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PSORIASISDR CHIA KOK KINGPEGAWAI PERUBATAN & KESIHATANGRED U44KLINIK KESIHATAN KUAH, LANGKAWI

PSORIASIS Chronic skin disorder Psora = itch Also termed psoriasis vulgaris T-cell mediated inflammatory disease

Accelerated epidermal turnover with hyperproliferation 2O to activation of immune system

Altered maturation of epidermal keratinocytes InflammationVascular changes

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DERMIS

STRATUMBASALE

STRATUM SPINOSUM

STRATUM GRANULOSUM

STRATUMCORNEUM

Proliferation

Immaturity

Neutrophilaccumulation

Disorganized

NORMAL

PSORIASIS

PREVALENCE Psoriasis occurs in 2% of the world’s population Highest in Caucasians (Scandinavian/European

descent) In Africans, African Americans and Asians between

0.4% and 0.7% Equal frequency in males and females May occur at any age from infancy to the 10th

decade of life First signs of psoriasis

Females mean age of 27 yearsMales mean age of 29 years

PREVALENCE Two Peaks of Occurrence

One at 20-30 yearsOne at 50-60 years

Psoriasis in childrenLow – between 0.5 and 1.1% in children 16

years old and youngerMean age of onset - between 8 and 12.5 years

PREVALENCE Two-thirds of patients have mild disease One-third have moderate to severe disease Early onset (prior to age 15)

Associated with more severe diseaseMore likely to have a positive family history

Life-long disease Remitting and relapsing unpredictably Spontaneous remissions of up to 5 years have been

reported in approximately 5% of patients

PSORIASIS, AN INHERITED DISEASE

If you have psoriasis, what is the risk to:

Your unrelated neighbor? About 2% Your sibling? 15-20% Your identical twin? 65-70% Your child? 25%

PSORIASIS: ASSOCIATED FACTORS

Genetic Factors:- 30% of people with psoriasis have had psoriasis in family- Autosomal dominant inheritance

Nongenetic Factors:- Mechanical, ultraviolet, chemical injury- Infections: Strep, viral, HIV- Prescription drugs, stress, endocrine, hormonal, obesity, alcohol, smoking

WHY MIGHT PSORIASIS BE A SYSTEMIC INFLAMMATORY DISEASE?

1. Immune abnormalities are profound

2. Psoriasis severity is associated with greater levels of systemic inflammation (e.g. CRP, Th-1 cytokines)

3. Inflammation may be a common pathway to a variety of diseases including atherosclerosis, obesity, and insulin resistance Krueger JG, Bowcock, A.

Ann Rheum Dis 2005;64:30-36.

PSORIASIS AS A SYSTEMIC DISEASE

Koebner Phenomenon Elevated ESR Increased uric acid levels → gout Mild anemia Elevated α2-macroglobulin Elevated IgA levels Increased quantities of Immune Complexes Psoriatic arthropathy Aggravation of psoriasis by systemic factors

Medication Focal infections Stress

Life-threatening forms of psoriasis

ESR / CRP IN PSORIASIS

Although psoriatic arthritis sometimes causes an increased erythrocyte sedimentation rate (ESR), mild anemia, and elevated blood uric acid levels, these symptoms are also associated with other rheumatic diseases, including gout

ESR and CRP can be normal in psoriatic arthritis

Increasing PASI was linked to increasing CRP and a trend to higher elastase and lactoferrin. CRP levels were shown to correlate with PASI, total leucocytes, neutrophils, elastase, lactoferrin and α1-antitrypsin.

Psoriatic arthritis, CP Rajendran, SG Ledge, Kanaka P Rani, Radha Madhavan JAPI • VOL. 51 • NOVEMBER 2003

Journal of the European Academy of Dermatology & Venereology , 24(7):789-796

NATURAL HISTORY OF PSORIASIS

Disease severity85% Mild, 10% Moderate, 5% severe

Control of severe disease50% of patients intensively treated continue to have very

active disease (PUVA cohort)75% of patients with severe disease are not receiving

appropriate therapies (NPF survey) Pathways affected and possible outcomes

Inflammatory atherosclerosis, thrombosisAngiogenesis endothelial (endothelial

progenitor cells)dysfunction

Metabolic oxidative stress

PSORIASIS

PARADIGM OF THE NATURAL HISTORY OF PSORIASIS AND CO-MORBIDITIES

Risk factors•Genes•Environment

Outcomes• Cancer• Cardiovascular disease

• Metabolic disease

• Arthritis• Mortality

Mediating Factors• Pathophysiology

(inflammation,hyper-proliferation, angiogenesis)

• Treatment • Psychosocial impact

PSORIASIS IS ASSOCIATED WITH CARDIOVASCULAR RISK FACTORS

• Smoking• Obesity• Dyslipidemia• Hypertension• Diabetes

Neiman AN, Porter S, and Gelfand JM. Expert Review of Derm. 2006;1:63-75

PSORIASIS: A RISK FACTOR FOR CAD AND MI?

Psoriasis CAD MI

SmokingHTNDM

ObesityLipids

Psoriasis is independently associated with carotid atherosclerotic disease and impaired endothelial function

Balci DD et al, Increased carotid artery intima-media thickness and impaired endothelial function in psoriasis JEADV ISSN 1468-3083

In patients with Psoriatic arthritis, psoriasis severity is an independent predictor of cardiovascular disease

Gladman, DD et al. Cardiovascular morbidity in psoriatic arthritis. Ann Rheum Dis 2008.094839

CLINICAL PRESENTATION

Sharply demarcated ERYTHEMATOUS plaque with silvery white scales typically on extensor surfaces

Symmetric Pruritic/ Painful Pitting Nails Inflammatory arthropathy in 10-20% of patients, which in

severe cases may be the dominant cause of morbidity Histopathology

Thickening of the epidermisTortuous and dilated blood vessels Inflammatory infiltrate primarily of lymphocytes

Type Characteristics Plaque psoriasis Guttate psoriasis Erythrodermic psoriasis Flexural psoriasis Pustular psoriasis Nail psoriasis Palmar/Plantar psoriasis Psoriatic arthritis Scalp psoriasis

Dry scaling patches (AKA common psoriasis) 75% Drop-like dots, occurs after strep or viral infection 12% Exfoliation of fine scales (total body “dandruff”), widespread, often accompanied by severe itching and pain 7% Smooth, dry, red inflamed, lack of scales, appear on skin folds (underarm, buttocks, groin, breasts) Pus-like blisters, noninfectious, fluid contains white blood cells 2% Seen on toenails and fingernails, starts as numerous pits, at times progresses to yellowing, crumbly, and thickened nail; nails may slough Erythema, thickening and peeling of the skin, blistering is often present. Can lead to disability. Inflammation, swelling, and joint destruction Plaque-type lesion

PLAQUE PSORIASIS AKA psoriasis vulgaris is the most common form of

psoriasis. It affects 80 to 90% of people with psoriasis. Typically appears as raised areas of inflamed skin

covered with silvery white scaly skin (plaques)

Plaques may be as large as 20 cm Symmetrical disease Sites of predilection

ElbowsKneesPresacrumScalpHands and Feet

PSORIATIC PLAQUE

SYMPTOMS OF PLAQUE PSORIASIS

Pruritus Pain Excessive heat loss Patient Complaints

Unsightliness of the lesionsLow self-esteemFeelings of being socially outcastExcessive scale

May be widespread – up to 90% BSA Genitalia involved in up to 30% of patients Most patients have nail changes

Nail pitting“Oil Spots”Involvement of the entire nail bed

OnychodystrophyLoss of nail plate

Plaque Psoriasis

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Guttate Psoriasis

GUTTATE PSORIASIS Characterized by numerous 0.5 to 1.5 cm small oval

(tear drop shaped) papules and plaques Appear over large areas of the body, such as the

trunk, limbs, and scalp. Early age of onset Most common form in children Streptococcal throat infection often a trigger and

rashes develop 1-2 weeks following infection Spontaneous remissions in children Often chronic in adults

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Guttate Psoriasis

AKA inverse psoriasis appears as smooth

inflamed patches of skin.

Occurs in skin folds, particularly around

the genitals (between the thigh and groin),

the armpits, under an overweight stomach

(pannus), and under the breasts

(inframammary fold).

It is aggravated by friction and sweat, and

is vulnerable to fungal infections.

Flexural psoriasis

appears as raised bumps that are filled with non-infectious pus (pustules).

skin under and surrounding pustules is red and tender.

can be localised, commonly to the hands and feet , or generalised with widespread patches occurring randomly on any part of the body.

May cause long lasting disability include palmoplantar chronic pustular psoriasis (palmoplantar pustulosis), acrodermatitis continua of Hallopeau (acropustulosis)

Pustular psoriasis

Changes in the appearance of finger and toe nails including discolouring under the nail plate, pitting of the nails, lines going across the nails, thickening of the skin under the nail, and the loosening (onycholysis) and crumbling of the nail.

Nail psoriasis

Psoriatic arthritis involves joint and connective tissue inflammation.

Psoriatic arthritis can affect any joint but is most common in the joints of the fingers and toes.

This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis.

Psoriatic arthritis can also affect the hips, knees and spine (spondylitis).

About 10-15% of people who have psoriasis also have psoriatic arthritis.

Psoriatic arthritis

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1. Generalized Pustular Psoriasis

2. Erythrodermic Psoriasis

May be complicated by high-output cardiac failure, temperature dysregulation, and septicaemia, particularly in elderly patients.

Life–Threatening Forms of Psoriasis

GENERALIZED PUSTULAR PSORIASIS

Unusual manifestation of psoriasis Can have a gradual or an acute onset Characterized by waves of pustules on

erythematous skin often after short episodes of fever of 39˚ to 40˚C

Weight loss Muscle Weakness Hypocalcemia Leukocytosis Elevated ESR

Cause is obscure Triggering Factors

InfectionPregnancyLithiumHypocalcemia secondary to hypoalbuminemiaIrritant contact dermatitisWithdrawal of glucocorticosteroids, primarily

systemic

GENERALIZED PUSTULAR PSORIASIS

ERYTHRODERMIC PSORIASIS

Classic lesion is lost Entire skin surface becomes markedly

erythematous with desquamative scaling. It may be accompanied by severe itching,

swelling and pain. Often only clues to underlying psoriasis are

the nail changes and usually facial sparing

Triggering FactorsSystemic InfectionWithdrawal of high potency topical or oral steroidsWithdrawal of MethotrexatePhototoxicity Irritant contact dermatitis

Often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic treatment.

This form of psoriasis can be fatal, as the extreme inflammation and exfoliation disrupt the body's ability to regulate temperature and for the skin to perform barrier functions.

ERYTHRODERMIC PSORIASIS

NAIL CHANGES

In 78% of psoriatic patients Fingernails>Toenails Four changes

1. Onycholysis (= separation from nail bed)2. Pitting*3. Subungual debris accumulation4. Color alterations

*Pitting rules out a fungal infection

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PSORIATIC ARTHRITIS In 10-20% of psoriasis patients Often seen in patients with nail and

scalp psoriasis Peripheral interphalangeal joints No elevated serum levels of

rheumatoid factors (as seen in rheumatoid arthritis, yet has all other features)

Diagnosis: 1. Based on the appearance of the skin.

2. There are no special blood tests or diagnostic procedures.

3. A skin biopsy (or scraping) may be needed to rule out other disorders and to confirm the diagnosis.

4. When the plaques are scraped, one can see pinpoint bleeding from the skin below (Auspitz's sign)

27/03/2011University of Jordan/Faculty of Pharmacy

SEVERITY OF DISEASE

Three Cardinal Signs of Psoriatic Lesions Plaque elevation Erythema Scale

Body Surface Area

The Psoriasis Area Severity Index (PASI):

- The most widely used measurement tool for psoriasis.

- Combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease).

http://www.pasitraining.com/pasi_score/

http://pasi.corti.li/

Severity:

- Mild

- Moderate

- Severe

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MANAGEMENT

DISCUSS WITH PATIENT Explanation/no cure Treatment options (including none) Patient’s expectation

WHEN TO REFER?1. Diagnostic difficulty

2. Education

3. Failed Topical

4. >30% skin surface

5. Increasing steroids

6. Pustular/erythrodermic

7. Systemic therapy

THE MAJORITY OF MODERATE-SEVERE PSORIASIS PATIENTS ARE

UNDER-TREATED 50% of patients with moderate or worse disease

are currently untreated46% have topical therapy only

Reason dermatologists do not use

more aggressive therapiesSafety concernsTime consuming Cost

1 Leonardi, 2003; 2 Market Measures/Cozint LLP, June 2003.

Othertherapies

54%

Topicalsonly

46%

TARGETING DUAL DISEASE PROCESSES

1. Ryan S. Br J Nurs 2010;19:822-5

Two key disease processes underlie psoriasis1

Cell proliferation

AIM:

Prevent the infiltration of inflammatory cells into the

epidermis

AIM:

Reduced cell turnover time and

reduce scale

Inflammation

THREE STEP MANAGEMENT

Step 1- Topical1

•First step of treatment for mild-to-moderate plaque psoriasis

•Calcipotriol + betamethasone dipropionate combination (Dovobet®) is recommended first-line therapy by the PCDS for most patients

Step 2 – Second line1

•Patients with moderate-severe psoriasis at onset or patients with inadequate response to topicals

•Phototherapy or oral agents i.e. methotrexate, acitretin, ciclosporin

Step 3 – Biologics1

•Etanercept, infliximab, adalimumab, ustekinumab

•If 2nd-line treatments ineffective or not tolerated – as per NICE guidance

1. Adapted from Primary Care Dermatology Society (PCDS) 2010. Available from www.pcds.org.uk (Last accessed 24 January 2012)

TREATMENT OPTIONS - TOPICAL

Treatment type Mode of actionTreats

inflammationTreats cell

proliferation

Emollients1 Reduce dryness, scaling and cracking ?

Topical corticosteroids2 Dampen down inflammation

Tar preparations1 Remove loose scales may act as an anti-inflammatory

Dithranol2 Suppresses production of skin cells

Vitamin D analogues2 Reduce excessive skin cell production

Vitamin D + steroid combination3

Reduce excessive skin cell production + dampen down inflammation

Tazarotene2 Slows production of skin cells 1.British National Formulary (BNF) BNF 62 Section 13.5.2; September 2011: 62. Available from www.bnf.org

(Last accessed 19 January 2012) 2.Menter A et al. J Am Acad Dermatol 2009:60;643-6593.Dovobet® Gel Summary of Product Characteristics. Available from www.medicines.org.uk (Last accessed 9

January 2012)

TREATMENT OPTIONS - PHOTOTHERAPY

Bandwidth Characteristics

Narrowband UVB(311nm)

• Patients receive TL01 narrowband UVB1

• UVB slows keratinocyte proliferation and differentiation2

• 3x weekly for 6-8 weeks (max. once weekly)

• Equivalent to a two week holiday in the Mediterranean

PUVA(Psoralen + UVA)

• Penetrates skin more deeply than UVB3

• Used for those with a long history of PsO unresponsive to NBUVB3 – or considered first line for palmoplantar PsO

• Maximum 150 exposures in a lifetime

• Twice weekly for 5-10 weeks

.1. Gambichler T et al. J Am Acad Dermatol 2005:52;660-6702. Menter A et al. J Am Acad Dermatol 2010:62;114-1353. Lapolla, W et al. J Am Acad Dermatol 2011:64:936-949

TREATMENT OPTIONS - SYSTEMIC

Treatment Action

Systemics

Methotrexate1

5-25mg weekly (PO or SC)Folate antagonist with immunosuppressive, cytostatic and anti-

inflammatory effects

Acitretin1

(10-75mg OD)Retinoid – reduces keratinocyte production/turnover. Anti-

inflammatory effects. Can combine with TLO1

Ciclosporin1

(3-5mg/kg/day)Calcineurin inhibitor – prevents T-cell activation from translation

into the release of inflammatory cytokines

Others Fumaric acid esters, Mycophenolate mofetil, Calcitriol

Biologics

TNF-α blockers2

Etanercept, Adalimumab,Infliximab

Block activity of TNF alpha – the master regulator (central cytokine) involved in psoriasis2

Anti IL-12/23p40Ustekinumab

Neutralises all Th1(IL-12) and Th17(IL-23) cell-mediated responses

1. Menter A et al. J Am Acad Dermatol 2009;61:451-4852. Menter A et al. J Am Acad Dermatol 2008;58:826-850

Medications with the least potential for adverse reactions are preferentially employed.

As a first step, medicated ointments or creams are applied to the skin. If topical treatment fails to achieve the desired goal then the next step would be to expose the skin to ultraviolet (UV) radiation. This type of treatment is called phototherapy.

The third step involves the use of medications which are taken internally by pill or injection : systemic treatment.

Over time, psoriasis can become resistant to a specific therapy. Treatments may be periodically changed to prevent resistance developing (tachyphylaxis) and to reduce the chance of adverse reactions occurring: treatment rotation.

http://en.wikipedia.org/wiki/Image:Psoriasis_treatment_ladder.svg

GENERALMANAGEMENT

SUN EXPOSURE

MOISTURISE ADEQUATE CLOTHING

PROPERBATHING

SUPPORT NETWORK

PSYCHO-LOGICALIMPLICATIONS

SOCIAL ISOLATION

AND LONELINESS

ANXIETY

LOW SELF-ESTEEMDEPRESSION

EMBARRASSMENT

PSORIASIS: TREATMENT Lubrication Removal of scales Slow down lesion proliferation Pruritus management Prevent complications Lessen patient stress Season and climate

TOPICAL AGENTS AVAILABLE IN KLINIK KESIHATAN

Aqueous cream Hydrocortisone cream 1% Betamethasone cream 0.025% Betamethasone cream 0.1% Clobetasol propionate cream 0.05%

EMOLLIENTS AND MOISTURIZERS

Moisturizes, lubricates and soothes dry and flaky skin *Recommended*

May be the only treatment for mild psoriasis ?Minimises Koebner phenomenon Produces occlusive film to limit water evaporation from

skin/by osmotic effect increased hydration allows stratum corneum to swell scaling decreases, skin is more pliable, less itch, less scaling

Adverse Effect : contact dermatitis, folliculitis (rare) When in control of psoriasis, regular use of emollients

should continue to be encouraged The only option available in our KK AQUEOUS CREAM

CORTICOSTEROIDS Reduce inflammation, itching and scaling Anti-inflammatory effect

Decrease in vascular permeability, decreasing dermal edema and leukocyte penetration into skin

Antiproliferative effect Immunosuppressive effect

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TOPICAL CORTICOSTEROIDS Not indicated for widespread psoriasis – careful supervision

Can enhance effects by occlusion ONLY in suitable patients

Reduce inflammation, itching and scaling Anti-inflammatory effect

Decrease in vascular permeability, decreasing dermal edema and leukocyte penetration into skin

Antiproliferative effect Immunosuppressive effect

Use for specific targeted flares, e.g. scalp (Dovobet® gel, Etrivex®

Shampoo)

Consider combination products, e.g. Diprosalic® ointment for thick

scale

Maybe hazardous for a number of reasons including:

Rebound relapses

Development of tolerance

Risk of generalised pustular psoriasis

Development of local/systemic toxicity due to impaired barrier function

Ointments: helps hydrate; good for dry, hyperkeratotic, scaly lesions

Cream: for use on all areas, useful for infected lesions

Solutions: for scalp psoriasis, often contain alcohols which can be painful with open lesions

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HYDROCORTISONE

BETAMETHASONE

CLOBETASOL

Adverse Effects: (esp. with occlusion)Systemic absorptionDermal atrophyTelangiectasisEcchymosesPeri-orbital acnePoor wound healingPyogenic infections

I HOPE NO QUESTION

Thank you for

bearing this

with me