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The use of phase-adapted wound dressings represents best practice (BP) in chronic wound treatment. However, efficacy is often limited and associated care requirements are high. Cold atmospheric plasmajet (CAP-jet) is a promising new therapeutic tool for these wounds. In the present multicenter, randomized, open-label, prospective, clinical trial, non-inferiority of the CAP-jet versus BP was assessed in 78 patients with infected or non-infected chronic wounds of different etiology. Primary outcome measure was the sum of granulation tissue, furthermore wound area reduction, healing rate, time to complete healing, changes in wound pH value, infection score, exudate level and local tolerability were assessed. In CAP-jet treated wounds compared to control, the sum of granulation tissue was significantly higher (p

The aim of this study was to assess the knowledge and influence of predatory journals in the field of dermatology in Austria. A total of 286 physicians (50.5% men) completed a questionnaire. The vast majority of subjects read scientific articles (n = 281, 98.3%) and took them into consideration in their clinical decision-making (n = 271, 98.5% of participants that regularly read scientific literature). Open access was known by 161 (56.3%), predatory journals by 84 (29.4%), and the Beall's list by 19 physicians (6.7%). A total of 117 participants (40.9%) had been challenged by patients with results from the scientific literature, including 9 predatory papers. Participants who knew of predatory journals had a higher level of education as well as scientific experience, and were more familiar with the open-access system (p < 0.001). These results indicate that the majority of dermatologists are not familiar with predatory journals. This is particularly the case for physicians in training and in the early stages of their career.

The epithelioid sarcoma classic, "distal" type was first published in 1970. It is a very rare, malignant, aggressive subcutaneous soft tissue sarcoma that shows characteristic positivity for both epithelial and mesenchymal immunohistochemical markers. It grows very slowly and mostly presents in young men. Clinically the tumor is characterized as a coarse cutaneous or subcutaneous nodular induration that often ulcerates in the course of the disease. An association with trauma is often described and can lengthen time to diagnosis. Most frequently it is found on the flexural side of fingers, the back of the hands, soles of the feet, and extensor sides of arms and legs. Specific for this type of sarcoma is the progression along nerves, tendons, and fasciae. Treatment of choice should be wide excision of the tumor, sentinel node biopsy, and possibly even localized postoperative radiation therapy. Unfortunately the epithelioid sarcoma is very likely to recur and is then associated with metastases in the lung and lymph nodes.

Background Imiquimod has shown to be efficacious in basal cell carcinoma and actinic keratosis, but with therapeutic burden such as strong skin reactions and long treatment periods. Objectives To compare the safety and efficacy of different application frequencies of the new laser skin microporation device combined with topical 5% imiquimod and the standard use of imiquimod alone for the treatment of actinic keratosis and basal cell carcinomas. Methods In two prospective, randomised, dose finding, pilot studies for basal cell carcinoma and actinic keratosis, we used either imiquimod alone according to the approved dosage (control arm 1) or on microporated skin for 1x/2x/3x/week (arm 1-4), respectively. Strength of imiquimod-induced skin reactions at day 20 (study end) represented the primary endpoint. Secondary study parameters comprised the development and strength of skin erythema including crusting and erosions during the whole study, clearence at day 20 and tolerability as well as safety parameters. Results In both studies (patients/lesions treated and analysed: basal cell carcinoma 16/20 and 13/15; actinic keratosis 18/21 and 13/15) the combined laser and imiquimod therapy led to stronger skin erythema, crusting and erosion levels in the early study phase. Well tolerated without new safety signals, total clearence rates (arms 2-4/control arm 1) were 78%/75% (basal cell carcinoma) and 77%/50% (actinic keratosis), respectively. Conclusions We suggest to call this new treatment approach laser dynamic therapy. Based on our data, the most appropriate laser and imiquimod application frequency might be 2x/week (2-3 shots each at 3 pulses) with a suggested time to heal of 3 weeks. Further studies with larger patient cohorts are needed to substantiate our data. J O U R N A L O F D E R M A T O L O G I C A L R E S E A R C H A N D T H E R A P Y ISSN NO: 2471-2175 RESEARCH DOI : 10.14302/issn.2471-2175.jdrt-14-552 Corresponding Author: Robert Strohal, MD; Professor of Dermatology, Head of Dep. Dept. of Dermatology and Venereology; Federal Academic Teaching Hospital Feldkirch Carinagasse 45-47, 6800 Feldkirch; Austria Telephone: +43/5522/303.1200,-9121; Mobile: +43/664/1142140; Fax: +43/5522/303-7547 Robert.strohal@lkhf.at Running title: Skin microporation and imiquimod in actinic keratosis and basal cell carcinoma

Background The group of autoinflammatory syndromes associated with Pyoderma gangrenosum, Acne, and Suppurative Hidradenitis are poorly defined and difficult to control with currently available treatment modalities. Objectives We describe a patient with PASH syndrome and report about the successful multimodal treatment with infliximab, cyclosporine, and dapsone. Methods A review of the available literature to date about this group of autoinflammatory diseases was performed. We performed genetic analysis for PSTPIP1 mutations associated with PAPA syndrome. Results A 22-year-old woman presented to our department with pyoderma gangrenosum, concomitant acne, and suppurative hidradenitis. She had previously been treated unsuccessfully with etanercept, adalimumab, fumaric acid and the IL-1 receptor antagonist (IL-1RA) anakinra without prolonged remission. Treatment with intravenous infliximab in combination with cyclosporine and dapsone lead to sudden and prolonged improvement of the clinical symptoms that we classified as PASH syndrome. We review the literature about this group of diseases and report the third case of PASH syndrome to date. Conclusion PASH syndrome and associated diseases should be considered whenever hidradenitis suppurativa is found in association with pyoderma gangrenosum. We provide a systematic overview about PASH syndrome and suggest a novel multimodal therapeutic regimen beyond isolated inhibition of TNF or IL-1.

Bei der allergischen Rhinitis handelt es sich um ein weltweit unterschatztes Gesundheitsproblem. Untersuchungen zeigen, dass neben den belastenden Symptomen selbst auch das soziale Leben, der Schlaf sowie Schul- und Arbeitsleistungen durch die ganzjahrigen oder saisonalen Beschwerden mitunter erheblich beeintrachtigt werden. Auch die anfallenden Kosten durch Krankenstande, schulische Fehlzeiten sowie Produktivitatsausfalle sind erheblich. Zudem kann eine zu spat oder unbehandelte allergische Rhinitis schwere Folgeerkrankungen nach sich ziehen (z. B. allergisches Asthma). Die spezifische Immuntherapie ist die einzige kausale Therapie einer allergischen Rhinitis und kann bei allergischen Patienten nicht nur die Symptome und den Verbrauch symptomatischer Medikamente reduzieren, sondern auch die Lebensqualitat der Betroffenen deutlich verbessern. Um die subjektiven Einschatzungen von einzelnen Patienten zur Lebensqualitat objektivierbar und damit auch statistisch messbar machen, dienen in erster Linie standardisierte und validierte Fragebogen. Fur die schnelllosliche Grasertablette GRAZAX® wurde in mehreren grosen Studien belegt, dass die Therapie neben einer guten Wirksamkeit und Sicherheit auch eine signifikante Verbesserung der Lebensqualitat fur Graserpollen-allergische Patienten aufweist.

The challenges of modern wound management, such as the treatment of chronic wounds and their phase-specific handling, are demanding and require optimally adapted therapeutic measures. The principles of moist wound care as well as an adequate debridement have priority here. To support these necessary measures, different options are available, e.g., a new product group operating across several wound phases.A new treatment principle in modern wound management based on an expert consensus is presented.On the basis of clinical experience reports and published evidence, the current and new principles of wound treatment were discussed in a panel of experts and formulated as a consensus statement.Enzyme alginogels represent a combination of agents that allow phase-specific wound care. They exhibit autolytic, absorbent, and antimicrobial properties and simultaneously cover three components of wound management based on the TIME framework. Thus, according to the experts, they differ from other wound healing products and can be classified in a distinct product group. Clinical studies, as well as clinical experiences, provide evidence for the efficacy of enzyme alginogels.According to the experts, the potential of enzyme alginogels used considering the principles of moist wound care, comprises the three-fold effect (continuous and significantly simplified debridement, maintaining a moist wound environment and antimicrobial effect without cytotoxicity), the ease of use, and the flexible application. In addition, the flexibility of the product class regarding frequency of application, duration of treatment and combinability with secondary dressings, are of economic benefit in the health care sector.

Routine care of non-healing acute and chronic wounds often comprises either cleaning or debridement. Consequently, debridement is a basic necessity to induce the functional process of tissue repair, which makes it a central medical intervention in the management of acute and chronic, non-healing wounds.

Summary Background Fumaric acid esters are considered efficacious and safe drugs for the treatment of psoriasis. Renal damage, caused either by acute renal injury or Fanconi syndrome, is a recognized side-effect of this therapy. Objectives To investigate whether the measurement of urinary excretion of β2-microglobulin, a marker of renal proximal tubular dysfunction, allows early detection of kidney damage before an increase in serum creatinine or significant proteinuria occurs. Methods Urinary β2-microglobulin excretion was measured regularly in 23 patients undergoing fumaric acid ester therapy. Results Urinary β2-microglobulin remained normal in all 10 male patients. Three (23%) out of 13 female patients experienced an increase in urinary β2-microglobulin excretion. In two of these patients a sharp increase was observed in association with high doses. One further patient had moderately elevated levels on rather low doses of fumaric acid esters. After discontinuing treatment, urinary β2-microglobulin levels returned to normal within a few weeks. Conclusion Determination of urinary β2-microglobulin possibly allows early detection of renal damage by fumaric acid esters. Female patients seem to be prone to this side-effect, especially when taking high doses.

Thy-1 Ag and CD3-associated TCR-gamma (V gamma 3)/delta (V delta 1) are coexpressed on virtually all dendritic epidermal T cells (DETC) in the adult mouse. In contrast, day 16 fetal mouse skin contains small numbers of CD45+/Thy-1+/CD3- but no CD3+ cells. To see whether the CD45+/Thy-1+/CD3- fetal skin cells can qualify as DETC precursors, we transplanted day 16 fetal skin of C57BL/6 (Thy-1.2) mice onto adult B6Pl-Thy-1a (Thy-1.1) animals. At certain time points after transplantation, grafts were analyzed for the presence of Thy-1 and CD3/TCR Ag. Examination of the grafts, 4 days after transplantation, revealed the presence of few donor-type Thy-1.2+/CD3- and some Thy-1.2+/CD3+ epidermal cells of either round or dendritic configuration. At 10 weeks after transplantation, essentially all CD45+/Thy-1.2+ epidermal cells were anti-TCR V gamma 3 and anti-CD3-reactive, displayed a uniformly dendritic configuration, and, thus, represent DETC. Our assumption that CD45+/Thy-1+/CD3- cells are the only lymphocytes within day 16 fetal skin gained additional support by the observations: 1) that unfractionated as well as anti-CD45 gated single cell suspensions prepared from day 16 fetal skin were consistently devoid of anti-CD3 epsilon and anti-TCR V gamma 3-reactive cells; and 2) that stimulation of these cell suspensions with either Con A plus IL-2 or IL-2 alone regularly resulted in the outgrowth of CD45+/Thy-1+/CD3-/TCR V gamma 3- cells, but never in the appearance of CD45+/Thy-1+/CD3+/TCR V gamma 3+ cells. Our additional finding that Con A plus IL-2- or IL-2-stimulated day 16 fetal skin cells and cell lines derived therefrom contain transcripts of some (CD3 gamma, TCR C beta, TCR C gamma 1, TCR C gamma 4) but not of other (CD3 delta, CD3 epsilon, TCR C alpha, TCR C delta) genes encoding the CD3/TCR complex suggests that Thy-1+/CD3- fetal murine skin cells are of T cell lineage. We therefore propose that the fetal skin microenvironment can provide the stimuli promoting growth and maturation of CD3/TCR V gamma 3/V delta 1-expressing DETC from their CD3- precursors.

The existence of CD3/TCR-bearing lymphocytes in athymic and thymectomized chimeric mice implies that T cell maturation can occur in the absence of a thymus. Considering the possibility that the epidermis may be one of the organs providing T cell educating stimuli, we attempted to characterize the Thy-1+ epidermal lymphocyte population of athymic mice. Immunohistologic studies of epidermal sheets revealed (1) that Thy-1+ epidermal cells of C57BL/6 nu/nu mice are CD5-, CD4-, and predominantly CD8-, and (2) that a minor subset of these cells displays anti-CD3 epsilon reactivity. Although these CD3+ epidermal cells could hardly be detected at 6 wk of age, they comprised approximately 2% of all Thy-1+ epidermal cells in 12-mo-old athymic mice. Most of these CD3+ cells expressed TCR-gamma/delta, but TCR-alpha/beta+ cells were also present. TCR-gamma/delta+ epidermal T cells of athymic mice preferentially expressed TCR V gamma 2, V gamma 4, and V gamma 5 specificities rather than TCR V gamma 3 as found on DETC of euthymic mice. Using mitogenic stimuli, we have succeeded in establishing cell lines and clones from BALB/c nu/nu and C57BL/6 nu/nu epidermis. Their marker profile corresponds to that seen on resident CD3+ epidermal cells, as well as on a very small subset of CD3+ splenic and lymph node lymphocytes of athymic mice. The ontogenetic relationship, if any, between the epidermal and lymphoid CD3+, CD5-, CD4-, CD8- cells, has yet to be clarified. Cell lines/clones representative of resident CD3+ epidermal cells of nu/nu mice should provide a useful tool in the elucidation of homing patterns and functional properties of extrathymically matured T cells.

Summary Occupational skin diseases are among the most frequent causes for disablement. Although workers in the oil, gas and petrol industry are especially exposed to a variety of skin toxic/irritating substances, no data exists on the extent of the problem and how to define/introduce adequate skin protection measures. As a pilot, a 3 phase skin disease prevention and safety program was created for the Austrian OMV location at Gaenserndorf. Phase 1 (examination phase) showed that workers who substantially lacked information on dermal risk factors and behavior presented with irritant contact dermatitis of the hands at a rate of 55.4%. In addition, the company offered 27 different skin cleaning, protection and care products which were not clearly in line with workplace specific patterns of chemical skin burden. To specifically target these problems, phase 2 (realization phase) introduced new workplace adapted skin products with defined location specific sets of dispensers labeled for the role of its products, introduced skin safety plans at workplaces and a series of teaching courses based an a standardized newly developed education slide kit. By re-assessing (phase 3, evaluation phase) the most objective phase 1 parameters for the quality of skin protection measures, we found a decrease of the rate of irritant hand dermatitis from 55.4% to 19.7% and the rate of uninformed workers got down from about 60% to 20%. Taken together, the process oriented, skin safety standards herein presented have shown to specifically identify, analyze, target and unravel the relevant company related features of occupational skin diseases. The basic structure and design of this programme might be suggestive for its health supportive role in the oil, gas and petrol industry as a whole.

The emergence of multi-drug-resistant strains of bacteria represents a particular challenge in the field of wound management. The aim of the current study was to investigate whether nanocrystalline silver dressings possess the physical properties to act as a barrier to the transmission of methicillin-resistant Staphylococcus aureus (MRSA) in the laboratory setting and in a clinical setting. Initially, MRSA suspension and colony culture experiments were performed showing that nanocrystalline silver dressings act as potent and sustained antimicrobial agents, efficiently inhibiting MRSA penetration. Subsequently, a double-centre clinical trial was initiated using nanocrystalline silver dressings as a cover for 10 MRSA colonized wounds in a total of seven patients. By delineating the MRSA load on the upper side of the dressing and the wound bed each time the dressing was changed (i.e. after 1, 24, 48 and 72 h), nanocrystalline silver dressings were found to provide a complete, or almost complete, barrier to the penetration/spread of MRSA in 95% of readings. In addition, 67% of all wound observations showed a decrease in the MRSA load with an eradication rate of 11%. We believe that nanocrystalline silver dressings may become an important part of local MRSA management, with cost benefits to both patients and the healthcare system.

Lymphocytes infiltrating solid tumors can be propagated in vitro with interleukin 2 and are then capable, as CD8+ cytotoxic T-cells, of specific lysis of autologous tumor targets in a class I-restricted manner. Since the specificity of these cells is determined by their T-cell receptor (TCR) configuration, the aim of this study was to delineate the TCR V alpha repertoire of tumor-infiltrating lymphocytes within 24 melanoma specimens and to compare these data with the TCR expression pattern of unaffected peritumoral and normal human skin. While lymphocytes within all skin specimens tested expressed a substantial, albeit limited, heterogeneity of V alpha specificities with an average number of 9.0 different V alpha gene segments, the V alpha repertoire within cutaneous melanoma lesions was significantly more restricted (mean of V alpha expression, 3.86; P0.001) with a predominance of only 3 V alpha families (V alpha 13, V alpha 15, and V alpha 16), all of which were also found to be expressed within normal skin. Collectively, the fact that the TCR V alpha repertoire in melanoma is skewed toward the predominance of only a few V alpha regions may be indicative of a limited number of melanoma-associated antigenic determinants being involved in the anti-tumor immune response.

Our attempts to clarify the contribution of the thymic vs. the cutaneous microenvironment in the maturation of dendritic epidermal T cell (DETC) precursors into DETC gave diverse results. In one series of experiments, we found that i.v. injection of fetal thymocytes (containing a TCR V gamma 3-expressing subpopulation), but not of adult thymocytes (containing no TCR V gamma 3+ cells) results in the appearance of CD3/TCR V gamma 3+ dendritic epidermal cells (=DETC). In other experiments, we have obtained evidence that transplantation of day 16 fetal skin onto a Thy-1-disparate recipient results in the appearance of donor-type DETC. Our further observation that the transplanted skin contains CD45+/Thy-1+/CD3- lymphocytes, but no mature T cells, therefore implies that fetal skin can provide stimuli promoting the expression of CD3/TCR genes in immature (CD3-) DETC precursors. It remains to be seen whether both or only one of these maturational pathways are (is) followed under physiological conditions.

We have investigated the genetic origin of autoantibody production in several strains of mice that spontaneously develop a systemic lupus erythematosus-like disease. Restriction fragment length polymorphism analyses of gene loci encoding kappa light chain variable regions (Igk-V) demonstrated, as shown previously for the Ig heavy chain locus, that autoantibody production and disease occur in different Igk-V haplotypes. Moreover, autoimmune mice with known genetic derivation inherited their Igk-V loci essentially unaltered from their nonautoimmune ancestors. New Zealand black lupus mice, with unknown genetic derivation, had a possibly recombinant Igk-V haplotype, composed of V kappa loci that were primarily indistinguishable from those of nonautoimmune strains from either of the two potential donor haplotypes. The heavy and light chain gene segments (variable, diversity, joining) encoding anti-DNA antibodies were diverse and often closely related, or even identical, to those found in antibodies to foreign antigens in normal mice. Only 1 of 11 sequenced variable region genes could not be assigned to existing variable region gene families; however, corresponding germline genes were present in the genome of normal mice as well. These data argue against abnormalities in the genes and mechanisms generating antibody diversity in lupus mice and suggest a remarkable genetic and structural diversity in the generation of anti-DNA binding sites.

Systemic lupus erythematosus and rheumatoid arthritis in human and murine systems are characterized by circulating autoantibodies and immune complex deposition in various organs causing tissue damage and disease. To define the molecular and clonotypic origin of these anti-self responses, and to determine whether abnormalities in Ig genes or somatic mechanisms generating autoantibody diversity may contribute to lupus etiology, we performed molecular analyses of the Ig germline gene organization and the Ig gene segments expressed in monoclonal autoantibodies from autoimmune mice. Comparative restriction fragment length polymorphism analysis of a large number of Ig gene loci from autoimmune and normal mice indicated that (a) lupus can develop in different Ig heavy and kappa light chain variable region gene haplotypes, and (b) the Ig germline genes in lupus mice might be normal. To determine whether autoantibodies are encoded by unique Ig gene segments present in the normal germline repertoire, but not expressed in exogenous responses, we compared nucleic acid sequences encoding lupus autoantibodies and antibodies against foreign antigens. Similar, and in some instances even identical, gene segments were expressed in both types of antibodies, indicating that anti-self and anti-foreign responses use the same, or at least an overlapping, germline gene repertoire. A large variety of Ig variable, diversity, and joining gene segments encoded these autoantibodies with different specificities. Hence, the overall murine lupus-associated anti-self response may be essentially unrestricted. Furthermore, limited evidence has been obtained that both germline genes and somatically mutated genes encode autospecificity, making gross abnormalities in mechanisms for somatic mutation of Ig variable genes unlikely. Based on the studies performed thus far, the general principles governing murine lupus-associated anti-self responses and responses against exogenous antigens appear to be the same.

Immunoglobulin (Ig) heavy (H) and light (L) chain variable (V) region genes are assembled somatically during B-cell differentiation by stage-specific DNA rearrangements of multiple V, diversity (D, H chains only), and joining (J) germline gene segments (reviewed by Alt et al, 1986). Different combinations and imprecise joining of V, D and J elements, random insertion of nucleotides during the joining process (N regions), as well as somatic mutation, contribute to the generation of antibody diversity and ultimately determine the specificity (self or non-self antigen) of a given antibody. Murine lupus is characterised by high titres of circulating autoantibodies (AAb) leading to immune complex mediated lesions (Theofilopoulos and Dixon, 1985). We have previously shown, by means of restriction fragment length polymorphism analysis, that lupus mice and non-lupus mice of the same haplotypes share highly conserved H chain variable region loci (Kofler et al., 1985b). In the present study, we report a detailed analysis of nucleotide sequences corresponding to H and L chains of nine monoclonal AAb with different specificities frequently expressed during lupus disease (single stranded DNA, histone and various Ig isotypes). The following questions were addressed: Arc there any primary structures common to ail AAb regardless of their specificity, which might signal their autoreactive nature? Do AAb employ Ig genes in a restricted manner and are there unique Ig genes different from the germline pool used in the response to exogenous antigens? To what extent is self-specificity germline encoded or acquired during B-cell development?

This review summarizes studies from our and other laboratories attempting to define the molecular and clonotypic origin of autoantibodies that typify systemic autoimmune diseases such as lupus and rheumatoid arthritis. Comparative restriction fragment length polymorphism (RFLP) studies investigating the immunoglobulin (Ig) germline gene organization in lupus-prone strains of mice suggested that the disease can develop in different Ig heavy (H) and light (L) chain haplotypes, and that the Ig germline genes in lupus mice are probably normal. Analysis of the Ig gene segments expressed in monoclonal autoantibodies from autoimmune mice revealed that similar, and in some instances even identical, gene segments are expressed in autoantibodies and in antibodies to exogenous antigens, and that anti-self and anti-non-self responses are encoded by the same, or at least an overlapping germline gene repertoire. A large variety of Ig variable (V), diversity (D), and joining (J) gene segments can encode autoantibodies with different specificities, and both germline genes and somatically-mutated genes can be expressed in such antibodies.

In the course of a previous study addressing autoantibody generation in murine models for generalized autoimmune disorders, we observed a nonfunctional immunoglobulin heavy chain transcript in a B cell hybridoma from lupus-prone MRL-Mp-lpr/lpr mice. This transcript, the cDNA sequence of which is presented here, is of general interest for murine immunoglobulin genetics as it cannot be ascribed to any known heavy chain variable region gene (Vh) family by nucleic acid sequence homology criteria and, hence, may represent a new Vh gene family. The sequence showed about equal nucleotide similarity (70-73%) to 3 other Vh gene families (S107, J606, 7183) and less than 65% similarity to members of the remaining 6 Vh gene families. Nucleic acid sequence comparisons with unpublished immunoglobulin sequences uncovered a highly homologous (greater than 95%) functional Vh transcript indicating that the suggested Vh gene family also encodes expressed antibody molecules.