Documentation of psoriasis in routine care - expert consensus on a German data set.

BACKGROUND AND OBJECTIVES: Documenting patient data in psoriasis clinical practice can improve care, but standardized and transparent documentation is rare. The current project aimed to develop a data set for the documentation of psoriasis in daily practice. MATERIAL AND METHODS: In four online Delphi rounds and one in-person meeting, 27 psoriasis experts allocated variables to a standard, an optimal and an optional data set. Most of the questions were standardized. Open questions were included to allow for the provision of reasons and to enlarge the data sets. Furthermore, in the in-person meeting we considered a) patients' attitudes and b) dermatologists' information on the current usage and acceptability in Germany. RESULTS: The consensus approach resulted in a data set with 69 variables. The standard data set includes 20, the optimal data set 31 and the optional data set 18 variables. In summary, the data set can mainly be grouped into master data, general status and medical history data, medical history of psoriasis, status of psoriasis, diagnostics and comorbidity, therapies and patient-reported outcomes. CONCLUSIONS: The consensus recommendation of a standard, an optimal and an optional data set for routine care of psoriasis intends to be a decision-making aid and an orientation for both daily practice and further development of documentation systems.

Clinical assessment of a foam dressing containing growth factor-enhancing hydrated polyurethanes.

OBJECTIVE: This study assesses a novel dressing concept in venous leg ulcer (VLU) patients. It is based on boosting endogenous growth factor activities synthesised by functional granulation tissue. METHODS: Patients received treatment for eight weeks with a hydrated polyurethane-containing foam dressing plus concomitant compression therapy. Wound area reduction (WAR), percentage of wounds achieving a relative WAR of ≥40% and ≥60%, wound pain ratings for the last 24 hours and at dressing changes, EQ-5D Quality of Life questionnaire data, dressing handling and safety parameters were recorded. RESULTS: There were 128 patients who received treatment and data for 123 wound treatment courses were documented. Wound area size decreased from 13.3±9.8cm2 to 10.5±12.2cm2 at week eight and median relative WAR was 48.8%. At week eight, a relative WAR ≥40% was reached by 54.5% of the wounds, 41.5% reached a relative WAR of ≥60% and complete healing was observed in 13.5% of wounds. Median wound pain ratings (last 24 hours before dressing change) declined significantly from 30 to 15.5 (100 visual analogue scale [VAS], p=0.0001) and pain at dressing changes from 30 to 12.5 (p≤0.0001). The EQ-5D VAS rating increased from 58.4±19.2mm to 63.1±19.1mm (p=0.0059). CONCLUSION: This clinical assessment shows that the concept of boosting endogenous growth factors through hydrated polyurethanes has the potential to accelerate WAR in VLU patients while decreasing pain levels and improving quality of life parameters.

Sustained remission of blastic plasmacytoid dendritic cell neoplasm after unrelated allogeneic stem cell transplantation--a single center experience.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematodermic neoplasm which typically presents with skin infiltrates with or without lymphadenopathy and bone marrow involvement. No standard of care exists for this aggressive disease and prognosis is particularly poor. Here, we present our experience with nine BPDCN patients diagnosed at our institution between 2005 and 2012. BPDCN patients were identified in the databases at the Department of Hematology and Oncology, the Department of Dermatology, and the Institute of Pathology at the Otto-von-Guericke-University Magdeburg. There were six male and three female patients with a median age at diagnosis of 66 years. Sites involved were skin (five cases), lymph nodes (five cases), and bone marrow (five cases). Treatments varied from single agent chemotherapy to polychemotherapy and allogeneic stem cell transplantation for consolidation. The three patients that were treated with acute leukemia-type induction therapy followed by allogeneic stem cell transplantation (one after standard conditioning and two after reduced intensity conditioning using fludarabine in combination with thiotepa) achieved sustained remissions and are alive with a follow-up of 8, 35, and 41 months. In contrast, median survival in the less intensively treated patients was only 9.5 (range 1 to 29) months.

Topical long-term therapy of psoriasis with vitamin D3 analogues, corticosteroids and their two compound formulations: position paper on evidence and use in daily practice.

BACKGROUND: Current data from daily practice show that vitamin D3 analogues, corticosteroids and their fixed combination products are used heterogeneously for topical long-term treatment of psoriasis. AIM: To evaluate scientific evidence about topical long-term therapy with vitamin D3 analogues, corticosteroids and their two-compound-products in psoriasis vulgaris and scalp psoriasis and to develop daily practice recommendations. METHODS: Systematic literature review via PubMed and Embase and informal expert consensus. RESULTS: The search strategy identified 21 relevant clinical trials. Best evidence regarding topical long term treatment was available for the two-compound-formulation containing calcipotriene and betamethasone. In a comparative trial in psoriasis vulgaris the two-compound-formulation showed superior tolerability and cost effectiveness compared to monotherapy. In scalp psoriasis the two-compound-gel was superior compared to calcipotriene monotherapy. Standardized and simplified treatment application modes resulted in a better clinical outcome comparing to on-demand therapies. DAILY PRACTICE RECOMMENDATIONS: Patients should be proactively involved in the choice of treatment, formulation and mode of application. Besides long-term treatment with the two-compound-formulation other treatment regimens including calcipotriene monotherapy can also be considered. Due to a favorable risk-benefit ratio in maintenance trials and due to better cost-effectiveness the application of two-compound-products once or twice a week after initial therapy is recommended.

Prevention of intraprocedural puncture site bleeding during arterial port implantation by use of a suture-mediated arterial closure system: a prospective randomized trial.

PURPOSE: To investigate a modified technique for arterial port placement that uses a suture-mediated closure system with the aim to reduce delays caused by intraprocedural oozing around the catheter. MATERIALS AND METHODS: Forty consecutive patients (age, 63.9 y ± 11.8) stratified for regional arterial infusion chemotherapy were prospectively randomized to undergo conventional or modified port implantation. Time for device placement, total procedure time, number of catheters, size of largest and final catheters placed, duration of bleeding from puncture site, procedural delays, and time until hemostasis was achieved were recorded. RESULTS: Time for device placement was 3.7 minutes ± 1.1, with no complications encountered. Total procedure times were 133.0 minutes ± 62.8 for conventional port implantation and 100.0 minutes ± 49.5 for modified implantation (P = .13). No differences were found in the number of catheters or size of largest or final catheter used. Duration of groin bleeding necessitating manual compression was 21.8 minutes ± 24.4 for conventional port implantation, resulting in a mean procedural delay of 6.2 minutes ± 7.0. Hemostasis was achieved after a mean of 17.1 minutes ± 20.9. Groin hematoma was observed in three patients. In contrast, with the modified technique, mean duration of oozing and intraprocedural delays were only 0.2 minutes ± 0.6 and 0.1 minutes ± 0.5, respectively (both P < .0001 vs conventional technique). Hemostasis was achieved within 3.2 minutes ± 4.1 (P < .0001), with no cases of hematoma found. CONCLUSIONS: Use of a suture-mediated closure system facilitated arterial port implantation by effective prevention of groin bleeding while allowing the use of a sheath.

Varicella outbreak in Indian students in Magdeburg with detection of the African-Indian VZV clade 5.

Varicella has the highest contagiosity index of all viral diseases. We report an endemic outbreak of varicella among 4 Indian students in Magdeburg in November and December 2008. An initially severe course was observed in three of these patients with a negative vaccination status. Large vesicular skin lesions with a diameter of up to 8 mm were found in all patients. Molecular genetic tests revealed African/Indian clade 5 in 2 patients, although the European clades (i.e., clade 1 and 3) are the most common in Germany, accounting for 85 %. All patients recovered without any complications after administration of intravenous aciclovir at a dosage of 10 mg per kg body weight. Although isolated cases of varicella are not notifiable according to the German Protection against Infection Act, endemic outbreaks must be reported to the appropriate health surveillance authorities.

Comparative in situ topoproteome analysis reveals differences in patch test-induced eczema: cytotoxicity-dominated nickel versus pleiotrope pollen reaction.

A subgroup of patients with atopic eczema develops acute eczematous reactions to type I allergy-inducing agents such as pollen that clinically resemble type IV allergies induced by haptens like metal ions. To clarify the underlying immunologic mechanisms, this study was designed to map the inflammatory in situ topoproteome of eczematous responses to grass/birch pollen and nickel by using atopy patch test (APT) and nickel patch test (NPT) as an appropriate clinical model, respectively. Biopsies from NPT (n = 6) and APT (n = 6) with positive reactions at 72 h were analysed by multiple epitope ligand cartography (MELC), which enabled to investigate coexpression of 49 different epitopes immunohistochemically in a single given tissue section. Colocalisation of IgE and FcepsilonRI was investigated by confocal microscopy. Compared with APT responses, NPT reactions were dominated by cytotoxic TIA-1 + and CD8 + T cells. In contrast, the immune response in APT reactions appeared more pleiotrope - as detected by colocalisation analysis. Multiple combinatorial molecular phenotype (CMP) motifs containing naive, early maturation and memory T cell (CD45RA, CD7, CD44, CD45R0), and general activation markers (CLA, HLA-DR, CD13, CD29, CD58, CD71, CD138) were significantly higher expressed in APT when compared with NPT reactions. APT response was confirmed to be accompanied by IgE bound to FcepsilonRI. In summary, our results demonstrate that the NPT reaction is clearly dominated by cytotoxic events, while the APT reaction to pollen grains is more heterogeneous and elicits a combined humoral and cellular immune reaction.

Analyzing proteome topology and function by automated multidimensional fluorescence microscopy.

Temporal and spatial regulation of proteins contributes to function. We describe a multidimensional microscopic robot technology for high-throughput protein colocalization studies that runs cycles of fluorescence tagging, imaging and bleaching in situ. This technology combines three advances: a fluorescence technique capable of mapping hundreds of different proteins in one tissue section or cell sample; a method selecting the most prominent combinatorial molecular patterns by representing the data as binary vectors; and a system for imaging the distribution of these protein clusters in a so-called toponome map. By analyzing many cell and tissue types, we show that this approach reveals rules of hierarchical protein network organization, in which the frequency distribution of different protein clusters obeys Zipf's law, and state-specific lead proteins appear to control protein network topology and function. The technology may facilitate the development of diagnostics and targeted therapies.

Low-dose combination therapy of severe digital ulcers in diffuse progressive systemic sclerosis with the endothelin-1 receptor antagonist bosentan and the phosphodiesterase V inhibitor sildenafil.

Digital ulcers in progressive systemic sclerosis (PSS) are often refractory to therapy. A frequently chronic aggressive course can lead to the loss of acral limbs involved. A 73-year-old woman developed a dramatic worsening of her ulcerations despite maximum conventional therapy. Switching therapy to bosentan and sildenafil, both in low-dose regimens, resulted for the first time in ten years in a complete healing of the ulcers. If substantiated in a series of patients, the additive and perhaps synergistic clinical benefits of combining bosentan and sildenafil may be a valuable option for the treatment of acral ulcers in PSS.

Brodalumab for the treatment of moderate-to-severe psoriasis: case series and literature review.

Brodalumab, a recombinant fully human monoclonal immunoglobulin IgG2 antibody with high affinity to human interleukin (IL)-17RA, is approved for the treatment of moderate-to-severe plaque psoriasis. In controlled clinical trials, brodalumab 210 mg administered by subcutaneous injection at weeks 0, 1, and 2, then 210 mg every 2 weeks, produced a rapid onset and sustained clinical response. Consistently, >80% of patients achieved PASI-75 and efficacy was maintained for >2 years. The benefits are apparent soon after the start of therapy and are maintained in the long term. Such results, from the reviewed literature, support the findings from 4 'real world' cases in mainstream clinical practice which are reported here. Psoriatic plaques, including on the scalp, nails, soles and palms, were largely resolved, and quality of life improved markedly. Therapeutic success was achieved in patients naïve to biologics (2 cases) and in those responding inadequately to other biologics (2 cases). The high affinity of brodalumab to human IL-17RA blocks the biological activities of the pro-inflammatory cytokines IL-17A, IL-17C, IL-17E, IL-17F, and IL-17A/F heterodimer, resulting in inhibition of the inflammation and clinical symptoms associated with psoriasis. This mechanism of blocking multiple IL-17 family cytokines differs from that of other available biologics which selectively target some parts of the Th-17 axis and may account for the effectiveness of brodalumab in patients poorly responsive to other biologics, a feature which has also been shown where subgroup analysis has been undertaken in clinical trials. The drug is well tolerated during the normal 12-week induction phase and with prolonged treatment (52 to 120 weeks), as it was in the current case series.

In-situ-topoproteome analysis of cutaneous lymphomas: perspectives of assistance for dermatohistologic diagnostics by Multi Epitope Ligand Cartography (MELC).

BACKGROUND: Immunophenotyping is essential for diagnostics of cutaneous lymphomas. In this regard we present a skin tissue-adapted application platform of MELC technology. PATIENTS AND METHODS: This topoproteome analysis allows the subcellular colocalization of at least n = 100 epitopes in situ. For this purpose the specimen is processed by a Toponome Imaging Cycler for a n-fold repetition of the following cycle: 1) staining with a fluorophore-labeld antibody, 2) fluorescence-imaging, and 3) photobleaching. Overlay and binarization of fluorescence images lead to combinatorial molecular phenotypes (CMP), which relate to a pixel or microtopographic unit (450 x 450 nm2, 20x objective). Skin biopsies were derived from patients with mycosis fungoides (patch/plaque lesions), psoriasis, atopic eczema and from healthy skin donors. RESULTS: In orientation to the WHO-EORTC-classification of cutaneous lymphomas a MELC-library of 23 markers was established. According to an inaugurative detailed procedure the CMP frequency was determined in a normalization to 100 microm horizontal skin width. By a TopoMiner strategy mycosis fungoides could be separated from the other states with a maximum of significance (p < or = 0.03) by at least 10-fold overexpression of the following tumor cell-representative CMP-motif: CD3+/CD4+/CD1a-/CD7-/CD8-/CD45R0+/CD45RA-/CD11a+. CONCLUSIONS: The skin tissue-adapted MELC-application-platform extends substantially conventional lymphoma diagnostics by an unprecedented dimension of in-situ-analysis of marker combinatorics including its exact quantification and visualization.

Cowpox infection transmitted from a domestic cat.

A 21-year-old immunocompetent woman developed a cowpox infec-tion,while working as a veterinarian's assistant in a rural area. She had never received vaccinia immunization and came in contact with a fatally-infected house cat. Under symptomatic treatment, the infection remained localized to one cheek and cleared over 3 weeks with substantial dermal-subcutaneous tissue destruction. Orthopoxvirus detection by PCR is a modern diagnostic standard, in addition to identification by negative-contrast electron microscopy. A promising therapeutic option is cidofovir, but this virostatic drug is not yet approved for the treatment of cowpox.

UVB irradiation-induced impairment of keratinocytes and adaptive responses to oxidative stress.

UVB irradiation of human skin is known to induce pathophysiological processes as oxidative stress and inflammation. HaCaT keratinocytes represent a well-established in vitro model system to investigate the influence of UVB irradiation on cell cultures. It was the aim of these investigations to study the effects of moderate UVB doses on cellular and mitochondrial integrity of HaCaT keratinocytes, biomarkers of oxidative stress and antioxidant protection by superoxide dismutases. F(2)-isoprostane concentrations were UVB dose-dependently enhanced reaching a plateau at 50 mJ/cm(2). Cell viability was reduced and apoptosis was enhanced with increasing UVB doses. The activities of the respiratory chain complexes were practically not altered at lower UVB doses, up to 50 mJ/cm(2), whereas remarkable decreases, also for the levels of cardiolipin species, were seen at 100 mJ/cm(2). As an adaptive response to the enhanced oxidative stress, protein levels of MnSOD increased about 3-fold at 50 mJ/cm(2) and decreased at higher doses. From the data it can be concluded that keratinocytes are sufficiently protected at low UVB doses, whereas higher doses lead to irreversible cell damage.

Profiling lymphocyte subpopulations in peripheral blood under efalizumab treatment of psoriasis by multi epitope ligand cartography (MELC) robot microscopy.

CD11a-blocking efalizumab has recently been approved as a systemic treatment of moderate to severe chronic plaque psoriasis. When treating 6 psoriasis patients with efalizumab over 12 weeks in the present study, we observed an overall good tolerability and 5 treatment responders characterized by a decrease of PASI from 21.3 +/- 5.4 to 3.9 +/- 0.6. The accompanying significant increase of peripheral blood lymphocytes from 1.9 +/- 0.7 to 4.3 +/- 1.0 x 10(9)/L (p < 0.05) was analyzed by multi epitope ligand cartography (MELC) robot microscopy. Thereby a high-dimension simultaneous multiplex immunophenotyping was pursued using 39 fluorophore-labeled antibodies including labeled efalizumab and 3 other affinity reagents such as lectins. Due to efalizumab treatment there was a substantial decrease of the cellular expression of CD11a (detected by mab clone 25.3.1) and efalizumab binding sites (EfaBSs). This was paralleled by an increase of the number of EfaBS- and EfaBS+ lymphocytes by a factor of 2.4x and 2.2x, respectively. The latter effect was mainly derived from a subpopulation showing a low degree of EfaBS expression. Efalizumab treatment led furthermore to an increase of the numbers of CD3+, CD4+, CD8+, CD44+, CD45+, CD45R0+, CD45 RA+, CD52+, CD58+, CD247+, HLA-DR+ and Sambucus nigra lectin-reactive lymphocytes (by factors from 2.0 to 3.3x). In terms of a combinatorial molecular phenotype we identified a CD3+/CD4+/CD44+/CD52+ lymphocyte subpopulation which accumulated most predominantly from 0.824 +/- 0.270 x 10(9)/L up to 1.616 +/- 0.152 x 10(9)/L under efalizumab treatment (p < 0.01). Thus, the current study extends the knowledge of efalizumab-dependent perturbations of recirculating blood lymphocyte subpopulations in psoriasis patients.