الفهرس 
PsoriasisOnly 14 pages are availabe for public view
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Abstract
Psoriasis is an immunologically mediated, probably autoimmune disease in which T helper type 1 cytokine play an important role and it is characterized by hyperplasia and altered differentiation of epidermal keratinocytes. The etiology of psoriasis is unknown. It is associated with a strong genetic predisposition and various environmental and/or life style factors seem to be involved in the onset and/or exacerbation of psoriasis such as: infections, psychological factors, metabolic factors, trauma and drugs.
Psoriasis is recognized as a disease requiring the presence of activated T lymphocytes for its induction, expression and maintenance. There is growing evidence that activated T cells are the primary modulators in the pathogenesis of psoriasis. This is further supported by the fact that increased levels of activated T lymphocytes are present in psoriatic skin plaques and blood of patients especially elevated levels of activated CD4+ T helper lymphocytes were seen in both peripheral blood and lesional tissue. In addition, there is an increased number of effector T-cell subsets that have been shown in the epidermis and dermis of psoriatic plaques. Effector elements include skin homing CD4+ T helper cells and intraepidermal CD8+ T cell alter epidermal keratinocyte growth and drive the disease process.
One of the initial events that are thought to trigger psoriasis is the migration of activated T cells into lesional skin. This is dependent on the expression of cell adhesion molecules that facilitate T-lymphocyte trafficking. Intercellular adhesion molecule (ICAM)-1 and E-selectin are upregulated on endothelial cells. Activated T lymphocytes show increased expression of cutaneous lymphocyte antigen (CLA) and leukocyte-function-associated antigen (LFA) type 1 (LFA-1), which binds to E-selectin and ICAM-1, respectively, on endothelial cells. Following adhesion, these T cells are extravasated into the dermis in a process called diapedesis, in which the cells flatten and migrate through the endothelium. A key mediator that traffics lymphocytes as well as neutrophils into psoriatic plaques is the proinflammatory cytokine, interleukin (IL)-8.
The majority of T lymphocytes that localize to the dermis are of the CD4+ helper type, while those that migrate to the epidermis are predominantly of the CD8+ cytotoxic type. T lymphocytes derived from psoriatic lesions show oligoclonal expansion of the T-cell receptor repertoire.
The activation of T cells by antigen-presenting cells (APCs) involves a cascade of pathways that ultimately leads to the production of a variety of cytokines. CD4+ T-cell stimulation by APC in the context of major histocompatibility complex class II antigen presentation results in upregulation of the CD40 ligand on T lymphocytes. Ligation of the CD40 ligand by CD40 which is present on APCs in turn induces the expression of a set of costimulatory molecules, termed CD80 and CD86, on activated T cells. The ligand for CD80 and CD86 is CD28, which is present on APCs. In addition, when another surface molecule, CD2, which is present on all T-lymphocyte subgroups, binds to LFA-3 on APCs, cytotoxic T-lymphocyte effector functions are enhanced. The interaction of these surface molecules all contribute to the induction of various cytokines which subsequently stimulates further T-cell activation.
Gaining a basic understanding of the pathogenesis of psoriasis is crucial in developing new strategies to control the inflammatory process. Several key points in the cascade of events that lead to psoriasis can be targeted for interventional therapy.
For many years, phototherapy has been known as an effective agent for the treatment of psoriasis, and has been combined with topical and systemic agents to augment its therapeutic effect. Photochemotherapy is the combined use of photosensitizing chemical compound and nonionizing electromagnetic radiation to induce a beneficial result not produced by either alone. Psoralens are the most important of these photsensitzing compounds. Psoralen + ultraviolet A (PUVA) have demonstrated an excellent efficacy in the treatment of psoriasis.
In bath PUVA, psoralen derivates such as trimethoxypsoralen or methoxsalen are dissolved in a warm water bath usually with concentrations ranging from 0.5 to 5 mg/L. Delivery of psoralens by bath prevents systemic adverse effects associated with oral PUVA. Bath PUVA has the advantage of selective and shorter photosensitization, leading to a significantly lower cumulative UVA exposure. Furthermore, it avoids typical variations in therapeutic effect due to large interindividual differences in the gastrointestinal tract absorption of psoralens. A large Scandinavian retrospective analysis demonstrated that bath PUVA with trimethoxypsoralen bears only a low risk of long-term carcinogenicity. In recent years, bath PUVA has increasingly replaced oral PUVA in Germany and other European countries. In contrast to Scandinavia, in central Europe methoxsalen is commonly used instead of trimethoxypsoralen as a photosensitizer. UVA dose requirements in bath-PUVA treatment decrease linearly with increasing 8-MOP concentrations.
Narrowband UVB is an established and effective treatment for psoriasis. NB-UVB uses a special lamp (the philipis TL01 lamp); the efficacy of NB-UVB for treatment of psoriasis has been attributed to interference with DNA, RNA and protein synthesis in the hyperproliferative psoriatic epidermis, alteration of various cytokines and other mediators of inflammation, as well as to some immunological effects. The PASI score has been used to give an objective quantification of severity of psoriasis before and after treatment.
Bath PUVA therapy has some advantages over UVB phototherapy in the treatment of psoriasis: fewer UV-related acute side effects and a longer period of remission after therapy. However, the choice of treatment with NB-UVB, bath-PUVA or systemic PUVA should also be based on a history of previous response to treatment and patient considerations, including compliance and responsibility for following the precautions to avoid potential side effects.
The aim of this work was to compare the effect of bath PUVA photochemotherapy and narrow band phototherapy on the T helper CD4+ cells and T suppressor CD8+ cells in blood of patients with psoriasis.
This study was done on thirty four psoriatic patients who had not received any local or systemic treatment for at least one month prior to the study. They were divided into two groups: The first including 18 patients who received bath PUVA photochemotherapy treatment, with ages ranging from 13-59 years and the second including 16 patients who received NB-UVB phototherapy treatment, with ages ranging from 18-63 years.
Samples of peripheral blood were taken from patients with psoriasis before and after treatment with bath PUVA and narrow band UVB to determine the serum counts of CD4+ T cells, CD8+ T cells and CD4+/CD8+ ratio.
We found a statistically significant lower mean value of PASI score in the bath PUVA and NB-UVB groups after treatment when compared to that before treatment.
However, after treatment bath PUVA group showed a statistically significant lower mean PASI score and a statistically higher mean cumulative dose when compared to NB-UVB group.
On the other hand no statistically significant difference was detected between the two groups as regards the mean serum CD4+ T cell counts, serum CD8+ T cell counts, CD4+/CD8+ ratio, lymphocyte counts and number of sessions before treatment.
There was a statistically significant lower mean value of serum CD4+ counts and CD4+CD8+ ratio in the bath PUVA group after treatment when compared to those before treatment.
Also on comparing the mean difference (decrease) between the two groups : PUVA showed a statistically significant decrease after treatment in serum CD4+ counts and PASI score than UVB group but the difference between the two groups was not significant regarding the other variables.
In conclusion this study shows that bath PUVA is superior to NB-UVB treatment as bath PUVA showed higher rates of improvement than NB-UVB group and also bath PUVA showed a statistically significant decrease after treatment in serum CD4+ counts and PASI score than NB-UVB group.
The fact that many factors are implicated in the pathogenesis of psoriasis can explain the variability in the results produced by different studies. Since we did not study CD4+ T cells and CD8+ T in the skin, we could not exclude that the decrease in CD4+ T cells in the peripheral blood might come from the decrease of CD4+T cells in the skin lesions. Further studies are needed to elucidate the direct role ofCD4+ and CD8+ T cells in the skin of patients with psoriasis before and after treatment with bath PUVA and NB-UVB and its relation to serum finding.