Lesional Skin (lesional + skin)

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Terms modified by Lesional Skin

  • lesional skin biopsy

  • Selected Abstracts

    The cannabinoid receptor CB2 exerts antifibrotic effects in experimental dermal fibrosis

    ARTHRITIS & RHEUMATISM, Issue 4 2009
    Alfiya Akhmetshina
    Objective The cannabinoid receptor CB2 is predominantly expressed in non-neuronal tissue and exerts potent immunomodulatory effects. This study was undertaken to evaluate the role of CB2 in the pathogenesis of dermal fibrosis. Methods Mice deficient in CB2 (CB2,/, mice) and their wild-type littermates (CB2+/+ mice) were injected with bleomycin to induce experimental fibrosis. Mice were treated with selective agonists and antagonists of CB2. Lesional skin was evaluated for dermal thickness and numbers of infiltrating leukocytes. Bone marrow transplantation experiments were performed. Results CB2,/, mice were more sensitive to bleomycin-induced dermal fibrosis than were CB2+/+ mice, and showed increased dermal thickness. Leukocyte counts were significantly higher in the lesional skin of CB2+/+ mice. Increased dermal fibrosis was also observed upon treatment with the CB2 antagonist AM-630. In contrast, the selective CB2 agonist JWH-133 reduced leukocyte infiltration and dermal thickening. The phenotype of CB2,/, mice was mimicked by transplantation of CB2,/, bone marrow into CB2+/+ mice, whereas CB2,/, mice transplanted with bone marrow from CB2+/+ mice did not display an increased sensitivity to bleomycin-induced fibrosis, indicating that leukocyte expression of CB2 critically influences experimental fibrosis. Conclusion Our findings indicate that CB2 limits leukocyte infiltration and tissue fibrosis in experimental dermal fibrosis. Since selective CB2 agonists are available and well tolerated, CB2 might be an interesting molecular target for the treatment of early inflammatory stages of systemic sclerosis. [source]

    Non-pigmenting fixed drug eruption caused by allylisopropylacetylurea

    CONTACT DERMATITIS, Issue 4 2003
    Yukikazu Numata
    An unusual case of a non-pigmenting fixed drug eruption caused by allylisopropylacetylurea is reported. Several hours after taking an analgesic (New Kaiteki A), a 30-year-old Japanese woman, who had experienced similar eruptions several times after taking other analgesics, developed numerous variously sized, itchy, round-to-oval erythematous eruptions on the trunk and extremities. After she discontinued taking this drug, all such eruptions resolved within 2 weeks, without leaving postinflammatory pigmentation. Patch testing with New Kaiteki A itself and one of its active ingredients, allylisopropylacetylurea, on lesional skin, but not on uninvolved skin, showed positive erythematous reactions after 2 days. [source]

    CCL17 transgenic mice show an enhanced Th2-type response to both allergic and non-allergic stimuli

    Yuichiro Tsunemi Dr.
    Abstract CC chemokine ligand (CCL)17 is implicated in the pathogenesis of atopic dermatitis (AD). To study the effect of CCL17 produced by keratinocytes (KC) during inflammation, we created transgenic (Tg) mice in which CCL17 is overexpressed in KC. Th2-type contact hypersensitivity (CHS) was enhanced and Th1-type CHS was suppressed in these mice. Increased numbers of CC chemokine receptor (CCR)4+ cells and mast cells infiltrated in Tg mice. Levels of IL-4 mRNA were higher and those of IFN-, mRNA were lower in both acute and chronic CHS. Higher levels of serum IgE were observed after CHS. Numbers of CCR4+ cells among PBMC were increased in Tg mice challenged acutely on the trunk. Chronic irritation with croton oil induced dermatitis and an elevation of serum IgE levels. Tg mice showed enhanced ear swelling after tape stripping. CCL17 was thought to modify the inflammation caused by sensitizing reagents as well as irritant reagents by attracting CCR4+ cells into the lesional skin and creating a Th2-dominant condition. AD-like conditions such as increased number of mast cells and elevated levels of serum IgE were observed. Thus, CCL17 may participate in the pathogenesis of skin diseases such as AD by regulating both allergic and irritant inflammation. [source]

    Frequency, function and CLA expression of CD4+CD25+FOXP3+ regulatory T cells in bullous pemphigoid

    Anne Rensing-Ehl
    Abstract:, Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with autoantibodies to collagen XVII and tissue-separation along the dermo-epidermal junction. We addressed the question whether the loss of tolerance in BP patients is associated with a reduction and/or functional impairment of CD4+CD25+FOXP3+ regulatory T cells, which are essential for the active maintenance of self tolerance. The relative and absolute frequency of CD4+CD25+ and CD4+CD25high regulatory T cells in the peripheral blood of newly diagnosed, untreated patients was similar to that of healthy controls. Interestingly, more than 50% of circulating CD4+CD25high regulatory T cells from both patients as well as healthy controls expressed cutaneous lymphocyte-associated antigen. Considerable numbers of FOXP3+ cells were detected in lesional skin of patients. CD4+CD25+ regulatory T cells of patients were functionally intact as assessed by their ability to suppress allogeneic as well as antigen-specific T-cell proliferation. These data argue against a general defect of CD4+CD25+FOXP3+ regulatory T cells in patients with BP. [source]

    Expression pattern of somatostatin receptor subtypes 1,5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis

    Lena Hagstrmer
    Abstract:, In psoriasis and atopic dermatitis, the inflammatory events have neurogenic components and the neuropeptides modify the functions of immuno-active cells in the skin. Somatostatin is a neuropeptide with several neuroendocrine and immunomodulating properties and mediates its actions by five distinct subtypes of G-protein-coupled receptors (SSTR1-5). This study describes the distribution of SSTR1,5, analysed with immunohistochemistry, in psoriasis, atopic dermatitis and controls. Normal human skin and lesional skin from patients with psoriasis or atopic dermatitis showed many similarities, but also some differences, as regards SSTR expression. SSTR1,3 were strongly expressed in the epidermis of healthy skin, and in the skin of patients with psoriasis or atopic dermatitis. It is noteworthy that SSTR4 and 5 were strongly expressed in the epidermis of psoriasis patients, but weakly expressed in the epidermis of those with atopic dermatitis and normal skin. The intensity of the staining also varied considerably between the different layers of the epidermis, especially in psoriasis patients. In all cases, the dendritic cells, found mostly in the papillary and upper reticular dermis, showed a strong expression of SSTR1,4, but a weak expression of SSTR5. SSTR1,5 were strongly expressed in the sweat glands in all skin biopsies. Hair follicles and sebaceous glands expressed all five subtypes. Striated muscle fibres showed an intense positive expression of SSTR1,4, but a weak or negative expression of SSTR5. The wide distribution and expression pattern of all five SSTRs in human skin suggest that somatostatin is involved in the interactions between the nervous system and the skin. [source]

    Neuronal sensitization for itch in patients with chronic pruritus

    A. Ikoma
    Itch is one of the major symptoms of various skin diseases. Although specific neuronal pathways for itch were identified both peripherally and centrally, they still fail to explain itchy skin observed in patients with chronic pruritus. In this study, sensitivity to itchy and painful stimuli in patients with atopic dermatitis was investigated. Histamine-prick evoked enormous itch in their lesional skin, while less itch in their non-lesional skin than healthy subjects. Flare reaction was not significantly different between their non-lesional and lesional skin, rather smaller than healthy subjects. Mechanical (pin-pricks), electrical, heat and chemical (injection of pH3 solution) stimuli evoked intense itch in their lesional skin and partly also in their non-lesional skin, while only pain in healthy subjects. Itch was also, but not intensely, evoked in healthy subjects by injection of pH3 solution after sufficient histamine stimuli. These results confirm the presence of itchy skin with hyperkinesis (excessive itch by itchy stimuli) and allokinesis (itch by non-itchy stimuli) in patients with atopic dermatitis, which is so intense that painful stimuli cannot suppress but evoke itch, and suggest that neuronal sensitization is involved in their itch not only peripherally but also centrally. [source]

    Infiltrating cells and related cytokines in lesional skin of patients with chronic idiopathic urticaria and positive autologous serum skin test

    M. Caproni
    Abstract:, In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-,), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22,57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-, showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system. [source]

    Cutaneous vascular patterns in psoriasis

    Giuseppe Micali MD
    Microvascular abnormalities are a characteristic feature of psoriasis and play a crucial role in its pathogenesis. Investigational studies have shown that activated keratinocytes in lesional skin undergo an accelerated epidermal cell turnover and are a major source of pro-angiogenic cytokines, like as VEGF, ESAF, PDECGE/TP, TNF-,, TGF-, and PDGF, suggesting that the epidermis is capable of inducing vascular proliferation. On the other hand, microvascular alterations are essential for the development and persistence of the psoriatic lesions as they provide cellular and tissue nutrition to hyperplastic keratinocytes and promote inflammatory cell migration. Also, dilated and slightly tortuous blood vessels within dermal papillae represent one of the earliest detectable histological changes for all stages of lesional development. Videodermatoscopy is a new non invasive imaging technique able to identify modifications of microvascular architecture in vivo and such evaluation will be useful for the dermatologist both for diagnostic and prognostic evaluation, as well as for post-therapeutic follow-up. In this review, the role of microvascular abnormalities in the pathogenesis of psoriasis as well as the mechanisms underlying vascular changes and their primary therapeutic implications will be reviewed and discussed. [source]

    Progressive macular hypomelanosis in Singapore: a clinico-pathological study

    Sujith Prasad W. Kumarasinghe MBBS
    Introduction, Progressive macular hypomelanosis (PMH), a condition of uncertain etiology, is characterized by asymptomatic hypopigmented macules predominantly located on the trunk. To date, there are no reports from South-East Asia concerning this condition. We sought to record the clinical features of PMH in Asian patients, identify etiologic factors, and study the structural and ultrastructural features of melanocytes in this disorder. Methods, Patients who presented to the National Skin Center with acquired, hypopigmented macules on the trunk, without a history of inflammation or infection, were recruited. Erythrocyte sedimentation rate (ESR), complete blood count, fasting blood glucose, liver function tests, skin scrapings for fungi, and skin biopsy specimens (from lesional and normal skin) were obtained. Biopsies were stained with hematoxylin and eosin (H&E), Fontana Masson, an immunohistochemical panel for identification of melanocyte differentiation antibodies (HMB 45, Melan A, and S100) and CD 68. Electron microscopy (EM) was also performed. The patients were evaluated every 3 months. Results, During a 9 month period, eight patients (all Chinese) presented with hypopigmented, ill-defined, confluent macules involving the lower aspect of the trunk. There were four men and four women, and the mean age was 25.9 years (range 19,45 years). Skin scrapings were negative for fungi and laboratory tests were normal. Microscopic evaluation of skin biopsy speciments showed reduced pigmentation of lesional as compared with normal appearing skin, but H&E-stained sections revealed only minimal histologic differences between lesional and normal skin. EM demonstrated a statistically significant (P = 0.047, Wilcoxon Signed Rank Test, Wilcoxon 95% CI 0.02,0.62) higher ratio of stage IV and late stage III (dark) melanosomes in normal vs. lesional skin. Conclusions, PMH may occur among young adults in Singapore. Its etiology is uncertain. The melanin content of lesional skin appears to be less than that in normal sites. EM shows a higher ratio of immature melanosomes in lesional vs. normal skin. [source]

    Reassessment of microarray expression data of porokeratosis by quantitative real-time polymerase chain reaction

    Zheng-Hua Zhang
    Background: Porokeratosis (PK) is a heterogeneous group of keratinization disorders that exhibit similarities with psoriasis at both the clinical and molecular levels. Methods: The transcript levels of keratin (KRT) 6A, 16, 17, S100A7, A8, A9, p53 and three candidate genes (i.e. SART3, SSH1 and ARPC3) were reassessed in pairwise lesional and uninvolved skin from nine patients with PK by real-time quantitative polymerase chain reaction (RTQ,PCR). Results: The results of RTQ,PCR confirmed that KRT6A, 16, S100A7, A8 and A9 (p = 0.008) were mostly up-regulated in the lesional skin when compared with uninvolved skin. Different from the microarray data, there was no significant difference observed in KRT17 expression patterns between lesional and normal-appearing skin (p = 0.066). No statistical difference was observed in p53 and three candidate genes' expression patterns between lesional and uninvolved skin. Conclusions: In the present study, 9 of the 10 gene expression measured by RTQ,PCR in PK were statistically comparable to microarray data. KRT6A was identified as specific biomarker for porokeratotic keratinocytes, as it was the most significantly up-regulated gene in the nine patient samples. Zhang Z-H, Wang Z-M, Crosby ME, Kang KF, Luan J, Huang W, Xiang L-H, Zheng Z-Z. Reassessment of microarray expression data of porokeratosis by quantitative real-time polymerase chain reaction. [source]

    Lymphangiogenesis and angiogenesis in non-phymatous rosacea

    Amal H. A. Gomaa
    Background:, Our study evaluated the expression of vascular endothelial growth factor (VEGF), CD31 and D2-40 in involved and uninvolved skin of 18 patients with rosacea. Methods:, Immunostaining of facial skin specimens with VEGF, CD31 and D2-40 was compared between the lesional and the non-lesional skin of patients with erythemotelangiectatic and papulopustular rosacea. Results:, Significantly increased dermal expression of VEGF in lesional vs. non-lesional skin (88.9% and 55.6%) was observed. Dermal expression of CD31 and D2-40 was also increased in lesional vs. non-lesional skin. There was no statistically significant difference in cutaneous expression of VEGF, CD31 and D2-40 between patients with papulopustular and erythemotelangiectatic rosacea, and no correlation was found between disease duration and immunoreactivity of VEGF, CD31or D2-40. Conclusions:, Our study showed marked immunostaining of lesional skin with VEGF, CD31 and D2-40 compared with non-lesional skin. Increased immunoreactivity of D2-40 in lesional skin is interesting, given that none of the patients had facial edema. There are no published data regarding the role of lymphangiogenesis in patients with non-phymatous rosacea; thus, our study represents a new understanding of its pathogenesis. Lack of correlation between D2-40 expression and disease duration suggests that lymphatics are involved early in the pathogenesis of rosacea and do not constitute a late event. [source]

    Mid-dermal elastolysis preceded by acute neutrophilic dermatosis

    Kevan G. Lewis
    Background:, Mid-dermal elastolysis is a rare idiopathic elastic tissue disorder that is characterized by localized patches of finely wrinkled skin and a ,band-like' loss of elastic tissue in the mid-reticular dermis. Lesions may be preceded by erythema and/or urticaria, and histological examination of inflamed lesional skin may demonstrate lymphohistiocytic dermal infiltration. Case report:, We report a case of mid-dermal elastolysis in a 31-year-old woman who developed multiple erythematous and urticarial plaques on the arms and trunk. Histologic examination of a representative lesion revealed a neutrophilic infiltrate and a normal pattern of elastic tissue. Several months later, the erythema and urticaria was noted to have resolved, leaving soft, pendulous plaques with overlying finely wrinkled skin. A follow-up biopsy at this time showed minimal lymphocytic inflammation but almost complete absence of elastic tissue in the mid-reticular dermis. Conclusions:, To our knowledge, acute neutrophilic dermatosis resulting in mid-dermal elastolysis has not been previously described. This observation lends support to an emerging theory that the pathogenesis of mid-dermal elastolysis may be inflammatory. [source]

    MMP-2, TIMP-2 and MT1-MMP are differentially expressed in lesional skin of melanocytic nevi and their expression is modulated by UVB-light

    S. Krengel
    Background:, In malignant melanoma, recent studies have demonstrated an important role of matrix-metalloproteinase 2 (MMP-2), its co-activating enzyme membrane-type matrix-metalloproteinase 1 (MT1-MMP), and the endogenous inhibitor of MMP-2, tissue-inhibitor of matrix metalloproteinase 2 (TIMP-2). Melanocytic nevi are benign neoplasms of the melanocytic lineage, but may exhibit dysplastic features that can be difficult to distinguish from early stage melanoma. As shown in earlier studies, nevi show important morphological and phenotypical changes in response to ultraviolet light (UVB) irradiation. Objective:, To clarify the role of MMP-2, TIMP-2 and MT1-MMP in UVB-irradiated vs. non-irradiated melanocytic nevi. Methods:, Immunohistochemical comparison of the MMP-2, TIMP-2 and MT1-MMP expression pattern. Results:, MMP-2 is expressed by lesional keratinocytes and its expression is up-regulated by UVB-irradiation. MMP-2 expression was not observed in melanocytic cells. TIMP-2, by contrast, is predominantly expressed by melanocytic nevus cells, and its expression is in part down-regulated by UVB-irradiation. MT1-MMP is expressed by basal keratinocytes and to a weaker extent by melanocytic nevus cells. Conclusions:, MMP-2 expression by keratinocytes in nevi probably represents the result of activation of keratinocyte turnover in lesional epidermis. MMP-2 could play a role in the downward movement of junctional nevus cells into the dermis. The reduction of TIMP-2 expression in melanocytic cells by UV-light together with the enhanced expression of MMP-2 in the adjacent epidermis may promote basement membrane degradation. The expression pattern of MT1-MMP in close proximity to epithelial,mesenchymal interfaces underlines the synergistic role of MT1-MMP in this process. [source]

    Absence of Borrelia burgdorferi DNA in cutaneous B-cell lymphomas from the United States

    Gary S. Wood
    Background: An association between Borrelia burgdorferi and cutaneous B-cell lymphoma (CBCL) has been made in several European countries. The evidence in favor of such an association has recently been based on more definitive tests for the pathogenetic role of B. burgdorferi in CBCL, including positive cultures or polymerase chain reaction (PCR) amplification of borrelial DNA from lesional skin. However, there is only one report of B. burgdorferi in four North American cases of B-cell lymphoma. Methods: We retrieved 38 cases of primary and secondary CBCL from different geographic regions of the United States. Two separate techniques were used to detect borrelial DNA by PCR, a nested PCR method to amplify a B. burgdorferi -specific gene as well as a borrelial chromosomal Ly-1 clone amplification method. Southern blot hybridization was used for confirmation of the PCR results. Results: No B. burgdorferi -specific DNA was detected in any of the 38 CBCL cases, whereas detectable PCR products were obtained with our positive controls. Conclusions: Our findings, in light of previous studies, suggest that B. burgdorferi plays a minimal role in the development or pathogenesis of CBCL in the United States. The findings also suggest that the geographic variations in the clinical manifestations of B. burgdorferi are indeed real and may be secondary to the genetic and phenotypic differences between B. burgdorferi strains present in Europe and North America. [source]

    Upregulation of P-cadherin expression in the lesional skin of pemphigus, Hailey-Hailey disease and Darier's disease

    Megumi Hakuno
    Background: Autoimmune blistering diseases, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are known to be caused by binding of autoantibodies to the desmosomal cadherins, desmoglein 3 and desmoglein 1, respectively. Recently, mutations in the genes coding Ca2+ pumps leads to inherited blistering diseases, Hailey-Hailey disease (HHD) and Darier's disease (DD). Cadherins are a family of Ca2+ -dependent cell adhesion molecules and P-cadherin is one of the major cadherins expressed in the epidermis. Although detailed mechanisms of acantholysis of these blistering diseases have not been fully clarified, abnormal expression of cadherins caused by altered Ca2+ concentration due to the binding of autoantibodies to cell surface or by mutations in Ca2+ pumps is suggested to be involved in mechanisms of acantholysis of these atuoimmune and inherited blistering diseases. The purpose of the present study was to determine whether altered P-cadherin expression is present in these diseases. Method: Distribution patterns of P-cadherin in skin specimens from patients with PV (n=2), PF (n=2), HHD (n=4) and DD (n=3), were examined with confocal laser scanning microscopy using two anti-P-cadherin antibodies, 6A9 and NCC-CAD-299. Results: In normal control skin, P-cadherin expression was restricted to the basal layer. In contrast, positive immunostaining of P-cadherin was observed not only in the basal cells, but also in the suprabasal cells in lesional skin of all the acantholytic diseases. Conclusions: The present results clearly demonstrated that upregulation of P-cadherin expression occurs in the acantholysis in all the four blistering diseases PV, PF, HHD and DD. Upregulation of P-cadherin may be involved in the pathomechanism of both the autoimmune blistering diseases and the inherited blistering diseases. [source]

    Expression of VCAM-1, ICAM-1, E-selectin, and P-selectin on endothelium in situ in patients with erythroderma, mycosis fungoides and atopic dermatitis

    Vigfs Sigurdsson
    Background: Erythroderma may result from different causes. At present it is unclear whether the patho-mechanisms that lead to these different types of erythroderma are identical or different. Adhesion molecules and their ligands play a major role in endothelial-leukocyte interactions, which affect the binding, transmigration and infiltration of lymphocytes and mononuclear cells during inflammation, injury, or immunological stimulation. The aim of this study was to investigate the adhesion molecule expression on endothelial cells in erythroderma in situ. Methods: Snap-frozen skin biopsy specimens from 23 patients with erythroderma were studied. Eight had idiopathic erythroderma, 5 erythrodermic atopic dermatitis, 4 Szary syndrome and 6 had erythroderma from miscellaneous causes. As a control we studied skin specimens from 10 patients with mycosis fungoides, 5 patients with atopic dermatitis and 5 healthy non-atopic volunteers. To determine adhesion molecule expression on endothelial cells in situ, sections were immuno-histochemically double stained with biotinylated Ulex Europaeus agglutinin 1 as a pan-endothelial cell marker, and for the adhesion molecules VCAM-1, ICAM-1, E-, and P-selectin. All double- and single-stained blood vessels in the dermis were counted. Results: Mean endothelial expression in erythroderma was as follows: VCAM-1 51.4%, ICAM-1 70.1%, E-selectin 43.5%, and P-selectin 52.6%. There was no statistical difference between different groups of erythroderma. Mean expression of all adhesion molecules tested, was in Szary syndrome higher than in mycosis fungoides albeit not significant. In erythrodermic atopic dermatitis only VCAM-1 expression was significantly higher than in lesional skin of atopic dermatitis. No differences were observed in expression of the other three adhesion molecules. Conclusions: There is no difference regarding adhesion molecule expression on endothelial cells between different types of erythroderma. [source]

    Atrophodermia vermiculata: case report and review of the literature

    T Jansen
    ABSTRACT A 21-year-old woman with an 11-year history of symmetric reticular atrophy on both cheeks, pre-auricular areas, and forehead is presented. The depressions gave a worm-eaten appearance to the skin. Histopathological findings from a biopsy specimen of lesional skin revealed an atrophic follicle. The connective tissue showed mild inflammation in perifollicular and perivascular distribution. The hair follicle was widely dilated and was filled with a keratotic plug. This case points out many of the outstanding clinical and histopathological features of atrophodermia vermiculata as described previously. Atrophodermia vermiculata appears to be one of a group of closely related conditions characterized by keratosis pilaris and atrophy of the skin. [source]

    Natural killer T cells expressing IFN-, and IL-4 in lesional skin of atopic eczema

    ALLERGY, Issue 11 2009
    D. Simon
    Background:, The inflammation of atopic eczema (AE) is orchestrated not only by T cells predominantly but also B cells, eosinophils and dendritic cells. Recently, a role of invariant natural killer T (NKT) cells has been reported in bronchial asthma and allergy. Natural killer T cells express a restricted repertoire of T-cell receptor ,/, and produce interferon (IFN)-, and/or interleukin (IL)-4 upon activation. Aim of the study:, To determine the presence of NKT cells in lesional AE skin in comparison with other eczematous disorders and to analyse their cytokine expression. Methods:, Immunofluorescence stainings were carried out using antibodies recognizing NKT cells, CD3+ and CD4+ cells, IFN-, and IL-4. Results:, Natural killer T cells have been detected in small numbers in the majority of AE specimens as well as in atopy patch test (APT) reactions, allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). In AE, the proportion of NKT cells among CD3+ cells was approximately 5%. NKT cells expressed both IFN-, and IL-4 in AE, APT and ACD but predominantly IFN-, in ICD. Conclusion:, Natural killer T cells are part of the inflammatory infiltrate of AE as well as APT, ACD and ICD, suggesting a pathogenic role of NKT cells in eczematous skin disorders. The pattern of IFN-, and IL-4 cytokine expression by NKT cells varied depending on the type of eczematous disease. [source]

    Double-Blind, Randomized, Placebo-Controlled Trial of the Use of Topical 10% Potassium Hydroxide Solution in the Treatment of Molluscum Contagiosum

    Katherine A. Short M.R.C.P.
    Lesions take between 6 and 18 months to resolve spontaneously and are a source of great embarrassment to both caretakers and children, often affecting attendance at school and limiting social activity. Treatment options to date have been poorly tolerated by children but recent studies have suggested that potassium hydroxide may be beneficial. This double-blind, randomized, placebo-controlled study compared 10% potassium hydroxide with placebo (normal saline). Twenty patients, aged 2 to 12 years, were recruited. Parents applied a solution twice daily to lesional skin until signs of inflammation appeared. Children were examined by the same observer on days 0, 15, 30, 60, and 90. Seventy percent of children receiving topical potassium hydroxide cleared, compared with 20% in the placebo group. Further dosing studies are required to identify whether weaker concentrations of potassium hydroxide are as efficacious, with less irritancy. [source]

    Expression of p53 in lesions and unaffected skin of patients with plaque-type and guttate psoriasis: A quantitative comparative study

    Aya Cordan YAZICI
    ABSTRACT Psoriasis is a common inflammatory and hyperproliferative skin disease characterized by hyperproliferation of keratinocytes. The pathogenesis of psoriasis has yet to be determined. The control of cell growth is a delicately balanced process, regulated by external signals or the internal genetic program of an individual cell. In psoriasis, these processes are disturbed and some candidate genes like p53 are suspected of being involved in the pathogenesis of the disease. The p53 protein is essential for the regulation of cell proliferation. The study was performed on 32 patients with psoriasis (24 plaque type, eight guttate type). Biopsy specimens for immunohistochemical determination of p53 protein expression were collected from both the lesional and the nonlesional skin sites that were not exposed to sun in all of the patients (n = 32). Taking the ultraviolet (UV) exposure of the skin into consideration, a third skin sample was taken from each patient (n = 7) who had lesions on the sun-exposed areas. Immunohistochemical assessment of p53 expression in skin was determined as p53 protein expression per 1000 cells (keratinocytes). The statistical analysis revealed that the expressions of p53 per 1000 cells were higher in non-sun-exposed lesional skin than the non-sun-exposed nonlesional skin, also in plaque-type psoriasis than guttate-type psoriasis (P = 0.000, P = 0.046, P = 0.037, respectively). There was a positive correlation between the p53 expression in non-sun-exposed lesional skin versus expression in sun-exposed lesional skin (cubic centimeters = 0.811, P = 0.027). Our results show a stronger association of elevated p53 expression with chronic rather than acute inflammatory psoriasis. This may indicate a mechanistic difference between plaque-type and guttate psoriasis. Alternatively, this could reflect a chronological course as the disease transitions from an acute to a chronic phase. [source]

    Neutralization of interferon-,/,,inducible genes and downstream effect in a phase I trial of an anti,interferon-, monoclonal antibody in systemic lupus erythematosus,

    ARTHRITIS & RHEUMATISM, Issue 6 2009
    Yihong Yao
    Objective Type I interferons (IFNs) play an important role in the pathogenesis of systemic lupus erythematosus (SLE). This phase Ia trial was undertaken to evaluate the safety, pharmacokinetics, and immunogenicity of anti-IFN, monoclonal antibody (mAb) therapy in SLE. During the trial, we also examined whether overexpression of an IFN,/,-inducible gene signature in whole blood could serve as a pharmacodynamic biomarker to evaluate IFN, neutralization and investigated downstream effects of neutralizing IFN, on BAFF and other key signaling pathways, i.e., granulocyte,macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), tumor necrosis factor , (TNF,), and IL-1,, in SLE. Methods Affymetrix Human Genome U133 Plus 2.0 microarrays were used to profile whole blood and lesional skin of patients receiving standard therapy for mild to moderate SLE. Selected IFN,/,-inducible proteins were analyzed by immunohistochemistry. Results With the study treatment, we observed anti-IFN, mAb,specific and dose-dependent inhibition of overexpression of IFN,/,-inducible genes in whole blood and skin lesions from SLE patients, at both the transcript and the protein levels. In SLE patients with overexpression of messenger RNA for BAFF, TNF,, IL-10, IL-1,, GM-CSF, and their respective inducible gene signatures in whole blood and/or skin lesions, we observed a general trend toward suppression of the expression of these genes and/or gene signatures upon treatment with anti-IFN, mAb. Conclusion IFN,/,-inducible gene signatures in whole blood are effective pharmacodynamic biomarkers to evaluate anti-IFN, mAb therapy in SLE. Anti-IFN, mAb can neutralize overexpression of IFN,/,-inducible genes in whole blood and lesional skin from SLE patients and has profound effects on signaling pathways that may be downstream of IFN, in SLE. [source]

    The cannabinoid receptor CB2 exerts antifibrotic effects in experimental dermal fibrosis

    ARTHRITIS & RHEUMATISM, Issue 4 2009
    Alfiya Akhmetshina
    Objective The cannabinoid receptor CB2 is predominantly expressed in non-neuronal tissue and exerts potent immunomodulatory effects. This study was undertaken to evaluate the role of CB2 in the pathogenesis of dermal fibrosis. Methods Mice deficient in CB2 (CB2,/, mice) and their wild-type littermates (CB2+/+ mice) were injected with bleomycin to induce experimental fibrosis. Mice were treated with selective agonists and antagonists of CB2. Lesional skin was evaluated for dermal thickness and numbers of infiltrating leukocytes. Bone marrow transplantation experiments were performed. Results CB2,/, mice were more sensitive to bleomycin-induced dermal fibrosis than were CB2+/+ mice, and showed increased dermal thickness. Leukocyte counts were significantly higher in the lesional skin of CB2+/+ mice. Increased dermal fibrosis was also observed upon treatment with the CB2 antagonist AM-630. In contrast, the selective CB2 agonist JWH-133 reduced leukocyte infiltration and dermal thickening. The phenotype of CB2,/, mice was mimicked by transplantation of CB2,/, bone marrow into CB2+/+ mice, whereas CB2,/, mice transplanted with bone marrow from CB2+/+ mice did not display an increased sensitivity to bleomycin-induced fibrosis, indicating that leukocyte expression of CB2 critically influences experimental fibrosis. Conclusion Our findings indicate that CB2 limits leukocyte infiltration and tissue fibrosis in experimental dermal fibrosis. Since selective CB2 agonists are available and well tolerated, CB2 might be an interesting molecular target for the treatment of early inflammatory stages of systemic sclerosis. [source]

    Evidence for a pathogenetic role of interleukin-18 in cutaneous lupus erythematosus

    ARTHRITIS & RHEUMATISM, Issue 10 2008
    Dong Wang
    Objective Cutaneous manifestations are the most common clinical features of lupus erythematosus (LE). The aim of this study was to analyze differences in the inflammatory response of keratinocytes from patients with cutaneous LE (CLE) compared with healthy controls. Methods Keratinocytes from LE patients and controls were cultured from epidermal stem cells of the hair follicle of anagen head hairs. Functional responses of keratinocytes to cytokine stimulation were determined by flow cytometry and enzyme-linked immunosorbent assay. Biopsy samples of lesional skin were analyzed by immunohistochemistry. Results Keratinocytes from CLE patients expressed higher levels of IL-18 receptor on their cell surface in response to tumor necrosis factor , (TNF,) or interferon-, stimulation. In response to IL-18 stimulation, these cells produced large amounts of TNF,. Of note, in the presence of IL-18, CLE keratinocytes failed to express IL-12. IL-12 has previously been shown to protect keratinocytes from ultraviolet irradiation,induced apoptosis. Keratinocytes from LE patients were more prone to die upon exposure to IL-18, and this increased apoptosis was abrogated by blockade of endogenously produced TNF, as well as by the addition of exogenous IL-12. IL-18 was highly expressed in biopsy samples of lesional skin from CLE patients. Conclusion Our results demonstrate an intrinsic difference in the inflammatory response of keratinocytes and indicate an autocrine feedback loop involving TNF,, IL-18, and IL-12 family members. Our results suggest that IL-18 may occupy an important position in the cytokine hierarchy in CLE, indicating the potential benefit of a local agent that blocks IL-18 activity in the treatment of the manifestations of CLE. [source]

    Presence of CD4+CD8+ double-positive T cells with very high interleukin-4 production potential in lesional skin of patients with systemic sclerosis

    ARTHRITIS & RHEUMATISM, Issue 10 2007
    Yann Parel
    Objective Fibrotic skin changes in systemic sclerosis (SSc) are preceded by the appearance of an inflammatory infiltrate rich in T cells. Since no direct comparison with T cells in normal skin has been performed previously, this study was undertaken to functionally characterize T cells in the skin of patients with early active SSc and in normal skin. Methods We characterized coreceptor expression, T cell receptor (TCR) usage, cytokine production, and helper and cytolytic activity of T cell lines and clones established from skin biopsy specimens from 6 SSc patients and 4 healthy individuals. Immunofluorescence analysis of skin biopsy and peripheral blood samples was performed to confirm the presence of specific subsets in vivo. Results A distinct subset expressing both CD4 and CD8,/, coreceptors at high levels (double-positive [DP]) was present in T cell lines from SSc and normal skin. DP T cells actively transcribed both accessory molecules, exerted clonally distributed cytolytic and helper activity, and expressed TCR clonotypes distinct from those in CD4+ or CD8+ single-positive (SP) T cells. In SSc skin, DP T cells produced very high levels of interleukin-4 (IL-4) compared with CD4+ SP T cells. Furthermore, DP T cells were directly identified in SSc skin, thus providing evidence that they are a distinct subset in vivo. Conclusion The present findings show that T cells with the unusual CD4+CD8+ DP phenotype are present in the skin. Their very high level of IL-4 production in early active SSc may contribute to enhanced extracellular matrix deposition by fibroblasts. [source]

    Neutrophilic fixed drug eruption

    Karen L Agnew
    SUMMARY A 49-year-old man presented with a reproducible, localized amoxycillin,clavulanic acid-induced eruption. The histopathology from lesional skin revealed a neutrophilic dermatosis. These histological findings have not been reported in previous fixed drug eruptions. A brief review is undertaken comparing fixed drug eruption and the group of neutrophilic dermatoses with our case presentation. We propose a new entity of neutrophilic fixed drug eruption. [source]

    Purification, crystallization and preliminary X-ray diffraction of human S100A15

    Karen M. Boeshans
    Human S100A15 is a novel member of the S100 family of EF-hand calcium-binding proteins and was recently identified in psoriasis, where it is significantly upregulated in lesional skin. The protein is implicated as an effector in calcium-mediated signal transduction pathways. Although its biological function is unclear, the association of the 11.2,kDa S100A15 with psoriasis suggests that it contributes to the pathogenesis of the disease and could provide a molecular target for therapy. To provide insight into the function of S100A15, the protein was crystallized to visualize its structure and to further the understanding of how the many similar calcium-binding mediator proteins in the cell distinguish their cognate target molecules. The S100A15 protein has been cloned, expressed and purified to homogeneity and produced two crystal forms. Crystals of form I are triclinic, with unit-cell parameters a = 33.5, b = 44.3, c = 44.8,, , = 71.2, , = 68.1, , = 67.8 and an estimated two molecules in the asymmetric unit, and diffract to 1.7, resolution. Crystals of form II are monoclinic, with unit-cell parameters a = 82.1, b = 33.6, c = 52.2,, , = 128.2 and an estimated one molecule in the asymmetric unit, and diffract to 2.0, resolution. This structural analysis of the human S100A15 will further aid in the phylogenic comparison between the other members of the S100 protein family, especially the highly homologous paralog S100A7. [source]

    Evaluation of zinc level in skin of patients with necrolytic acral erythema

    H.A.M. Moneib
    Summary Background, Necrolytic acral erythema (NAE) is considered a cutaneous sign of hepatitis C virus infection. Its exact pathogenesis is still not fully understood, with some reports about decreased serum zinc levels but none about its level in the skin. Objectives, To assess skin (lesional and perilesional) and serum zinc levels in patients with NAE and compare them with levels in control subjects. Methods, Fifteen patients with NAE and 10 healthy controls were included in this study. Assessment of zinc level, in serum by graphite furnace atomic absorption spectrophotometry and in lesional and perilesional skin biopsies by flame atomic absorption spectrometry, was done in all subjects. Re-evaluation of serum and lesional skin zinc level was done after oral zinc treatment. Results, Mean SD zinc levels were significantly lower in patients (serum 044 013 mg L,1; lesional skin 426 189 mg L,1; perilesional skin 325 172 mg L,1) than controls (serum 117 029 mg L,1; skin 1001 277 mg L,1), with a positive correlation between lesional and perilesional skin zinc (r = 091, P < 001). Oral zinc supplementation significantly increased serum and skin zinc levels (by 159% and 4%, respectively; P < 005). Conclusions, NAE is associated with decreased serum and skin zinc levels. Oral zinc supplementation corrects decreased levels of plasma and skin zinc much earlier than the desired clinical benefits appear. [source]

    Regulatory T cells in atopic dermatitis: epidermal dendritic cell clusters may contribute to their local expansion

    A. Szegedi
    Summary Background, Regulatory T cells (Tregs) have an essential role in tolerance and immune regulation. However, few and controversial data have been published to date on the role and number of these cells in atopic dermatitis (AD). Objectives, To investigate the number of CD4+CD25+FOXP3+ Tregs and interleukin 10-producing T regulatory type 1 (Tr1) cells in patients with AD. Methods, Peripheral blood and skin biopsy samples from atopy patch test (APT)-positive patients with acute- and chronic-phase AD were investigated. Immunohistochemistry was applied to identify CD4+CD25+FOXP3+ Tregs in the skin, while flow cytometry was used to detect CD4+CD25highFOXP3+ Tregs and Tr1 cells in the peripheral blood. Results, In the peripheral blood samples of patients with AD significantly elevated numbers of Tr1 cells were found. Although neither the absolute number nor the percentage of CD4+CD25highFOXP3+ Tregs showed significant alteration in the peripheral blood of patients, increased numbers of FOXP3+ Tregs were detected in skin biopsy specimens. All of the APT-positive skin samples showed epidermal dendritic cell aggregates, morphologically consistent with so-called Langerhans cell microgranulomas, which also contained intermingled FOXP3+ Tregs. Conclusions, Tr1 cell numbers were elevated in the peripheral blood and increased numbers of CD4+CD25highFOXP3+ Tregs were detected in the skin of patients with AD. The epidermal dendritic cell clusters in APT-positive lesional skin showed a close connection to the FOXP3+ Tregs. [source]

    Immunological effects of stress in psoriasis

    G. Schmid-Ott
    Summary Background, Psychological stress causes phenotypic changes in circulating lymphocytes and is regarded as an important trigger of the Th1-polarized inflammatory skin disease psoriasis. Objective, To study the effects of psychological stress on immunological parameters, i.e. membrane molecules relevant to the pathophysiology of psoriasis, especially cutaneous lymphocyte-associated antigens (CLA) involved in T and natural killer (NK) cells homing in on the skin. Methods, The severity of psoriasis was assessed in patients using the Psoriasis Area and Severity Index. Patients with psoriasis (n = 15) and healthy volunteers (n = 15) were exposed to brief psychological stress in the laboratory. In vitro analyses were conducted 1 h before, immediately following and 1 h after stress exposure. Peripheral T- and NK-cell subsets including CD8+ T lymphocytes, CLA+ lymphocytes and lymphocyte function-associated antigen type 1 (LFA-1)+ lymphocytes were analysed by flow cytometry. Results, We found a significant stress-induced increase of CD3+ T lymphocytes in patients with psoriasis only. Analyses of T-cell subsets revealed that this increase was observable for cytotoxic CD8+ T lymphocytes and CLA+ CD3+ lymphocytes. The total number of circulating NK cells (CD16+, CD56+) increased immediately after stress in both groups whereas only patients with psoriasis showed a significant increase in CLA+ NK cells. Conclusions, A higher stress-induced increase of CLA+ T and CLA+ NK cells in the circulation of patients with psoriasis might point to an increased ability of T and NK cells in the presence of psoriasis to home in on the skin during mental stress. Further studies are needed to verify these relationships in more detail and to investigate the time point at which these cells accumulate within lesional skin, and whether or not psychotherapy improves the quality of life of patients with psoriasis and influences stress-dependent parameters. [source]

    Expression of insulin-like growth factor-I in lesional and non-lesional skin of patients with morphoea

    M.M.T. Fawzi
    Summary Background, Morphoea (scleroderma) is a chronic disorder characterized by circumscribed sclerotic plaques with the hallmark of increased fibroblast activation and fibrosis. Through its effect on connective tissue cells and immune cells, insulin-like growth factor (IGF)-I has been found to play a role in some autoimmune connective tissue diseases and has been implicated in the pathogenesis of several fibrotic disorders. Objectives, To evaluate the role of IGF-I in the pathogenesis of morphoea. Methods, The study was carried out on 15 patients with morphoea and nine healthy controls. Two 5-mm punch skin biopsies were taken from every patient (one from lesional and one from non-lesional skin) and a single biopsy was taken from the normal skin of each control. A 10-mL blood sample was also taken from each patient and control. Quantitative detection of tissue and serum levels of IGF-I was done using an enzyme-linked immunosorbent assay technique. Results, IGF-I in lesional skin was significantly higher than in non-lesional and control skin (P = 0001 and P = 0021, respectively). Moreover, a significantly higher level of IGF-I was detected in patient serum when compared with control serum (P < 0001). A direct significant correlation existed between lesional and non-lesional skin level (r = 0618, P = 0014), and between lesional skin level and Rodnan score (r = 0538, P = 0039). Conclusions, Despite the small sample size, this study suggests that IGF-I plays an important role in the pathogenesis of fibrosis, characteristic of morphoea. Studies on a larger number of patients with morphoea as well as on patients with systemic sclerosis are recommended. Furthermore, therapeutic trials using IGF-I antagonist (octreotide) are highly recommended in patients with morphoea. [source]