Psoriasis -cb

Psoriasis

Christopher Betts (PGY I)

What is Psoriasis?

• Papulosquamous proliferative skin condition that is generally chronic and inflammatory in nature and often associated with systemic manifestations.

• Characterized as erythematous scaly papules and plaques with additional involvement of the nails and joints; pustular and erythrodermic eruptions can occur.

• Contributed w/ trauma (Koebner’s phenomenon)

Psoriasis: Epidemiology

• Affects about 2-3% of US adults • Prevalence ranges from 0.1% to 3% in various

populations• Prevalence equal in males and females• Onset commonly around the ages 15-30, but

also can occur at any age

Psoriasis: Risk factors & Etiology• Immune-mediated disease with genetic predisposition

– Approximately 1/3rd of pts w/ psoriasis have a first-degree relative w/ psoriasis

• Many stressful physiologic and psychological events and environmental factors a/w onset and worsening of the condition

• Lesions tend to develop in areas of trauma (Koebner's phenomena)• Strep throat infection is an example of a trigger and exacerbating

factor• HIV infection (more seen as an exacerbating factor)• Other risk factors, but not shown to be clearly causative, include

smoking, obesity, and alcohol use

Psoriasis: Clinical presentation• Holds much weight in diagnosis, but skin bx is definitive• Typically as a erythematous, scaly patch or plaque which can be

itchy or painful• A scale in psoriasis is typically white and thin and when removed,

leaves pinpoint foci of bleeding (Auspitz sign). • The plaques and micaceous scales are easily recognizable in light-

skinned pts but to a lesser degree in dark-skinned pts and more difficult to discern.

• 90% of patients present with well-defined round or oval plaques that differ in size and often coalesce and situated over the extensor surfaces of extremities, scalp, buttocks, and trunk (plaque psoriasis).

Psoriasis: Non-cutaneous involvement

• Psoriatic onchodystrophy seen in 80-90% of patients w/ psoriasis over the lifetime (fingernails > toenails) – Pitting (most common), – Subungual hyperkeratosis (abnl keratinization of

the distal nail bed; accumulation of scales under distal nail plate)

– Onycholysis (separation of nail from its bed).

onycholysis

pitting

Subungual keratosis

Psoriasis: Clinical presentation

Guttate psoriasis• More common in patients younger than 30 yo• Truncal distribution• Comprises 2% of psoriasis cases• 1- to 10-mm pink papules w/ fine scaling• Can present several weeks after a Grp A beta-

hemolytic strep URI.

Psoriasis: Atypical presentations

• Inverse psoriasis: less scaly; occurs in skin folds and flexor surfaces; distribution includes perineal, inframammary, axillary, inguinal, and intergluteal areas; contributed by heat, trauma, and infection

Psoriasis: Atypical presentations

• Erythrodermic psoriasis: widespread and generalized erythema and associated w/ systemic symptoms; may be slow and incidious in chronic psoriasis or eruptive and abrupt in pts w/ mild psoriasis.

Psoriasis: Atypical presentations

• Pustular psoriasis: pustules over palms and soles w/o plaque formation.

Psoriatic arthritis

• Prevalence ranges from 6-42% of pts w/ psoriasis; male to female ratio 1:1

• Seronegative inflammatory arthritis w/ various clinical presentations

• On average, develops 12 yrs after the onset of skin symptoms.

Classification Criteria for Psoriatic ArthritisSpecificity of 98.7% and sensitivity of 91.4%

Psoriasis: Comorbid conditions• Association based on either pathophysiology, shared risk factors, or adverse

effects from treatments• Significant social morbidity• One survey conducted on patients w/ diagnosed psoriasis, 79% of them

thought that the disease negatively affected their lives by causing problems w/ work, activities of daily living, and socialization.

• Social isolation may contribute to incr risk of medical conditions that are mediated and prevented by exercise and lifestyle modifying practices.

• Incr disease severity a/w lower income, higher number of consultations w/ multiple physicians, and reduced satisfaction w/ treatment.

• Younger and female patients are most affected by psoriasis.• One survey found that more than one half of patients w/ severe psoriasis

thought physicians could do more to help, and 78% reported frustration w/ the effectiveness of treatment.

Psoriasis: Comorbid conditions

Psoriasis: Management

Psoriasis: Management – overview

• Treatment goals include improvement of skin, nail, and joint lesions plus enhanced quality of life.

• Based on level of severity – in this case amt of BSA covered

• … and how systemic the condition is– Skin only vs. Skin + joint +/- other extra-dermal sites

• Major modalities of Tx: topical, phototherapy, systemic/biologic agents

• Management of compound co-morbidities (previous slide)

Psoriasis: Management – overview

• Severity: Mild/moderate or Severe

– Mild/Moderate is <5% BSA affected• Genitals, hands, feet, face usually spared

– Severe is 5% or greater of BSA affected

Psoriasis: Management – overview

• If Mild/Moderate, is the patient needing prn therapy or continuous therapy?– PRN/intermittent therapy: • Topical corticosteroids, • Vitamin D analogs, • Tazarotene (Tazorac) (SORT A)

– Continuous therapy: Calcineurin inhibitors• Tacrolimus, Pimecrolimus

Psoriasis: Management – overview

• If Severe, is the BSA affected greater or less than 20%?– <20% BSA affected calls for Vitamin D analogs w/

phototherapy– >20% BSA affected calls for more systemic therapy

w/ phototherapy (SORT A)• Systemic tx: Methotrexate, Acitretin, Cyclosporine

– Any arthritic involvement calls for biologic therapy (not necessarily the same as systemic tx)• Adalimumab, Infliximab, Etanercept (SORT A)

Psoriasis: Topical Tx’s in general• Ointment vs. cream vs. gel vs. lotion?? • Level of penetration: Lotion, gel < cream < ointment• The choice of formulation depends on area to cover, examples:

– Lotion for scalp– Cream for moist weeping lesions– Ointment for dry, lichenified, scaly lesions

• Emollients are ointments or thick creams that are used to reduce scaling and irritation.

• Ointment emollient example is Aquaphore• Thick cream emollient examples include Cerave, Nivea, Eucerin• Overall, individualized and based on a personal preference, level of

compliance, and dermatologic factors like skin type and plaque thickness.• Twice daily application

Psoriasis: Topical Corticosteroids

• These, combined with emollients, are the most common and effective treatment to limited plaque psoriasis.

• Anti-inflammatory, ant proliferative, and immunosuppressive effects

• Twice daily application• The greater the potency the greater the improvement

in symptoms, based on systematic reviews• Common localized adverse effects are poor wound

healing, skin atropy, and irritation.

Psoriasis: Topical Corticosteroids• Extended use of high potency steroids, although topical, can bring

about systemic effects similar to those from oral steroid use.• Children have a high ratio of BSA to weight, hence are most

vulnerable to adverse effects of steroid use in general. • Once symptoms improve, recommend to taper.• Tachyphylaxis of topical steroids is not uncommon and is either

related to genuine tolerance to long-term treatment or low adherence.

• Expense: a 60 g tube can be as high as $80. Foam and spray forms are new-type of formulations for better adherence but are also expensive. Generic forms available are shown below.

Psoriasis: Topical Corticosteroids• US-graded potency scale ranges

– Grade I (most potent) to VII (least potent)• Some are the same name in different classes but varied in

potency based on formulations – Betamethasone: ointment (I) > cream (II) > lotion (III)

• The more sensitive or thinner the skin (i.e. face, intertrigous areas) the lower the potency called for (grades VI-VII)

• The thicker and angrier the lesion in areas of thicker skin (i.e. extremities) the higher the potency called for (grades I-III)

• Can be used in sequence for tapering effect.

Psoriasis: Topical CorticosteroidsMost commonly used ones for psoriatic plaques

– Hydrocortisone topical 2.5% (VII)– Triamcinolone topical 0.025% and 0.1% (IV and VI)– Fluocinonide topical 0.05% (II to III)– Halobetasol topical 0.05% (I)– Betamethasone Diproprionate topical 0.05% - Grade I to V

Three-dollar list ones: – Betamethasone diproprionate 0.05% cream (I,II), – Betamethasone valerate 0.01% cream (V) and ointment (III), – Fluocinolone soln 0.01% (VI), – Fluocinonide cream 0.05% (II), – Hydrocortisone cream 1% and 2.5% (VI, VII), – Triamcinolone cream 0.025% (VI), 0.1% (IV), 0.5% (III), – Triamcinolone 0.1% ointment (III)

Psoriasis: Topical Vitamin D analogs

• Hypoproliferative effect on keratinocytes; questionable immunomodulating effect; inactivated by UVA light

• Monotherapy < combination therapy either w/ phototherapy or topical steroid; combined emollient use also common

• Slower onset of action (6-8 wks) but longer disease-free interval than topical steroids

• Adverse effects: hypercalcemia, PTH suppression– High risk: pts w/ supratherapeutic doses and those w/ renal

insufficiency

Psoriasis: Topical Vitamin D analogs

• Calcipotriene (Dovonex) 0.005% ($)– Twice a day application; generic form as well– Available in all types of formulations

• Calcitriol (Vectical) – 3 mcg/g ($$)– Only in ointment form; originally was available only in Europe;

demonstrated in one systematic review study to have less skin irritative effects compared to calcipotriene

– One 52-wk open labeled study in 2009 demonstrated less hypercalcemic adverse effects

• Both are well tolerated agents; safe for pediatric use; both are expensive

Psoriasis: Topical Vitamin D analogs

• Combination Vit D + topical steroids available but very expensive– Calcipotriene + Betamethasone diproprionate

0.064% (Talconex) = $400 for 60g tube

Psoriasis: Tazarotene• Chemically related to Vitamin A; regulate epithelial growth• Topical retinoid 0.1% and 0.05%: cream, foam, gel (pediatric use)• Two RVCT double-blind study (Amer J of Derm, 2003) of 1303 pts w/

psoriasis using 0.1% and 0.05% creams qd for 12 weeks: – Significant reductions in severity of clinical signs of psoriasis– Therapeutic effect maintained during post-treatment period

(unspecified duration)– 0.1% cream w/ more skin irritative effects than 0.05% cream

• As effective as potent topical corticosteroids in alleviating symptoms of psoriasis and a/w longer disease-free intervals

• Approved for psoriasis in patients older than 18 yo and tx of acne in pts > 12 yo

Psoriasis: Tazarotene

• Adverse effect: perilesional itching and burning (common); teratogenic

• Regimen of alternating days w/ topical corticosteroid and moisturizers

• One multicentre, non-controlled study in 2006 studying short-term tazarotene therapy in 43 pts w/ psoriasis vulgaris– Results showed that short-term treatment (20 min of

application followed by washing) was just as effective as traditional treatment

Psoriasis: Calcineurin inhibitors• Tacrolimus > Pimecrolimus• From two RCTs in 2004: Effective in facial and intertriginous

psoriasis• Approved for use in patients > 2 yo • FDA approved?: Mainly approved for therapy for mod-severe

atopic dermatitis.• A considered alternative to chronic topical steroid use over

sensitive areas• Improve symptoms w/ less skin atrophy than topical

corticosteroids• Boxed warning: skin malignancy and lymphoma (FDA report 2005)

Psoriasis: Calcineurin inhibitors

• In 2004, 8 wk double-blind RVCT study of 167 pts >16 yo with intertriginous and facial psoriasis applying twice a day 0.1% tacrolimus ointment; results showed more patients achieving clearance of lesions or excellent improvement compared to placebo (65% to 32%)

• Second study in 2004, RVCT of 57 pts w/ mod-to-severe inverse psoriasis for 8 weeks of bid usage pimecrolimus: 1% cream is an effective tx for inverse psoriasis w/ rapid onset of action, safe, well-tolerated

Psoriasis: Phototherapy

• Mainly for refractory and/or severe psoriasis

Psoriasis: Systemic therapiesMethotrexate• MTX used for patients of severe psoriasis (BSA >5%)• used to treat psoriatic disease for >50 yrs• Administered weeklyCyclosporine• Rapid alleviation of symptoms• multiple adverse effects and drug interactions preclude long-term

use• often used for suppressing crises and as bridge therapy during

initiation of slower-onset maintanence therapies.• Both MTX and cyclosporine are not approved for treating severe

psoriasis in children

Psoriasis: Systemic therapies

Acitretin• Oral retinoid w/ slow onset of effect (up to 6

mo)• teratogenic, causes mucocutaneous lesions,

hyperlipidemia, and elevated LFTs• more effective when combined w/

phototherapy.

Psoriasis: Biologic therapy• Increasingly used in treating moderate-to-severe psoriasis

and in psoriatic arthritis• Tumor necrosis factor inhibitors (Humira, Enbrel, Remicade)• Etanercept (Enbrel) commonly combined w/ MTX for

effective use.• Infliximab (Remicade) reported in clinical trials to have the

most rapid and sustained response• Risk of infection: Usage of any TNF inhibitor contrainidcates

for live vaccine usage and calls for a baseline PPD tuberculin skin test.

Psoriasis: Management

Psoriasis: Management

Questions and critics welcomed…

Resources:• AAFP article: Psoriasis (May 2013)• http://www.psoriasis.org/• http://www.guideline.gov/content.aspx?id=12

505• Medscape Reference, Up To Date, Epocrates

online