الفهرس 
PATHOGENESIS OF PSORIASISOnly 14 pages are availabe for public view
 |  | from | 183 |  |  |
| | | from | 183 | | |
Abstract
Psoriasis is a chronic, incurable skin disease that causes significant distress and morbidity. It varies greatly in severity, ranging from mild localized distribution to more severe erythrodermic form. It shows a discrepancy between different races and geographical regions, as it is most common in white patients and is more widespread in places of higher than lower latitudes. Psoriasis has been traditionally viewed as an inflammatory skin disorder of unknown etiology. Recent advances in understanding of the immunopathogenesis and genetics of the disease have shifted the focus from a single organ disease confined to dermal structures to a systemic inflammatory condition analogous to other inflammatory immune disorders. Indeed, several immune-modulating therapies that are effective in autoimmune diseases are also effective in treating refractory psoriasis. The pathogenesis of psoriasis is still an enigma. However, there are some hints that the immune system participates in the etiology and pathogenesis of psoriasis. The question whether psoriasis is an epithelial disease or an immune-mediated disease has generated considerable debate over the past decades, but remains essentially unresolved. For the past three decades, psoriasis was primarily regarded as an immune-mediated disease, although the pendulum has begun to swing back lately. In psoriatic lesions, keratinocytes actively participate in the complex events leading to the activation of immune system through the presentation of bacterial or viral products as well as keratin-derived autoantigens. Furthermore, keratinocytes produce chemotactic chemokines and adhesion molecules for the recruitment of leukocytes, contribute to the proinflammatory cytokine milieu and release growth factors that influence histological changes typical for psoriasis. Although the pathogenesis of psoriasis is still unclear, abnormal T-cell-mediated immune responses are critical to manifestation of the disease. This process includes the contribution of both T-helper (Th) 1 and Th17 cell subsets to inflammation by producing cytokines including TNF-α, IFN-γ, IL-12, IL-17A, IL-22 and IL-23. TNF-α is a pleiotropic inflammatory cytokine produced by various cells including the activated T and B cells and NK cells. When inflammation is present, it is primarily synthesized by macrophages in response to various proinflammatory stimuli. It is found in high levels in the skin, joints and plasma of patients with psoriasis and is related to the activity of the disease. Biological activities of TNF-α are mediated by two distinct cell surface receptors: TNFR1 and TNFR2. Analysis of mice lacking either TNFR1 or TNFR2 has demonstrated that TNFR1 is critical for induction of skin inflammation by TNF-α. In lesional psoriasis skin, TNFRI was detected in the parakeratotic stratum corneum; its increased expression was found in the upper dermal blood vessels. In contrast, staining of the TNFRII in normal skin was restricted to eccrine sweat ducts and dermal dendritic cells, but was absent in the epidermis TNF-α has a short half-life (20 min); therefore, accurate measurement of the blood levels is difficult. TNFR1 and TNFR2 are released into the blood as soluble TNFR1 (sTNFR1) and soluble TNFR2 (sTNFR2) after proteolysis of their extracellular domains in response to activators, including TNF-α itself. Their presence in the peripheral blood is reflective of an inflammatory response occurring within the body. sTNFR1 and sTNFR2 also have very long half-life; thus, they are more stable than TNF-α. These receptors may provide better serum biomarkers than TNF-α Phototherapy, in the form of natural sunlight, has been utilized for thousands of years for treatment of numerous skin diseases. Although large amounts of data support the efficacy of phototherapy in the treatment of psoriasis, there remains considerable variability in its application around the world. The mechanisms of action of UV-based therapy in psoriasis include local immunosuppression through the effect on Langerhans cells, cytokines, and adhesion molecules, inhibition of proliferation of keratinocytes and angiogenesis, and induction of T-cell apoptosis. The present study was to evaluate the role of sTNFR1 in pathogenesis of psoriasis by measuring its serum level and the effect of phototherapy on its serum level. The present study was done on 50 psoriatic patients and 25 normal controls. Psoriatic patients were subdivided into two groups; PUVA group and NB-UVB group. Each patient was exposed to 20 sessions of phototherapy. Serum level of sTNFR1 was measured in this study in psoriatic patients before and after 20 sessions of phototherapy and in control group. The result of this study showed the following: 1. Elevation of serum level of sTNFR1 in psoriatic patients before phototherapy than in controls. This reflects the importance of TNF-α- sTNFR1 system in psoriasis pathogenesis. 2. Serum level of sTNFR1 in psoriatic patients was positively statistically correlated with severity of psoriasis measured by PASI score. Being chronic inflammatory disease, TNF-α- sTNFR1 is a main player in chronicity of psoriasis 3. Body weight has a negative impact on psoriasis severity and serum level of sTNFR1. Intra-abdominal fat is an endocrine organ producing multiple adipokines including TNF-α, which increase psoriasis severity. 4. There was no statistically difference of PASI score after 20 sessions of NB-UVB or PUVA. In era of biologics, phototherapy remains an important line of therapy for psoriasis. 5. Serum level of sTNFR1 was reduced after phototherapy with statistically correlation with reduction of PASI score. Reduction of sTNFR1 after phototherapy reveals the decrease of inflammatory milieu in psoriasis. 6. Total cumulative doses of phototherapy are varied by skin phototype. Patients with dark skin need higher starting dose and rapid increments of phototherapy. 7. Serum sTNFR1 can be used as a biomarker of activity in psoriasis. CONCLUSION Serum level of sTNFR1 was elevated in psoriatic patients comparing its level in controls; this indicated that sTNFR1 is a component of the pathophysiological process in psoriasis. Being more stable and prolonged half-life than TNF-α; sTNFR1 is good marker of psoriasis severity than TNF-α. After phototherapy, there was parallel reduction of both Serum level of sTNFR1 and PASI; this supports that phototherapy is still an important method of treatment for psoriasis in era of biological therapy.