الفهرس 
PsoriasisOnly 14 pages are availabe for public view
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Abstract
Psoriasis is a common, chronic, inflammatory skin disorder affecting 1-3% of the world population. It is considered a multifactorial polygenic inflammatory skin disease characterized by epidermal proliferation and altered keratinocyte (KC) differentiation pathway.
In the treatment of psoriasis, topical corticosteroids are widely used as they reduce inflammation and the turnover of skin cells, and they suppress the immune system. They are available in different strengths. High-potency corticosteroids may be prescribed for plaques that don’t improve with other treatment, particularly those on the hands or feet. In situations where the objective of treatment is comfort, medium-potency corticosteroids may be prescribed for the broader skin areas. Low-potency preparations are used on delicate skin areas. Thus, topical corticosteroids are the milestone of topical anti psoriatic therapy.
Physiologically, glucocorticoids (GCs) participate in numerous processes, such as glucose homeostasis, protein, lipid, and carbohydrate metabolism; development; neurobiology; and programmed cell death. GCs exert potent immunosuppressive and anti-inflammatory actions in a cell type–specific manner largely through the interruption of cytokine-mediated pathways. GCs, which are widely used in therapy, exert their immunosuppressive actions through specific receptors; the glucocorticoid receptor (GRs), characterized in cultured human skin fibroblasts and KCs.GRs belong to the nuclear receptor subfamily that includes receptors for mineralocorticoids, estrogen and thyroid hormones, retinoic acid, and vitamin D.
This study included 20 patients with psoriasis: 10 of them are males and 10 are female. The patients’ age ranged between 30 and 50 years. Eleven patients presented with psoriasis vulgaris, five patients presented with guttate psoriasis, two patients presented with scalp psoriasis and two patients presented with palmoplanter psoriasis. Patients were classified according to the clinical severity of psoriasis by PASI score into 3 groups: mild psoriasis if PASI < 15, moderate psoriasis if PASI =15-25, and severe psoriasis in case of PASI > 25. Punch biopsies were taken from the non-lesional and central lesional skin of patients, stained and examined under light microscope. The immunoreactivity of GR in the different epidermal layers was studied. Their expression in the dermis was also evaluated.
This is the first study to evaluate the expression of GRs in psoriasis; to the best of our knowledge. We found significant increase in GR expression in epidermis taken from the center of diseased areas, compared to epidermis of apparently normal skin, and highly significant increase in GR expression of diseased dermis, compared to normal dermis. In addition, there was significant positive correlation between GR expression in epidermis, and both dermis taken from psoriatic plaques, as well as epidermis of apparently normal skin.
An explanation to our findings could be due to receptor up-regulation as a result of low cortisol level, and it was used before as a marker for sustained sensitivity to the effect of GCs. However, previous studies regarding abnormalities in hypothalamic pituitary adrenal axis in psoriatic patients showed controversial results for further investigation.
All of our patients reported that disease eruption and/or progression was related to stress events. However, variable GR expression was detected among them. Moreover, disease activity or stability did not influence GR expression in our studied patients.
Six of our patients expressed GRs strongly in epidermis of apparently normal skin, which may denote predisposition of the apparently normal skin expressing GRs in psoriatic patients to be converted to psoriasis; i.e. prepsoriatic phenotype.
GR expression in epidermis taken from normal areas in males was significantly higher than in females. However, we found no significant difference in both epidermis and dermis of male and female specimens taken from lesional skin. Previous studies showed gender-related differences in relative GC sensitivity, as determined by GR polymorphisms, rather than receptor expression.
There was no significant correlation between PASI score and GR expression in epidermis or dermis in diseased areas. However, there was highly significant positive correlation between PASI score and GR expression in epidermis taken from normal skin, although there was no significant correlation in dermis taken from control specimens. Besides, there was no significant correlation between the age of the patients or psoriasis duration and GR expression in epidermis or dermis of the diseased or the normal skin. Future studies are warranted to investigate these findings and their possible correlation with general or local adrenal hormone levels, epidermal differentiation and keratin expression profile, disease activity, and receptor polymorphism or ligand affinity.