Psoriasis. Overview. Epidemiology. Epidemiology 08/08/2015. Dr Nigel Burrows Consultant Dermatologist Addenbrooke s Hospital

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1 Overview Psoriasis 1. Epidemiology of psoriasis 2. Histology Dr Nigel Burrows Consultant Dermatologist Addenbrooke s Hospital Aug Types of psoriasis 4. Assessing severity 5. Treatments Topical Systemic Epidemiology 2% of population M=F Peak onset 20s-30s (Type I) 75% Positive Family Hx Severe disease Later peak in 50s (Type II) 25% Family Hx rare Mild, localized disease Epidemiology Population, family and twin studies point to genetic component Common in Caucasians, rare in Japanese Various chromosomal loci eg PSORS 1, 2,3 Association with HLA antigens e.g. B13, B17 HLA Cw6 in 80% of type I psoriasis, 50% of type II Possession of Cw6 13x risk of having psoriasis HLA antigens regulate T cell function 1

2 Psoriasis Psoriasis Hyperkeratosis, parakeratosis, regular hyperplasia, suprapapillary thinning Hyperkeratosis, parakeratosis Hyperplasia, squirting papilla Munro intraepidermal microabscess Psoriasis Spongiform pustule Psoriasiform dermatitis histological differential diagnosis Psoriasis Chronic dermatitis/lichen simplex chronicus Drug reactions Superficial fungal infections Pityriasis rosea (herald patch) Pityriasis rubra pilaris Chronic superficial dermatitis Syphilis Scabies Reiter s syndrome Necrolytic migratory erythema (glucagonoma syndrome) Clinicopathological correlation 2

3 Chronic Plaque Psoriasis Types of Psoriasis Psora - to itch Commonest type of psoriasis 85% of all cases Onset before 35 yrs Symmetrically distributed thickened plaques on extensor aspects of limbs, trunk Chronic Plaque Psoriasis Other sites Hair line Sacrum Umbilicus Köebner Phenomenon 3

4 Other types of Psoriasis Scalp - thick plaques or diffuse scaling (dandruff) Flexural Other types of Psoriasis Other types/sites of psoriasis Palmar-plantar Pustular Hyperkeratotic Other types/sites of psoriasis Guttate Psoriasis Latin word gutta = drop 4

5 Guttate Psoriasis 2% of patients with psoriasis Younger patients (< 30yrs, usually children) 60% precipitated by infection (usually URTI due to Streptococci) Rapid onset (~1 week) of drop-like lesions on trunk Pustular Psoriasis Localised PP multiple pustules on localised erythema palms and soles (Palmar-Plantar pustulosis) association with smoking Pustular Psoriasis Erythrodermic Psoriasis Erythrodermic (generalised) PP widespread pustules on background of erythroderma may coalesce to form large bullae 5

6 Erythrodermic Psoriasis Entire body surface involved Fever, leucocytosis Impaired thermoregulation, cardiac problems Precipitants: infection, inappropriate steroid use, sunburn, phototherapy Needs admission Nail involvement in Psoriasis Pitting small, discrete depressions in nail surface Onycholysis separation of distal nail from nail bed white / yellow discoloration of distal nail Subungual hyperkeratosis - Crusting under free edge of nail Joint involvement in psoriasis 30% of psoriasis patients have arthralgia but only 10% have true psoriatic arthritis 65% skin precedes joints 5 patterns DIPJ + associated nail changes Symmetrical polyarthritis very similar to RA Arthritis mutilans ( pencil in cup deformity on XR) Asymmetrical oligoarthritis Psoriatic spondylarthropathy (like Ankylosing Spondylitis with sacroiliitis) Metabolic syndrome Combination of obesity, hypertension, dyslipidaemia and insulin resistance 40% among psoriasis cases and 23% among controls. - Love TJ et al Arch Dermatol 2011 Apr;147(4): Higher prevalence of psoriasis amongst obese patients than the general population. Thought to be due to the chronic inflammation associated with metabolic syndrome central obesity is associated with: abnormal levels of various inflammatory markers, including TNF-alpha and interleukin 6 6

7 Measuring the severity of psoriasis PASI & DLQI scoring PASI Scoring sheet Dermatology Life Quality Index (DLQI) 7

8 Psoriasis and Quality of Life Psoriasis has severe impact on QOL Similar impact to IHD, DM and COPD Depression and alcoholism more common in patients with psoriasis General principles of treatment Emphasise treatment NOT cure Remissions and relapses Lifestyle changes alcohol smoking Stress Avoid precipitating medications Corticosteroids (potent topical or oral) Beta blockers Lithium Antimalarials (e.g. chloroquine) General principles of treatment Which aspects of psoriasis affect patient? Which treatments are acceptable / feasible? Explain how treatments should be applied and for how long Warn about side effects Consider concurrent medical problems / medications Be aware of poor adherence 40% are estimated to be non-adherent >30% stop using treatment due to: - time consuming applications - lack of efficacy - unpleasant 8

9 Psoriasis - treatments Cat faeces Onion, sea salt and urine Goose oil and semen Wasp droppings in sycamore milk Topical arsenic Razoxane All these treatments have fallen out of favour (Wikipaedia) Topical treatments Regular emollients moisturise skin improve penetration of other treatments relieve itch Keratolytic agents e.g. salicylic acid reduce scale Often combined with other preparations (e.g. Diprosalic = Salicylic acid + Steroid) Topical treatments Topical corticosteroids anti-inflammatory / immunomodulatory rapid control of disease loss of efficacy with long-term use (tachyphylaxis) avoid by intermittent use Risk of rebound or pustular flare on withdrawal Topical treatments Topical corticosteroids contd. potent preparations on trunk milder preparations on face / flexural sites may be combined with other preparations (e.g. salicylic acid (keratolytic), propylene glycol (improves tissue penetration), vitamin D 3 analogues) 9

10 Topical treatments Vitamin D 3 analogues inhibit keratinocyte proliferation enhance normal keratinization inhibit inflammatory cells (e.g. lymphocytes) e.g. calcipotriol (Dovonex ) sting / irritate skin (cannot used if psoriasis very inflamed) slower onset of action compared to corticosteroids (faster if used in combination) Topical treatments Coal Tar coal tar distillate dilute in white soft paraffin (1-5%) suppresses DNA synthesis and therefore reduces epidermal hyperproliferation unpleasant smell, stains skin and clothing theoretical oncogenic potential Topical treatments Dithranol used for over 80 years but less popular now usually combination with steroids or photo therapy (Ingram s regimen) inhibits DNA synthesis, reduces epidermal hyperproliferation Irritant (esp to normal perilesional skin) may stain skin and clothing Phototherapy UVB absorbed by epidermis- most useful Broad band ( nm) Narrow band (TL-01; nm) UVA absorbed by deeper structuresneeds to be given with a topical or oral photosensitizer (Psoralen + UVA = PUVA) 10

11 Phototherapy Multiple trips to hospital (2 per week for PUVA, 3 per week for narrow band UVB) Treatment course for up to 10 weeks Generally well-tolerated Psoralens can cause nausea Premature skin ageing & increased risk of skin cancer - contraindicated in patients with history or skin cancer or photosensitivity (e.g. lupus) Systemic treatments Used when: poor response to topical treatment or phototherapy large area of skin involved psoriasis is severe and inflammatory (e.g. erythrodermic) associated joint symptoms Systemic treatments Methotrexate antimetabolite: blocks action of dihydrofolate reductase, leading to reduced cell turnover Once weekly dosing Highly toxic in overdose- needs careful monitoring with FBC, LFT Side effects: nausea (prevent with folic acid) neutropenia, liver toxicity, lung fibrosis (commoner in RA patients), teratogenicity Interacts with trimethoprim (antifolate) neutropenia and overwhelming sepsis Systemic treatments Retinoids Acitretin (metabolite of etretinate) can be combined with UVA or UVB Side effects: teratogenic, dryness of skin, eyes & lips, hypercholesterolaemia 11

12 Systemic treatments Ciclosporin Anti - T cell often used in pulsed fashion (e.g. for 3 months) rapid clearance of psoriasis (including inflammatory forms) Side effects: nephrotoxicity, hypertension, gum hypertrophy, hypertrichosis, increased skin cancer risk in patients who have received PUVA treatment Systemic treatments Hydroxycarbamide Mycophenolate mofetil (MMF) Azathioprine Biological therapies inhibit T cell function Anti-TNF agents Etanercept: Human recombinant TNF receptor fusion protein (binds soluble and membrane-bound TNF) Infliximab: Human murine chimeric monclonal antibody to TNF-α Adalimumab: fully human monoclonal Anti IL12/23 Ustekinumab Biological therapies Side effects: influenza-like symptoms, heart failure, TB reactivation, (demyelination) Very expensive! Patient must have failed treatment with systemic agents and have PASI > 10 and DLQI > 10 Anti IL 17 Secukinumab 12

13 Summary Psoriasis is common (2%) Many different patterns and may look different at different body sites Chronic condition Effective treatments are available but need to tailor to patient s needs 13