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The human skin, as the boundary organ between the human body and the environment, is under the constant influence of free radicals (FR), both from the outside in and from the inside out. Carotenoids are known to be powerful antioxidant substances playing an essential role in the reactions of neutralization of FR (mainly reactive oxygen species ROS). Carotenoid molecules present in the tissue are capable of neutralizing several attacks of FR, especially ROS, and are then destroyed. Human skin contains carotenoids, such as α-, γ-, β-carotene, lutein, zeaxanthin, lycopene and their isomers, which serve the living cells as a protection against oxidation. Recent studies have reported the possibility to investigate carotenoids in human skin quickly and non-invasively by spectroscopic means. Results obtained from in-vivo studies on human skin have shown that carotenoids are vital components of the antioxidative protective system of the human skin and could serve as marker substances for the overall antioxidative status. Reflecting the nutritional and stress situation of volunteers, carotenoids must be administered by means of antioxidant-rich products, e.g., in the form of fruit and vegetables. Carotenoids are degraded by stress factors of any type, inter alia, sun radiation, contact with environmental hazards, illness, etc. The kinetics of the accumulation and degradation of carotenoids in the skin have been investigated. [ABSTRACT FROM AUTHOR]

Abstract: Psoriasis is a common chronic skin disease. Its pathogenesis has intensively been investigated in the last 3 decades. In the 1970s, the observed increased proliferation of keratinocytes and their altered differentiation were considered to be the most important signs and causes of psoriatic skin lesions. Since the early 1980s, T cells slid into the focus of psoriasis research. It was then postulated that a subpopulation of T cells, so-called T1 cells, and their prominent cytokine interferon-γ, had a dominant role in the pathogenesis of psoriasis. In the last decade, new data regarding macrophages and dendritic cells and the high therapeutic success of anti–tumor necrosis factor α biologics led to the assumption that antigen-presenting cells are important not only in the induction of psoriasis but also in its maintenance. The knowledge gained over the past 3 decades let us postulate that psoriasis is an immunologically induced, overshot, regeneration-like reaction of the skin in which various cells play a dominant role at different stages. This hypothesis is also supported by the very recent discoveries about interleukin (IL)-22, IL-20, and IL-23. [Copyright &y& Elsevier]

The cellular and molecular events taking place during epidermal antigen exposure in sensitized individuals are principally well understood. Epidermal Langerhans cells (LC) are supposed to take up, process, and express a given foreign substance on their cell surface. The antigen is then recognized by T cells bearing the appropriate T-cell receptor (TCR). Because LC do not bear variable antigen (Ag)- specific binding sites, one could postulate that the epidermal exposure of any substance should activate LC and other cells of the skin immune system. To test this hypothesis, we analyzed immunophenotypically the cellular trafficking events in positive (n = 5) and negative epicutaneous patch-test reactions (n = 10), using a panel of monoclonal antibodies against CD1a, CD11c (Ki- M1, LeuM5), CD68 (Ki-M6), Ki-M8, and CD3 (Leu4). We can demonstrate that irrespective of whether or not an antigen will be responded to by the immune system (i.e., positive or negative test reaction), epidermal antigen exposure causes a decrease of LC density in the epidermis and simultaneously causes an increase of LC in the dermis. More- over, monocytes and T cells immigrate into the dermis both in positive and negative patch-test reactions. As is to be expected, the degree of this cellular traffic is more pronounced in positive test reactions, which may be due to amplification mechanisms caused by antigen recognition of sensitized T cells. This finding demonstrates that human skin contains cell migration programs that ensure that any foreign substance will be accessible to the skin immune and phagocytic system. [ABSTRACT FROM AUTHOR]

Monocytes and macrophages are known to be important for a variety of functions; however, whereas epidermal Langerhans cells have been studied in great detail, few data are available for the dermal monocyte/macrophage system. Therefore we investigated the density, distribution, and phenotype of dermal macrophages in normal human skin using a panel of monoclonal antibodies for single and double labeling. We demonstrate here that within normal human dermis macrophages reside with a remarkable density. Principally, these cells exhibit the phenotype of the phagocytic macrophage system (CD11c+, KiM8+), whereas members of the immune phagocyte system (CD11c+, KiM8-) are absent from normal dermis with the exception of a few Langerhans cells in the papillary body. Within the dermal phagocytic macrophage system we uncover an unexpected phenotypical and morphologic heterogeneity, which correlates with the tissue localization. This study provides a basis for investigating the participation and change of the dermal macrophage system in cutaneous disorders. [ABSTRACT FROM AUTHOR]

CD4+ T cells are heterogenous and include at least two subsets that differ in their influence to immunoglobin synthesis, cytokine secretion pattern and immunophenotype. Among others these subsets have been designated as suppressor/inducer or naive T cells (CD45RA+, CDw29-) and helper/inducer or memory T cells (CD45RA-, CDw29+). Current theories suggest that these CD4+ T-cell subsets either reflect sequential stages of maturation before and after activation (antigen contact) or represent distinct lineages. In this study, we systematically analyzed the participation of both suppressor/inducer (CD45RA+) and helper/inducer (CDw29+) T cells in the dermal lymphohistiocytic infiltrate of various CD4+ cutaneous T-cell lymphomas. Although in peripheral blood both subsets are equally distributed, we present evidence that all CD4+ cutaneous T-cell lymphomas are of the helper/inducer T cell phenotype. These findings are of importance both for pathogenetic and clinical considerations: the presence of plasma cells in dermal infiltrates and the elevation of serum immunoglobulins in patients of mycosis fungoides may be the consequence of interleukin-4 secretion of the neoplastic CD+ helper/inducer cells. The exclusive memory T cell phenotype of cutaneous T-cell lymphomas may be due to a general predominance of this subset in the skin, or be the consequence of cellular activation during malignant transformation. [ABSTRACT FROM AUTHOR]

Epidermal dendritic cells showing a diffuse activity of acid nonspecific esterase were observed in three cases of mycosis fungoides stage 1. As these cells by their appearance and localization resemble Langerhans cells, and dermal histiocytes and macrophages react in the same manner, this is another enzyme cytochemical suggestion of a relationship between Langerhans cells and the monocyte-macrophage-system. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Prevalence of the MspI and Ile462Val SNPs of Cytochrome P-450 1A1 in Hidradenitis Suppurativa. Experimental Dermatology 2010; 19: 541–542. Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease that affects the hair follicles in the axillary, perianal and inguinal area. Its cause and pathogenesis are unknown, but cigarette smoking increases the risk of developing HS conceivably by accumulating toxic metabolites in sweat. The xenobiotic compounds from tobacco are metabolized by the cytochromes P-450. The cytochrome P-450 1A1 (CYP1A1), one of the most active isoenzymes, harbours several polymorphisms. Two of them, MspI and Ile462Val single nucleotide polymorphism (SNP), are associated with enhanced activity and inducibility. Performing direct DNA sequencing, we investigated the frequencies of these SNP in 51 patients with HS, 45 of these were smokers. We found similar overall SNP rates in our patients in comparison with previous data for Caucasian or German controls. Obviously, there is no relation between the occurrence of these SNPs and the risk of developing HS. [ABSTRACT FROM AUTHOR]

Presents letters to the editor regarding the effect of sunlight exposure on the skin.

Examines the role of pentoxifylline drug on the reduction of side effect of fumaric acid ester (FAE) therapy on patients with Psoriasis. Influence of releasing of tumor necrosis factor-alpha during initial phase of therapy on the adverse effect of FAE; Standard doses of FAE for treatment; Symptoms of the disease.

The article cites a case study related to a contact urticaria and dermatitis from self-adhesive pads. Self-adhesive pads for everyday use find increasing distribution, since they have direct contact with intertriginous skin, adverse reactions are not unexpected. A 47-year-old patient had genital pruritus and mild eczematous changes after having used self-adhesive pads for several months. Patch tests with the different layers of a pad gave a positive reaction to the layer which contained a fragrance and a disinfecting agent, Cu(II)-acetyl acetonate.

The article presents a study related to the in situ identification and documentation and enumeration of helper T lymphocytes in cutaneous malignant lymphomas by dipeptidyl-peptidase IV (DPP IV). DPP IV, a protease which hydrolyzes glycyl-proline residues from tri- or tetrapeptides and naphthylamides, occurs in about 40% of peripheral blood lymphocytes, while it is totally absent in the granulocyte and monocyte series. A small number of DPP IV-positive lymphocytes is also present in cutaneous B-cell lymphomas and lymphoblastic lymphomas.

Presents a letter to the editor about differential expression of lymphocyte function-associated Antigen 1 on epidermotropic and non-epidermotropic T-cell clones.

The article focuses on a randomised, double blind study which compared the effectiveness of two etanercept regimens in treating psoriasis and psoriatic arthritis. Participants of the study were treated with either etanercept 50 milligrams (mg) twice weekly or 50 mg once weekly for 12 weeks by subcutaneous injection. Study participants who received etanercept 50 mg twice weekly achieved a physician's global assessment of psoriasis of clear or almost clear compared with 32% in the group treated with 50 mg weekly.

The International League of Dermatological Societies (ILDS), a global, not-for-profit organization representing 157 dermatological societies worldwide, has identified the consequences of skin aging as one of the most important grand challenges in global skin health. Reduced functional capacity and increased susceptibility of the skin with development of dermatoses such as dry skin, itching, ulcers, dyspigmentation, wrinkles, fungal infections, as well as benign and malignant tumors are the most common skin conditions in aged populations worldwide. Environmental (e.g., pollution) and lifestyle factors (e.g., smoking, sunbed use) negatively affect skin health. In turn altered appearance, dry skin, chronic wounds, and other conditions decrease general health and reduce the likelihood for healthy and active aging. Preventive skin care includes primary, secondary, and tertiary interventions. Continuous sun protection from early childhood onward is most important, to avoid extrinsic skin damage and skin cancer. Exposure to irritants, allergens, or other molecules damaging the skin must be avoided or reduced to a minimum. Public health approaches are needed to implement preventive and basic skin care worldwide to reach high numbers of dermatological patients and care receivers. Education of primary caregivers and implementation of community dermatology are successful strategies in resource-poor countries. Besides specialist physicians, nurses and other health care professionals play important roles in preventing and managing age-related skin conditions in developing as well as in developed countries. Healthy skin across the life course leads to better mental and emotional health, positive impact on social engagement, and healthier, more active, and productive lives. [ABSTRACT FROM AUTHOR]

Presents a response by the authors of the study on organization of monocyte/macrophage system of normal human skin, to the letter to the editor published in the July 1991 issue of the "Journal of Investigative Dermatology," on the study.

Background The objective of the present study was the investigation of hair follicle morphology in eight mammalian species in order to evaluate the species-specific contribution of hair follicles to skin penetration particularly with regard to the utilization of the different animal species as skin models for human skin. Methods Cyanoacrylate skin surface biopsy method (CSSB), light microscopy and also digital photography were used for the measurements of hair follicle morphology. Results The results revealed species-specific differences regarding the pattern of hair follicle distribution and also differences with regard to hair follicle parameters and characteristics. The results also showed that hair follicles generally possess enormous reservoir capacities, regarding the follicular volume. In all examined species, hair follicles reached at least one-fifth of stratum corneum storage capacity. The results were compared with human data obtained in a previous study. Conclusion With regard to hair follicle morphology and skin structure, the porcine skin seems to be the most appropriate skin model for human skin analog to previous investigations, whereas the skin of dog, cat, and rabbit showed the most significant differences. [ABSTRACT FROM AUTHOR]

Carotenoids are important substances for human skin due to their powerful antioxidant properties in reaction of neutralization of free radicals and especially reactive oxygen species, including singlet oxygen. Concentration of carotenoids in the skin could mirror the current redox status of the skin and should be investigated in vivo. Optical methods are ideally suited for determination of carotenoids in mammalian skin in vivo as they are both noninvasive and quick. Four different optical methods could be used for in vivo measurement of carotenoids in the human or animal skin: (1) resonance Raman spectroscopy; (2) Raman microscopy; (3) reflection spectroscopy; (4) skin color measurements. The advantages, shortcomings, and limitations of the above-mentioned optical methods are discussed. [ABSTRACT FROM AUTHOR]

Recent advances in the field of nanotechnology have allowed the manufacturing of elaborated nanometer-sized particles for various biomedical applications. A broad spectrum of particles, extending from various lipid nanostructures such as liposomes and solid lipid nanoparticles, to metal, nanocrystalline and polymer particles have already been tested as drug delivery systems in different animal models with remarkable results, promising an extensive commercialization in the coming years. Controlled drug release to skin and skin appendages, targeting of hair follicle-specific cell populations, transcutaneous vaccination and transdermal gene therapy are only a few of these new applications. Carrier systems of the new generation take advantage of improved skin penetration properties, depot effect with sustained drug release and of surface functionalization (e.g., the binding to specific ligands) allowing specific cellular and subcellular targeting. Drug delivery to skin by means of microparticles and nanocarriers could revolutionize the treatment of several skin disorders. However, the toxicological and environmental safety of micro- and nanoparticles has to be evaluated using specific toxicological studies prior to a wider implementation of the new technology. This review aims to give an overview of the most investigated applications of transcutaneously applied particle-based formulations in the fields of cosmetics and dermatology. [ABSTRACT FROM AUTHOR]

The interaction of free radicals with antioxidants is a topic of increasing interest in the development of prevention strategies against skin ageing. Carotenoids can serve as marker substances for the complete antioxidative network of human skin. Recently, it has become possible to measure the carotenoids non-invasively and online using resonance Raman spectroscopy. This method has been used in various studies to investigate the interaction of carotenoid antioxidants and free radicals in human skin. In this review, the results of the selected studies are summarized and compared. It could be demonstrated that the carotenoid concentration of the skin reflects the lifestyle of individuals. A high level of carotenoids can be achieved with a healthy diet rich, for instance, in fruit and vegetables. Stress factors such as illness, UV and IR radiation of the sun, and smoking and alcohol consumption reduce the concentration of the carotenoids in the skin. It could be demonstrated that premature skin ageing was less in people with a high level of antioxidants in their tissue. Consequently, the furrows and wrinkles were not so deep and dense as in the skin of individuals with a low antioxidant level. The measurements are highly suited for the development of anti-ageing strategies and can be efficiently used in the medical diagnostics and therapy control. [ABSTRACT FROM AUTHOR]

Proteome serology may complement expression library-based approaches as strategy utilizing the patients' immune responses for the identification pathogenesis factors and potential targets for therapy and markers for diagnosis. Melanoma is a relatively immunogenic tumor and antigens recognized by melanoma-specific T cells have been extensively studied. The specificities of antibody responses to this malignancy have been analyzed to some extent by molecular genetic but not proteomics approaches. We screened sera of 94 melanoma patients for anti-melanoma reactivity and detected seropositivity in two-thirds of the patients with 2-6 antigens per case detected by 1D and an average of 2.3 per case by 2D Western blot analysis. For identification, antigen spots in Western blots were aligned with proteins in 2-DE and analyzed by mass spectrometry. 18 antigens were identified, 17 of which for the first time for melanoma. One of these antigens, galectin-3, has been related to various oncogenic processes including metastasis formation and invasiveness. Similarly, enolase has been found deregulated in different cancers. With at least 2 of 18 identified proteins implicated in oncogenic processes, the work confirms the potential of proteome-based antigen discovery to identify pathologically relevant proteins. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and efficacy of multiple courses of alefacept in combination with traditional psoriasis therapy for the treatment of chronic plaque psoriasis (CPP). Methods: Patients with CPP requiring systemic therapy were eligible for this study. Patients received up to three courses of intramuscular alefacept 15 mg once weekly for 12 weeks. One concomitant psoriasis therapy (topical agents, methotrexate, cyclosporine, systemic retinoids, or ultraviolet B [UVB]) per course was allowed. The extent of disease was determined using the 7-point Physician Global Assessment (PGA; scale ranging from 0 = clear to 6 = severe). Results: More than 73% of patients improved by ≥ one PGA category and ≥44% of patients improved by ≥ two PGA categories across all concomitant treatments. Clinical responses tended to be greatest in patients who received alefacept plus UVB. The incidences of serious infections (≤1%) and malignancies (≤2%) were low across all courses and all combinations. Conclusion: Multiple courses of alefacept appear to be well tolerated and demonstrate efficacy in patients with CPP when administered with other psoriasis therapies. [ABSTRACT FROM AUTHOR]

Cutaneous characteristics, e.g., thickness of the SC and density of follicles, affect the penetration of topically applied substances. In the present study, the penetration of benzyl nicotinate, causing a vasodilation, was studied on three anatomic sites (forearm, forehead and calf) differing in their skin characteristics. Therefore, the blood flow of the superficial dermal plexus and that of the larger capillaries in the deeper skin layers was simultaneously measured using a laser Doppler flowmeter. In addition, the cutaneous temperature and redness were determined as a function of time. These four biological reactions were measured in turn on a skin area treated with a gel containing benzyl nicotinate and on an untreated control area. The highest basal levels were observed on the forehead. Topical application of benzyl nicotinate resulted in an increase in each biological response. Compared to the other sites, the maximal values were reached earliest on the forehead, which also showed the fastest decrease. No significant differences were obtained comparing the kinetic data of the calf with that of the forearm. The results indicate an additional contribution by the numerous vellus hair follicles of the forehead to the penetration and exposure of the drug. [ABSTRACT FROM AUTHOR]

Polymerase chain reaction (PCR)-based detection of clonal T- and B-cells is widely used in the diagnosis of various lymphomas, including those of the skin. A large number of corresponding methods have been published. Recently, for the first time, standardized PCR protocols were developed in common by 14 European centers of lymphoma diagnosis and research (Biomed-2 protocols). Here, we have applied Biomed-2 immunoglobulin heavy chain (IgH)-PCR for clonality detection in primary cutaneous B-cell lymphoma (CBCL) and compared it with previously established methods. The DNA of 43 paraffin-embedded lesional skin biopsies of confirmed CBCL cases [27 follicle center cell lymphoma (FCCL), 11 marginal zone B-cell lymphoma/immunocytoma (MZL/IC) and five large CBCL of the lower leg (CBCL-LL)] were amplified by the Biomed-2 IgH-PCR protocols as well as using four other assays, priming also the three IgH framework regions (FR) 1–3. All PCR products were analysed by fluorescence fragment analysis. Twenty-nine of 43 (67%) CBCL samples (5/5, 100% of CBCL-LL; six of 11, 54.5% of IC/MZL; 18 of 27, 66.7% of FCCL) showed monoclonal B-cell presence complementary in all of the IgH-PCR. The three Biomed-2 PCR indicated together clonality in 24 of 43 samples (56%). Considering each method separately, the Biomed-2 FR3-PCR showed the highest rate of clonality detection (20 of 43, 47%). In conclusion, the Biomed-2 FR3-PCR is recommended for detecting B-cell clonality in archival skin samples of CBCL but should be completed by FR1- and/or FR2-PCR. [ABSTRACT FROM AUTHOR]

Ethanol intake is associated with a variety of skin diseases. The aim of the present study was (1) to identify the pathways of release of orally administered ethanol through the skin, and (2) to investigate the effects of a single oral dose of ethanol on the penetration of topically applied substances into the skin. Ethanol evaporation via the skin was measured using the new technique of ion mobility spectrometry (IMS). Transepidermal water loss (TEWL) and skin surface temperature were simultaneously measured before and after ethanol consumption. Measurements were performed on skin sites with different stratum corneum (SC) thickness, and density of follicles and sweat glands. These appendages were selectively sealed to investigate their participation in ethanol evaporation. The penetration of a topically applied UV filter substance was studied before and after ethanol consumption after removing the SC with adhesive tape. Ethanol evaporation was measured within 5 min of consumption, while the skin surface temperature remained nearly constant. The sealing of the appendages did not have a significant effect on ethanol evaporation. On the forehead, a higher TEWL value was measured than on the forearm. On both skin sites, an increase in TEWL was observed after ethanol ingestion. No influence of orally administered ethanol on the penetration of the topically applied UV filter substance was observed. The results indicate that ethanol evaporation occurs via the lipid layers without a significant effect on the penetration of the topically applied substance. [ABSTRACT FROM AUTHOR]

We examined the practicability, reproducibility and analytical sensitivity of classical immunohistochemistry (IHC) and IHC with microagitation. Two monoclonal antibodies, Ki-67 (proliferation marker) and p53 (tumor suppressor marker), were used. Consecutive paraffin sections of biopsies of suspicious lesions of patients with non-melanoma skin cancer were used in the study. Reproducibility was examined using specimens from four patients in three independent experiments with antibodies against Ki-67 and p53. Analytical sensitivity of the two methods was determined using serial dilutions in two independent experiments. IHC with microagitation could be carried out without destroying the tissue. The new technique was consistent and reproducible, and no background staining was observed. The primary antibodies Ki-67 and p53 could be used at higher dilutions (four to ten times) with microagitation compared with classical IHC. Microagitation can be used for immunohistochemistry; it was reproducible, highly sensitive, and antibodies could be used at higher dilutions. Further analyses with other antibodies using this technique are warranted. [ABSTRACT FROM AUTHOR]

The role of T cells in the pathogenesis of psoriasis is widely acknowledged. However, key aspects of their precise function in the disease as well as the relative pathogenic contribution of T-cell subsets are still unknown. T-cell clones have been isolated from psoriatic plaques but a study of conditions affecting the isolation and expansion of T-cell clones from psoriatic skin has not been reported to date. Here, we observe a correlation of disease activity with the frequency of the CD3± CD8± CD25± subset. We show that prolonged in vitro culture changes the phenotypic subset distribution of T-cell lines derived from psoriatic skin and that T-cell clones can be isolated by sorting of CD25± cells emigrated from skin fragments after 7 days. We evaluate various conditions affecting expansion of psoriatic T-cell clones in vitro and show that blocking apoptosis can facilitate proliferation of activated T-cell clones in vitro. Our results indicate a prominent role of the CD8± CD25± T-cell subset in disease pathogenesis and should be useful in the design of experiments aiming at a systematic analysis of the specificity of clones present in psoriatic plaques. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection has been suggested to be involved in the development of nonmelanoma skin cancer, the most common malignancy after solid-organ transplantation. The objective of this study was to analyze the prevalence of different HPV types in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) of transplant recipients and nonimmunosuppressed patients. To include the complete spectrum of HPV types in skin lesions, a comprehensive polymerase chain reaction assay with five different primer combinations was used. For SCC, HPV DNA was detected more frequently in tumors of transplant recipients (12/16, 75%) than of nonimmunosuppressed patients (7/19, 37%). In contrast, the HPV detection rate was similar in BCC specimens (4/8 or 50% in transplanted patients; 27/56 or 48% in nonimmunosupressed patients). Overall, 22 different HPV types were identified. HPV types 5 and 8 were detected predominately in SCC from transplant recipients. The amount of viral DNA was slightly higher in SCC of transplanted than in nonimmunosuppressed patients, but much lower than in both cutaneous and genital warts. Cutaneous infections with HPV5 and HPV8 may represent an increased risk for SCC development in transplant recipients. The mechanisms by which these viruses may contribute to skin cancer development still remain unclear. E. STOCKFLETH, MD, I. NINDL, PHD, W. STERRY, MD, C. ULRICH, MD, T. SCHMOOK, MD, T. MEYER, PHD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [ABSTRACT FROM AUTHOR]

Ultraviolet irradiation represents a well-established treatment modality for inflammatory skin diseases. The aim of this study was to investigate the mechanisms of ultraviolet B radiation-induced keratinocyte insensitivity towards interferon-γ. Flow cytometric analyses indicated that ultraviolet B radiation temporarily inhibits the interferon-γ-induced activation of primary keratinocyte and HaCaT cells as measured by reduced intercellular adhesion molecule-1 (CD54) and HLA-DR upregulation. Western blot experiments have suggested that this is mediated by the ultraviolet B radiation-induced inhibition of signal transduction and transcription factor-1 phosphorylation. Neither interleukin-10 neutralization nor interleukin-10 addition had any effect on the ultraviolet B radiation-induced inhibition of interferon-γ induced intercellular adhesion molecule-1 expression. Furthermore, the supernatant from ultraviolet B-irradiated cells failed to inhibit the interferon-γ-induced CD54 and HLA-DR upregulation in nonradiated HaCaT cells. Moreover, irradiated cells from whom the supernatant was withdrawn 4 h after irradiation still showed a diminished interferon-γinduced response after 24 h. Thus, not soluble but intracellular factors might be involved in the ultraviolet B radiation-induced inhibition of interferon-γ-induced keratinocyte activation. Therefore, we analyzed the expression of members of suppressors of cytokine-signaling (SOCS) molecules using real-time polymerase chain reaction. We found a fast and strong upregulation of SOCS1 and SOCS3 but not of SOCS2 after ultraviolet B radiation. Similarly, ultraviolet B radiation induced the expression of these particular SOCS molecules in lesional psoriatic skin. As SOCS molecules are known inhibitors of signal transduction and transcription factor phosphorylation, which is essential for interferon-γ-induced intercellular adhesion molecule-1 and HLA-DR upregulation, this may explain the interferon-γ unresponsiveness after ultraviolet B radiation. [ABSTRACT FROM AUTHOR]

New insights into the pathophysiology of psoriasis have suggested possibilities for targeted therapeutic intervention. Several novel, systemic immunomodulatory therapies are currently in clinical development and results of recent clinical trials are remarkable. These include approaches targeting antigen presentation and costimulation, T–cell activation and leukocyte adhesion, the action of proinflammatory mediators and the administration of anti-inflammatory cytokines. These trials contribute to our further understanding of the disease, indicating which mechanisms play a greater or lesser part in its development. Moreover, they will lead to new therapeutic options. If psoriasis is considered as a visible model disease for T–cell-mediated disorders characterized by a type–1 cytokine pattern these recent findings might have a more general impact on the treatment of autoimmune disorders. [Copyright &y& Elsevier]

SummaryLichen sclerosus et atrophicus is a chronic dermatosis of unknown etiology and pathogenesis. Lichen sclerosus et atrophicus associated skin lesions show T cell enriched infiltrates, sometimes resembling the histologic picture of early mycosis fungoides. It is supposed that the infiltrating T cells participate in the pathogenesis of atrophy and sclerosis. We investigated skin biopsies from 39 lichen sclerosus et atrophicus patients by histology, immunohistochemistry and, in order to establish the status of T cell clonality, by polymerase chain reaction amplifying the T cell receptor-γ rearrangements. A stage-dependent shift of the CD3-positive T cells was observed from a predominantly CD4-positive to a predominantly CD8-positive phenotype. The increase of CD8-positive cells was associated with more pronounced epidermotropism and basal degeneration. Nearly all CD8-positive cells expressed cytotoxic granules (TIA1), possibly causing the basal destruction. In the late fibrotic stage of the disease, only a weak or no infiltrate was found. Regarding the T cell receptor-γ polymerase chain reaction, the presence of clonally expanded T cells was demonstrated in 19 of 39 patients (49%) by at least one of two different high resolution electrophoresis techniques applied to separate the amplification products. Thus, for the first time clonally expanded infiltrating T cells were detected in lichen sclerosus et atrophicus. Furthermore, this is one of the first reports on the detection of clonally expanded infiltrating T cells in an inflammatory skin disease. The clonal T cells could not be assigned to the CD4 or CD8 subtype. Most likely, their presence is not the result of a malignant transformation but a response to an as yet unknown lichen sclerosus et atrophicus associated antigen. [ABSTRACT FROM AUTHOR]

Background. While sclerotherapy in chronic venous insufficiency and in hemorrhoids is well established, the use of sclerotherapy for hemangiomas of the skin is widely unknown. Objective. The aim of the study was to analyze the clinical value of sclerotherapy with polidocanol in a larger population. Methods. Over a period of 20 years (1975–1995) we performed sclerotherapy of hemangiomas and vascular malformations in a total of 157 patients. Their ages ranged from 3 months to 75 years. Among these were 87 (55.4%) children and adolescents (up to the age of 18). Sclerotherapy with polidocanol was carried out mostly at monstrous or rapidly growing cavernous hemangiomas mainly localized in the face. Results. One to three injections was usually sufficient to obtain the sclerosis effect; aesthetically, long-term results were convincing. Severe complications were not observed. Conclusion. Sclerotherapy of hemangiomas is a relatively simple, effective, and inexpensive method that is a valuable and promising treatment. [ABSTRACT FROM AUTHOR]

The article offers information on the 2015 World Congress of Dermatology (WCD) to be held in Vancouver, British Columbia in June 2015 on topics including new treatments techniques for skin diseases, clinical practice guidelines to dermatologists and patient care.

Despite their different pathogeneses, allergic and irritant contact dermatitis show a remarkable similarity with respect to clinical appearance, histology, and immunohistology. To further analyze this apparent contradiction, our study was designed to meticulously compare cellular infiltrates in irritant and allergic patch-test reactions by immunostaining with a broad panel of monoclonal antibodies. For this purpose, skin biopsies from allergic and irritant patch-test reactions of similar inflammatory degree were obtained from the same probands. We found that after 72 h both types of reaction were characterized by an identical dermal infiltrate consisting mainly of memory T cells, many of which were activated, and macrophages. Dermal and epidermal Langerhans cell density and HLA--DR expression of keratinocytes were also virtually identical. Our results show that antigen recognition by specific memory T cells as well as irritants can finally induce the same pattern of inflammation, including activation of T cells obviously independent of exogenous antigen. [ABSTRACT FROM AUTHOR]

T-cell rich, small lymphoid infiltrates of the skin may cause considerable problems in the differential diagnosis of reactive versus neoplastic lymphoproliferations, particularly when they lack the morphologic and immunophenotypical criteria for a malignant lymphoma. We did histologic, immunohistologic, and gene rearrangement studies on 10 biopsies from patients with persistent nodular T-cell - rich skin lesions refractory to topical therapy. Based on clinical and immuno-histochemical findings, no discrimination was possible between reactive lesions and malignant lymphoproliferations. Histologically, most of the cases contained T-lymphocytic infiltrations that were assumed to be reactive; however, in four biopsies a neoplastic infiltration could not be excluded. Although the T-cell receptor (TCR) /β chain and the immunoglobulin heavy chain (IgH) genes were in germ-line configuration in nine of 10 cases, indicating a predominantly polyclonal lymphocellular infiltrate, in one patient without clinical evidence of malignant lymphorna at presentation a clonally rearranged TCR β chain gene with the IgH gene in germ-line configuration was detected. One year later, the patient developed a cutaneous pkomorphic T-cell lymphoma and subsequently a large cell anaplastic (CD3O+) T-cell lymphoma in an inguinal lymph node. We conclude that clonal T-cell proliferations can be detected by molecular genetic analysis of T-cell--rich, small lymphoid infiltrates of the skin. This finding may precede development of an overt malignant T-cell lymphoma. [ABSTRACT FROM AUTHOR]

Reports on cases involving the administration of thalidomide on patients with Langerhans' cell histiocytosis (LCH). Characteristics of LCH; Efficacy of thalidomide in alleviating LCH; Method used to minimize the sedative effects of the drug.

Patients with atopic dermatitis frequently blame food for worsening their eczema. Recently, a sugar-free diet has become very popular among German patients. In order to investigate whether sucrose is an aggravating factor in atopic dermatitis, we conducted a prospective study in 30 patients. Double-blind, placebo-controlled food challenges with sugar were performed during a sugar-free diet period, which was started one week prior to the first challenge. Study parameters included the SCORAD index and eosinophilic cationic protein levels, which were determined before diet, on food challenges and one day after. In 29 evaluable patients we observed no significant difference in study parameters after the verum challenge compared to the placebo challenge. From these results, we conclude that sugar is not an aggravating factor in atopic dermatitis, which contradicts the view of many patients and underlines the importance of evidence-based medicine in the guidance of patients. [ABSTRACT FROM AUTHOR]

Acne inversa (AI; also designated as hidradenitis suppurativa) is a chronic inflammatory disease with still unknown pathogenesis that affects the intertriginous skin of perianal, inguinal, and axillary sites. It leads to painful nodules, abscesses, and fistulas with malodorous secretion and is frequently associated with metabolic alterations. Here, we demonstrate that one of the most highly upregulated molecules in AI lesions is matrix metalloproteinase 8 (MMP8), an enzyme specialized in the degradation of extracellular matrix components and the HDL component apolipoprotein A-I. Granulocytes, which were present in AI lesions, secreted high amounts of MMP8 especially after TNF-α stimulation. Furthermore, activated fibroblasts but not keratinocytes were found to express MMP8. The high lesional MMP8 levels were accompanied by elevated blood levels that positively correlated with TNF-α blood levels and disease severity assessed by Sartorius score, especially with the number of regions with inflammatory nodules/abscesses and fistulas. Additionally, we found a negative correlation between blood MMP8 and HDL-cholesterol levels, suggesting a contributory role of MMP8 in metabolic alterations in AI. In summary, we demonstrate elevated MMP8 levels in AI lesions, suggest their role in skin destruction and metabolic alterations, and recommend the use of MMP8 as blood biomarker for AI disease activity assessment. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about primary cutaneous B cell lymphomas.

Psoriasis is considered as a model for chronic immune-mediated disorders. Th17-cells are pivotal players in those diseases. Recently, we demonstrated that Th17-cells produce interleukin (IL)-29 and that IL-29 is highly present in psoriatic lesions. Whether IL-29, with its action on epithelial cells and melanocytes, contributes to psoriasis pathogenesis, was unknown so far. Analysis of IL-29-treated human keratinocytes revealed induction of the chemokines CXCL10, CXCL11, and, to a much lesser extent, CXCL9. Unlike these CXCR3A ligands, known to attract Th1-, CD8, NK-, and Th1/Th17 transient cells, no influence was found on chemokines attracting other immune cell populations or on molecules modulating the CXCR3A/CXCR3A ligand interaction. CXCR3A ligand expression was also induced by IL-29 in melanocytes and in epidermis models and explanted skin. Regarding other psoriasis-relevant cytokines, interferon-γ and, less potently, tumor necrosis factor-α and IL-1β shared and strengthened IL-29's capacity. Murine IL-29 counterpart injected into mouse skin provoked local CXCL10 and CXCL11 expression, T-cell infiltration, and, in consequence, skin swelling. The elevated IL-29 expression in psoriatic lesions was associated with upregulation of CXCR3A ligands compared to non-lesional skin of these patients and to the skin of healthy donors and atopic dermatitis patients, which lack IL-29 production. Importantly, neutralization of IL-29 reduced CXCR3A ligand levels in explant cultures of psoriatic lesions. Finally, elevated blood CXCL11 levels were found in psoriasis that might be useful for monitoring lesional activity of the IL-29 axis. In summary, the Th17-cytokine IL-29 induces specific chemokines and, in consequence, provokes skin infiltration of potentially pathogenic T-cells. Key messages: [ABSTRACT FROM AUTHOR]

Background: The formation of free radicals in human skin by solar ultraviolet radiation is considered to be the main reason for extrinsic skin aging. The antioxidants in human tissue represent an efficient protection system against the destructive action of these reactive free radicals. In this study, the parameters of the skin, epidermal thickness, stratum corneum moisture, elasticity and wrinkle volume, were determined before and after the treatment with antioxidant- or placebo-containing tablets and creams. Methods: The study included 5 groups of 15 volunteers each, who were treated for 2 months with antioxidant-containing or placebo tablets, creams or a combination of antioxidant-containing tablets and cream. The skin parameters were measured at time point 0 and at week 8 utilizing ultrasound for the determination of epidermal thickness, a corneometer for stratum corneum moisture measurements, skin profilometry for quantifying the wrinkle volume and a cutometer for determining the elasticity. Results: The verum cream had a positive influence on epidermal thickness, elasticity and skin moisture, but the verum tablets improved the epidermal thickness only. The combined application of verum tablets and creams led to a significant improvement of all investigated skin parameters, whereas the application of placebo tablets or cream did not influence any parameters. Conclusion: The topical and oral supplementation of antioxidants can be an instrument to improve several skin parameters and potentially counteract or decelerate the process of extrinsic skin aging. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphomas (CTCLs) form a heterogeneous group of non-Hodgkin's lymphomas characterized by only poor prognosis in advanced stage. Despite significant progress made in the identification of novel genes and pathways involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of these findings has still to be proven. Here, we demonstrate by gene expression arrays that Aurora kinase A is one of the highly overexpressed genes of the serine/threonine kinase in CTCL. The finding was confirmed by quantitative reverse transcriptase-PCR, western blotting, and immunohistochemistry in CTCL cell lines and primary patient samples. Moreover, treatment with a specific Aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest in G2 phase, as well as apoptosis in CTCL cell lines. These data provide a promising rationale for using Aurora kinase A inhibition as a therapeutic modality of CTCL. [ABSTRACT FROM AUTHOR]

Psoriasis is a common chronic inflammatory disease with characteristic skin alterations and functions as a model of immune-mediated disorders. Cytokines have a key role in psoriasis pathogenesis. Here, we demonstrated that out of 30 individually quantified cytokines, IL-19 showed the strongest differential expression between psoriatic lesions and healthy skin. Cutaneous IL-19 overproduction was reflected by elevated IL-19 blood levels that correlated with psoriasis severity. Accordingly, anti-psoriatic therapies substantially reduced both cutaneous and systemic IL-19 levels. IL-19 production was induced in keratinocytes by IL-17A and was further amplified by tumor necrosis factor-α and IL-22. Among skin cells, keratinocytes were found to be important targets of IL-19. IL-19 alone, however, regulated only a few keratinocyte functions. While increasing the production of S100A7/8/9 and, to a moderate extent, also IL-1β, IL-20, chemokine C-X-C motif ligand 8, and matrix metalloproteinase 1, IL-19 had no clear influence on the differentiation, proliferation, or migration of these cells. Importantly, IL-19 amplified many IL-17A effects on keratinocytes, including the induction of β-defensins, IL-19, IL-23p19, and T helper type 17-cell- and neutrophil-attracting chemokines. In summary, IL-19 as a component of the IL-23/IL-17 axis strengthens the IL-17A action and might be a biomarker for the activity of this axis in chronic inflammatory disorders. [ABSTRACT FROM AUTHOR]

Background: The antioxidant status of the human skin provides protection against the destructive action of free radicals. Most antioxidants cannot be synthesized by the human organism itself, but have to be ingested with a healthy nutrition rich in fruit and vegetables. The Korean cuisine is known to be one of the healthiest worldwide. This binational study investigated the cutaneous carotenoid concentrations in German subjects, South Korean subjects and immigrant Korean subjects resident in Germany and examined whether dietary- and lifestyle-related differences are reflected in the cutaneous carotenoid concentrations. Methods: Measurements of the carotenoid concentrations of 714 healthy volunteers were performed using a non-invasive spectroscopic measurement system based on reflectance spectroscopy. Results: In the present study South Korean residents showed a significantly higher antioxidant status than both native German residents and Korean immigrants living in Germany (p < 0.001). The first generation of Korean immigrants to Germany over the age of 50 mostly preserved Korean dietary habits, showing significantly higher concentrations (p < 0.001) than the German-born second and third Korean generations under the age of 50. Conclusion: The results of the study indicate that a healthy nutrition alone does not provide a high antioxidant status unless the stress exposure can be reduced simultaneously. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: The palmoplantar erythrodysaesthesia (PPE) is an inflammatory cutaneous side effect in patients under chemotherapy with pegylated liposomal doxorubicin (PLD), with indications that also other chemotherapeutics induce similar side effects. Recently, it has been demonstrated that PLD escapes with the sweat onto the skin inducing radical-forming processes that damage the skin. The topical application of antioxidants with a high radical protection factor has proven to be a very efficient prevention strategy for PLD-treated patients. Methods: 68 patients, who had been treated with 12 different chemotherapeutics and experienced side effects similar to PPE, were treated with a meanwhile commercially available ointment. Results: At the beginning of the therapy, 46 patients suffered from a PPE of severity grade III, while in 22 patients a PPE of severity grade II was diagnosed. The application of the ointment resulted in a significant improvement of the clinical symptoms and the skin status in all these patients; their chemotherapies could be continued. Conclusion: The obtained results suggest that radical-forming processes play an essential role in a great number of chemotherapeutics which induce dermal side effects. The topical application of the antioxidant-containing ointment proved to be a good therapeutic option which needs further evaluation. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Detection of a dominant T-cell clone by T-cell receptor ( TCR) gene rearrangement analysis is often essential for the diagnosis of cutaneous T-cell lymphomas ( CTCL). The occurrence of T-cell clones in addition to the diagnostic T-cell clone during the course of CTCL has been reported, but the data of these studies have been contradictory. We retrospectively evaluated the data of 114 lesional skin biopsies from 26 patients with Mycosis fungoides and two patients with primary cutaneous anaplastic large cell lymphoma, which were analysed with the standardized Biomed-2 PCR for the TCR γ and TCR β locus. A dominant T-cell clone was repetitively detected in 93% (26/28) of patients. Additional T-cell clones appeared temporarily in 39% (11/28) of patients. Correlation with the clinical data did not show an association of the presence of additional T-cell clones with age, number of treatments, progression of disease or survival. Our findings demonstrate that a persistent T-cell clone, most likely the disease causing tumor clone, is detectable in almost all CTCL patients. In addition, transiently appearing T-cell clones frequently occur during the course of disease. The biological relevance of these additional clones has still to be determined. However, it is important to take the possibility of additional T-cell clones into account for diagnostic analyses. [ABSTRACT FROM AUTHOR]

Background The monitoring of wound-healing processes is indispensable for the therapeutic effectiveness and improved care of chronic wounds. Histological sections provide the best morphological assessment of wound recovery, but cause further tissue destruction and increase the risk of infection. Therefore, it is reasonable to apply a diagnostic tool that allows a non-invasive and reliable observation of morphological changes in wound healing. Methods Optical coherence tomography ( OCT) is an imaging technique for in vivo evaluation of skin diseases with a resolution close to histopathology. The aim of this study was to investigate whether OCT is suited to display the phases of wound healing. For this purpose, six patients with chronic wounds were objectively characterized by OCT during a period of 2 weeks. Results Comparable results between histological findings and OCT were achieved. OCT allowed the detection of partial loss of the epidermis, vasoconstriction, vasodilatation and epithelialization. Conclusion Consequently, OCT could be a potential non-invasive diagnostic tool for the characterization and monitoring of cutaneous wound-healing processes over time. [ABSTRACT FROM AUTHOR]

Background: Pegylated liposomal doxorubicin (PLD) is a highly efficient chemotherapeutic; however, it induces dermal side effects such as palmar-plantar erythrodysesthesia (PPE) in up to 80% of cases, probably by being emitted with the sweat onto the skin surface. Aim: The aim of the present study was to examine whether a topically applied ointment containing antioxidants with a high radical protection factor is able to prevent the formation of PPE. Methods: Twenty patients suffering from ovarian carcinoma and treated with PLD were observed. Results: 60% of the patients tolerated the regular application of the cream and developed no PPE. The remaining 40% interrupted the application. Six of them developed PPE and resumed ointment application thereafter. In these cases the PPE disappeared or was strongly reduced. Conclusion: The results of the observation clearly demonstrate that topical application of the ointment is an efficient strategy against the development of PPE during chemotherapy with PLD. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The 6q23-27 region, recurrently deleted in Sézary syndrome (SS), was characterized at the molecular level in 13 SS patients and SS cell line SeAx. Using fine-tiling comparative genomic hybridization, deletions within the 6q23-27 region were detected in half of the samples (six patients and SeAx). All samples with deletions were further analyzed by ligation-mediated PCR. In addition, in one patient sample and in SeAx, paired-end next-generation sequencing was performed on the HiSeq2000 Illumina platform. Using those techniques, 23 rearrangements associated with the deletions were identified. The majority of rearrangements showed enormous complexity and diversity, including eight inversions, three transpositions, and four translocations (with chromosomes 3, 17, 10, and 12). Fifteen genes were disrupted by those rearrangements, the MYB proto-oncogene three times and the interleukin-22 receptor subunit alpha-2 gene (IL22RA2) twice. All three patients with MYB alterations showed low MYB expression, whereas seven of the remaining patients showed overexpression. Most patients overexpressing MYB also presented increased expression of MYC, HSPA8, and BCL2. Five gene fusions were identified, of which two, CCDC28A-IL22RA2 and AIG1-GOSR1, both in SeAx, were in the same orientation and were expressed at the messenger RNA level. [ABSTRACT FROM AUTHOR]