Transcript Psoriasisx

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.
• 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,
tetracycline's exacerbate psoriasis
NSAIDS,
and
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
•
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, timeconsuming 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