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

3. 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.

4. 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

5. 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

6. 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

7. - 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

10. 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

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

12. 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

13. 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%

14. 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

15. 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

16. 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

17. 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

18. 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.

19. 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

20. 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

21. 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

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

23. 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

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

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

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

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

28. THANK YOU