Phenotypes and Classification of Psoriasis

Rheumatology 2010

Birmingham 21 April 2010

Phenotypes and Classification of

Psoriasis

Declaration of Interests

1808

Translational Medicine

Psoriasis Phenotypes

Psoriasis

 Common, 2-3% population UK

 75% onset < 40 yrs

 Peaks of onset 16-22 yrs and 55-60 yrs

 Male = female  Gene/environment interaction  Triggers: Streptococcal infection Stress Drugs

Chronic Plaque Psoriasis

 Red, scaling symmetrical plaques

 Elbows, knees , scalp & sacrum

 Plaque (90% of cases)

 Guttate

 Sebo-psoriasis

 Flexural

 Acrodermatitis Continua of Hallopeau

 Generalised Pustular

 Erythrodermic

What is the natural history of psoriasis?

What is the natural history of psoriasis?

40% patients with guttate develop chronic plaque

Koebner Phenomenon Marker of disease activity

Acrodermatitis Continua of

Hallopeau

Genetics of Psoriasis

Psors

1

Psors

2

Psors

3

Psors

4

Psors

5

Psors

6

Psors

7

6p

17q

4q

1q

3q

19p

1p

2q

6q

8q

16q

20p

Genetics of Psoriasis

Psors

1

Psors

2

Psors

3

Psors

4

Psors

5

Psors

6

Psors

7

6p

17q

4q

1q

3q

19p

1p

2q

6q

8q

16q

20p

Genome-Wide Association Study

Genome-Wide Association Study

Genome-Wide Association Study

Palmo-Plantar Pustulosis

Not Psoriasis

No Association with HLA Cw6

25% have chronic plaque psoriasis Onset 40+ y

9 Female : 1 Male

HLA-Cw6-Positive and HLA-Cw6-Negative

Patients have Differing Phenotypes

Gudjonsson et al J Invest Dermatol 2002; 118:362-5

HLA Cw6 Negative associated with: • Arthritis

• Nail dystrophy • Later age of onset

Late-onset Psoriasis is NOT

Associated with PSORS1

 Patients with onset > 50 yrs of age

 Unlike early onset psoriasis there is no link to HLA-Cw6, Corneodesmosin or HCR

Late-onset Psoriasis is NOT

Associated with PSORS1

 Patients with onset > 50 yrs of age

 Unlike early onset psoriasis there is no link to HLA-Cw6, Corneodesmosin or HCR

Allen et al J Invest Dermatol 2005; 124:103 Are Early and Late-Onset Psoriasis Separate Diseases?

Human Epidermal Langerhans’ Cells

TNF and IL-1β induce LC

2 4 6 8 10 12 14 16 LC/ m m 2 (x 1 0 -2 ) DPC ac DPC (27.5) 2 4 6 8 10 12 14 16 TNF-α sal TNF-α (23.2) 2 4 6 8 10 12 14 16 IL-1β sal IL-1β (21.8) NORMAL 2 4 6 8 10 12 14 16 LC/ m m 2 (x 1 0 -2 ) DPC ac DPC (5.2) 2 4 6 8 10 12 14 16 IL-1β sal IL-1β (0.4) 2 4 6 8 10 12 14 16 TNF-α sal TNF-α (1.5) PSORIASIS

LCs in Early Onset Psoriasis : No Response to Cytokine Stimuli

Late-onset psoriasis: LC migration to IL-1

β

is normal

NORMAL LATE ONSET

2 4 6 8 10 12 14 16 LC/ m m 2 (x 1 0 -2 ) sal IL-1β Mean decrease 25.4% (+/-7.6) 2 4 6 8 10 12 14 16 LC/ m m 2 (x 1 0 -2 ) sal IL-1β Mean decrease 28.7% (+/-4.2) LC/ m m 2 (x 1 0 -2 ) 1.6% decrease 2 4 6 8 10 12 14 16 sal IL-1β EARLY ONSET

“

Drug therapies are replacing

a lot of medicines as we

used to know it ”

What do biologics tell us about

psoriasis?

Patient with severe disease and where standard therapy cannot be used or continued

PASI >10

Dermatology Life Quality Index (DLQI > 10 Patient with severe disease

and where standard therapy cannot be used or continued

IL-23 is associated with psoriasis and drives epidermal hyperplasia in

mice

Ustekinumab Anti-IL12/IL23 Responses at 12

Weeks are Superior to Etanercept

*p=0.012 for superiority vs. etanercept; **p<0.001 for superiority vs. etanercept; ***p<0.001 vs. etanercept

100 80 40 20 Pa ti en ts (%) 60 0 Number of injections: 24 2 2 Etanercept (n=347) Ustekinumab 45 mg (n=209) Ustekinumab 90 mg (n=347) 57 68* 74** PASI 75 Etanercept (n=347) Ustekinumab 45 mg (n=209) Ustekinumab 90 mg (n=347) 23 36*** 45*** PASI 90 24 2 2

New-Onset Psoriasis in Patients with RA

Receiving Anti-TNF

Harrison et al Ann Rheum Dis 2008

9826 anti-TNF; 2880 DMARDs BSR Registry Manchester

25 incident cases of new psoriasis; and 9 flares of psoriasis in anti-TNF group; none in DMARDs

IR 1.04 anti-TNF; 0 DMARDs

Adalimumab sig high rate compared to Etanercept (4.6) and Infliximab (3.5)

New-Onset Psoriasis in Patients with RA

Receiving Anti-TNF

Harrison et al Ann Rheum Dis 2008

9826 anti-TNF; 2880 DMARDs BSR Registry Manchester

25 incident cases of new psoriasis; and 9 flares of psoriasis in anti-TNF group; none in DMARDs

IR 1.04 anti-TNF; 0 DMARDs

Adalimumab sig high rate compared to

Etanercept (4.6) and Infliximab (3.5) TNF down-regulates IFNα

T-cell targeted therapies

 Alefacept and Efalizumab – 25% response

 Is this due to polymorphisms in LFA or are these

Genetics of Psoriasis

Psors

1

Psors

2

Psors

3

Psors

4

Psors

5

Psors

6

Psors

7

6p

17q

4q

1q

3q

19p

1p

2q

6q

8q

16q

20p

Phenotypes

Large Plaque

Phenotypes of Plaque Psoriasis

Phenotypes of Plaque Psoriasis

Br J Dermatol 2007;156:258

In future may classify according to molecular

Plaque Psoriasis and other forms

Psychosocial burden

•Reactive Depression

•Higher suicidal ideation

•Alcoholism

 Metabolic Syndrome:

• Arterial Hypertension

• Dyslipidaemia

• Insulin resistent Diabetes

• Obesity ⇒ higher CVD risk Nail psoriasis 40-50% Ocular inflammation (Iritis/Uveitis/ Episcleritis) Crohn‘s Disease Ulcerative Colitis

Comorbidities in Psoriasis Patients

Psoriatic Arthritis 7-30%

Summary

 Different forms of psoriasis: clinical observational research

 Genotypes

 Biologics provide insights

 Severity incorporates physical & psychosocial measures

 Need to ascertain determinants of CVD risk