Background Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time-dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. Objectives To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. Methods This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. Results A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long-term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naivety, its superiority vanished and drug survival rates were similar for ixekizumab (91.6%), secukinumab (90.2%) and ustekinumab (92.8%), all of them superior to adalimumab (76.5%) and etanercept (71 .9%) at 12 months and beyond. Besides biologic non-naivety (2 .10, P < 0.001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1.6, P = 0.001) and female gender (1.50, P = 0 .019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1.12, P = 0.21). Conclusions The time-dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment.

Das epitheloide Sarkom vom klassischen, „distalen“ Typ wurde 1970 erstmals beschrieben. Es handelt sich um einen äußerst seltenen, malignen, subkutan gelegenen, langsam wachsenden aggressiven Weichteiltumor, der sowohl epitheliale wie auch mesenchymale Marker stark exprimiert. Er tritt v. a. bei jungen männlichen Erwachsenen auf und manifestiert sich klinisch als derbe meist schmerzhafte, kutan bis subkutan gelegene knotige Induration, die im Verlauf häufig exulzeriert. Eine Assoziation mit einem Trauma wird häufig berichtet und lenkt von der korrekten Diagnose ab. Prädilektionsstellen sind v. a. die Beugeseiten der Finger, Handrücken, Fußsohlen sowie Streckseiten der Unterarme und Unterschenkel. Ein Spezifikum des Tumors ist die Ausbreitung entlang von Nerven, Sehnen und Faszien. Die Therapie der Wahl ist die großzügige Exzision des Tumors, eine Sentinelnodebiopsie und ggf. die prä- oder postoperative Bestrahlungstherapie. Das epitheloide Sarkom zeigt eine ausgeprägte Rezidivneigung in den ersten Jahren, die häufig mit Lungen- und/oder Lymphknotenmetastasen vergesellschaftet ist und dann eine infauste Prognose aufweist.

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.

Psoriasis is a chronic, immune-mediated disease affecting more than 100 million people worldwide and up to 2.2% of the UK population. The aetiology of psoriasis is thought to originate from an interplay of genetic, environmental, infectious and lifestyle factors. The manner in which genetic and environmental factors interact to contribute to the molecular disease mechanisms has remained elusive. However, the interleukin 23 (IL-23)/T-helper 17 (TH 17) immune axis has been identified as a major immune pathway in psoriasis disease pathogenesis. Central to this pathway is the cytokine IL-23, a heterodimer composed of a p40 subunit also found in IL-12 and a p19 subunit exclusive to IL-23. IL-23 is important for maintaining TH 17 responses, and levels of IL-23 are elevated in psoriatic skin compared with non-lesional skin. A number of agents that specifically inhibit IL-23p19 are currently in development for the treatment of moderate-to-severe plaque psoriasis, with recent clinical trials demonstrating efficacy with a good safety and tolerability profile. These data support the role of this cytokine in the pathogenesis of psoriasis. A better understanding of the IL-23/TH 17 immune axis is vital and will promote the development of additional targets for psoriasis and other inflammatory diseases that share similar genetic aetiology and pathogenetic pathways.

Three Austrian patients presented with severe palmoplantar keratoderma associated with ichthyosis and sensorineural deafness. Exome sequencing revealed biallelic mutations in VPS33B, encoding VPS33B, a Sec1/Munc18 family protein which interacts with Rab11a and Rab25 proteins and is involved in trafficking of the collagen modifying enzyme LH3. Two patients showed the homozygous missense variant p.Gly131Glu, whilst one patient was compound heterozygous for p.Gly131Glu and the splice site mutation c.240-1G>C, previously reported in patients with arthrogryposis renal dysfunction and cholestasis syndrome. The pathogenicity of variant p.Gly131Glu was demonstrated by assessing the interactions of the mutant VPS33B construct and its ability to traffic LH3. Compared with wild-type, p.Gly131Glu mutant VPS33B had reduced coimmunoprecipitation and colocalization with Rab11a and Rab25 and did not rescue LH3 trafficking. Confirming the cell-based experiments, we found deficient LH3-specific collagen lysine modifications in urine and skin fibroblasts of the patients. Additionally, epidermal ultrastructure of the p.Gly131Glu patients mirrored defects in tamoxifen-inducible VPS33B deficient Vps33bfl/fl–ERT2 mice. Both patients and murine models revealed an impaired basement membrane zone and epidermal barrier structure with less prominent hemidesmosomes, a reduced number of anchoring fibrils, insufficiently fixed collagen fibers to the fibrils and aberrant secretion of lamellar bodies. Our results show that p.Gly131Glu mutant VPS33B causes Autosomal Recessive Keratoderma-Ichthyosis-Deafness (ARKID) syndrome.

Die Herausforderungen der modernen Wundversorgung wie die Behandlung chronischer Wunden oder eine phasengerechte Versorgung sind anspruchsvoll und erfordern optimal angepasste Therapiemaßnahmen. Die Prinzipien der feuchten Wundbehandlung sowie ein adäquates Débridement stehen dabei im Vordergrund. Um diese erforderlichen Maßnahmen zu unterstützen, stehen mehrere Optionen zu Verfügung, u. a. eine neue Produktklasse mit phasenübergreifender Wirkung.

BACKGROUND: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. OBJECTIVE:A new treatment principle in modern wound management based on an expert consensus is presented. METHODS: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. RESULTS: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. DISCUSSION: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.

Background Each individual psoriasis patient has different expectations and goals for biological treatment, which may differ from those of the clinician. As such, a patient-centred approach to treatment goals remains an unmet need in psoriasis.Objective The aim of this study was to review available data on patients' and physicians' decision criteria and expectations of biological treatment for moderate-to-severe psoriasis with the aim of developing a core set of questions for clinicians to ask patients routinely to understand what is important to them and thus better align physicians' and patients' expectations of treatment with biologics and its outcomes.Methods A literature search was conducted to identify key themes and data gaps. Aspects of treatment relevant when choosing a biological agent for an individual patient were identified and compared to an existing validated instrument. A series of questions aimed at helping the physician to identify the particular aspects of treatment that are recognised as important to individual psoriasis patients was developed.Results Key findings of the literature search were grouped under themes of adherence, decision-making, quality of life, patient/physician goals, communication, patient-reported outcomes, satisfaction and patient benefit index. Several aspects of treatment were identified as being relevant when choosing a biological agent for an individual patient. The questionnaire is devised in two parts. The first part asks questions about patients' experience of psoriasis and satisfaction with previous treatments. The second part aims to identify the treatment attributes patients consider to be important and may as such affect their preference for a particular biological treatment. The questionnaire results will allow the physician to understand the key factors that can be influenced by biological drug choice that are of importance to the patient. This information can be used be the physician in clinical decision making.Conclusion The questionnaire has been developed to provide a new tool to better understand and align patients' and physicians' preferences and goals for biological treatment of psoriasis.

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 unterschätztes Gesundheitsproblem. Untersuchungen zeigen, dass neben den belastenden Symptomen selbst auch das soziale Leben, der Schlaf sowie Schul- und Arbeitsleistungen durch die ganzjährigen oder saisonalen Beschwerden mitunter erheblich beeinträchtigt werden. Auch die anfallenden Kosten durch Krankenstände, schulische Fehlzeiten sowie Produktivitätsausfälle sind erheblich. Zudem kann eine zu spät 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 Lebensqualität der Betroffenen deutlich verbessern. Um die subjektiven Einschätzungen von einzelnen Patienten zur Lebensqualität objektivierbar und damit auch statistisch messbar machen, dienen in erster Linie standardisierte und validierte Fragebögen. Für die schnelllösliche Gräsertablette GRAZAX® wurde in mehreren großen Studien belegt, dass die Therapie neben einer guten Wirksamkeit und Sicherheit auch eine signifikante Verbesserung der Lebensqualität für Gräserpollen-allergische Patienten aufweist.

BACKGROUND:Psoriatic arthritis (PsA) and co-morbidities of psoriasis represent a significant clinical and economic burden for patients with moderate-to-severe psoriasis. Often these co-morbidities may go unrecognized or undertreated. While published data are available on the incidence and impact of some of them, practical guidance for dermatologists on detection and management of these co-morbidities is lacking. OBJECTIVE:To prepare expert recommendations to improve the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis. METHODS:A systematic literature review was conducted on some common co-morbidities of psoriasis-cardiovascular (CV) diseases (including obesity, hypertension, hyperglycaemia and dyslipidaemia), psychological co-morbidities (including depression, alcohol abuse and smoking) and PsA-to establish the incidence and impact of each. Data gaps were identified and a Delphi survey was carried out to obtain consensus on the detection and management of each co-morbidity. The expert panel members for the Delphi survey comprised 10 dermatologists with substantial clinical expertise in managing moderate-to-severe psoriasis patients, as well as a cardiologist and a psychologist (see appendix) with an interest in dermatology. Agreement was defined using a Likert scale of 1-7. Consensus regarding agreement for each statement was defined as ≥75% of respondents scoring either 1 (strongly agree) or 2 (agree). RESULTS:The expert panel members addressed several topics including screening, intervention, monitoring frequency, and the effects of anti-psoriatic treatment on each co-morbidity. Consensus was achieved on 12 statements out of 22 (3 relating to PsA, 4 relating to psychological factors, 5 relating to CV factors). The panel members felt that dermatologists have an important role in screening their psoriasis patients for PsA and in assessing them for psychological and CV co-morbidities. In most cases, however, patients should be referred for specialist management if other co-morbidities are detected. CONCLUSION:This article provides useful and practical guidance for the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis.

OBJECTIVE:This study compares treatment with a polihexanide-containing biocellulose wound dressing (BWD+PHMB) versus the best local standard of silver dressings (Ag) in painful, critically colonised (wounds-at-risk) or locally-infected wounds.METHOD:Patients with wounds of various aetiologies, a baseline VAS pain score >4 and a semi-quantitative bacterial load of ++ or higher were randomly allocated to receive treatment with either BWD+PHMB or Ag. Patients with systemic infections and/or using systemic antibiotics were excluded. The primary endpoint, patient-reported pain (VAS total pain, including the sub-scores pain at night, during the day, before, and 15min after dressing changes), was compared between treatment groups and scored on days 0, 1, 3, 7, 14, 21 and 28. Secondary outcomes of bacterial load, wound bed and periwound skin condition, quality of life and dressing handling were assessed at the same visits.RESULTS:Thirty-eight patients (BWD+PHMB, n=21 [24 wounds]; Ag, n=17 [18 wounds]) were included in the analyses. Baseline variables showed no significant differences. Wound pain was reduced significantly in both groups, with a better pain reduction noted for BWD+ PHMB (p<0.001) before dressing changes. Compared with Ag, in the BWD+PHMB group critical colonisation and local wound infection had been reduced significantly faster and better (p<0.001) over the 28-day study period. Improved quality of life, good tolerability and no adverse events were demonstrated for both groups.CONCLUSION:Both BWD+PHMB and AG were effective in reducing pain and bacterial burden. However, that BWD+PHMB was significantly faster and better in removing the critical bacterial load, makes this dressing an attractive therapeutic option to treat critically colonised and locally-infected wounds.

Currently, there are no generally accepted definitions for wounds at risk of infection. In clinical practice, too many chronic wounds are regarded as being at risk of infection, and therefore many topical antimicrobials – in terms of frequency and duration of use – are applied to wounds. Based on expert discussion and current knowledge, a clinical assessment score was developed. The objective of this wounds at risk (W.A.R.) score is to allow decision-making on the indication for the use of antiseptics on the basis of polihexanide. The proposed clinical classification of W.A.R. shall facilitate the decision for wound antisepsis and allow an appropriate general treatment regimen with the focus on the prevention of wound infection. The W.A.R. score is based on a clinically oriented risk assessment using concrete patient circumstances. The indication for the use of antiseptics results from the addition of differently weighted risk causes, for which points are assigned. Antimicrobial treatment is justified in the case of 3 or more points.

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.

The problem of wound infection presents a special challenge in the treatment of acute as well as chronic wounds. Typical complications not only jeopardise the successful outcome of treatment modalities as a whole; they may result in amputation or even become life-threatening.Polihexanide is an antimicrobial substance which is highly appropriate for use in critically colonised or infected acute and chronic wounds. This finding is based primarily on the broad antimicrobial spectrum and good cell and tissue compatibility of polihexanide, its capability of binding to organic matrix, the low risk of contact sensitisation, and the fact that it promotes wound healing. Furthermore, there has been no conclusive evidence to date of any pathogens developing resistances under the use of polihexanide.Summary: Wound infections are special and challenging situations in therapy of acute and chronic wounds. Typical complications are riskful not only for therapeutic process but also for amputation and viability of patients.Polihexanide is an exceedingly appropriate antimicrobial substance for using in critical colonised and local infected acute and chronic wounds. This evaluation is based on different properties of the compound like the broad antimicrobial spectrum, the excellent cell and tissue tolerability, the binding capacity to organic matrix, low risk of contact sensitisation and adjuvant effects to wound healing. Up to now there are no microbial resistances observed. (C) 2010 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Wound infections are special and challenging situations in the therapy of acute and chronic wounds. Typical complications are riskful not only for the therapeutic process but also for amputation and viability of patients.Polihexanide is an exceedingly appropriate antimicrobial substance for using in critical colonised and local infected acute and chronic wounds. This evaluation is based on different properties of the compound like the broad antimicrobial spectrum, the excellent cell and tissue tolerability, the binding capacity to organic matrix, the low risk of contact sensitization and the adjuvant effects to wound healing. Up to now there are no microbial resistances observed.