Psoriasis Pathophysiology

Localized and systemic inflammation

Increased antigen presentation
Defects in T regulatory cells
Upregulation of Th1 and Th17 cells,
APCs, and cytokines
Associated with increased CRP values and
other markers of inflammation
Epidermal hyperproliferation
Clinically appreciated as scaling, cracking
Associated with elevated uric acid and
oxidative stress
Angiogenesis
Clinically appreciated as Auspitz sign
Associated with increased circulating VEGF

Th = T helper; APCs = antigen-presenting cell; CRP = C-reactive

protein; VEGF = vascular endothelial growth factor.
Top photo courtesy of Joel Gelfand, MD, Department of Dermatology, University of
Pennsylvania. Bottom photo courtesy of Rose Elenitsas, MD, Department of
Dermatology, University of Pennsylvania.

Plaque Psoriasis

Most common type

80%-90% of psoriasis patients
Plaques:
10 mm to several cm
Well-defined
Erythematous
Irregular, round to oval in shape
Most often located on the scalp,
trunk, buttocks, and limbs,
(especially elbows and knees)
Have a dry, thin, silvery white or
micaceous scale
Tend to be symmetrically
distributed over the body

Bottom right photo by Dr Joel Gelfand, used with permission.

Other photos by National Psoriasis Foundation.
Menter A, et al. J Am Acad Dermatol. 2008;58:826-850.

Psoriasis Risk Factors

Genetics:
~40% of people with psoriasis have a positive family history for
the disease1
At least 9 chromosomal loci are linked to psoriasis
(PSORS1-PSORS9)2
PSORS1 accounts for 35%-50% of heritability of psoriasis2
Environmental and behavioral triggers:
Smoking3
Obesity4
Medications (eg, lithium, antimalarials, -blockers)5
Infection (streptococcal infection can trigger guttate psoriasis)5

1. Swanbeck G, et al. Br J Dermatol. 1994;131:32-39. 2. Nestle FO, et al. N Engl J Med.

2009;361:496-509. 3. Naldi L, et al. J Invest Dermatol. 2005;125:61-67. 4. Setty AR, et al.
Arch Intern Med. 2007;167:1670-1675. 5. National Psoriasis Foundation.
http://www.psoriasis.org/netcommunity/sublearn01_pscauses. Accessed August 27, 2009.

Guttate Psoriasis

Characterized by dew droplike, 1- to

10-mm salmon-pink papules, usually with
a fine scale
Common in those younger than 30 years
Primarily found on trunk and proximal
extremities
Occurs in <2% of patients with psoriasis
Often associated with upper respiratory
streptococcal infection
Sudden appearance of lesions may be
first manifestation of psoriasis or an
acute exacerbation in patients with
established psoriasis

Photo by National Psoriasis Foundation.

Menter A, et al. J Am Acad Dermatol. 2008;58:826-850.

Psoriasis Assessment
Tools in Clinical Practice
Clinicians generally assess psoriasis severity (mild,
moderate, or severe) by combining assessments of:
BSA involvement, disease location, thickness,
symptoms, presence/absence of PsA,
presence/absence of nail involvement
Impact on QOL (ie, physical, financial, and emotional
impact of the disease)
QOL measures may be generic (eg, SF-36 Health
Survey Form) or skin-specific (eg, Dermatology Life
Quality Index [SKINDEX])

Menter A, et al. J Am Acad Dermatol. 2008;58:826-850.

Differential Diagnosis of Psoriasis

Other inflammatory skin disorders

Atopic dermatitis, eczema,
localized scratch dermatitis
(lichen simplex chronicus),
nummular dermatitis
Lichen planus
Pityriasis rosea
Pityriasis rubra pilaris
Seborrheic dermatitis
Stasis dermatitis
Autoimmune disorders
Dermatomyositis
Subacute cutaneous lupus
erythematosus

Infections
Candidiasis
Onychomycosis
Scabies
Syphilis
Tinea corporis
Cancers
Basal cell carcinoma
Mycosis fungoides
Squamous cell carcinoma
Other
Contact dermatitis
Drug eruptions
Reiter disease

http://www.mdguidelines.com/psoriasis/differential-diagnosis. Accessed August 31, 2009.

Psoriasis and CVD Risk

Presence of CVD Risk Factors in
Psoriasis Patients and Controls
40
35

Percent

30

Controls
Mild psoriasis
Severe psoriasis

25
20
15
10
5
0
DM

Hypertension Hyperlipidemia

DM = diabetes mellitus.
Neimann AL, et al. J Am Acad Dermatol. 2006;55:829-835.

Smoking

BMI 25-30

BMI >30

Psoriasis and Increased

Risks for MI and Mortality
Patients with severe psoriasis have a 50% increased risk of mortality1
Die 3.5-4.4 years younger than patients without psoriasis
Psoriasis patients have an increased risk for MI2
Risk increases with increasing disease severity
Relative risk of MI in psoriasis patients, adjusted for major CV risk factorsa

Age, y

Mild Psoriasis

Severe Psoriasis

30

1.29

3.10

60

1.08

1.36

Results suggest that psoriasis may confer an independent risk for MI.

Hypertension, diabetes, history of MI, hyperlipidemia, age, sex, smoking, and BMI.
1. Gelfand JM, et al. Arch Dermatol. 2007;143:1493-1499. 2. Gelfand JM, et al. JAMA.
2006;296:1735-1741.

Psoriasis Comorbidities
Autoimmune diseases
Crohns disease/ulcerative colitis1
Multiple sclerosis2
Malignancies3
Lymphoma
Cutaneous T-cell lymphoma
NonHodgkins lymphoma
Hodgkins lymphoma
1

Najarian DJ, Gottlieb AB. J Am Acad Dermatol. 2003;48:805-821. 2Broadley SA, et al. Brain.
2000;123:1102-1111. 3. Gelfand JM, et al. J Invest Dermatol. 2006;126:2194-2201.

Psoriasis Comorbidities
PsA
Inflammatory arthritis associated with psoriasis
Occurs in 6%-40% of patients with psoriasis,
depending on population studied1
Prevalence increases with increasing BSA
affected2
Typically develops 7-10 years after onset of
psoriasis, at an average age of 36 years1
May be progressive, severe, deforming
10

1. Kimball AB, et al. J Am Acad Dermatol. 2008;58:1031-1042. 2. Gelfand JM, et al. J Am

Acad Dermatol. 2005;53:573-577.

PsA: Clinical Features

Stiffness, pain, swelling,
tenderness of joints,
ligaments, and tendons
Nail disease is common
Dactylitis (sausage digit)
is common; usually affects
feet in an asymmetric
distribution

11

Photos by Dr Joel Gelfand, used with permission.

Gottlieb A, et al. J Am Acad Dermatol. 2008;58:851-864.

Prevalence of Associated Diseases in

Severe Psoriasis Patients vs Controls

12

Condition

Psoriasis (n=581)

Control (n=1044)

Odds Ratioa (95%

Confidence Interval)

Type 2 diabetes

11.7%

5.8%

2.48 (1.70-3.61)b

Hypertension (arterial)

21.9%

10.2%

3.27 (2.41-4.43)b

Hyperlipoproteinemia

5.2%

2.8%

2.09 (1.23-3.54)c

Metabolic syndrome

4.3%

1.1%

5.92 (2.78-12.8)b

Coronary heart disease

5.5%

3.6%

1.77 (1.07-2.93)d

Common odds ratio adjusted for age and sex. bP <.0001. cP <.01. dP <.05.
Sommer DM, et al. Arch Dermatol Res. 2006;298:321-328.

Natural History of
Psoriasis and Comorbidities

Risk factors

Outcomes

Genes
Environment

Mediating factors
Pathophysiology (inflammation,
hyperproliferation, angiogenesis)
Treatment
Psychosocial impact
13

Photo by Dr Joel Gelfand, used with permission.

Cancer
Vascular disease
Metabolic disease
Arthritis
Mortality

Recommendations for Monitoring

Psoriasis and Comorbidities
NPF Consensus Statement1
Approach psoriasis as a
potentially multisystem
disorder
Alert patients to the
potentially negative effects
of psoriasis as it relates to
other aspects of their health

14

AJC Editors Consensus:

Medical Evaluation of
Moderate-to-Severe
Psoriasis2
Medical history of CAD risk
Annual physical examination
and blood pressure check
Blood lipids and glucose
measurements

AJC = The American Journal of Cardiology; CAD = coronary artery disease.

1. Kimball AB, et al. J Am Acad Dermatol. 2008;58:1031-1042. 2.
Friedewald VE, et al. Am J Cardiol. 2008;102:1631-1643.

General Recommendations
for Topical Therapy
Most mild to moderate psoriasis can be treated with topical agents
May require continuous intense regimen
Patient adherence is important
Treatment should be tailored to individuals needs
Body location, lesion thickness, degree of erythema, amount of
scaling, patient preferences
May be used in combination with other agents; must be aware of
possible compatibility issues
Potent agents should be used short-term, then intermittently
Patients who require continuous treatment should use the leastpotent agent that allows for disease control

15

Menter A, et al. J Am Acad Dermatol. 2009;60:643-659.

General Recommendations
for Topical Therapy
Choice of vehicle (eg, ointment, cream, gel, foam) may
alter use, penetration, and efficacy of the medication
Optimal choice is vehicle the patient will most likely use
Patients should receive regular examinations to assess
side effects
Approximately 400 g of a topical agent is required to cover
the entire body surface of an average adult when used
twice daily for 1 week
60-g tube = about 4% BSA per month

16

Menter A, et al. J Am Acad Dermatol. 2009;60:643-659.

Topical Therapy: Corticosteroids and

Vitamin D Analogs
Corticosteroids
Cornerstone of treatment for most patients
Lower potency agents for face, intertriginous areas, areas
with thin skin
Mid-high potency agents for initial therapy
Class I corticosteroids: 2-4 weeks of use
Taper usage following clinical response
Side effects (eg, stretch marks, atrophy) may limit use
Vitamin D analogs (eg, calcipotriene, calcitriol)
Most useful as a steroid-sparing adjuvant
Not to exceed 100 g/wk (risk of hypercalcemia)
17

Menter A, et al. J Am Acad Dermatol. 2009;60:643-659.

Topical Therapy: Topical Retinoids

and Calcineurin Inhibitors
Topical retinoids (tazarotene)
Most useful as a steroid-sparing adjuvant
Teratogenic/pregnancy category X
Calcineurin inhibitors (tacrolimus, pimecrolimus)
Useful for facial and intertriginous psoriasis
Black box warning regarding malignancy
Not FDA approved for psoriasis

18

Menter A, et al. J Am Acad Dermatol. 2009;60:643-659.

General Recommendations
for Phototherapy

19

UVB
Safe, effective, cost-effective
Narrowband UVB
More effective than broadband UVB
20 to 25 treatments, given 2 to 3 times a week, usually required for significant
improvement
Administered in the office or at home
PUVA
Very effective for most patients
Potential for long remissions
Long-term treatment in Caucasians is associated with an increased risk of skin
cancers
Induces photoaging and other skin changes
Ingestion of psoralen may produce nausea/contraindicated in pregnancy
Narrowband UVB therapy avoids some of the adverse side effects of PUVA, but slightly
less effective than PUVA

Menter A, et al. J Am Acad Dermatol. 2008;58:826-850.

Conventional Systemic Therapies:

Dosing and Efficacy

20

Methotrexate
Most commonly prescribed systemic therapy
Usually administered as a single weekly oral dose of 7.5 mg to 25 mg
Gradually increased until optimal response is achieved
PASI-75 achieved in 36%-60% of patients after 16 weeks
Recommended for treatment of moderate or severe PsA
Cyclosporine
Use is limited to 1 year
Generally prescribed for patients with severe psoriasis who have not responded to 1 other
systemic therapy
Dosing is given as 2.5 mg/kg to 5.0 mg/kg per day in 2 divided doses
Dose is decreased when psoriasis is cleared
PASI-75 achieved in 50%-70% of patients after 8-16 weeks
Recommended for treatment of moderate or severe PsA
Acitretin
Often used in conjunction with UV light
Dosing ranges from 10 mg to 50 mg per day as single dose
Generally takes 3-6 months for response
Efficacy is dose-dependent

Menter A, et al. J Am Acad Dermatol. 2009;61:451-485. Ritchlin CT, et al. Ann Rheum Dis.
2009;68:1387-1394.

Biologic Agents for the

Treatment of Psoriasis
Biologic

Structure

Target

Dosing

Half-Life, d

Adalimumab

Human monoclonal
antibody

Soluble and
membrane-bound
TNF-

80 mg SC,
followed by 40 mg
SC every other wk

10-20

Alefacept

Human IgG1 Fc region

fused to LFA-3
extracellular domain

LFA-3

15 mg IM weekly
for 12 weeks

11.25 (IV)

Etanercept

Human IgG1 Fc region

fused to TNF type II
receptor

Soluble TNF-,
lymphotoxin

50 mg SC BIW for
12 wk, then 50 mg
SC each wk

4-12.5

Infliximab

Chimeric monoclonal
antibody

Soluble and
membrane-bound
TNF-

5 mg/kg IV at wk
0, 2, 6, then every
8 wk

8-9

Ustekinumab

Human monoclonal
antibody

IL-12 and IL-23

45 or 90 mg SC at
wk 0 and 4, then
once every 12 wk

15-46

SC = subcutaneously; BIW = biweekly; IV = intravenously; LFA-3 = leukocyte functionassociated antigen-3; IM = intramuscularly.

21

Kurd SK, et al. Expert Rev Clin Immunol. 2007;3:171-185.

Stelara [package insert]. Horsham, PA: Centocor Ortho Biotech Inc.; 2009.

Psoriasis: Nail Involvement

May occur in all psoriasis subtypes
Fingernails are involved in ~50% of patients
Toenails are involved in ~35% of patients
Includes pitting, onycholysis, subungual hyperkeratosis, the oil drop sign,
and nail plate dystrophy
Difficult to treat

Onycholysis
22

Pitting

Right photo by Dr Joel Gelfand, used with permission. All other photos by DermAtlas.
Menter A, et al. J Am Acad Dermatol. 2008;58:826-850.

Nail plate dystrophy

Psoriasis: Impact on QOL vs Other Major

Morbidities
QOL outcome was SF-36 physical and mental health domains
Mental Functioning

Physical Functioning

Depression

Congestive heart failure

Lung disease

Psoriasis

Psoriasis

Type 2 diabetes

Arthritis

Lung disease

Congestive heart failure

MI

MI

Arthritis

Type 2 diabetes

Depression

Healthy adults

Healthy adults

20

40

SF-36 = short form 36.

23

Rapp SR, et al. J Am Acad Dermatol. 1999;41:401-407.

60

20

40

60

2008 NPF Survey:

Psoriasis Impact on QOL
71% report that psoriasis is a significant problem
in everyday life
49% have significant pain
53% report that psoriasis significantly affects their
emotional well-being
63% experience significantly self-consciousness
58% experience significant embarrassment

24

National Psoriasis Foundation. Available at:

http://www.psoriasis.org/NetCommunity/Document.Doc?id=193. Accessed August 25, 2009.

Limitations of Conventional
Systemic Therapies

25

Agent

Adverse Event

Contraindications

Methotrexate

Hepatotoxicity, drug interactions,

immunosuppression, bone marrow
suppression, pneumonitis, birth defects,
decreased sperm count, miscarriage

Pregnancy, renal
impairment, hepatitis,
cirrhosis, leukemia,
thrombocytopenia,
alcohol abuse,
unreliability in patients

Cyclosporine

Immunosuppression, impaired renal

function, hypertension, malignancies, drug
interactions

Acute infections, active

malignancies,
uncontrolled
hypertension, impaired
renal function

Acitretin

Birth defects, mucocutaneous effects,

dyslipidemia

Pregnancy, breastfeeding

Menter A, et al. J Am Acad Dermatol. 2008;58:826-850. Menter A, et al. J Am Acad

Dermatol. 2009;61:451-485.

Biologic Agents: Adverse Events

Biologic

Common (>5%)

Uncommon (0.1%-5%)

Rare (<0.1%)

Black Box

Adalimumab

Injection site
reaction, +ANA,
elevated alkaline
phosphatase,
cholesterol

Neutralizing antibodies,
serious infections

TB, malignancy
Lupus-like syndrome,
hypersensitivity, hepatitis B
reactivation, demyelination,
CHF, pancytopenia

Infection (TB, sepsis,

fungal, and
opportunistic)

Alefacept

Lymphopenia

Elevated liver function test

values, serious infection

Malignancy,
hypersensitivity

None

Etanercept

Injection site
reaction, +ANA

Serious infection

TB, malignancy
Lupus-like syndrome,
hypersensitivity, hepatitis B
reactivation, demyelination,
CHF, pancytopenia

Infection (TB, sepsis,

fungal, and
opportunistic)

Infliximab

Infusion reactions,
+ANA, elevated
liver function test
values,
neutralizing
antibodies

Hypersensitivity, serious
infection

Severe hepatic injury, TB,

malignancy, lupus like
syndrome, hypersensitivity,
hepatitis B reactivation,
demyelination, CHF,
pancytopenia

Infection (TB, sepsis,

fungal, and
opportunistic),
hepatosplenic T-cell
lymphoma

Ustekinumab

Nasopharyngitis

Upper respiratory tract

infection, headache,
fatigue.

Cellulitis, injection site

reactions

None

Information obtained from prescribing information December 2008.

26 +ANA = positive antinuclear antibody;

General Recommendations
for Biologic Therapy
Obtain at baseline: age-appropriate history, physical
examination, updated medication list, baseline laboratory studies
Chemistry screen with liver function tests, complete blood cell
count including platelet count, hepatitis panel, and TB testing
Periodically re-evaluate for development of new symptoms
including infection and malignancy
Use all approaches to prevent infection, including vaccinations
Administer vaccinations prior to initiating biologic therapy
Biologic therapies may impair the immunologic response to
vaccinations
Administration of live vaccines must be avoided
27

Menter A, et al. J Am Acad Dermatol. 2008;58:826-850.