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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
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