08/08/2015

1

Psoriasis

Dr Nigel Burrows

Consultant Dermatologist

Addenbrooke’s Hospital

Aug 2015

Overview

1. Epidemiology of psoriasis

2. Histology

3. 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

08/08/2015

2

Psoriasis

Hyperkeratosis, parakeratosis, regular hyperplasia, suprapapillary thinning

Munro intraepidermal

microabscess Hyperkeratosis, parakeratosis

Hyperplasia, squirting papilla

Psoriasis

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

08/08/2015

3

Types of Psoriasis

Psora - to itch

Chronic Plaque Psoriasis

• 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

08/08/2015

4

Other types of Psoriasis

Scalp

- thick plaques or diffuse scaling

(dandruff)

Other types of Psoriasis

Flexural

Other types/sites of psoriasis

Palmar-plantar

Pustular Hyperkeratotic Guttate Psoriasis

Other types/sites of psoriasis

Latin word gutta = drop

08/08/2015

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 (generalised) PP

– widespread pustules on background of

erythroderma

– may coalesce to form large bullae

Erythrodermic Psoriasis

08/08/2015

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):419-24.

• 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

08/08/2015

7

Measuring the severity of

psoriasis

PASI & DLQI scoring

PASI

Scoring

sheet

Dermatology Life

Quality Index (DLQI)

08/08/2015

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

08/08/2015

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

D3 analogues)

08/08/2015

10

Topical treatments

• Vitamin D3 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 (270-350nm)

– Narrow band (TL-01; 311-313nm)

• UVA absorbed by deeper structures-

needs to be given with a topical or oral

photosensitizer (Psoralen + UVA = PUVA)

08/08/2015

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

08/08/2015

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

Anti IL 17

• Secukinumab

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

08/08/2015

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