By AFSAR FATHIMA Dept. of Pharmacology Psoriasis By AFSAR FATHIMA Dept. of Pharmacology

Psoriasis A non-infectious, chronic inflammatory disease of the skin, characterized by well-defined erythematous plaques with silvery scale, with a predilection for the extensor surfaces and scalp, and a chronic fluctuating course.

with interaction between environmental factors A complex and multi-factorial disease associated with interaction between environmental factors (exogenous or endogenous antigens) A specific genetic background

Etiology Climate, stress, alcohol, smoking, infection, trauma, drugs. Skin injury (rubbing, venipuncture, bites, mechanical pressure induce Psoriatic lesions Lithium carbonate, β-adrenergic blocking agents, some antimalarial agents, NSAIDS, and tetracycline's exacerbate psoriasis

Pathophysiology Immunologic mechanisms: Cutaneous inflammatory T-cell–mediated immune activation requires two T-cell signals that are mediated via cell–cell interactions by surface proteins antigen-presenting cells (APCs) Once T cells are activated, they migrate from lymph nodes and the circulation into skin In psoriatic lesions, T cells migrate into the epidermis Once in the skin, activated T cells secrete various cytokines that induce the pathologic changes of psoriasis

- The germinative cell population increases in psoriatic skin Defects in epidermal cell cycle: As a result of pathogenic T-cell production and activation, psoriatic epidermal cells proliferate at a rate sevenfold faster than normal epidermal cells - The germinative cell population increases in psoriatic skin - Duration of the epidermal cell cycle is nearly eight times faster than normal skin

Treatment Goals: directed at skin normalization reduction or clearing of erythema, papules, and plaques, as well as scales to achieve resolution of lesions Assessment of extent The psoriasis area and severity index (PASI) Mild: PASI score 12 Moderate: PASI Score 12 to 18 Severe: PASI Score >18

Treatment General Approach Keratolytic: Salicylates Non-pharmacologic Emollients Balneotherapy Pharmacologic Topical Systemic Phototherapy: Sunlight, UVB, PUVA

Keratolytic Used to remove scale, smooth the skin, and decrease hyperkeratosis. Salicylic acid Mechanism of action: Disruption in corneocyte-to-corneocyte cohesion in the abnormal horny layer of psoriatic skin. The keratolytic effect of salicylic acid enhances penetration and efficacy of some other topical agents such as corticosteroids

Adverse Events: salicylism, with symptoms of nausea, vomiting, tinnitus, and hyperventilation. Fatal cases of percutaneous salicylate intoxication have been reported in children and adults. Administration as a gel or lotion, is usually applied two to three times a day in concentrations of 2% to 10%

Non Pharmacologic Treatment Emollients: used during therapy-free periods to minimize skin dryness that can lead to early recurrence These agents hydrate stratum corneum and minimize cutaneous transepidermal water loss Hydration causes the stratum corneum to swell and flattens the surface contour Effective as moisturizers decrease binding forces within the horny layer, enhance desquamation, and eliminate scaling Increase pliability of the skin, have antipruritic activity, and possess mild vasoconstrictor activity

Adverse Effects: Folliculitis and allergic or irritant contact dermatitis lotions, creams, or ointments, often need to be applied several times per day (about four times per day) Balneotherapy: Saltwater bath Bath at Dead Sea with UV B exposure (by virtue of it being below sea level). The Kangal hot spring in Turkey The Blue Lagoon in Iceland

Pharmacologic Treatment Mild to Moderate Psoriasis Topical Treatment Eg: corticosteroids, vitamin D analogues, tazarotene Moderate to Severe Psoriasis Systemic Treatment Eg: biologic agents, cyclosporine, acitretin

Corticosteroids Class I corticosteroids: very high-potency include products such as clobetasol propionate, halobetasol propionate, and betamethasone dipropionate (optimized vehicle) Used primarily as alternatives to systemic adrenocorticoid therapy when local therapy is feasible They should be used for finite periods of time (as short as possible) and on relatively small body surface areas

Class VII corticosteroids are agents with the lowest level of vaso constricting potency. They have a weak anti-inflammatory effect Hydrocortisone 1%, safest for long-term application. safest products for use on the face and intertriginous areas.

Intermediate classes: include products with a medium-potency ranking, used in moderate inflammatory dermatoses. can be used on the face and intertriginous areas for limited periods of time

Vitamin D analogs inhibits keratinocyte differentiation and proliferation provide antiinflammatory benefits Tazarotene a synthetic retinoid, Like other topical retinoids, it modulates keratinocyte proliferation and differentiation Effective for the treatment of mild to moderate plaque psoriasis adverse effects are mild to moderate pruritus, burning, stinging, or erythema. These local reactions have been shown to be dose- and frequency-related Tazarotene is available as a 0.05 or 0.1% gel and cream, and is applied once a day, usually in the evening. Tazarotene is often used in combination with topical corticosteroids to decrease the incidence of local adverse events and to increase efficacy

Topical Therapy: Second Line agents Coal Tar Down regulates epidermal prolifereation Coal tar, when applied to normal skin, stimulates transient epidermal hyperplasia followed by a cytostatic effect with epidermal thinning Coal tar preparations of 2% to 5% tar are available in lotions, creams, shampoos, ointments, gels, and solutions Coal tar treatment is a burdensome, time-consuming treatment

Adverse events: local irritation, unpleasant odor, staining of skin and clothing, and increased sensitivity to UV light, including the sun.

Antralin: Topical anthralin, particularly with UV light, is long established as an effective approach to the treatment of psoriasis Anthralin possesses antiproliferative activity on human keratinocytes, inhibiting DNA synthesis

Calcinurin hinhibitors: Pimecrolimus and tacrolimus capable of exerting a local immunomodulating effect normalize hyper proliferation of epidermis

Systemic Therapy: First Line Agents Biologic Therapy: TNF inhibitors Infliximab Etanercept Adalimumab T-Cell Activation inhibitors Alefacept Efalizuman

Systemic Therapy : Second Line Acitretin Cyclosporine Tacrolimus Methotrexate Sulfasalazine 6-thioguanine Hydroxy urea Tazarotene

Combination, Rotation, sequential therapy Acitretin + UVB light Acitretin + PUVA (UVA combined with psoralen, usually methoxsalen) Methotrexate + UVB light PUVA + UVB light Methotrexate + cyclosporine

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