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Abstract
Psoriasis is a common genetically determined clinically well demarcated inflammatory, hyperproliferative skin disease. It results partly from chronic dysregulation of the immune system, the interaction between Tlymphocytes and keratinocytes via cytokines is likely to play an important role in the pathogenesis of psoriasis.
Psoriatic epidermis demonstrates as aberrant expression of antigens associated with hyper proliferation, such as the heterodimer keratin 16, in addition, induced expression of ICAM-1 is observed.
Several investigators have suggested that a proinflammatory THI cytokine profile predominates in the psoriatic T-cell response.
Recent studies have revealed that the dominate role of IL-23 involves the stimulation of survival of proliferation of IL-17 T cells to produce IL-17 A which is a critical component in establishment and perpetuation of auto immune inflammation.
This study was a trial to assess the effect of some of some therapeutic modalities on some histopathological parameters including epidermal thickness and ICAM-1, Kt6 immundnistochemistry and on one serological parameter IL-23 serum level in psorials and their correlation to the clinical severity of the disease.
This study included 60 patients with chronic generalized psoriasis attending the outpatient clinic od the dermatology, venereology and Andrology department. The patients were divided into three groups each included 20 patients: the first group (group A) were treated with acitritin ,patients in group (B) were treated with methotrexate and patients in group (C) were treated with PUVA, the treatment duration was 3 months. PASI score was used to evaluate the severity of the disease and was measured monthly during the therapy duration .
Before treatment there was no significant difference as regard’s PASI score in the three groups. After treatment PASI was significantly reduced in all three groups showing more reduction in group B then group C & finally group A.
Similarly the percent of improvement was significantly increased in group B then group C & finally group A.
Degree of improvement was subdivided into three grades: marked (> 70%) moderate (30% - 70%) & minimal (<30%) improvements. Three was a significant relation between severity of the disease and the degree of improvement the milder the disease the better the response.
In order to confirm our subjective clinical results, skin biopsies were taken from all patients before and after treatment and were studied to measure epidermal thickness using H&E stain, on the other hand sections stained with Kl6 monoclonal antibodies which was used to compare reversal of regenerative hyperplasia in psoriatic plaques.
ICAM-1 monoclonal antibodies were used to assess the effect of therapy and the inflammatory process in psoriatic plaques.
Results revealed no significant difference between the 3 groups regarding the 3 previously mentioned parameters before starting therapy.
But after treatment results revealed the following:
There was a significant decrease in epidermal thickness after treatment in the 3 groups all like each other.
There was a significant decrease in the mean ICAM-1 immune stain intensity in the three groups but significantly lower in group B.
There was a significant decrease in the mean Kl6 immune stain intensity in the three groups but significantly lower in group (A).
IL-23 mean serum level was also measured in Blood samples taken from patient under study before of after treatment. The result revealed no significant difference between the three groups before treatment, but the mean JL-23 serum level was significantly higher in psoriatic patients than in the control groups.
After treatment there was significant decrease in the mean IL- 23 serum level in each of the three groups. But again no significance was found between the three groups.
After treatment there was no significant correlation between the mean IL-23 serum level neither with the disease severity nor with degree of clinical response.
After the interpretation of the above results, several points were concluded., the first one there is no advantage of one type systemic treatment over another in treatment of recalcitrant psoriasis but approaches to treatment of psoriasis must be individualized and based on several factors, severity, body surface area involvement, anatomical location, quality of life implications. co-existent psoriatic arthritis, triggering factors and patient’s commitment to therapy, also psychological assessments & response to previous treatment should also be considered when selecting therapies.
Second, ICAM-1 is constitutively expressed by endothelial cells, kerationcytes and mononuclear infilterate in psoriatic skin. & it might play an important role in pathogenesis of psoriasis, it could be considered as marker of the disease activity.
ICAM-1 immune stain level was more affected with methotrexate than other types of treatment. This might be due to methotrexate exerts its antiinflammatory effect by altering T-cell activation of adhesion molecule expression.
Third, Kl6 is highly expressed by kerationcytes in psoriatic lesions and also it could be a marker for the disease activity, it is directly related to disease severity also to the degree of improvement. Kl6 immune stain level which a marker for hyperproliferation is more affected by acitretin therapy than other types of treatment this might be due to acitretin and other retinoids modulate epidermal proliferation.
Fourth, IL-23 is one of the important cytokines involved in inflammatory processes in psoriasis but it cannot be marker to the disease severity or to the degree of response but further studies are recommended to verify or to confirm its role .
Also new therapeutic strategies should be targeted at IL-23 to be another potential tool in the treatment of psoriasis.