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Inflammatory Skin Diseases (inflammatory + skin_diseases)
Selected AbstractsThe role of corticotropin-releasing hormone in immune-mediated cutaneous inflammatory diseaseEXPERIMENTAL DERMATOLOGY, Issue 3 2006Marina O' Kane Abstract:, Corticotropin-releasing hormone (CRH) coordinates the systemic stress response via hypothalamic-pituitary-adrenal (HPA) axis activation with subsequent modulation of the inflammatory response. Stress is known to affect expression of immune-mediated inflammatory diseases, many of which are associated with HPA axis abnormalities. HPA axis components including CRH and its receptors (CRH-R) exist in the skin and exhibit differential expression according to cell type, physiological fluctuations and disease states. This confirms a local functioning cutaneous HPA-like system. Peripheral CRH may exhibit proinflammatory effects. Animal studies confirm that peripheral CRH is required for induction of the inflammatory response in vivo. CRH and CRH-R are upregulated in inflammatory arthritis synovium and psoriatic skin. CRH may influence mast cell activation, direct modulation of immune cells, angiogenesis and induction of the novel orphan nuclear receptor NURR1. This transcription factor is part of the steroid/thyroid superfamily of related nuclear receptors that includes receptors for steroids, retinoids and vitamin D; ligands of these receptors are effective in treating psoriasis. The roles of CRH and NURR1 in psoriasis and inflammatory skin diseases, especially those associated with stress, remain to be elucidated. This stress may be psychological or physical. CRH, produced locally or delivered by peripheral nerves, may mediate interactions between a cutaneous HPA axis-like system and the central HPA axis , the ,brain-skin axis'. [source] CCL28 production in HaCaT cells was mediated by different signal pathways from CCL27EXPERIMENTAL DERMATOLOGY, Issue 2 2006Shinji Kagami Abstract:, Both CCL27 and CCL28 are ligands for CCR10 and attract CCR10+ lymphocytes. We previously demonstrated that CCL27 and CCL28 were strongly expressed in sera and lesional keratinocytes of patients with atopic dermatitis and psoriasis vulgaris. However, the regulation of CCL27 and CCL28 production in keratinocytes has not been well documented. In this study, we showed that CCL27 and CCL28 expression and production by a human keratinocyte cell line, HaCaT cells, were strongly induced by inflammatory cytokines tumor necrosis factor-, and interleukin-1,. CCL27 production was downregulated by inhibitors of p38 mitogen-activated protein kinase and nuclear factor-kappa B (NF-,B). By contrast, CCL28 production was downregulated by inhibitors of extracellular signal-regulated kinase and NF-,B. Our study results suggest that CCL28 produced by keratinocytes is mediated by different signal pathways from CCL27 and that both CCL27 and CCL28 are involved in the pathogenesis of inflammatory skin diseases. [source] In vitro culture of skin-homing T lymphocytes from inflammatory skin diseasesEXPERIMENTAL DERMATOLOGY, Issue 5 2005Karen Bang Abstract:, We, in this study, describe how T lymphocytes in a skin biopsy can proliferate in vitro for up to 3 months by using T-cell growth factors , interleukin-2 (IL-2) and IL-4 yielding approximately 100,160 million T lymphocytes within 1 month. We established cell lines from three tuberculin skin tests, four positive patch tests, 15 of 16 biopsies from atopic dermatitis (AD), 15 of 19 biopsies from mycosis fungoides (MF), 12 of 24 biopsies from psoriasis vulgaris, which was significantly less than AD (P < 0.05), and with a reduced cumulative number of lymphocytes (P < 0.05). Omitting IL-2 and IL-4 led to immediate halt of proliferation. Blood mononuclear cells from patients and biopsies from healthy persons never gave cell lines. All cells were T lymphocytes expressing CD45RO+, HLA-DR+ and CD150. The CD7 expression was significantly increased in cell lines from AD (P < 0.05). T-cell receptor ,-chain studies by using reverse transcription-polymerase chain reaction showed that all T lymphocytes had access to the skin compartment. Single-stranded conformational analysis showed clonally expanded T cells numbering between 40 and 60 clones. After approximately 2 months of growth, the mean CD4+ : CD8+ ratio was for AD 1.20, MF 0.65 and psoriasis 0.85. Patients with AD treated with cyclosporin-A had almost no growth of CD8+ cells in vitro. Our findings indicate a changed homeostasis among skin-homing lymphocytes for in vitro culture. Our culture system of skin-homing T lymphocytes leads to a prominent cellular expansion allowing for a range of studies of in vivo activated skin T lymphocytes. [source] Pimecrolimus , an anti-inflammatory drug targeting the skinEXPERIMENTAL DERMATOLOGY, Issue 12 2004M. Grassberger Abstract:, Pimecrolimus is the most recent member of calcineurin inhibitors available for the therapy for inflammatory skin diseases. It targets T-cells and mast cells and inhibits the production and release of cytokines and other inflammatory mediators, as well as the expression of signals essential for the activation of inflammatory T-lymphocytes. Pimecrolimus has a cell-selective mode of action. In contrast to corticosteroids, it does not affect, e.g., Langerhans'cells/dendritic cells (LC/DC), as demonstrated in vitro with human monocyte-derived DC and in vivo with epidermal LC in mice, nor human primary fibroblasts. As shown in vitro with human skin and by comparison of clinical pharmacokinetic data from patients with atopic dermatitis, pimecrolimus permeates less through skin than tacrolimus and much less than corticosteroids. It, thus, has a lower potential for transcutaneous resorption after topical administration, resulting in a lower risk of systemic effects. Pimecrolimus has high anti-inflammatory activity in animal models of skin inflammation, including a model reflecting neurogenic inflammation, but a more favourable balance of anti-inflammatory vs. immunosuppressive activity than tacrolimus. Pimecrolimus does not affect sensitization in a murine model of allergic contact dermatitis and has a lower potency in various models of immunosuppression after systemic administration, compared to tacrolimus. In conclusion, the results of preclinical studies show that pimecrolimus has a selective pharmacological profile, suited for effective and safe treatment for inflammatory skin diseases. [source] Vitamin D and skin: new aspects for dermatologyEXPERIMENTAL DERMATOLOGY, Issue 2004Bodo Lehmann Abstract:, It has been shown that epidermal keratinocytes have the capacity for the UVB-induced photochemical conversion of 7-dehydrocholesterol to vitamin D3, and also for the enzymatically controlled hydroxylation of the photolysis product. This metabolic loop results in the formation of the biologically active final product 1,,25-dihydroxyvitamin D3 (1,,25(OH)2D3, calcitriol). The epidermal synthesis of calcitriol is of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and immunocompetent cells. Because of their anti-proliferative and prodifferentiating effects, calcitriol and other vitamin D analogs are highly efficient in the treatment of psoriasis vulgaris. In addition, the known therapeutic effect of UVB light therapy in the treatment of psoriasis may, at least in part, be mediated via UVB-induced synthesis of calcitriol. Increasing evidence now indicates that cutaneous vitamin D synthesis is of great importance for the prevention of a broad variety of diseases, including various malignancies. It has been postulated that cancer mortality could be reduced via careful UV exposure or, more safely, via oral substitution with vitamin D. These new findings must be taken into account when establishing new sun protection guidelines for the prevention of skin cancer. In addition, better understanding of the metabolism of vitamin D in the skin has opened up new perspectives for the therapeutic application of vitamin D analogs, e.g. in inflammatory skin diseases. [source] Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skinEXPERIMENTAL DERMATOLOGY, Issue 3 2002László Virág Abstract: In the last decade it has become well established that in the skin, nitric oxide (NO), a diffusable gas, mediates various physiologic functions ranging from the regulation of cutaneous blood flow to melanogenesis. If produced in excess, NO combines with superoxide anion to form peroxynitrite (ONOO,), a cytotoxic oxidant that has been made responsible for tissue injury during shock, inflammation and ischemia-reperfusion. The opposite effects of NO and ONOO, on various cellular processes may explain the ,double-edged sword' nature of NO depending on whether or not cellular conditions favour peroxynitrite formation. Peroxynitrite has been shown to activate the nuclear nick sensor enzyme, poly(ADP-ribose) polymerase (PARP). Overactivation of PARP depletes the cellular stores of NAD+, the substrate of PARP, and the ensuing ,cellular energetic catastrophy' results in necrotic cell death. Whereas the role of NO in numerous skin diseases including wound healing, burn injury, psoriasis, irritant and allergic contact dermatitis, ultraviolet (UV) light-induced sunburn erythema and the control of skin infections has been extensively documented, the intracutaneous role of peroxynitrite and PARP has not been fully explored. We have recently demonstrated peroxynitrite production, DNA breakage and PARP activation in a murine model of contact hypersensitivity, and propose that the peroxynitrite-PARP route represents a common pathway in the pathomechanism of inflammatory skin diseases. Here we briefly review the role of NO in skin pathology and focus on the possible roles played by peroxynitrite and PARP in various skin diseases. [source] ,Activation-induced cell death': a special program able to preserve the homeostasis of the skin?EXPERIMENTAL DERMATOLOGY, Issue 1 2002Giuseppe De Panfilis Abstract: The ,activation-induced cell death' (AICD) is a molecular system leading to death of antigen-activated T lymphocytes, in order to avoid accumulation of harmful cytokine-releasing cells. This article reviews both the molecular mechanisms working in AICD and the role played by such mechanisms in preventing a number of skin diseases. Specifically, because AICD removes activated and autoreactive T cells through a CD95-/CD95-L-mediated suicide, skin diseases were scrutinized in which such valuable machinery could be lacking. Indeed, at least some inflammatory skin diseases, including psoriasis and atopic dermatitis, can be sustained by an increased survival of activated T lymphocytes associated with deficient CD95-/CD95-L-mediated AICD of such strong pro-inflammatory cells. In addition, autoreactive skin diseases, including, e.g. alopecia areata, lichen planus and other lichenoid tissue reactions, can be related to autoreactive T lymphocytes which could be unable to undergo CD95-/CD95-L-mediated AICD. Finally, a lack of AICD may be executive even in favoring cutaneous T cell lymphoma. Thus, because inflammatory, autoreactive and neoplastic skin diseases can be associated with a deficient CD95-/CD95-L-mediated suicide of activated T cells, AICD is likely to represent a fundamental program to preserve the homeostasis of the skin. Therapeutic approaches able to restore the AICD machinery promise to successfully treat such relevant skin diseases. [source] Pimecrolimus in dermatology: atopic dermatitis and beyondINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2005Paolo Gisondi Summary Pimecrolimus is a calcineurin inhibitor developed for the topical therapy of inflammatory skin diseases, particularly atopic dermatitis (AD). Pimecrolimus selectively targets T cells and mast cells. Pimecrolimus inhibits T-cell proliferation, as well as production and release of interleukin-2 (IL-2), IL-4, interferon-, and tumour necrosis factor-,. Moreover, pimecrolimus inhibits mast cell degranulation. In contrast to tacrolimus, pimecrolimus has no effects on the differentiation, maturation and functions of dendritic cells. In contrast to corticosteroids, pimecrolimus does not affect endothelial cells and fibroblasts and does not induce skin atrophy. Given the low capacity of pimecrolimus to permeate through the skin, it has a very low risk of systemic exposure and subsequent systemic side-effects. In different randomised controlled trials, topical pimecrolimus as cream 1% (Elidel®) has been shown to be effective, well tolerated and safe in both adults and children with mild to moderate AD. In addition, pimecrolimus has been successfully used in inflammatory skin diseases other than AD, including seborrheic dermatitis, intertriginous psoriasis, lichen planus and cutaneous lupus erythematosus. [source] What is a role of haeme oxygenase-1 in psoriasis?INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2007Current concepts of pathogenesis Summary The skin is constantly exposed to endogenous and environmental pro-oxidant agents, which lead to harmful generation of reactive oxygen species (ROS). Healthy skin, being a potential target for oxidative stress, is equipped with a large number of defence mechanisms including antioxidant systems. This protection can be corrupted by an imbalance between ROS and antioxidants with pathological level of oxidants prevailing. There is a great body of evidence indicating that some inflammatory skin diseases, such as psoriasis, are mediated by oxidative stress. Keratinocytes of normal skin, the primary target for pro-oxidant agents, show strong expression of ROS-detoxifying enzymes. In addition, normal keratinocytes express haeme oxygenase (HO), an enzyme which might be involved in the protection of cells against oxidative stress. HO (inducible HO-1, constitutive HO-2 and HO-3) is the rate-limiting enzyme in haeme catabolism, which leads to the generation of biliverdin, iron, and carbon monoxide. HO-1 is a stress-responsive protein whose expression is induced by various oxidative agents. HO-1 is known for its cytoprotective, antioxidant and anti-inflammatory properties. Interestingly, a strong overexpression of HO-1 was observed in psoriatic skin. However, the role of HO-1 in psoriasis remains unclear. In this review, we will discuss some current concepts concerning pathogenesis of psoriasis and the contribution of HO-1 in skin inflammation to show the relationships between HO-1, ROS and cytokine network in psoriatic skin. We will try to answer a question whether enhanced HO-1 expression in keratinocytes results in beneficial or detrimental effect on the development and severity of psoriatic lesions. [source] Pimecrolimus versus placebo in genital aphthous ulcers of Behcet's disease: a randomized double-blind controlled trialINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2010Cheyda CHAMS-DAVATCHI Abstract Background:, Genital aphthous ulcers of Behcet's disease (BD) are painful and usually resistant to local treatments. Pimecrolimus is an ascomycin macrolactam, used in inflammatory skin diseases. Objective:, To discover if pimecrolimus can accelerate the healing of BD genital aphthous ulcers. Methods:, Ninety patients with genital aphthous ulcers were enrolled. Only patients treated with colchicine alone were selected. All patients signed a written consent form. Patients were randomly assigned to pimecrolimus or placebo cream, applied twice daily for 1 week. The primary outcome was the healing period. Up to 7 days, it was considered as a positive result. Results were compared by chi-square test. The mean healing time was compared by analysis of variance. Analyses were done both by the ,intention-to-treat' and ,treatment-completed' methods. Results:, Both groups were similar at the entry (gender, age, ulcer size, pain intensity and treatment delay). By intention-to-treat analysis, in the pimecrolimus group, 18 patients had positive and 27 negative results. In the control group, four had positive and 41 negative results. The difference was significant (,2 = 10.167, P = 0.001). By treatment-completed analysis, with pimecrolimus, 18 patients had positive and 22 negative results. With placebo, four had positive, and 41 negative results. The difference was significant (,2 = 12.574, P = 0.0004). Comparison of mean healing time in the pimecrolimus versus placebo group, demonstrated a significant acceleration both in intention-to-treat analysis (10.7 vs. 20.7 days, F = 17.466, P < 0.0001) and treatment-completed analysis (8.3 vs. 20.7 days, F = 29.289, P < 0.0001). Conclusion:, Pimecrolimus is safe and efficient in the treatment of BD genital ulcers, by accelerating the healing process. [source] A preliminary examination of the role of NFAT 3 in human skin, cultured keratocytes and dermal fibroblastsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2010Wael I. Al-Daraji Background: Ciclosporin A (CsA) is widely utilized for the treatment of inflammatory skin diseases such as psoriasis. The therapeutic effects of CsA are thought to be mediated via its immunosuppressive action on infiltrating lymphocytes in skin lesions. CsA and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). Methods: RT-PCR and Western Analysis were used to investigate the presence of NFAT-3 mRNA and protein in human keratocytes. Tissue culture of human keratocytes and immunostaining of cells on coverslips and confocal microscopy were used to assess the degree of nuclear localisation of NFAT-3 in cultured cells. Keratome biopsies were taken from patients with psoriasis (lesional and non-lesional skin) and normal skin and immunohistochemistry was used to assess the NFAT-3 localisation in these biopsies using a well characterized anti-NFAT-3 antibody. Results: The NFAT-3 mRNA and protein expression was demonstrated using RT-PCR and Western blotting. The expression of NFAT-3 in human keratocytes and response to different agonists provides perhaps a unique opportunity to examine the regulation, subcellular localization and kinetics of translocation of different NFATs in primary cultured human cells. As with NFAT 1, NFAT 2 and recently NFAT 5, differentiation-promoting agents that increase intracellular calcium concentration induced nuclear translocation of NFAT-3 in cultured keratocytes but with different kinetics. Conclusion: These data provide the first evidence of that NFAT-3 is expressed in normal skin, psoriasis and that NFAT-3 functionally active in human keratocytes and that nuclear translocation of NFAT-3 in human skin cells has different kinetics than NFAT 1 suggesting that NFAT-3 may play an important role in regulation of keratocytes proliferation and differentiation at a different stage. Inhibition of this pathway in human epidermal keratocytes many account, in part for the therapeutic effects of CsA and tacrolimus in skin disorders such as psoriasis. Al-Daraji WI. A preliminary examination of the role of NFAT 3 in human skin, cultured keratocytes and dermal fibroblasts. [source] Herpetic Folliculitis is Usually a Consequence of Varicella Zoster Virus InfectionJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005J Blair Skin biopsies of 8 patients diagnosed with herpetic folliculitis by light microscopy were retrieved from the files of the UCSF Dermatopathology Service. Clinical and microscopical features were reviewed and tabulated, and PCR analysis was employed to seek DNA sequences specific for herpes simplex virus (HSV) and varicella zoster virus (VZV). The study group included 4 women and 4 men, ages 15 to 54. Five patients (62%) were immunosuppressed, with underlying conditions including HIV infection, leukemia, rheumatoid arthritis, and lupus erythematosus with polyarteritis nodosa. Microscopically, herpetic cytopathic changes involved the isthmus in 7/8 cases (87%), and involved the sebaceous apparatus in 4/8 cases (50%). Herpetic viropathic changes were not found within eccrine epithelium. A moderate to dense perifollicular infiltrate, comprised mostly of lymphocytes, was evident in 7/8 cases (87%). After PCR expansion of genetic material extracted from the original paraffin blocks, VZV-specific DNA sequences were detected in 8/8 cases. We conclude that herpetic folliculitis is a consequence of VZV infection. Because follicular herpetic infection is often accompanied by a dense perifollicular lymphoid infiltrate, the microscopical presentation can simulate inflammatory skin diseases such as lupus erythematosus. Level sections may be required for a specific diagnosis to be made. [source] In-vitro Antioxidant and In-vivo Photoprotective Effect of Three Lyophilized Extracts of Sedum telephium L. LeavesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2000FRANCESCO BONINA Sedum telephium L. is a medicinal plant used in antiquity to cure many types of inflammatory skin diseases. The leaves (without the external cuticle), are used to promote healing and reduce skin inflammation and pain, and contain various components. We found two major components: flavonol glycosides and polysaccharides, with molecular weight between 13 000 and 13 500 Da. We evaluated the in-vitro antioxidant and in-vivo skin photoprotective effects of three lyophilized extracts obtained from the juice of S. telephium L. leaves: a total lyophilized juice, a lyophilized flavonolic fraction, and a lyophilized polysaccharidic fraction. Two in-vitro models were used: the bleaching of the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH*) radical, and the protective effect against UV-induced peroxidation on phosphatidylcholine multilamellar vesicles, as model membranes. The antioxidant/radical scavenging activity of each lyophilized extract was also assessed in-vivo by determining their ability to reduce UVB-induced skin erythema (monitored by reflectance spectrophotometry) in healthy human volunteers. The findings of the in-vitro experiments clearly demonstrated that, unlike the lyophilized polysaccharidic fraction, the lyophilized flavonolic fraction and total lyophilized juice possess strong antioxidant/free radical scavenging properties, which are likely due to phenolic compounds. Consistent with these findings, gel formulations of both the total lyophilized juice and, to a greater degree, the lyophilized flavonolic fraction appeared to possess a strong protective effect against UV-induced skin erythema in-vivo, whereas the lyophilized polysaccharidic fraction was completely ineffective. The in-vitro and in-vivo results suggest that, both the total lyophilized juice and, in particular, the lyophilized flavonolic fraction, but not the lyophilized polysaccharidic fraction of S. telephium L. leaves, have photoprotective effects against UVB-induced skin damage. [source] Treatment of inflammatory dermatoses by tumour necrosis factor antagonistsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2006A Jacobi Abstract Background, The treatment of inflammatory skin diseases is at present often empirical as causal therapeutic approaches, based on an incomplete knowledge of the immune pathogenesis, are mostly unavailable. The currently applied treatments can in fact lead to remission of the disease; however, under certain circumstances undesirable side-effects must be expected. On the basis of experience gained in cytokine modulation therapy of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, the application of TNF-, inhibitors represents a novel, more specific, and effective therapeutic option for distinct chronic inflammatory diseases. Patients and methods, The current status of the therapeutic effect of TNF-, blockers is discussed based on our own observations and a review of the current literature. Also discussed are potential undesirable side-effects and possible contraindications of this therapy. Results and conclusions, Based on recent findings, the use of TNF-, blockers seems to be promising in the treatment of therapy-resistant inflammatory dermatoses. At present, guidelines for indications and contraindications of anti-TNF-, treatment of inflammatory skin disorders are rare. Such guidelines are necessary to improve the efficacy of anticytokine treatment and the reduction of side-effects. [source] Psoriasis under the microscopeJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2006BJ Cribier Abstract Histopathology is a major diagnostic tool in dermatology, particularly in psoriasiform diseases. Morphological studies showed that the initial event in psoriatic lesions is perivascular infiltrate, followed by dilatation of superficial papillary vessels. Proliferation of keratinocytes and neutrophil exocytosis are secondary events. Fully developed psoriasis has a very characteristic pattern, which includes elongation of rete ridges leading to regular acanthosis, oedema of the papillary dermis associated with tortuous dilated vessels, thinning of suprapapillar area, decreased thickness of granular layer, and exocytosis of neutrophils in the spinous layer (Kogoj's pustule) or in the cornified parakeratotic layer (Munro microabscesses). Pustular psoriasis is characterized by large or confluent intra-epidermal multilocular pustules. Whatever the clinical variant of psoriasis, common morphological signs suggest that it is basically a unique pathological process, with many possible presentations according to various factors such as age, size and localization of lesions, or therapy. Similar microscopic elementary lesions indicate that Hallopeau's acrodermatitis continua, Reiter's disease and geographical tongue are variants of psoriasis. Because of the many faces of the disease, psoriasis can resemble many other squamous or pustular disorders. Differential diagnosis by microscopic analysis is based on pattern analysis, PAS (Periodic Acid Schiff) staining to rule out fungal infection, and immunohistochemistry to characterize lymphocytic infiltrate. Psoriasis is one of the most common inflammatory skin diseases. In its characteristic presentation, psoriasis comprises well-circumscribed red scaly papules and plaques. In this form, the disease is generally easy to identify, especially when the elbows, knees and scalp are affected. Nevertheless, the term ,psoriasis' includes more clinical variants than any other inflammatory dermatosis: psoriasis vulgaris vs. pustular, localized vs. generalized, topographic variants, mucous membranes involvement, hair and nail lesions. Although some of these conditions might be extremely different from psoriasis vulgaris, common pathological findings can be identified in all of them. Microscopic analysis of psoriatic lesions may therefore help clinicians to make the diagnosis and to understand that, whatever the clinical presentation, signs and symptoms are mainly due to a unique pathological process. [source] Different expression of adhesion molecules and tetraspanins of monocytes of patients with atopic eczemaALLERGY, Issue 12 2006J. J. Jockers Background:, Atopic eczema (AE) and psoriasis vulgaris (Pso) represent the most frequent chronic inflammatory skin diseases, which have a high number of characteristics in common but differ in their clinical picture and immunological background. A shared feature of both AE and Pso is a high recruitment of distinct proinflammatory cells from the blood into the skin at the initiation of the disease. A multistep adhesion cascade via different adhesion receptors consisting of ,tethering' and ,rolling' mediated by selectins, , -integrins and , -integrins and the ,arrest' of the cells is initiated during this process. Aims of the study:, To evaluate the expression of adhesion molecules and tetraspanins of monocytes of patients with AE and Pso in comparison with healthy controls. Methods:, We analysed the expression of adhesion molecules and tetraspanins on monocytes freshly isolated from the peripheral blood of patients with AE (n = 40) and Pso (n = 65) during exacerbation of their disease in comparison with healthy, non-atopic controls (n = 50). Results:, A high number of similarities between monocytes of patients with AE and patients with Pso, and disease-related differences in the expression of CD62L, CD62P, CD11a, CD11b, CD11c, CD49b, CD49d, CD49e and CD18 and the tetraspanins CD9, CD53, CD63 and CD151, which were elevated on monocytes of patients with AE could be observed. Conclusion:, A distinct expression pattern of adhesion molecules and tetraspanins on monocytes of patients with AE and Pso might influence the recruitment process of inflammatory precursor cells and facilitate new approaches for therapeutic strategies aimed at interrupting the very earliest steps of the fateful recruitment process. [source] Successful Treatment of Pediatric Psoriasis with Indigo naturalis Composite OintmentPEDIATRIC DERMATOLOGY, Issue 5 2006Yin-Ku Lin M.D. Many modes of therapy are currently in use but the disease is often resistant to treatment owing to the unacceptable toxicity that leads to poor compliance. Therefore, to develop an alternative treatment is indispensable. Traditional Chinese medicine has been documented for over 1000 years to provide various effective treatments for inflammatory skin diseases. Herein, we report an 8-year-old boy with recalcitrant pediatric psoriasis who, after multiple treatment failures with conventional antipsoriatic medications, showed remarkable clinical improvement with 8 weeks of topical treatment with Indigo naturalis composite ointment. Remission has lasted for over 2 years until now. Our patient's response suggests that topical Indigo naturalis composite ointment may provide a safe and effective alternative treatment for pediatric psoriasis. [source] Photochemistry and Phototoxicity of Fluocinolone 16,17-Acetonide,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2005Giorgia Miolo ABSTRACT Fluocinolone 16,17-acetonide is a corticosteroid used topically to treat various inflammatory skin diseases. Its photoreactivity was studied under UV-A and UV-B light in aqueous buffer in the presence of oxygen. This drug is photolabile under UV-B light and, to a lesser extent, under UV-A light, which is absorbed far less. In phosphate buffer, approximately 80% of fluocinolone acetonide decomposes after 5 J/cm2 of UV-B irradiation, whereas under 30 J/cm2 of UV-A light approximately only 20% decomposes. Both the drug and its photoproducts have been evaluated through a battery of in vitro studies and found to cause photohemolysis and induce photodamage to proteins (erythrocyte ghosts, bovine serum albumin) and linoleic acid. In addition, one of the photoproducts (the 17-hydroperoxy derivative) is highly toxic in the dark. Therefore, both loss of therapeutic activity and light-induced adverse effects may be expected when patients expose themselves to sunlight after drug administration. A major mechanism for phototoxicity involves radicals forming from drug breakdown, at least under UV-B, although reactive oxygen species may play a role, particularly under UV-A. [source] 006 Efficacy of photochemotherapy and UVA-1 therapy in patients with morphea or lichen sclerosusPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 2 2002K. Ghoreschi Morphea and lichen sclerosus are inflammatory skin diseases of unknown aetiology. Morphea can be subdivided into plaque morphea, linear morphea and disabling or generalized morphea. In most patients morphea leads to superficial or deep sclerosis of the skin. The characteristic features of lichen sclerosus which often affects the genital area are edema of upper dermis, inflammatory infiltration and hyalinisation to the dermis at advanced stages. Patients with morphea or lichen sclerosus suffer especially from scar formation and morphea may lead to severe disfigurement, contractures and reduction of quality of life. Skin sclerosis seems to be the result of vascular damage, T cell activation and altered connective tissue production. Various therapies have been reported for lichen sclerosus and morphea. Whereas the topical use of ultrapotent corticosteroids is well established for genital lichen sclerosus, immunosuppressive agents are normally not successful in resolving extragenital skin sclerosis. In a retrospective study we confirmed the efficacy of phototherapy in more than 50 patients with morphea. Fourty treatments with 30 J/cm2 UVA-1 or PUVA-bath photochemotherapy resulted in a significant improvement, reduced skin thickness, as determined by high frequency ultrasound and reconstitution of functional mobility of the skin and even the underlying fasciae. In lichen sclerosus phototherapy was successful only in some patients. Thus for lichen sclerosus the use of topical corticosteroids is the first choice therapy, while phototherapy using either PUVA-bath or medium dose UVA-1 are the most effective treatments for morphea. [source] Effects of etanercept on urine neopterin levels in patients with psoriasis in a controlled, open-label studyTHE JOURNAL OF DERMATOLOGY, Issue 4 2009Erol KOC ABSTRACT Neopterin is an immunological marker of cellular immune activation. Etanercept is a tumor necrosis factor-, (TNF-,) antagonist that decreases excessive levels of TNF-, associated with inflammatory disease down to physiological levels. The objective of this study was to investigate urine neopterin levels in psoriatic patients treated with etanercept, to study the effect of etanercept as a TNF-, blocker on urine neopterin levels. Urine neopterin levels and urine neopterin/creatinine ratios were measured by high-performance liquid chromatography in 22 patients with psoriasis before and after treatment with etanercept. Results were compared with a group of 20 healthy volunteers, and 20 patients with inflammatory skin diseases as control groups. Urine neopterin levels, neopterin/creatinine ratios and Psoriasis Area and Severity Index (PASI) scores were evaluated at baseline, and the 12th and 24th week after treatment. Urine neopterin levels were significantly elevated in the psoriatic group compared with control and inflammatory skin diseases groups (P < 0.05). Urine neopterin levels were significantly reduced after etanercept treatment. Statistically we did not find any correlation between neopterin levels and PASI scores. Our findings indicate that urine neopterin concentrations may reflect the disease activity in psoriasis, and may be used as a marker for monitoring disease activity and response to treatment with etanercept in psoriatic patients. [source] Immune response profiles in human skinBRITISH JOURNAL OF DERMATOLOGY, Issue 2007T. Meyer Summary In addition to the function as a physical barrier human skin has been shown to be an important immune organ displaying various defense mechanisms, which can be divided into three major functional compartiments: (i) Epithelial defense, which is characterized by antimicrobial peptides and proteins (AP) and which can be induced in inflammatory lesions but also in the absence of inflammation. (ii) Innate-inflammatory immunity, which involves recognition of microbial compounds by particular receptors like Toll-like receptors (TLR) and subsequent activation of signalling pathways resulting in expression of pro-inflammatory cytokines and interferons, as well as genes of adaptive immunity. Interferon , (IFN,) produced by plasmacytoid dendritic cells (DC) may stimulate myeloid DC to produce IL-12 resulting in classical T-cell activation or to produce IL-23 activating IL-17 producing T-cells (IL-23/IL-17 pathway). (iii) Adaptive immunity, which is based on antigen presenting cells, T-cells and B-cells and which is characterized by specificity and memory. In contrast to epithelial defense and innate-inflammatory immunity, adaptive immune functions provide slowly reacting protection. Recent improvements of our knowledge of dysregulated immune pathways associated with inflammatory skin diseases represent an important basis of novel immunomodulatory treatment modalities. [source] The Family Dermatology Life Quality Index: measuring the secondary impact of skin diseaseBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2007M.K.A. Basra Summary, Background, Skin diseases are known to have a major impact on the lives of patients and their families. Many instruments are available to measure the health-related quality of life (HRQoL) of patients but no measure has been developed so far to quantify the secondary impact on family members of the patients. Objectives, To develop and validate a dermatology-specific instrument to measure the adverse impact on the HRQoL of family members of patients with skin disease. Methods, Detailed semi-structured interviews were conducted with family members of patients to identify different aspects of HRQoL affected. An initial draft version of the questionnaire based on the main topic areas was pilot tested to assess the face and content validity. A 10-item questionnaire, the Family Dermatology Life Quality Index (FDLQI), was finalized after modifications to the draft questionnaire based on feedback from families and dermatology professionals and on item reduction. Psychometric evaluation was conducted on a new cohort of family members (n = 132) who completed the FDLQI and the patients (n = 109) who completed the Dermatology Life Quality Index (DLQI). Results, Fifty-nine different aspects of family members' HRQoL were identified from the analysis of the interviews, which were categorized into main topic areas. Factor analysis of 10 items of the final questionnaire revealed two factors and together these explained 60% of the common variance. The FDLQI demonstrated high internal consistency (Cronbach's , = 0·88) and test,retest (intraclass correlation coefficient = 0·94) reliabilities. The responsiveness of the instrument to change was shown by significant change in the family members' FDLQI scores in cases where patients' clinical condition either improved or worsened. Construct validity was assessed by testing a number of a priori hypotheses. A strong correlation was seen between the family members' FDLQI scores and patients' DLQI scores (r = 0·69), a significantly higher FDLQI score was seen for inflammatory skin diseases compared with noninflammatory diseases/isolated lesions (P < 0·0001), and there was a positive relationship between the family members' FDLQI scores and patients' disease severity (r = 0·49). Conclusions, The FDLQI is simple and practical and seems to have the potential to be used as an additional outcome measure in clinical practice and evaluation research. [source] Immunohistochemical detection for nuclear ,-catenin in sporadic basal cell carcinomaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2001F. Yamazaki Background Despite the increasing incidence of basal cell carcinoma (BCC), its pathogenesis has remained largely unknown. Recently, it was reported that genes involved in tissue morphogenesis, such as sonic hedgehog or patched, were found to be mutated in BCC, suggesting the involvement of those molecules in the pathogenesis of this tumour. Furthermore, there is evidence that the Wnt-mediated signalling pathway may be one of the downstream targets of sonic hedgehog -mediated signalling, which has led us to focus on molecular events on the Wnt pathway in BCC. Among the signal transducers involved in the Wnt pathway, it is clear that ,-catenin plays a pivotal role in the promotion of morphogenesis and cell growth. In respect to this, it has been reported that, in particular circumstances, as in colorectal cancers, ,-catenin migrates to the nuclei, where it exerts an ability to activate the transcription of various genes. Objectives To investigate the cellular distribution of ,-catenin in skin tumours, in particular, in BCC. Methods Twenty skin biopsy specimens derived from BCC, 10 from inflammatory skin diseases and five from squamous cell carcinomas were immunostained with an antibody directed against ,-catenin. Results Fourteen of the 20 BCC samples tested showed nuclear localization of ,-catenin, while none of the other samples gave rise to positive nuclear staining. Conclusions Nuclear localization of ,-catenin is a characteristic feature of BCC; this suggests its tumorigenic role in this tumour. This gives us a further insight into the molecular pathogenesis of BCC. [source] Photoactivation of an Inhibitor of the 12/15-Lipoxygenase PathwayCHEMBIOCHEM, Issue 7 2006Stephan Herre Abstract Lipoxygenases are lipid-peroxidizing enzymes that have been implicated in the pathogenesis of inflammatory diseases and lipoxygenase inhibitors may be developed as anti-inflammatory drugs. Structure comparison with known lipoxygenase inhibitors has suggested that (2Z)-2-(3-benzylidene)-3-oxo-2,3-dihydrobenzo[b]thiophene-7-carboxylic acid methyl ester might inhibit the lipoxygenase pathway but we found that it exhibited only a low inhibitory potency for the pure 12/15-lipoxygenase (IC50=0.7 mM). However, photoactivation, which induces a Z -to- E isomerization of the double bond, strongly augmented the inhibitory potency and an IC50 value of 0.021 mM was determined for the pure E isomer. Similar isomer-specific differences were observed with the recombinant enzyme and its 12-lipoxygenating Ile418Ala mutant, as well as in intracellular lipoxygenase activity. Structure modeling of the enzyme/inhibitor complex suggested the molecular reasons for this isomer specificity. Since light-induced isomerization may proceed in the skin, such photoreactive compounds might be developed as potential drugs for inflammatory skin diseases. [source] Autoantibodies against CD28 are associated with atopic diseasesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2006K. Neuber Summary The B7-1/B7-2-CD28/CTLA-4 pathway is crucial in regulating T cell activation and tolerance. Autoantibodies to surface molecules on lymphocytes have already been described in various immune conditions, such as autoimmune diseases, infections and blood transfusions. The objective of this study was to test sera from healthy individuals and from patients for association of CD28 autoantibodies with inflammatory and non-inflammatory diseases. First, CD28 was obtained by digestion of CD28-Ig fusion protein with trypsin. The cleavage products were separated by sodium dodecyl sulphate,page gel electrophoresis. Additionally, a CD28/GST fusion protein was expressed in Escherichia coli and was used to establish an enzyme-linked immunosorbent assay for detection of autoantibodies against CD28. Sera from healthy individuals (n = 72) and patients with different inflammatory and non-inflammatory skin diseases (n = 196) were tested for the presence of autoantibodies against CD28. Using mixed lymphocyte reaction (MLR), purified autoantibodies against CD28 were tested for their effects on CTLA-4-Ig-induced T cell anergy. In this study, for the first time, we describe the existence of autoantibodies against CD28 in humans which are associated with atopic diseases, e.g. allergic rhinitis and asthma. These antibodies stimulate T cells and overcome the CTLA-4-Ig-induced anergy of T cells in an MLR. The existence of autoantibodies against CD28, which may have a T cell-stimulating function, has been shown. The data indicate that autoantibodies against CD28 could be a new immunological mechanism in allergic inflammation. Additionally, autoantibodies against CD28 could be an important new marker to discriminate between atopic diseases and other inflammatory skin diseases. 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