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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 DC Naïve T cell Naïve T cell IL-23 Cytokines including IL-17 IL-22 TNF-α IL-12 Th17 Th1 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 Onycholysis + Oil drop changes • In 25-50% of patients • Often associated with arthritis • Pits most common • 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 Systemic Therapy • Cyclosporine • Methotrexate • Acitretin Phototherapy • UVB broadband • UVB narrowband • PUVA OTC Products • Emollients • Other Rx Topical Agents • Topical steroids • Vitamin D analogs • Topical retinoids • Calcineurin 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 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 Psoriasis has a significant Physical impact Congestive Heart Failure **Lower scores reflect worse 35 Psoriasis patient-reported outcomes 41 Diabetes 42 Chronic Lung Disease 42 MI 43 Arthritis 43 Hypertension 44 Depression 45 Cancer 45 0 10 20 30 40 50 Physical Component Summary Score 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 **Lower scores reflect worse patient-reported outcomes. 35 Chronic Lung Disease 44 Psoriasis 46 Arthritis 49 Cancer 49 Congestive Heart Failure 50 Diabetes 52 Hypertension 52 MI 52 0 10 20 30 40 50 Mental Component Summary Score 60 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. NAT I O NAL PS O R IAS I S F O U N DAT I O N PAT I E N T S U R V EY 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. NAT I O NAL PS O R IAS I S F O U N DAT I O N PAT I E N T S U R V EY Social Impact of Severe Psoriasis Telephone interview of patients with >10% BSA (n=502) Psoriasis Mistaken as Contagious 57% Psoriasis Mistaken as Other Disease Trouble Receiving Equal Treatment in Service Establishments 48% 40% (e.g. hair salons, pools, health clubs) 0 10 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 1 Diabetes (~1.5-fold)3 – Metabolic syndrome (~2-fold) 5 – Increased CV mortality among inpatients (~1.5-fold)6 – 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 • Adalimumab (Humira) • Etanercept (Enbrel) • Infliximab (Remicade) help psoriatic arthritis) – Anti-IL-12/23 • Ustekinumab Guenther L et al. J Cutan Med Surg 2004;321-337 Biologics target key steps in psoriasis Alefacept ↓ Ale↓acept DC DC Naïve T cell Naïve T cell Ustekinumab → IL-23 Cytokines including IL-17 IL-22 TNF-α IL-12 Th17 Th1 ←Ustekinumab Cytokines including IFN-γ TNF-α ← IL-2 { Etanercept Infliximab 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 responds to Biologics Baseline 12 weeks