Psoriasis

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Psoriasis:

Psoriasis By Minyahl Alebachew Ambo University

Outlines :

Outlines Introduction Risk factors Pathophysiology Clinical presentation Clinical patterns Diagnosis Management Evaluation of therapeutic outcomes References

Introduction :

Introduction Psoriasis is a common chronic inflammatory disease characterized by: recurrent exacerbations and remissions of thickened, erythematous , and scaling plaques Affecting 1.5 – 3 % of Caucasians

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In the United States prevalence among blacks (0.45% to 0.7%) is lower than in the remainder of the United States population (1.4% to 4.6%). It is equally common in males and females. Between 10% and 30% of patients develop psoriatic arthritis. In 10% to 15% joint symptoms appear prior to skin involvement. Cause Clinical depression 8% to 10% of psoriatic patients aged 18 to 54 years old actively contemplated suicide because of their psoriasis.

Risk factors :

Risk factors Psoriasis is a T-lymphocyte–mediated inflammatory disease that results from a complex interplay between multiple genetic factors and environmental factors Genetic factors MZ twins (73 %) show higher disease concordance than DZ twins (20 %) When both parents are affected the rate in siblings is as high as 50%, When one parent is affected, the rate is 16.4% When neither parent has psoriasis, only 7.8%

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Environmental Factors Local Trauma: e g, physical, chemical, electrical, surgical, infective, and inflammatory types of injury or even excessive scratching can aggravate or precipitate localized psoriasis ( Koebner reaction) strong sunlight Systemic Infection: Pharyngeal streptococcal infections ( guttate psoriasis) streptococcal colonization or overgrowth (refractory plaque psoriasis). HIV

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Drugs: Lithium, withdrawal from systemic corticosteroids ,Beta-blockers, antimalarials , and NSAIDs. psychological stress Smoking Alcohol Endocrine Disease incidence peaks at puberty and during menopause

Pathophysiology :

Pathophysiology Abnormal immune response Activation of T Lymphocytes central to initiation and maintenance of lesions certain types of T cells are overactive and migrate to the skin and bind via intracellular cell adhesion molecules (ICAM-1). Antigens in the skin presented to the T cells by APCs, and become activated. LFA-3–CD2 signal plays an important role

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Activated T cells releases cytokines : IL-2, IFN- γ ,TNF- α rapid proliferation and turnover of skin cells (2 weeks to 1 day), triggering the inflammatory process and the development of psoriatic skin lesions.

Clinical Presentation:

Clinical Presentation General Patients have small discrete to generalized confluent lesions over the entire body. Symptoms Patients may complain of severe itching. Signs raised and are red to violet in color Lesions Lesions have sharply demarcated borders except where confluent .

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loosely covered with silvery-white scales, if lifted off show small pinpoints of bleeding Auspitz sign Commonly involved areas elbows, knees, scalp, umbilicus, and lumbar areas, and the trunk, arms, legs, face, ears, palms, soles, and nails.

Clinical patterns:

Clinical patterns Psoriasis Vulgaris (Plaque-type) Guttate Psoriasis (Latin Gutta =drop)

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Flexural psoriasis Psoriatic erythroderma : affects all body sites

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Pustular psoriasis Napkin psoriasis: begins between the ages of 3 and 6 months

Diagnosis:

Diagnosis based on physical examination findings of the characteristic lesions of psoriasis Patient medical history onset and duration of lesions, family history of psoriasis, presence of exacerbating factors, previous history of antipsoriatic treatment exposure to chemicals and toxins, and allergies (food, drugs, and environmental) Skin biopsy confirming the diagnosis

Treatment :

Treatment Desired Outcome chronic illness with no known cure, the goals focus on controlling the signs and symptoms of disease: Minimizing or eliminating the signs of psoriasis Alleviating pruritus and minimizing excoriations Reducing the frequency of flare -ups. Ensuring appropriate treatment of associated conditions such as psoriatic arthritis. Maintaining or improving the patient’s quality of life.

Non pharmacologic Therapy:

Non pharmacologic Therapy Emollients (moisturizers) hydrate the stratum corneum and minimize water evaporation climatotherapy bathing in waters containing certain salts, often combined with natural sun exposure reduce activated T cells in skin

Pharmacotherapy :

Pharmacotherapy Topical Systemic Phototherapy

Topical Agents :

Topical Agents Salicylic acid (2% to 10% gel or lotion) keratolytic causes a disruption in corneocyte -to- corneocyte cohesion in the abnormal horny layer of psoriatic skin remove scales, smooth the skin, and decrease hyperkeratosis. May enhances penetration and efficacy of some other topical agents such as corticosteroids. Produces local irritation.

Topical corticosteroids :

Topical corticosteroids Inhibit synthesis and mitosis of DNA in epidermal cells inhibit phospholipase A, inhibit PG and LT synthesis , local vasoconstriction Reduce erythema , pruritus , and scaling

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Low-potency products (e.g., hydrocortisone 1%) weak anti-inflammatory effect safest for long-term application used on the face and intertriginous areas, in infants and young children Medium-potency products used in moderate inflammatory dermatoses used on the face and intertriginous areas for a limited time

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High-potency preparations used primarily as alternatives to systemic corticosteroids when local therapy is feasible. Very high potency products used for thick, chronic psoriatic lesions For short periods and small surface areas

Vitamin D Analogs:

Vitamin D Analogs Vitamin D and its analogs inhibit keratinocyte differentiation and proliferation and have anti-inflammatory effects by reducing IL-8, IL-2, and other cytokines. Use of vitamin D itself is limited by its propensity to cause hypercalcemia .

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Calcipotriene ( Dovonex ) synthetic vitamin D analog used for mild to moderate plaque psoriasis. Calcipotriene 0.005% cream, ointment, or solution is applied one or two times a day (no more than 100 g/wk). Calcitriol and tacalcitol

Tazarotene (Tazorac) :

Tazarotene ( Tazorac ) A synthetic retinoid hydrolyzed to its active metabolite, tazarotenic acid, which modulates keratinocyte proliferation and differentiation. often used with topical corticosteroids to decrease local adverse effects and increase efficacy

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Anthralin ( dithranol ) has a direct anti-proliferative effect on epidermal keratinocytes and is generally used only on thick plaque areas. It can be used continuously (0.1 %) or as short-contact anthralin therapy (SCAT 1 % - 4% ) high anthralin concentrations, may be highly irritating, especially if SCAT treatments are misused or used continuously.

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Coal tar keratolytic and may have anti-proliferative and anti- inflammatory effects. Crude coal tar and tar distillates available as ointments, creams, and shampoos in various strengths. stain clothing, and have an unpleasant odor. photosensitizing and can be combined with UVB phototherapy

Systemic Pharmacotherapy:

Systemic Pharmacotherapy Methotrexate indicated for moderate to severe psoriasis, psoriatic arthritis Patients refractory to topical or UV therapy. The starting dose is 7.5 to 15 mg per week (max 25 mg), Adverse effects N,V, mucosal ulceration, stomatitis , malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. oral folic acid 1 to 5 mg/day : Nausea and macrocytic anemia. contraindicated in pregnancy, patients with active infections and in those with liver disease

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Cyclosporine Posses immunosuppressive and anti- inflammatory activity used in the treatment of both cutaneous and arthritis manifestations of severe psoriasis. Adverse effects nephrotoxicity , hypertension, hypomagnesemia , hyperkalemia, alterations in liver function tests, elevations of serum lipids, GI intolerance, paresthesias , hypertrichosis , and gingival hyperplasia.

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Acitretin ( Soriatane ) a retinoic acid derivative indicated for severe psoriasis, Can be combined with PUVA , UVB and topical calcipotriol . better tolerated when taken with meals. Adverse effects hypervitaminosis A (dry lips/ cheilitis , dry mouth, dry nose, dry eyes/ conjunctivitis,dry skin, pruritus , scaling, and hair loss), hepatotoxicity , skeletal changes, hypercholesterolemia, and hypertriglyceridemia . contraindicated in pregnancy

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Others Sulfasalazine Hydroxyurea Tacrolimus Biologic therapy primarily immunomodulating agents designed to alter immune responses Comprise first-line systemic therapy Infliximab Etanercept Adalimumab

Phototherapy And Photochemotherapy:

Phototherapy And Photochemotherapy UVB light (290 to 320 nm) most effective wavelength is 310 to 315 nm, Combined with Topical( anthralin , calcipotriene ) and systemic ( methotrexate , oral retinoids ) psoriatic therapies for more effective treatment

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PUVA a photochemotherapeutic approach Indicated for moderate to severe, incapacitating Psoriasis, unresponsive to conventional topical and systemic therapies. Systemic PUVA consists of oral ingestion of a potent photosensitizer such as methoxsalen (8-methoxypsoralen), 0.6 to 0.8 mg/kg variable doses of UVA performed two or three times a week.

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Topically administration methoxsalen to the skin by adding it to bath water (bath PUVA) or as a topical cream (PUVA cream) dicreases risk of systemic effects

Combinational, Rotational, And Sequential Therapy:

Combinational, Rotational, And Sequential Therapy Combination therapy can be used when monotherpay is not effective lower toxicity Combinations include: Acitretin + UVB light Acitretin + photochemotherapy using UVA light (PUVA) Methotrexate + UVB light PUVA + UVB light Methotrexate + cyclosporine

Evaluation Of Therapeutic Outcomes:

Evaluation Of Therapeutic Outcomes Assessing adherence Monitoring for disease resolution Monitor the patient for specific adverse effects, depending on agent(s) used Methotrexate : CBC, and LFTs Cyclosporine: Monitor SCr , blood urea nitrogen, and BP Acitretin : Monitor serum lipids and LFTs Topical corticosteroids: skin thinning, telangiectasias , and HPAA suppression

References :

References Joseph T Dipiro et. al. Pharmacotherapy : A pathophysiologic approach, 7 th ed , 2008. Harrison’s Principle of Internal Medicine,17 th ed.2008. Joseph T Dipiro , T.L.Schwinghammer , C.Y.Dipiro.Pharmacotherapy Handbook, 7 th ed , 2009. M.A. Chisholm-burns, et.al. Pharmacotherapy: principles and practice, 2008. http://www.dr-suzan.com/ihab/wp-content/uploads/2010/10/psoriasis.ppt www.bradfordvts.co.uk/ONLINERESOURCES/15.../ psoriasis.ppt

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