Pharmacology-4 PHL 425 Fourth Lecture By Abdelkader Ashour, Ph.D. Phone: 4677212

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Pharmacology-4 PHL 425 Fourth Lecture By Abdelkader Ashour, Ph.D. Phone:

Psoriasis, Introduction  Clinical manifestations. There are two major types: 1.Eruptive, inflammatory type with multiple small guttate lesions and a greater tendency toward spontaneous resolution. It is relatively rare. It appears rapidly and in young adults, often following streptococcal pharyngitis 2.Chronic stable (plaque) psoriasis with chronic indolent lesions present for months and years, changing only slowly  It affects about 90% of the psoriatic patient population  Psoriasis is a non-infective, usually chronic inflammatory skin disease that is characterized mainly by well defined, red plaques covered by silvery scales. psora = "itch"  Plaque is an elevated, solid, superficial lesion more than 0.5 cm in diameter, which tends to be flat over the whole surface Chronic Plaque Psoriasis Guttate (eruptive) psoriasis

Psoriasis, Introduction  Clinical presentation varies among individuals, from those with only a few localized plaques to those with generalized skin involvement (erythroderma)  Although psoriasis may affect any part of the body, it has a tendency for the knees, elbows, scalp, palms and soles. Nail involvement occurs in up to 50% of patients  Psoriasis of the scalp does not lead to hair loss, even after years of thick plaque-type involvement  It usually gets distributed symmetrically  It can eventually progress to the joints (psoriatic arthritis)

Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004 44 DERMIS STRATUM BASALE STRATUM SPINOSUM STRATUM GRANULOSUM STRATUM CORNEUM Proliferation Immaturity Leukocyte accumulation Disorganized NORMALNORMAL PSORIASISPSORIASIS

Psoriasis, Etiology  Psoriasis etiological and triggering factors include:  Genetic background and heredity The tendency to develop psoriasis is genetically determined When one parent has psoriasis, 8% of offspring develop psoriasis; when both parents have psoriasis, 41% of children develop psoriasis  Physical trauma (Koebner phenomenon) It is a major factor in eliciting lesions Rubbing, scratching tattoo applications, and surgical incisions stimulate the psoriatic proliferative process and elicit psoriatic lesions  Psychosocial stress A factor in flares of psoriasis is said to be as high as 40% in adults and higher in children Psychosocial trauma can play a part in initiating the disease and causing relapse  Drugs Oral lithium, antimalarial drugs, interferon, NSAIDs and  -adrenergic blockers can cause flares in existing psoriasis The use of systemic corticosteroids, although helpful initially, may result in a dramatic flare, or the development of a pustular variant of psoriasis when the dose is reduced rapidly  Other nongenetic factors include obesity, smoking, alcohol ingestion, ultraviolet and chemical injury

Psoriasis, Etiology  Infections Acute streptococcal infection precipitates guttate psoriasis Psoriasis is strongly associated with streptococcal throat infection  Psoriasis now is known to be an autoimmune inflammatory disease mediated by group A streptococcal antigen–specific T lymphocytes that migrate to the dermis and react with epidermal keratinocytes  Then, T cells increase in number and secrete inflammatory mediators such as tumor necrosis factor-alpha (TNF  ) and interferon gamma (IFN  ), which in turn cause inflammation and induce keratinocyte proliferation  psoriasis The normal physiological role of T-lymphocyte is to help protect the body against infection Maintenance of psoriatic lesions is considered an ongoing autoreactive immune response Infiltration of T-cells occurs before obvious epidermal changes are seen Although psoriasis may vary widely in its clinical appearance, the tendency of the epidermis to hyperproliferate is common to all patients. Keratinocyte turnover is ten times more rapid than usual Keratinocyte maturation is abnormal (immature cells) Vascular changes (angiogenesis) also can occur

Psoriasis, Epidemiology, Course and Prognosis  Age of onset Early: Peak incidence occurs at 22.5 years of age Early onset predicts a more severe and long-lasting disease, and there is usually a positive family history of psoriasis Psoriasis in children younger than age 15 is rare Late: Presents about age 55  Incidence, race and sex Psoriasis affects 1% to 2% of the world's population. It may be more common among Scandinavians and less common among Native Americans and black Africans. Both sexes are affected equally  Course and Prognosis  Acute guttate psoriasis appears rapidly Sometimes this type of psoriasis disappears spontaneously in a few weeks without any treatment  More often, guttate psoriasis evolves into chronic plaque psoriasis. This is stable and may undergo remission after months or years, recur, and be a lifelong companion Remission and relapse occur unpredictably Spontaneous remissions of up to 5 years have been reported in approximately 5% of patients  Chronic generalized psoriasis is one of the "miseries that trouble mankind," causing shame and embarrassment and a compromised lifestyle

 Itching  Pain  Excessive heat loss  Patient complaints  Unsightliness of the lesions  Feelings of being socially outcast  Excessive scale Psoriasis, Symptoms of chronic plaque psoriasis