Practical Psoriasis

Dr Ben CM Lee MB BS MRCP(UK)

Speciality Doctor in Dermatology

Frimley Park Hospital

Content

• Introduction– Epidemiology– Clinical subtypes– Pathophysiology and immunology

• Clinical Assessment– PASI, DQLI, PEST

• Management Options:– Topicals– Common Systemics– Phototherapy– Biologics– Novel treatment

Introduction

• A chronic inflammatory papulosquamous disease affecting 2-4% of the population

• 1/3 have positive family history

• An immune-mediate inflammatory disease

– Multifactorial

• Genetic: determinant of clinical subtype and response to treatment

• HLA-Cw6 associated with early onset and guttate subtype

• Current theories about pathophysiology forms the basis for the research and development of new biologics*

*Nograles, Kristine E., Batya Davidovici, and James G. Krueger. “New Insights in the Immunologic Basis of Psoriasis.” Seminars in cutaneous medicine and surgery 29.1 (2010): 3–9. PMC. Web. 31 July 2016.

pathogenesis

Putting together the psoriasis puzzle: an update on developing targeted therapiesLeanne M. Johnson-Huang, Michelle A. Lowes, James G. KruegerDisease Models and Mechanisms 2012 5: 423-433; doi: 10.1242/dmm.009092

Clinical Features

• Typically (psoriasis vulgaris) symmetrically distributed

• Erythematous, Scaly Plaques

– White silvery scales

• Well defined margins

• Most common sites are scalp, extensive aspects of limbs, umbilicus, sacrum

• Plaques lesions clear up with PIH

Clinical Subtypes

Chronic plaque psoriasis

Post-Streptococcal acute guttatepsoriasis

Small plaque psoriasis

• Often late age of onset

• Plaques <3 cm

• This type of psoriasis often responds well to phototherapy

Flexural psoriasis

Sebopsoriasis

Scalp Psoriasis

Palmoplantar psoriasis

• 3 subtypes:

– Plaque psoriasis localised to palms and soles

– Acquired keratodermic type: patchy or generalised thickening and scaling of palmoplantar surfaces

– Palmoplantar pustulosis

Nail Psoriasis

Aggravating Factors

• Infection: sore throat, etc.

• Injuries and trauma, sunburn (koebner’sphenomenon)

• Obesity

• Smoking

• Excessive alcohol

• Stress

• Abrupt cessation of systemic steroids or high potency topical steroids

Clinical assessment

• Objective assessment of severity

– Psoriasis Area and Severity Index (PASI)

• Validated assessment tools of disablement

– Dermatology Life Quality Index (DLQI)

• Evaluation of health and comorbidities

– BMI, BP, blood glucose/Hba1c

– Lipid profile

– Psoriatic Epidemiology Screening Tool (PEST)

PASI

First Line Treatment

• General Lifestyle advise• Topical Therapy

– Mild, localised cases– Tailor to patients main concerns and lifestyle – compliance an issue!– Emollients– Erythema

• Topical steroid (betnovate)

– Scale• Salicylic acid• Coal tar preparations

– Vitamin D analogue (calcipotriol)– Vitamin D analogue/betnovate combination (Enstilar foam’s efficacy

superior to Dovobet gel/cream)

Systemic Therapy

• Methotrexate

• Ciclosporin

• Acitretin

Methotrexate

• A folic acid derivative• An anti-metabolite cytotoxic agent

– Anti-inflammatoyr at a low dose– Anti-proliferative at high doses (folate antagonist)

• Once weekly administration– Avoid concomitant administration of folic acid (competitive

inhibition)– First week of ‘test dose’ (5-10mg)

• FBC measured at 1 week

– Titrate up to effect by 2.5mg increments/week– Maximum licensed dose in psoriasis is 30mg/wk and low risk of

hepatotoxicity <15mg/wk– Clinical response takes 6-12 weeks.

Methotrexate: monitoring

• Hepatotoxicity is the main concern– Comorbidities such as T2DM, obesity, high alcohol intake, viral

hepatitis compounds the risk– MTX associated liver fibrosis is complex– LFTs do not correlate well with fibrotic liver disease– Liver biopsy as gold standard detection of liver fibrosis/cirrhosis

• PIINP– If available, 3 monthly testing– An immature type of collagen laid down in fibrosis/fibrinolysis– High risk defined at >8.0mg/L pre treatment; >4.2mg/l on at

least 3 occasions during treatment• If moderate risk, Fibroscan® • Liver biopsy a big decision, also take it into context of overall condition

of patient and discuss with Hepatologist.

MTX: contraindications

• Severe haematological abnormality

• Liver and renal dysfunction

• Pregnancy or breastfeeding

• Active peptic ulcer disease

• Active infectious disease

• Immunodeficiency

• Significant reduced lung function

Ciclosporin

• The original calcineurin inhibitor with immunosuppressive actions on T cell activation.

• Rapid onset of action; clinical effect apparent within 6 weeks.• Metabolised by CYP450 and drug interactions (enzyme

inhibitors/inducers) vast– Predominantly eliminated by liver

• Discontinue if inadequate response at 3monthsOnce sufficient improvement is observe dosage to be tapered by 0.5-1mg/kg/d to lowest effective dose.

• Treatment should be limited to 6mths maximum but exceptional cases exist.

• If deranged renal profile >20% reduce dosage by 1mg/kg/day and retesting in 2 weeks

Ciclosporin: contraindications

• Renal/hepatic dysfunction

• Uncontrolled hypertension

• Malignancy

• Active infection

• Concomitant phototherapy

• Immunodeficiency

• Ciclosporin has not been shown to be teratogenicin humans.

Acitretin

• Systemic retinoid – Antiproliferative and anti-inflammatory properties– A receptor binder

• Reduces keratinocyte proliferation and normalises differentiation and cornification

• Immunosuppressive effect on Th17 cells

– Starting dose of 0.5mg/kg once daily– Potential therapeutic use in reducing incidence of

NMSC amongst orggan transplant patients– Acitretin can be combined with PUVA/NB UVB with

superior efficacy (chemopreventive effect against NMSC)

Acetretin: Contraindications

• Pregnancy– Teratogenicity is the principal problem with all system

retinoids; a long half-life and recommended contraception for 3 years after cessation of therapy

– Highly effective contraception must be used and proven effective for 1 month prior to treatment

• Lactation• Uncontrolled severe hyperlipidaemia• Previous hypersensitivities

• Patient should not donate blood during and for 3 years after stopping therap.

Photo(chemo)therapy

• Narrowband UVB (Philips Tl-01)– 311-312nm most beneficial compoent of natural sunlight for psoriasis.– X2-x5 weekly; standing in the centre of cabinet in an upright sunbed – x2

weekly takes 50% longer to clear psoriasis vs x3/wk– More convenient; probably less carcinogenic (Man, et al. BJD 2005)

• Psoralens and UVA photochemotherapy– Used for severe/thicker plaques diseases– 8- or 5-methoxypsoralen may be used– Psoralens are botanical drug with photosensitising properties.– Taken orally or bathed– PUVA may be whole body or localised– Corticosteroids may be used with PUVA– Calcipotriol combined with PUVA results in increased effectiveness and less

radiation exposure – MTX may be combined with PUVA, but increased risk of skin cancer

BAD Guidelines on esculation of Therapy

Biologics

a. Severe disease defined as PASI >10/BSA?10% AND DLQI>10 or exceptional circumstances

b. At least one of:a. Phototherapy and alternative standard systemic

therapy are contraindicated or cannot be usedb. Treatment intolerance to standard systemic

therapyc. Lack or loss of response to standard systemic

therapyd. Have severe, unstable, life-threatening disease

Biologics: Anti TNF

• Etanercept (Enbrel®)– TNF blockers; binds to TNF and disrupts bonding with TNF receptors– s/c injection: 50mg twice weekly 12 weeks, then once weekly

• Adalimumab (Humira®)– Recombinant human monoclonal antibody vs TNF– Efficacy high in psoriatic arthropathy– s/c injection 80mg, then 40mg on the second week, followed by once

every fortnight

• Infliximab (Remicade®, Inflectra™)– Chimeric monoclonal abg vs TNF– Intravenous in specialist centre (over 2 hours); it is repeated after 2

and 6 weeks, 8 weekly thereafter– MTX may be added to prevent anti0infliximab abg

Biologics: IL antagonists

• Ustekinumab (STELARA™)

– Human monoclonal abg vs IL-12 and IL-23; preventing these cytokines from binding and activating T-lymphocytes

– s/c injections on week 1, 4, then 12 weekly

• Secukinumab (Cosentyx™)

– Human monoclonal abg vs IL-17A

– s/c at weeks 0, 1, 2, 3, 4, and 4 weekly thereafter

The Future