Dermatologikum Hamburg

Hamburg, Germany

Dermatologikum Hamburg

Hamburg, Germany
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Langley R.G.,Dalhousie University | Saurat J.H.,University of Geneva | Reich K.,Dermatologikum Hamburg
Journal of the European Academy of Dermatology and Venereology | Year: 2012

Background Nail involvement is common in psoriasis patients and is often associated with severe disease. Patients with nail psoriasis experience pain, functional impairment and social stigma, with significant restriction of daily activities and quality of life. However, nail psoriasis often goes untreated, as many physicians believe it is difficult to treat, despite the availability of effective treatment options. Clinical data and guidelines for managing and treating psoriasis patients with both skin and nail symptoms are limited. Objective To prepare recommendations for the management and treatment of patients with moderate to severe psoriasis with nail involvement. Methods A collaborative Delphi survey was used to obtain consensus on current practice in the management of nail disease in patients with moderate to severe psoriasis from an expert panel of 11 dermatologists from Europe and Canada with substantial clinical expertise in managing these patients. Agreement was defined utilizing a Likert scale of 1-9. Consensus regarding agreement was an interquartile range (IQR) ≥7; consensus regarding disagreement was an IQR ≤3. Results The expert panel addressed several topics including burden of disease, nail assessment, treatment goals and treatment options. The panel agreed that: it is extremely important to assess nail involvement in patients with psoriasis; nail assessments are rarely performed in routine clinical practice; full skin and nail clearance is an achievable goal with appropriate systemic therapy in patients with moderate to severe psoriasis with nail involvement. Conclusion This article provides useful and practical considerations for the management and treatment of patients with moderate to severe skin and nail psoriasis. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Reich K.,Dermatologikum Hamburg | Bewley A.,University of London
Journal of the European Academy of Dermatology and Venereology | Year: 2011

This article describes a recent development in topical therapies for psoriasis and is based on a presentation given by the authors at a satellite symposium convened during the 19th Congress of the European Academy of Dermatology and Venereology, 6-10 October 2010, in Gothenburg, Sweden. Topical therapies are the mainstay of treatment for psoriasis; however, for optimal outcomes to be achieved, medications need to be used as prescribed. Patients with psoriasis often report low treatment adherence rates; the reasons for this are multifactorial, but can include specific aspects of the treatments themselves. For example, physical properties, ease of use and the vehicle in which the active ingredients are dissolved can all play a role in an individual patient's adherence to treatment. Of the available topical therapies, corticosteroids and vitamin D analogues are the treatment of choice, with combined efficacy that is superior to monotherapy with either agent. To permit simultaneous once-daily dosing, an ointment was formulated that allowed calcipotriol and betamethasone dipropionate to be delivered together; this two-compound ointment had an improved efficacy and tolerability profile vs. either compound alone. To provide an alternative for patients who may dislike ointments, but still want to benefit from the high efficacy of combination therapy, a two-compound (calcipotriol/betamethasone dipropionate) gel has recently been developed; data from phase 2 and phase 3 studies show that it is more effective than the comparators it was tested against, with fewer adverse events, and a rapid onset of action. In a series of one-to-one interviews recently conducted with 150 patients with psoriasis, gel and cream formulations were preferred for ease of use and cosmetic acceptability compared with ointment. The availability of this new gel thus increases patient choice. Ultimately, treatment should always be tailored to match individual patients' needs. © 2011 European Academy of Dermatology and Venereology.

Murphy G.,National Photobiology Unit Beaumont and Materials Hospitals | Reich K.,Dermatologikum Hamburg
Journal of the European Academy of Dermatology and Venereology | Year: 2011

This article describes topical therapies and treatment guidelines for psoriasis and is based on a presentation given by the authors at a satellite symposium held during the 19th Congress of the European Academy of Dermatology and Venereology, 6-10 October, 2010, in Gothenburg, Sweden. The highly variable nature of psoriasis and its individual presentation in patients can make it difficult to choose the most appropriate treatment. There are many treatment options, from topical treatment with emollients for very mild psoriasis, to systemic therapy with fumaric acid esters, methotrexate or biologics for severe disease. For the treatment of mild-to-moderate psoriasis, topical therapy is generally the most appropriate and a variety of options, both historical and recent, are available. Newer therapies offer greater convenience and fewer side-effects. Of the more recently available therapies, vitamin D analogues and topical corticosteroids are the two with the greatest proven efficacy in randomized clinical trials. A recent Cochrane review showed the highest efficacy overall with the fixed combination vitamin D analogue (calcipotriol) and corticosteroid (betamethasone dipropionate). Indeed, clinical trials have shown that two-compound calcipotriol/betamethasone dipropionate ointment has higher efficacy than calcipotriol or betamethasone dipropionate alone. With regard to safety, two-compound calcipotriol/betamethasone dipropionate was shown to be suitable for intermittent long-term treatment of mild-to-moderate psoriasis. The findings of the Cochrane review are reflected in the current treatment guidelines from the USA and Germany regarding the treatment of mild-to-moderate psoriasis. In both these guidelines, which will be discussed in this article, the recommended treatments for this patient group are vitamin D analogues and corticosteroids, particularly when used in combination. © 2011 European Academy of Dermatology and Venereology.

Reich K.,Dermatologikum Hamburg | Burden A.D.,Western Infirmary | Eaton J.N.,Health Economics | Hawkins N.S.,Health Economics
British Journal of Dermatology | Year: 2012

Background Ustekinumab, a novel monoclonal antibody for the treatment of moderate to severe plaque-type psoriasis, has recently received regulatory approval in Europe, bringing the total number of biologic agents licensed in this indication to five. To assist treatment selection in daily practice it is essential to understand the benefit/risk profile of these agents and in the absence of a clinical trial comparing all available biologics a number of reviews have used statistical techniques to generate estimates of the comparative effectiveness of these therapies through the available network of randomized clinical trials. These estimates have previously been published for a limited range of psoriasis biologic treatments, although, to date no review has compared all the currently available agents in Europe. Objectives To estimate the comparative effectiveness of all biologic agents indicated in the treatment of moderate to severe psoriasis currently available in Europe based on the primary trial endpoints. Methods A number of databases were searched for details of randomized controlled trials of available biologics in the treatment of plaque-type psoriasis in adults. Comparative effectiveness was estimated based on the reported Psoriasis Area and Severity Index (PASI) 50, 75 and 90 response rates. A network meta-analysis conducted on the ordered probit scale and implemented as a Bayesian hierarchical model provided estimates for the probability of response and relative risk vs. placebo, based on all observed comparisons. Results Twenty trials were included in the meta-analysis including patients with a mean disease duration of 18-22 years. Based on the indirect comparison and given a placebo PASI 50 response of 13%, infliximab had the highest predicted mean probability of response at PASI levels 50 (93%), 75 (80%) and 90 (54%), followed by ustekinumab 90 mg at 90%, 74% and 46%, respectively, and then ustekinumab 45 mg, adalimumab, etanercept and efalizumab. Conclusions The ordered probit model allowed a quantitative comparison of all currently licensed biologics, providing estimates on comparative effectiveness and a suggested ranking of treatments that is of potential use to decision-makers. However, the analysis is based on indirect comparisons of the primary endpoint reported from short-term randomized trials. © 2011 British Association of Dermatologists.

Psoriasis is a chronic disease requiring long-term therapy, which makes finding treatments with favourable long-term safety and efficacy profiles crucial. The goal of this review is to provide the background needed to evaluate properly long-term studies of biologic treatments for psoriasis. Firstly, important elements of design and analysis strategies are described. Secondly, data from published trials of biologic therapies for psoriasis are reviewed in light of the design and analysis choices implemented in the studies. Published reports of clinical trials of biologic treatments (adalimumab, alefacept, etanercept, infliximab or ustekinumab) that lasted 33 weeks or longer and included efficacy results and statistical analysis were reviewed. Study designs and statistical analyses were evaluated and summarized, emphasizing patient follow-up methods and handling of missing data. Various trial designs and data handling methods are used in long-term studies of biologic psoriasis treatments. Responder analyses in long-term trials can be conducted in responder enrichment, re-treated nonresponder or intent-to-treat trials. Missing data can be handled in four ways, including, from most to least conservative, nonresponder imputation, last-observation-carried-forward, as-observed analysis and anytime analysis. Long-term clinical trials have shown that adalimumab, alefacept, etanercept, infliximab and ustekinumab are efficacious for psoriasis treatment; however, without common standards for these trials, direct comparisons of these agents are difficult. Understanding differences in trial design and data handling is essential to make informed treatment decisions. What's already known about this topic? The chronic nature of psoriasis makes long-term efficacy studies particularly valuable for making treatment decisions. Complicated trial designs and inconsistent data handling methods make direct comparisons between trials difficult. What does this study add? A thorough explanation of trial types and data handling variations is provided, allowing readers to analyse effectively efficacy data reports. Currently available clinical trial results of biologic psoriasis treatment agents are reviewed and evaluated. © 2013 British Association of Dermatologists.

Kirkham B.W.,Guys and St Thomas NHS Foundation Trust | Kavanaugh A.,University of California at San Diego | Reich K.,Dermatologikum Hamburg
Immunology | Year: 2014

Experimental evidence points to the importance of the cytokine interleukin-17A (IL-17A) in the pathogenesis of several immunoinflammatory diseases including psoriasis, psoriatic arthritis and rheumatoid arthritis. Although a principal effector of T helper type 17 cells, IL-17A is produced by many other cell types including CD8+ T cells and γδ T cells, and is found at high levels associated with mast cells and neutrophils at sites of skin and joint disease in humans. IL-17A up-regulates expression of numerous inflammation-related genes in target cells such as keratinocytes and fibroblasts, leading to increased production of chemokines, cytokines, antimicrobial peptides and other mediators that contribute to clinical disease features. Importantly, IL-17A must be considered within the context of the local microenvironment, because it acts synergistically or additively with other pro-inflammatory cytokines, including tumour necrosis factor. Several direct IL-17A inhibitors have shown promising activity in proof of concept and phase 2 clinical studies, thereby providing confirmation of experimental data supporting IL-17A in disease pathogenesis, although levels of response are not predicted by pre-clinical findings. IL-17A inhibitors produced rapid down-regulation of the psoriasis gene signature and high clinical response rates in patients with moderate-to-severe plaque psoriasis, consistent with an important role for IL-17A in psoriasis pathogenesis. Clinical response rates with IL-17A inhibitors in psoriatic arthritis and rheumatoid arthritis, however, were improved to a lesser degree compared with placebo, suggesting that IL-17A is either important in a subset of patients or plays a relatively minor role in inflammatory joint disease. Ongoing phase 3 clinical trials should provide further information on the role of IL-17A in these diseases. © 2013 John Wiley & Sons Ltd.

Boer-Auer A.,Dermatologikum Hamburg
Hautarzt | Year: 2014

Adnexal tumors of the skin are epithelial skin tumors with differentiation towards the adnexal epithelial structures of the skin, namely, hair follicle, sebaceous gland, apocrine gland, and eccrine gland. Adnexal tumors include hamartomas, benign and malignant neoplasms, and hyperplasias. The specific diagnosis of adnexal tumors is important because some lesions such as sebaceous neoplasms, cylindromas, or fibrofolliculomas are herald lesions of hereditary tumor syndromes (e.g., Muir-Torre syndrome, familial cylindromatosis, Birt-Hogg-Dubé syndrome). In this article, the classification of adnexal tumors of the skin is explained on the basis of embryology and histology and the main features of tumor-associated syndromes are summarized. Moreover, some conceptual controversies and problems in differential diagnosis of cutaneous adnexal tumors are discussed. © Springer-Verlag 2014.

Reich K.,Dermatologikum Hamburg
Journal of the European Academy of Dermatology and Venereology | Year: 2012

Psoriasis is a systemic, immune-mediated disorder, characterized by inflammatory skin and joint manifestations. A range of co-morbidities is associated with psoriasis, including metabolic diseases, such as diabetes, and psychological disorders. Although the systemic nature of psoriasis often remains unrecognized, the inflammatory processes involved may be associated with the development of co-morbidities, which, themselves, have a significant impact on the patient's health and quality of life. The relative risks of myocardial infarction (MI) and stroke are increased in patients with psoriasis compared with the general population. These are especially seen in younger patients with more severe disease, and are believed to contribute to the 3- to 4-year reduction in life expectancy among patients with severe psoriasis. The recent results of large studies indicate that the increased cardiovascular (CV) risk is at least partially attributable to psoriasis and independent of the presence of metabolic co-morbidities. The possible interplay between psoriasis and CV disease is complex. Metabolic diseases such as obesity and diabetes have overlapping genetic predispositions with psoriasis. Both conditions are likely to also interact at a functional level because obesity and the up-regulation of pro-inflammatory mediators in psoriasis appear to influence adipocyte homoeostasis, inducing non-professional immune functions. This may perpetuate psoriatic inflammation, displaying similarities to the immunopathogenesis of atherosclerosis. Finally, the disturbed adipokine profile and inflammation associated with psoriasis enhances insulin resistance, causing subsequent endothelial dysfunction, atherosclerosis and eventual coronary events. The differential contribution of psoriasis and uncontrolled classical CV risk factors to the increased CV risk seen in psoriasis patients is not clear. Successful treatment with methotrexate appears to lower the rates of MI in patients with psoriasis. Tumour necrosis factor-α (TNF-α) inhibitors are known to counteract insulin resistance and emerging studies demonstrate an even higher protective effect of TNF-α antagonist therapy against the development of diabetes or CV co-morbidities in patients. The recent data reviewed here indicate a role for earlier and more appropriate treatment of psoriasis with drugs such as TNF-α antagonists. Such an approach has the potential to significantly improve patient outcomes through the treatment of psoriasis itself and possibly also in protection against co-morbidities. © 2012 European Academy of Dermatology and Venereology.

Prager W.,Dermatologikum Hamburg
Clinical Pharmacology: Advances and Applications | Year: 2013

Objectives: This review examines the pharmacologic and clinical characteristics of incobotulinumtoxinA (Xeomin®/Xeomeen®/Bocouture®/XEOMIN Cosmetic™; botulinum toxin type A [150 kDa]), which is free from complexing proteins, and discusses its efficacy and safety in the treatment of glabellar frown lines. Differences between incobotulinumtoxinA and other commercially available botulinum neurotoxin type A (BoNT/A) products that have been approved by the European Medicines Agency, US Food and Drug Administration, and other regulatory agencies for this indication are also discussed. Findings: IncobotulinumtoxinA differs from other commercially available BoNT/A preparations, in that it is free from complexing proteins and contains only active neurotoxin, minimizing foreign protein load. IncobotulinumtoxinA is commonly used at a 1:1 dose ratio with onabotulinumtoxinA and displays comparable efficacy and safety; furthermore, it is associated with early onset and long duration of effect, and high levels of subject satisfaction. In terms of practical considerations, incobotulinumtoxinA does not require cold storage and demonstrates low spread, enabling precise treatment and good tolerability. Conclusion: IncobotulinumtoxinA is an efficacious and well-tolerated treatment for glabellar frown lines. It differs from other BoNT/A preparations, in that it is free from complexing proteins and contains only active neurotoxin, which is relevant clinically, as this reduces the foreign protein load and minimizes the risk of neutralizing antibody production. In practical terms, incobotulinumtoxinA has a long shelf-life, remaining stable without the need for refrigeration, and due to its limited spread is a precise localized treatment. © 2013 Prager, publisher and licensee Dove Medical Press Ltd.

Prager W.,Dermatologikum Hamburg | Steinkraus V.,Dermatologikum Hamburg
European Journal of Dermatology | Year: 2010

The aim of this prospective, rater-blind, randomized, intra-individual, 4-week study was to compare the effectiveness and safety of two hyaluronic acid dermal fillers, Belotero® Basic (monophasic) and Restylane® (biphasic), for correction of nasolabial folds (NLF). Twenty subjects with bilateral, symmetrical NLF were randomized to receive a single injection of Belotero® Basic and Restylane® in a split-face design. The primary endpoint measured intra-individual differences of treatment effects in mean depth and evenness of the NLF target area relative to its edges, from baseline to Week 4, as evaluated by the Phase-shift Rapid In-vivo Measurement of Skin (PRIMOS) system. Assessments were undertaken at Visit 2 (baseline) and Visit 3 (study endpoint). Treatment with Belotero® Basic resulted in a significantly greater improvement in evenness compared with Restylane® at Week 4 (mean intra-individual difference between treatments in PRIMOS measurement: -37.6 μm; 95% CI: -65.4; -9.9). Subject-rated secondary endpoints demonstrated numerical differences in favour of Belotero® Basic when compared with Restylane®. Both dermal fillers were equally well tolerated, as 85% (Belotero® Basic group) and 80% (Restylane® group) rated the tolerability of both treatments as "good" to "very good".

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