(\10%). ing lentigines. Ingestion of psoralen may also pro-
duce nausea. Oral psoralen is contraindicated in
Other measurement tools pregnancy. NB-UVB therapy avoids some of the
Measures such as the Physicians Global adversesideeffectsofPUVA,whilebeingslightlyless
Assessment(PGA)andtargetplaquescores,together effectivethanPUVA.