Psoriasis

Dr. Lyn Guenther, MD FRCPC

Professor of Dermatology UW O

Medical Director, The Guenther Dermatology Research Centre

Objectives

Very brief Overview today (more in group discussion)

• State the prevalence of Psoriasis

• Briefly discuss the pathogenesis of psoriasis

• Describe the variants of psoriasis

• Give an overview of the treatment of psoriasis

• Discuss the burden of disease/QOL

Psoriasis

• W hen does it onset? – Can onset from birth to 108 years

– 2 peaks • Type I age 20-30 onset, familial

• Type II age 60, not familial

• How common is it? – ~2% of population

– An estimated 1 million Canadians have psoriasis1

1. Guenther L et al. J Cut Med Surg 2004;8:321-37

Psoriasis

WWhat causes it? – Autoimmune with activated T cells

Nonlesional Skin Psoriatic Plaque

– 7-fold increase in transit rate of epidermal cells

Pathogenesis of Psoriasis

DC

IL-23

Cytokines including

IL-17 IL-22

TNF-α

Naïve Naïve T cell T cell

Th17 Th1

DC

IL-12

Cytokines including

IFN-γ TNF-α

IL-2

Inflammation, keratinocyte hyperplasia, neovascularization, vasodilatation, T cell/neutrophil influx

Plaque formation

Shear N, et al. J Cutan Med Surg 2008;2 Suppl 1:S1 Wilson NJ, et al. Nat Immunol 2007;8:950

Psoriasis Vulgaris (Plaque Psoriasis)

• Red, scaly, usually well demarcated plaques

• Elbows, knees, lower back, buttocks and scalp commonly affected

• May be generalized

• May be aggravated/triggered by:

– Beta blockers

– Lithium

– Antimalarials

– ACE inhibitors

• May occur in areas of injury

Guttate Psoriasis

• Many small, drop-like (gouttes) lesions suddenly develop

• Face commonly affected

• Primarily in children and young adults

• Usually associated with Streptococcal infections

Intertriginous (flexural) Psoriasis

• Under folds

• Under breasts

• Groin

• Axillae

• May have minimal scale

Erythrodermic Psoriasis

• Generalized, inflammatory redness and scaling

• Chills, hypothermia

• Edema

• Consider other causes:

– Drug reactions

– Atopic Dermatitis

– Contact Dermatitis

– Infections

Palmar Plantar Pustulosis • 0.05% of population

• Male:female=1:4• 95% are smokers at the onset of the

disease

• Sterile pustules

• May be associated with psoriasis vulgaris – 6-25%

• Difficult to treat – Recalcitrant to current treatments – High recurrence rates

Acropustulosis

•Distal phalynx •Often after trivial injury or infection •Blisters/pustules burst •Red, glazed, scaly, crusty

Generalized Von Zumbusch Pustular Psoriasis

• Unstable, reactive form

• Tender skin with pinpoint pustules

• Flexures and genitalia often affected

• Fever, malaise, ↑W BC

• Acutely ill; may die

Nail changes

Pitting

• In 25-50% of patients

• Often associated with arthritis

• Pits most common

• Onycholysis

• Oil drop changes Onycholysis + Oil drop changes

• Splinter hemorrhages

• Nail plate thickening and crumbling

Psoriatic Arthritis

• In 20-40% of patients

• Usually onsets 10 years after skin

• Single or multiple inflamed joints

• Small joints of hands and feet

– May have flexion deformities

• Back (spondylitis)

• May be mutilating

• Anti-TNFs can prevent radiographic progression

Distal interphalangeal Psoriatic Arthritis • Enthesitis

• Often severe nail changes

Psoriatic arthritis

• Caspar classification (Classification of Psoriatic Arthritis Study Group)

– Inflammatory MSK disease (joint, spine or enthesitis) + 3+ of the following:

• Evidence of psoriasis (Max of 2) (Current (2), history, family history) • Psoriatic nails • Negative RF (N.B. up to 15% with PSA have RF)

• Dactylitis (Current or history) • Radiological evidence of juxta-articular new bone

formation – 98.7% specificity, 91.4% sensitivity

Treatment Approach for Psoriasis

• Amenable to Topical Therapy

• Not amenable to topical therapy

Traditional Psoriasis Treatment Paradigm

• Patients must fail the previous “step” of therapy before initiating a more “aggressive” therapy

Rx Topical Agents • Topical steroids

Phototherapy • UVB broadband • UVB narrowband • PUVA

Systemic Therapy • Cyclosporine • Methotrexate • Acitretin

• Vitamin D analogs • Topical retinoids • Calcineurin

OTC Products • Emollients • Other

inhibitors • Tar

Typical Order of Treatment Progression

Panel Consensus - Integrating biologic agents in the management of moderate-to-severe psoriasis

Biologic agents: First-line therapy for moderate-to-severe psoriasis along with phototherapy & traditional systemic agents

Guenther L et al. J Cutan Med Surg. 8:321-37,2004.

Individual Patient Circumstances

• Failure of previous therapy (lack of efficacy +/- A/E’s)

• Distance from phototherapy and ability to attend

• Contraindication to therapy– Active, severe infections – Liver disease – Ethanol abuse – Hypertension – Renal disease – Hyperlipidemia – History of malignancy – Photosensitivity – Drug interactions – TB – CHF – Demyelinating diseases – Thrombocytopenia, low CD4+ counts

• Need for monitoring

• Availability of refrigeration

• Desire for injections

Generalized Plaque Psoriasis

• 32-year-old farmer

• Generally healthy

• 8-year history of generalizedskin eruption

• Can be quite itchy

– Itching can keep him up at night

• W ife tired of vacuuming up scales

• WW on’t swim

• Barber refuses to cut his hair due to scales and bleeding scalp lesions

Psoriasis has a significant Physical impact

Congestive Heart Failure

Psoriasis

Diabetes

Chronic Lung Disease

MI

Arthritis

Hypertension

Depression

Cancer

0

35

41

42

42

43

43

44

45

45

10 20 30 40 50

Physical Component Summary Score

**Lower scores reflect worse

patient-reported outcomes.

Rapp SR, et al. J Am Acad Dermatol. 1999;41:401-407. Ware JE Jr, et al. SF-36® Health Survey Manual and Interpretation Guide. The Health Institute; 1993.

Psoriasis has a significant Mental impact

Depression

Chronic Lung Disease

Psoriasis

Arthritis

Cancer Congestive

Heart Failure

Diabetes

Hypertension

MI

0 10

35

44

46

49

49

50

52

52

52

20 30 40 50

60

Mental Component Summary Score

**Lower scores reflect worse patient-reported outcomes.

Rapp SR, et al. J Am Acad Dermatol. 1999;41:401-407. Ware JE Jr, et al. SF-36® Health Survey Manual and Interpretation Guide. The Health Institute; 1993.

N A T I O N A L P S O R I A S I S F O U N D A T I O N P A T I E N T S U R V E Y

Emotional Impact of Psoriasis

18- to 34- Year-Old Respondents

Concern That Disease Would Worsen 88%

Feelings of Embarrassment 81%

Feelings of Unattractiveness 75%

Depression 54%

Contemplation of Suicide 10%

0 10 20 30 40 50 60 70 80 90 100

Percentage

Krueger G, et al. Arch Dermatol. 2001;137:280-284.

N A T I O N A L P S O R I A S I S F O U N D A T I O N P A T I E N T S U R V E Y

Social Impact of Severe Psoriasis

Telephone interview of patients with >10% BSA (n=502)

Psoriasis Mistaken as Contagious

Psoriasis Mistaken as Other Disease

Trouble Receiving Equal Treatment in Service Establishments (e.g. hair salons, pools, health clubs)

0 10

57%

48%

40%

20 30 40 50 60 70 80 90 100

Percentage of Respondents

Krueger G, et al. Arch Dermatol. 2001;137:280-284.

Psoriasis impacts patients

• Personal appearance

• Itching

• Anxiety/Depression

• Choice of clothing

• Daily activities

• Leisure activities

• W ork/school

• Personal relationships including intimacy

• Finances

• 5% decreased life span with moderate-to-severe psoriasis1

1, Gelfand JM et al. Arch Dermatol 2007;143:1493-9.

Cardiovascular/Metabolic Co-morbidities in Psoriasis Patients

• CV disease & risk factors increased

– Myocardial infarction (severe psoriasis ~7-

fold)2

– Hypertension (~2-fold)3

– Obesity (~2-fold)3,4 – Diabetes (~1.5-fold)3

5 – Metabolic syndrome (~2-fold) – Increased CV mortality among

inpatients (~1.5-fold)6

1

1. Kimball AB, et al. Dermatology 2008;217:27 2. Gelfand JM, et al. JAMA 2006;296:1735

3. Henseler T, Christophers E. J Am Acad Dermatol 1995;32:982 4. Herron MD, et al. Arch Dermatol 2005;141:1527

5. Sommer DM, et al. Arch Dermatol Res 2006;298:321 6. Mallbris L, et al. Eur J Epidemiol 2004;19:225

Phototherapy

• UVB

• PUVA (Psoralen + UVA) • 2-5 times/wk

• Access problems (# centers, hours)

• Contraindications: – Photosensitivity, LE – Skin cancer – Photodamage

• Adverse events: – Sunburn – Skin cancer – Photoaging

Traditional Systemics

• Methotrexate – Once a week – Hepatotoxicity, GI intolerance, bone marrow toxicity,

pulmonary fibrosis, teratogenic

• Cyclosporine – 2.5-5 mg/kg/day (BID dosing) – Nephrotoxicity, hypertension, tremors, hyperlipidemia – Drug interactions (cytochrome P450)

• Acitretin – Hyperlipidemia – Skeletal changes – Teratogenic (2-3 yrs)

Biologic Agents

• Large, well controlled studies – Good efficacy, safety & tolerability – Few drug interactions (Caution with other immunosuppressants)

– Have a significant impact on QOL in psoriasis – Long-term safety data still pending

• 5 approved Biologics – T cell agents:

• Alefacept (Amevive)

– Anti-TNF agents (also help psoriatic arthritis) • Adalimumab (Humira) • Etanercept (Enbrel) • Infliximab (Remicade)

– Anti-IL-12/23 • Ustekinumab

Guenther L et al. J Cutan Med Surg 2004;321-337

Biologics target key steps in psoriasis

DC

Ale↓acept

Naïve T cell

→

Alefacept ↓

DC

Naïve T cell

← Ustekinumab IL-23

Cytokines including

IL-17 IL-22

Th17 Th1

Ustekinumab IL-12

Cytokines including

IFN-γ TNF-α

TNF-α IL-2

Inflammation, keratinocyte hyperplasia, neovascularization, vasodilatation, T cell/neutrophil influx

Plaque formation

←{Etanercept

Infliximab

Shear N, et al. J Cutan Med Surg 2008;2 Suppl 1:S1 Wilson NJ, et al. Nat Immunol 2007;8:950

Psoriasis responds to Biologics

Baseline 12 weeks