1. Psoriasis Dr. Lyn Guenther, MD FRCPC Professor of Dermatology UW O Medical Director, The Guenther Dermatology Research Centre

2. 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

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

4. Psoriasis WWhat causes it? – Autoimmune with activated T cells Nonlesional SkinPsoriatic Plaque – 7-fold increase in transit rate of epidermal cells

5. Pathogenesis of Psoriasis DC IL-23 Cytokines including IL-17 IL-22 TNF-α Naïve 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

6. 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

7. Guttate Psoriasis Many small, drop-like (gouttes) lesions suddenly develop Face commonly affected Primarily in children and young adults Usually associated with Streptococcal infections

8. Intertriginous (flexural) Psoriasis Under folds Under breasts Groin Axillae May have minimal scale

9. Erythrodermic Psoriasis Generalized, inflammatory redness and scaling Chills, hypothermia Edema Consider other causes: – Drug reactions – Atopic Dermatitis – Contact Dermatitis – Infections

10. 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

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

12. 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

13. 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

14. 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

15. 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

16. Treatment Approach for Psoriasis Amenable to Topical Therapy Not amenable to topical therapy

17. 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

18. 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.

19. 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

20. Generalized Plaque Psoriasis 32-year-old farmer Generally healthy 8-year history of generalized skin 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

21. Psoriasis has a significant Physical impact Congestive Heart Failure Psoriasis Diabetes Chronic Lung Disease MI Arthritis Hypertension Depression Cancer 0 35 41 42 43 44 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.

22. Psoriasis has a significant Mental impact Depression Chronic Lung Disease Psoriasis Arthritis Cancer Congestive Heart Failure Diabetes Hypertension MI 010 35 44 46 49 50 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.

23. 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% 0102030405060708090100 Percentage Krueger G, et al. Arch Dermatol. 2001;137:280-284.

24. 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.

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

26. 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

27. 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

28. 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)

29. 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

30. 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

31. Psoriasis responds to Biologics Baseline12 weeks