Publications by authors named "Thomas Luger"

257 Publications

Atopic dermatitis: Role of the skin barrier, environment, microbiome, and therapeutic agents.

J Dermatol Sci 2021 Jun 2;102(3):142-157. Epub 2021 May 2.

Department of Dermatology, Medical University Innsbruck, Innsbruck, Austria.

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by eczematous and pruritic skin lesions. In recent decades, the prevalence of AD has increased worldwide, most notably in developing countries. The enormous progress in our understanding of the complex composition and functions of the epidermal barrier allows for a deeper appreciation of the active role that the skin barrier plays in the initiation and maintenance of skin inflammation. The epidermis forms a physical, chemical, immunological, neuro-sensory, and microbial barrier between the internal and external environment. Not only lesional, but also non-lesional areas of AD skin display many morphological, biochemical and functional differences compared with healthy skin. Supporting this notion, genetic defects affecting structural proteins of the skin barrier, including filaggrin, contribute to an increased risk of AD. There is evidence to suggest that natural environmental allergens and man-made pollutants are associated with an increased likelihood of developing AD. A compromised epidermal barrier predisposes the skin to increased permeability of these compounds. Numerous topical and systemic therapies for AD are currently available or in development; while anti-inflammatory therapy is central to the treatment of AD, some existing and novel therapies also appear to exert beneficial effects on skin barrier function. Further research on the skin barrier, particularly addressing epidermal differentiation and inflammation, lipid metabolism, and the role of bacterial communities for skin barrier function, will likely expand our understanding of the complex etiology of AD and lead to identification of novel targets and the development of new therapies.
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http://dx.doi.org/10.1016/j.jdermsci.2021.04.007DOI Listing
June 2021

Practical algorithm to inform clinical decision-making in the topical treatment of atopic dermatitis.

J Dermatol 2021 Aug 7;48(8):1139-1148. Epub 2021 May 7.

Department of Dermatology and Venereology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Diseases, Beijing, China.

Atopic dermatitis is a chronic relapsing, inflammatory skin disorder associated with skin barrier dysfunction, the prevalence of which has increased dramatically in developing countries. In this article, we propose a treatment algorithm for patients with mild-to-moderate and severe atopic dermatitis flares in daily clinical practice. An international panel of 15 dermatology and allergy experts from eight countries was formed to develop a practical algorithm for the treatment of patients with atopic dermatitis, with a particular focus on topical therapies. In cases of mild-to-moderate atopic dermatitis involving sensitive skin areas, the topical calcineurin inhibitor pimecrolimus should be applied twice daily at the first signs of atopic dermatitis. For other body locations, patients should apply a topical calcineurin inhibitor, either pimecrolimus or tacrolimus, twice daily at the first signs of atopic dermatitis, such as pruritus, or twice weekly in previously affected skin areas. Emollients should be used regularly. Patients experiencing acute atopic dermatitis flares in sensitive skin areas should apply a topical corticosteroid twice daily or alternate once-daily topical corticosteroid/topical calcineurin inhibitor until symptoms improve. Following improvement, topical corticosteroid therapy should be discontinued and patients switched to a topical calcineurin inhibitor. Maintenance therapy should include the use of pimecrolimus once daily for sensitive areas and tacrolimus for other body locations. This treatment algorithm can help guide clinical decision-making in the treatment of atopic dermatitis.
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http://dx.doi.org/10.1111/1346-8138.15921DOI Listing
August 2021

Relationship Among Treatment, Pruritus, Investigator's Static Global Assessment, and Quality of Life in Patients with Atopic Dermatitis.

Dermatol Ther (Heidelb) 2021 Apr 9;11(2):587-598. Epub 2021 Mar 9.

Pfizer Inc., Collegeville, PA, USA.

Introduction: The Investigator's Static Global Assessment (ISGA) is a 5-point rating scale that is recommended by the US Food and Drug Administration for assessing the severity of atopic dermatitis (AD), and ISGA success is a widely used endpoint in AD clinical studies. In this study, we seek to interpret the relationship of ISGA with treatment, pruritus, and quality of life (QoL) by conducting post hoc analyses of pooled data from two phase 3 crisaborole studies.

Methods: Patients aged ≥ 2 years with baseline ISGA of 2 (mild) or 3 (moderate) were randomly assigned 2:1 to receive crisaborole or vehicle for 28 days. Disease severity, pruritus severity, and QoL were assessed with the ISGA, Severity of Pruritus Scale (SPS), and Dermatology Life Quality Index (DLQI; patients aged ≥ 16 years), or Children's Dermatology Life Quality Index (CDLQI; patients aged 2-15 years), respectively. The effect of treatment on ISGA and the relationship between ISGA and QoL were analyzed using a longitudinal repeated-measures model. The interrelationship between treatment, disease severity, pruritus, and QoL was analyzed with a mediation model.

Results: Overall, 1522 patients (crisaborole, n = 1016; vehicle, n = 506) were included. Estimated longitudinal profiles indicated changes in ISGA by day 8 were large for crisaborole (effect size [ES]: - 0.68) and small for vehicle (ES: - 0.34). There was a direct relationship between ISGA and DLQI and CDLQI severity bands in the longitudinal repeated-measures model. For both QoL mediation models, treatment effects on QoL were mediated indirectly by reduction in pruritus (DLQI, 42.4%; CDLQI, 58.1%) and disease severity (DLQI, 12.2%; CDLQI, 33.1%).

Conclusions: These post hoc analyses suggest that ISGA success is a clinically meaningful endpoint associated with reduction in the severity of pruritus and improvement in QoL.
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http://dx.doi.org/10.1007/s13555-021-00506-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018915PMC
April 2021

Translating the Investigator's Static Global Assessment to the Eczema Area and Severity Index in Studies of Crisaborole for Atopic Dermatitis.

Dermatol Ther (Heidelb) 2021 Jun 13;11(3):845-853. Epub 2021 Mar 13.

Westphalian Wilhelms University of Münster, Münster, Germany.

Introduction: Atopic dermatitis (AD) severity was measured in two phase 3 US studies of crisaborole ointment, 2%, in patients aged ≥ 2 years using the Investigator's Static Global Assessment (ISGA), an FDA-recommended scale. Eczema Area and Severity Index (EASI) is a validated scale used globally to assess AD severity in clinical trials. The objective of this study is to aid interpretability of ISGA by translating ISGA scores to EASI scores.

Methods: ISGA was mapped to EASI using published EASI severity strata by Chopra et al. and Leshem et al. and pooled data from phase 3 trials CrisADe CORE 1 and CORE 2, which evaluated crisaborole in patients aged ≥ 2 years with mild-to-moderate AD (crisaborole, n = 1016; vehicle, n = 506). Least squares mean (LSM) percentage change from baseline (%CFB) in EASI and proportion of patients with 50%, 75%, and 90% improvement (EASI-50, EASI-75, and EASI-90, respectively) on day 29 were computed for mapped EASI. The relationship between changes in ISGA and changes in EASI was assessed using data from three abrocitinib trials.

Results: ISGA was mapped to EASI using 70,000 random simulations. LSM (standard error) for %CFB in mapped EASI at day 29 (crisaborole versus vehicle) was -26.3% (17) versus 45.2% (35) (P = 0.0671) using Chopra strata and -43.1% (4.6) versus -5.2% (8.4) (P < 0.0001) using Leshem strata. EASI-50, EASI-75, and EASI-90 rates were 72.1% versus 57.6%, 63.0% versus 47.8%, and 55.0% versus 40.1%, respectively, using Chopra strata (P < 0.0001 for each difference). These rates were 68.8% versus 54.0%, 54.8% versus 40.5%, and 38.9% versus 27.2%, respectively (P < 0.0001 for each difference) using Leshem strata. Mean two-point improvement in ISGA was comparable to EASI-90.

Conclusion: Mapped EASI results were consistent with ISGA results in crisaborole phase 3 trials. Simulation methodologies yielded consistent results and may aid in interpretability of ISGA across clinical studies.

Trial Registration: ClinicalTrials.gov identifier: NCT02118766, NCT02118792.
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http://dx.doi.org/10.1007/s13555-021-00509-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163913PMC
June 2021

Letter to the Editor Regarding 'Crisaborole Ointment, 2%, for Treatment of Patients with Mild-to-Moderate Atopic Dermatitis: Systematic Literature Review and Network Meta-Analysis'.

Dermatol Ther (Heidelb) 2021 Apr 4;11(2):639-642. Epub 2021 Mar 4.

SmartAnalyst, an Ashfield Advisory Company, DLF Plaza, DLF Phase 1, Gurugram, Haryana, India.

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http://dx.doi.org/10.1007/s13555-021-00503-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018911PMC
April 2021

Paediatric atopic eczema (atopic dermatitis) in South Africa: A practical algorithm for the management of mild-to-moderate disease in daily clinical practice.

S Afr Fam Pract (2004) 2020 Nov 23;62(1):e1-e9. Epub 2020 Nov 23.

Division of Dermatology, Department of Medicine, Faculty of Health Sciences, Stellenbosch University, Cape Town.

Background: Atopic eczema (AE) is a chronic, highly pruritic, inflammatory skin condition with increasing prevalence worldwide. Atopic eczema mostly affects children, impairing quality of life with poor disease control leading to progression of other atopic disorders. As most patients in South Africa have no access to specialist healthcare, a practical approach is needed for the management of mild-to-moderate AE in paediatric patients for daily clinical practice.

Methods: A panel of experts in AE convened to develop a practical algorithm for the management of AE for children and adolescents in South Africa.

Results: Regular moisturising with an oil-based emollient remains the mainstay of AE treatment. Severe AE flares should be managed with topical corticosteroids (TCSs). For mild-to-moderate AE flares in sensitive skin areas, a topical calcineurin inhibitor (TCI) should be applied twice daily from the first signs of AE until complete resolution. Topical corticosteroids may be used when TCIs are unavailable. In non-sensitive skin areas, TCSs should be used for mild-to-moderate AE, but TCIs twice daily may be considered. Proactive maintenance treatment with low-dose TCI or TCS 2-3 times weekly and the liberal use of emollients is recommended for patients with recurrent flares.

Conclusions: This algorithm aims to simplify treatment of paediatric AE, optimising clinical outcomes and reducing disease burden. This approach excludes treatment of patients with severe AE, who should be referred to specialist care. Emphasis has been given to the importance of general skincare, patient education and the topical anti-inflammatory medications available in South Africa (TCSs and TCIs).
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http://dx.doi.org/10.4102/safp.v62i1.5190DOI Listing
November 2020

Practical Recommendations for the Topical Treatment of Atopic Dermatitis in South and East Asia.

Dermatol Ther (Heidelb) 2021 Feb 12;11(1):275-291. Epub 2020 Dec 12.

Department of Dermatology, University of Münster, Münster, Germany.

Introduction: There is some evidence to suggest that the prevalence of atopic dermatitis (AD) in Asia is rising. We have therefore developed an algorithm for the topical treatment of AD throughout South and East Asia for use by primary care physicians, pediatricians and dermatologists.

Methods: Nine AD experts from South and East Asia and one from Europe developed the algorithm based upon treatment guidelines, relevant literature and local treatment practices. The algorithm outlines current best practice for the use of emollients, topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI), with the intention of simplifying the treatment regimen of mild-to-moderate AD in South and East Asia.

Results: Patients with AD should bathe and cleanse affected skin to remove crusts and scales daily. Emollients should also be applied daily as a maintenance treatment. When selecting appropriate topical anti-inflammatory treatment for AD flares, several factors should be taken into consideration, including the patient's age, attitude to treatment options and site of AD lesions. Given the concerns regarding the risk of skin atrophy with use of TCS, a TCI should be used to treat AD lesions in sensitive skin areas: pimecrolimus is recommended for mild-to-moderate AD in these locations, while tacrolimus should be considered for moderate and severe cases. Either pimecrolimus or tacrolimus is recommended for flares in other, non-sensitive body locations. A proactive or intermittent maintenance treatment strategy involving regular emollient use and twice-weekly application of a TCI to previously affected areas is encouraged to reduce the risk of flares.

Conclusions: The algorithm proposed here is intended to simplify the topical treatment of mild-to-moderate AD in daily practice in South and East Asian countries.
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http://dx.doi.org/10.1007/s13555-020-00467-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859143PMC
February 2021

Unmet medical needs in the treatment of atopic dermatitis in infants: An Expert consensus on safety and efficacy of pimecrolimus.

Pediatr Allergy Immunol 2021 04 27;32(3):414-424. Epub 2020 Dec 27.

Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.

Atopic dermatitis (AD) is a common skin disease during infancy, which imposes a considerable burden on patients, their families, and the society, requiring effective treatment options that result in rapid and sustained symptom relief. Additionally, early treatment may prevent the development of atopic comorbidities by restoring the skin barrier. Currently, topical standard-of-care for AD in infants includes emollients and topical corticosteroids (TCS) to treat and reduce the risk of flares. However, only few have been approved for infants and long-term maintenance therapy with TCS is not indicated due to potential local and systemic side effects, including skin atrophy. Accordingly, the recently updated European guidelines for treatment of AD recommend topical calcineurin inhibitors (TCIs) for long-term use, treatment of sensitive skin areas, and for use in the pediatric population. Evidence on the use of TCIs for infants has almost been exclusively collected for pimecrolimus, with >4000 infants evaluated in clinical trials, consistently confirming that pimecrolimus is a safe and effective treatment for infants with AD. Nevertheless, its use is still restricted in most countries to children above the age of 2 years due to initial and mostly theoretical safety concerns. Based on a careful review of the available evidence of clinical trials, post-marketing surveillance, and epidemiological studies, an Expert Panel of European dermatologists and pediatric allergologists concluded that these safety concerns are no longer valid. Therefore, pimecrolimus offers a safe and effective alternative to TCS in infants aged 3 months and above, and labeling restrictions in this age group are no longer justified.
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http://dx.doi.org/10.1111/pai.13422DOI Listing
April 2021

The Economic and Psychosocial Comorbidity Burden Among Adults with Moderate-to-Severe Atopic Dermatitis in Europe: Analysis of a Cross-Sectional Survey.

Dermatol Ther (Heidelb) 2021 Feb 12;11(1):117-130. Epub 2020 Nov 12.

Pfizer Inc., New York, NY, USA.

Introduction: Atopic dermatitis (AD) is a common inflammatory disease of the skin, which may have a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to quantify the economic burden (direct and indirect costs) of moderate-to-severe AD and evaluate the prevalence and impact of psychosocial comorbidities among patients in the European Union-5 (France, Germany, Italy, Spain, and the UK).

Methods: Data were analyzed from the 2017 EU5 National Health and Wellness Survey. Respondents with a physician diagnosis of AD/eczema who were considered to have moderate-to-severe AD based on a Dermatology Life Quality Index (DLQI) score  ≥ 6 were included. Direct costs, indirect costs, and psychosocial comorbidities (sleep difficulties and anxiety based on self-report, depression based on the Patient Health Questionnaire-9) were reported descriptively. Generalized linear models were used to examine the relationship between psychosocial comorbidities and health outcomes (the Short Form-36 version 2 [SF-36v2], EuroQoL 5-dimension 5-level, Work Productivity and Activity Impairment questionnaire, and healthcare resource utilization).

Results: Overall, 1014 patients were included in the analysis. Total annual direct costs ranged from €2242 to €6924 and total annual indirect costs ranged from €7277 to €14,236, depending on the level of disease severity. Sleep difficulties, anxiety, and depression were reported by 61.6%, 52.7%, and 75.8% of patients, respectively. These comorbidities were significantly associated with reduced physical and mental component summary scores from SF-36v2 and increased overall work impairment (p < 0.05 for all).

Conclusions: A significant economic burden was observed for patients with moderate-to-severe AD. Sleep difficulties, depression, and anxiety were observed in more than half of moderate-to-severe AD patients and were significantly associated with decrements in HRQoL and with work-related impairment. Reducing the burden of these psychosocial comorbidities in AD could have significant benefit to patients and society.
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http://dx.doi.org/10.1007/s13555-020-00459-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858996PMC
February 2021

ESDR-Foundation René Touraine Partnership: A Successful Liaison.

J Invest Dermatol 2020 Sep;140(9S):S191

Department of Dermatology, University of Münster, Münster, Germany.

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http://dx.doi.org/10.1016/j.jid.2020.03.954DOI Listing
September 2020

Topical Agents for the Treatment of Atopic Dermatitis

J Drugs Dermatol 2020 01;19(1):50-64

Approval of the new topical phosphodiesterase 4 inhibitor crisaborole ointment, 2%, to treat mild-to-moderate atopic dermatitis (AD) warrants careful consideration of available efficacy and safety data for topical therapies to contribute to a better understanding of the role of crisaborole in the treatment of mild-to-moderate AD. A literature review was conducted to identify results of randomized, blinded, vehicle-controlled trials of topical agents for the treatment of AD published from January 1, 1997 to April 30, 2018. This review summarizes the efficacy and safety data of topical therapies including corticosteroids, calcineurin inhibitors, and crisaborole and it shows that comparison among available agents is difficult because of differing methodologies used across clinical trials and that there is considerable variability in safety reporting among AD trials. Published clinical studies for crisaborole demonstrate its efficacy and manageable safety profile. J Drugs Dermatol. 2020;19(1):50-64. doi:10.36849/JDD.2020.4508
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http://dx.doi.org/10.36849DOI Listing
January 2020

Evidence and impact of neutrophil extracellular traps in malignant melanoma.

Pigment Cell Melanoma Res 2020 01 29;33(1):63-73. Epub 2019 Aug 29.

Department of Dermatology, University Hospital of Muenster, Muenster, Germany.

Ulceration of melanoma is associated with neutrophil infiltrates and lower survival rates opposite to non-ulcerated melanoma. Neutrophils release neutrophil extracellular traps (NETs) that are chromatin structures loaded with antimicrobial proteins. Since NETs have been correlated with tumor progression, we investigated whether NETs appear in melanoma and affect melanoma cells. Indeed, human primary melanoma biopsies revealed neutrophils releasing NETs in all of 27 ulcerated melanomas, whereas NETs were absent in all of 7 non-ulcerated melanomas. However, the quantity of intratumoral NETs did not correlate with tumor progression of melanoma. Interestingly, in vitro assays showed that melanoma cells attach to NETs via integrin-mediated adhesion and that NETs inhibit tumor cell migration. Moreover, co-culturing of NETs and melanoma cells had a cytotoxic effect on melanoma cells resulting in necrosis. Hence, we discovered in vitro an antineoplastic role of NETs in melanoma.
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http://dx.doi.org/10.1111/pcmr.12818DOI Listing
January 2020

Quality of Life in Psoriasis Vulgaris: Use of the ItchyQoL Question-naire in a Secukinumab Phase III Trial in Patients with Psoriasis Vulgaris.

Acta Derm Venereol 2019 Nov;99(12):1085-1090

Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, DE-48149 Münster, Germany.

Chronic pruritus is a bothersome symptom in psoriasis vulgaris and can profoundly reduce quality of life (QoL). In this exploratory analysis of the PSORITUS study, the impact of pruritus on QoL in 130 subjects with moderate-to-severe psoriasis was assessed using the ItchyQoL questionnaire. The majority of patients (n = 127) had to scratch their itchy skin regularly, which led to painful skin and frustration (mean ± standard deviation; SD ItchyQoL scores; 4.50 ± 0.56; 3.80 ± 1.09 and 4.20 ± 0.87, respectively). Changes in either temperature or season led to a worsening of itching in most of the patients (n = 126; mean ± SD ItchyQoL score; 3.80 ± 1.02). Many patients felt ashamed (n = 125) or embarrassed (n = 127) due to their itchy skin (mean ± SD ItchyQoL scores; 3.90 ± 1.26 and 3.40 ± 1.19, respectively). The results demonstrated the ItchyQoL questionnaire as a validated tool responsive to treatment for detailed insights into chronic pruritus in patients with psoriasis.
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http://dx.doi.org/10.2340/00015555-3275DOI Listing
November 2019

Zum 65. Geburtstag von Dr. Michael Reusch.

J Dtsch Dermatol Ges 2019 Jul;17(7):766-767

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http://dx.doi.org/10.1111/ddg.13872DOI Listing
July 2019

Direct and Indirect Effects of Crisaborole Ointment on Quality of Life in Patients with Atopic Dermatitis: A Mediation Analysis.

Acta Derm Venereol 2019 Jul;99(9):756-761

Department of Dermatology, Oregon Health and Science University, 97225 Portland, USA.

Crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis. Using pooled data from two phase 3 studies (NCT02118766/NCT02118792), mediation modeling determined the interrelationship among pruritus, quality of life (QoL), and treatment. Patients aged ≥ 2 years received crisaborole ointment 2% or vehicle twice daily for 28 days. QoL measures were Dermatology Life Quality Index (DLQI) (≥ 16 years) and Children's Dermatology Life Quality Index (CDLQI) (2-15 years). Pruritus was assessed by the Severity of Pruritus Scale (4-point scale from 0 to 3). The indirect effect of crisaborole on QoL mediated through its effect on pruritus was 51% (DLQI model, p < 0.05) and 72% (CDLQI model, p < 0.05). Direct effect (other effects) on QoL was 49% (DLQI model, p < 0.05) and 28% (CDLQI model, p > 0.05). Mediation modeling shows that crisaborole affects QoL mostly indirectly through pruritus severity reduction.
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http://dx.doi.org/10.2340/00015555-3181DOI Listing
July 2019

Serlopitant reduced pruritus in patients with prurigo nodularis in a phase 2, randomized, placebo-controlled trial.

J Am Acad Dermatol 2019 May 17;80(5):1395-1402. Epub 2019 Mar 17.

Department of Dermatology, University Hospital Münster, Münster, Germany.

Background: Anecdotal evidence suggests that neurokinin 1 receptor antagonism reduces pruritus intensity in chronic pruritic conditions such as prurigo nodularis (PN).

Objective: This study assessed safety and efficacy of the neurokinin 1 receptor antagonist serlopitant for treatment of pruritus in PN.

Methods: In this randomized, double-blind, placebo-controlled study, 128 patients with chronic, treatment-refractory PN for more than 6 weeks received serlopitant, 5 mg, or placebo orally once daily for 8 weeks. The primary end point was change in average itch visual analog scale score at weeks 4 and 8.

Results: Average itch visual analog scale scores significantly improved with serlopitant versus with placebo at weeks 4 and 8: the least squares mean difference (serlopitant minus placebo) was -1.0 at week 4 (P = .02) and -1.7 at week 8 (P < .001). The least squares mean difference between serlopitant and placebo reached statistical significance at week 2 (-0.9 [P = .011]). The most frequently reported treatment-emergent adverse events in the serlopitant group were nasopharyngitis, diarrhea, and fatigue.

Limitations: The 8-week duration may be insufficient to assess clinically relevant resolution of PN lesions.

Conclusions: Serlopitant reduced pruritus in patients with treatment-refractory PN and was well tolerated.
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http://dx.doi.org/10.1016/j.jaad.2019.01.052DOI Listing
May 2019

Are melanocortin peptides future therapeutics for cutaneous wound healing?

Exp Dermatol 2019 03 12;28(3):219-224. Epub 2019 Feb 12.

Department of Dermatology, Laboratory for Neuroendocrinology of the Skin and Interdisciplinary Endocrinology, University of Münster, Münster, Germany.

Cutaneous wound healing is a complex process divided into different phases, that is an inflammatory, proliferative and remodelling phase. During these phases, a variety of resident skin cell types but also cells of the immune system orchestrate the healing process. In the last year, it has been shown that the majority of cutaneous cell types express the melanocortin 1 receptor (MC1R) that binds α-melanocyte-stimulating hormone (α-MSH) with high affinity and elicits pleiotropic biological effects, for example modulation of inflammation and immune responses, cytoprotection, antioxidative defense and collagen turnover. Truncated α-MSH peptides such as Lys-Pro-Val (KPV) as well as derivatives like Lys-d-Pro-Thr (KdPT), the latter containing the amino acid sequence 193-195 of interleukin-1β, have been found to possess anti-inflammatory effects but to lack the pigment-inducing activity of α-MSH. We propose here that such peptides are promising future candidates for the treatment of cutaneous wounds and skin ulcers. Experimental approaches in silico, in vitro, ex vivo and in animal models are outlined. This is followed by an unbiased discussion of the pro and contra arguments of such peptides as future candidates for the therapeutic management of cutaneous wounds and a review of the so-far available data on melanocortin peptides and derivatives in wound healing.
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http://dx.doi.org/10.1111/exd.13887DOI Listing
March 2019

Aprepitant in Anti-histamine-refractory Chronic Nodular Prurigo: A Multicentre, Randomized, Double-blind, Placebo-controlled, Cross-over, Phase-II trial (APREPRU).

Acta Derm Venereol 2019 Apr;99(4):379-385

Department of Dermatology, University Hospital Muenster, Von-Esmarch-Str. 58, DE-48149 Münster, Germany.

The aim of this multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II study was to determine the antipruritic effect of aprepitant vs. placebo in 58 patients with anti-histamine-refractory chronic pruritus in chronic nodular prurigo. Patients were randomized to receive either first oral aprepitant 80 mg/day or placebo for 4 weeks. Following a 2-week wash-out phase, the patients were crossed-over to receive the other treatment for 4 weeks. Primary efficacy criterion was the intra-individual difference between mean itch intensity (visual analogue scale) at baseline compared with the end of treatment period. Prurigo lesions, pruritus course, quality of life, patient benefits, and safety were secondary parameters. No significant differences were found between aprepitant treatment and placebo for any of the parameters investigated. Under the experimental conditions of the study, aprepitant, 80 mg daily for 4 weeks, did not have an antipruritic effect in patients with chronic prurigo. (DRKS00005594; EudraCT Number: 2013-001601-85).
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http://dx.doi.org/10.2340/00015555-3120DOI Listing
April 2019

Melatonin and Its Metabolites Ameliorate UVR-Induced Mitochondrial Oxidative Stress in Human MNT-1 Melanoma Cells.

Int J Mol Sci 2018 Nov 28;19(12). Epub 2018 Nov 28.

Department of Dermatology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Melatonin (Mel) is the major biologically active molecule secreted by the pineal gland. Mel and its metabolites, 6-hydroxymelatonin (6(OH)Mel) and 5-methoxytryptamine (5-MT), possess a variety of functions, including the scavenging of free radicals and the induction of protective or reparative mechanisms in the cell. Their amphiphilic character allows them to cross cellular membranes and reach subcellular organelles, including the mitochondria. Herein, the action of Mel, 6(OH)Mel, and 5-MT in human MNT-1 melanoma cells against ultraviolet B (UVB) radiation was investigated. The dose of 50 mJ/cm² caused a significant reduction of cell viability up to 48%, while investigated compounds counteracted this deleterious effect. UVB exposure increased catalase activity and led to a simultaneous Ca influx (16%), while tested compounds prevented these disturbances. Additional analysis focused on mitochondrial respiration performed in isolated mitochondria from the liver of BALB/cJ mice where Mel, 6(OH)Mel, and 5-MT significantly enhanced the oxidative phosphorylation at the dose of 10 M with lower effects seen at 10 or 10 M. In conclusion, Mel, 6(OH)Mel and 5-MT protect MNT-1 cells, which express melatonin receptors (MT1 and MT2) against UVB-induced oxidative stress and mitochondrial dysfunction, including the uncoupling of oxidative phosphorylation.
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http://dx.doi.org/10.3390/ijms19123786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320988PMC
November 2018

The microbiome in patients with atopic dermatitis.

J Allergy Clin Immunol 2019 01 23;143(1):26-35. Epub 2018 Nov 23.

Paediatric Dermatology, Our Lady's Children's Hospital Crumlin, National Children's Research Centre and Trinity College, Dublin, Ireland. Electronic address:

As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies.
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http://dx.doi.org/10.1016/j.jaci.2018.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163929PMC
January 2019

Impact of Ixekizumab Treatment on Itch and Psoriasis Area and Severity Index in Patients with Moderate-to-Severe Plaque Psoriasis: An Integrated Analysis of Two Phase III Randomized Studies.

Dermatol Ther (Heidelb) 2018 Dec 21;8(4):621-637. Epub 2018 Nov 21.

Department of Dermatology, University of Muenster, Muenster, Germany.

Introduction: We evaluated baseline itch and its impact on the efficacy of ixekizumab (IXE) in clearing psoriasis and improving quality-of-life measures, and we explored the relationship between itch and psoriatic skin improvement.

Methods: Data were analyzed from two double-blind, randomized, controlled phase III studies (UNCOVER-2/3) comparing etanercept (ETN), IXE, and placebo (PBO) in patients with moderate-to-severe plaque psoriasis. Long-term analysis included UNCOVER-3 data from week 0 to week 156.

Results: At week 12, a clinically meaningful improvement in itch [Itch Numeric Rating Scale (NRS) reduction ≥ 4] was seen in 70.0%, 88.6%, and 90.8% of the IXE-treated patients in the baseline Itch NRS 4-6, 7-8, and 9-10 groups, respectively (all itch severity groups p < 0.001 versus ETN and PBO). Also, 68.9%, 67.1%, and 73.6% of the IXE-treated patients in the baseline Itch NRS 4-6, 7-8, and 9-10 groups, respectively, showed an improvement of ≥ 90.0% in the Psoriatic Area and Severity Index (PASI) at week 12 as compared to the baseline (PASI 90) (all itch severity groups p < 0.001 versus ETN and PBO). For most patients, itch reduction preceded psoriatic plaque improvement. Sustained effects of IXE on itch and PASI were observed during 3 years of treatment.

Conclusions: Regardless of baseline itch severity, IXE treatment provided a rapid improvement in itch followed by clinically meaningful improvements in psoriasis.

Funding: Eli Lilly and Company.

Trial Registration: ClinicalTrials.gov identifiers, NCT01597245 and NCT01646177.
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http://dx.doi.org/10.1007/s13555-018-0267-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261114PMC
December 2018

A practical algorithm for topical treatment of atopic dermatitis in the Middle East emphasizing the importance of sensitive skin areas.

J Dermatolog Treat 2019 Jun 21;30(4):366-373. Epub 2018 Nov 21.

f Dermatology Clinic , University of Münster , Münster , Germany.

There is a need for safe, effective treatment for atopic dermatitis (AD) in the Middle East. To propose a practical algorithm for the treatment of AD throughout the Middle East. An international panel of six experts from the Middle East and one from Europe developed the algorithm. The practical treatment guide was based on a review of published guidelines on AD, an evaluation of relevant literature published up to August 2016 and local treatment practices. Patients with an acute mild-to-moderate disease flare on sensitive body areas should apply the topical calcineurin inhibitor (TCI), pimecrolimus 1% cream twice daily until clearance. For other body locations, a TCI, either pimecrolimus 1% cream, tacrolimus 0.03% ointment in children or 0.1% ointment in adults, should be applied twice daily until clearance. Emollients should be used as needed. Patients experiencing acute severe disease flares should apply a topical corticosteroid (TCS) according to their label for a few days to reduce inflammation. After clinical improvement, pimecrolimus for sensitive skin areas or TCIs for other body locations should be used until there is a complete resolution of lesions. These recommendations are expected to optimize AD management in patients across the Middle East.
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http://dx.doi.org/10.1080/09546634.2018.1524823DOI Listing
June 2019

Functional characterization of the extranasal OR2A4/7 expressed in human melanocytes.

Exp Dermatol 2018 11 18;27(11):1216-1223. Epub 2018 Sep 18.

Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.

Olfactory receptors (ORs) were first described as specialized chemoreceptors in the nasal epithelium. In the last two decades, ORs have also been detected to be functionally expressed and active in different nonolfactory tissues of the human body, because they used to react to specific odour stimuli. In this study, we conducted a characterization of the extranasal OR2A4/7 expressed in primary human melanocytes and sections of the human skin. OR2A4/7 expression could be demonstrated at the transcript and protein level. We uncovered elevated intracellular cAMP and Ca levels accompanied by elevated p38 and reduced p42/44 MAPK phosphorylation following odourant (cyclohexyl salicylate; CHS) stimulation of melanocytes. These results were associated with enhanced melanin biosynthesis in conjunction with the growth inhibition and differentiation of melanocytes. Our findings highlight the participation of OR2A4/7 in human primary melanocyte physiology and suggest an alternate mechanism that regulates melanogenesis.
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http://dx.doi.org/10.1111/exd.13764DOI Listing
November 2018

Serlopitant for the treatment of chronic pruritus: Results of a randomized, multicenter, placebo-controlled phase 2 clinical trial.

J Am Acad Dermatol 2018 05 17;78(5):882-891.e10. Epub 2018 Feb 17.

Department of Dermatology, University of California San Diego, Dublin; Department of Dermatology, Weill Cornell University-Qatar, Hamad Medical Corporation, Doha, Qatar. Electronic address:

Background: The substance P/neurokinin 1 receptor pathway is critical in chronic pruritus; anecdotal evidence suggests that antagonism of this pathway can reduce chronic itch.

Objective: To assess the safety and efficacy of the substance P/neurokinin 1 receptor antagonist serlopitant in treating chronic pruritus.

Methods: Eligible patients with severe chronic pruritus who were refractory to antihistamines or topical steroids were randomized to serlopitant, 0.25, 1, or 5 mg, or to placebo, administered once daily for 6 weeks as monotherapy or with midpotency steroids and emollients. The primary efficacy end point was percentage change in visual analog scale pruritus score from baseline.

Results: Serlopitant treatment resulted in a dose-dependent decrease in pruritus. The mean percentage decreases from baseline visual analog scale pruritus scores were statistically significantly larger with the 1- and 5-mg doses of serlopitant (P = .022 and P = .013, respectively) than with placebo at week 6. No significant safety or tolerability differences were detected among the groups.

Limitations: The sample size was insufficient for subgroup analyses of the efficacy of serlopitant for chronic pruritus on the basis of underlying conditions.

Conclusions: Serlopitant, 1 mg and 5 mg daily, was associated with a statistically significant reduction in chronic pruritus and was well tolerated (NCT01951274).
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http://dx.doi.org/10.1016/j.jaad.2018.02.030DOI Listing
May 2018

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis/Outcome Measures in Rheumatology Consensus-Based Recommendations and Research Agenda for Use of Composite Measures and Treatment Targets in Psoriatic Arthritis.

Arthritis Rheumatol 2018 03 6;70(3):345-355. Epub 2018 Feb 6.

University of Leeds, Leeds, UK.

Objective: A meeting was convened by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) to further the development of consensus among physicians and patients regarding composite disease activity measures and targets in psoriatic arthritis (PsA).

Methods: Prior to the meeting, physicians and patients completed surveys on outcome measures. A consensus meeting of 26 rheumatologists, dermatologists, and patient research partners reviewed evidence on composite measures and potential treatment targets plus results of the surveys. The meeting consisted of plenary presentations, breakout sessions, and group discussions. International experts including members of GRAPPA and OMERACT were invited to the meeting, including the developers of all of the measures discussed. After discussions, participants voted on proposals for use, and consensus was established in a second survey.

Results: Survey results from 128 health care professionals and 139 patients were analyzed alongside a systematic literature review summarizing evidence. A weighted vote was cast for composite measures. For randomized controlled trials, the most popular measures were the PsA disease activity score (40 votes) and the GRAPPA composite index (28 votes). For clinical practice, the most popular measures were an average of scores on 3 visual analog scales (45 votes) and the disease activity in PsA score (26 votes). After discussion, there was no consensus on a composite measure. The group agreed that several composite measures could be used and that future studies should allow further validation and comparison. The group unanimously agreed that remission should be the ideal target, with minimal disease activity (MDA)/low disease activity as a feasible alternative. The target should include assessment of musculoskeletal disease, skin disease, and health-related quality of life. The group recommended a treatment target of very low disease activity (VLDA) or MDA.

Conclusion: Consensus was not reached on a continuous measure of disease activity. In the interim, the group recommended several composites. Consensus was reached on a treatment target of VLDA/MDA. An extensive research agenda was composed and recommends that data on all PsA clinical domains be collected in ongoing studies.
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http://dx.doi.org/10.1002/art.40391DOI Listing
March 2018

Validation of the Itch Severity Item as a Measurement Tool for Pruritus in Patients with Psoriasis: Results from a Phase 3 Tofacitinib Program.

Acta Derm Venereol 2018 Mar;98(3):340-345

Center for Chronic Pruritus, Department of Dermatology, University Hospital Münster, Von-Esmarch-Str. 58, DE-48149 Münster, Germany.

Tofacitinib is an oral Janus kinase inhibitor. This post-hoc analysis aimed to investigate the psychometric properties of the Itch Severity Item (ISI), a numeric rating scale from 0 (no itching) to 10 (worst possible itching) for pruritus in psoriasis, and review the effect of tofacitinib on pruritus in patients with psoriasis participating in Phase 3 studies (N = 3,641). The ISI showed high test-retest reliability (intra-class correlation coefficient: 0.84). The clinically important difference was defined as a 1.48-point change, using Patient Global Assessment as an anchor. Mean changes from baseline in ISI scores with tofacitinib were significantly greater than placebo by Day 2 and exceeded the clinically important difference by Week 4 and Week 2 for tofacitinib 5 and 10 mg twice daily, respectively. The sound psychometric properties of the ISI as an assessment tool for pruritus in psoriasis were confirmed. Tofacitinib provided clinically meaningful improvements in psoriatic pruritus versus placebo.
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http://dx.doi.org/10.2340/00015555-2856DOI Listing
March 2018

Long-term Impact of Ixekizumab on Psoriasis Itch Severity: Results from a Phase III Clinical Trial and Long-term Extension.

Acta Derm Venereol 2018 Jan;98(1):98-102

Beth Israel Deaconess Hospital and Harvard Medical School, 375 Longwood Ave, Boston, MA 02215, USA.

Itching is a prevalent plaque psoriasis symptom. Ixekizumab, an IL-17A antagonist, has demonstrated rapid, significant improvements in itch severity over 12 weeks in Phase III psoriasis trials (UNCOVER-1, UNCOVER-2). We assessed the long-term (through 60 weeks) effect of ixekizumab maintenance therapy (80-mg ixekizumab every 4 weeks [IXEQ4W]) on itch severity, using the Itch Numeric Rating Scale, in psoriasis patients who received ixekizumab, placebo, or etanercept for 12 weeks in the Phase III UNCOVER-3 trial. After 12 weeks, patients either continued or switched to IXEQ4W. Mean improvements in itch severity achieved with 12 weeks of ixekizumab (-4.7 to -5.1) were maintained through 60 weeks with IXEQ4W (-4.9 to -5.0). Patients who initially received placebo or etanercept experienced rapid itch severity improvements after switching to ixekizumab at Week 12 (Week 12, placebo: -0.6; etanercept: -3.8; Week 60, placebo/IXEQ4W: -4.9; etanercept/IXEQ4W: -4.7). Ixekizumab maintenance therapy sustained improvements in itch severity through 60 weeks.
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http://dx.doi.org/10.2340/00015555-2801DOI Listing
January 2018

Kongenitale Gefäß- und Pigmentmale mit Lymphödem, Beinlängendifferenz und Skoliose.

J Dtsch Dermatol Ges 2017 Jul;15(7):751-754

Klinik für Hautkrankheiten, Universitätsklinikum Münster, Von-Esmarch-Straße, Münster.

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http://dx.doi.org/10.1111/ddg.120_13075DOI Listing
July 2017

Congenital telangiectatic und pigmented lesions associated with lymphedema, difference in leg length, and scoliosis.

J Dtsch Dermatol Ges 2017 Jul 14;15(7):751-753. Epub 2017 Jun 14.

Department of Dermatology, University Medical Center Münster, Münster, Germany.

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http://dx.doi.org/10.1111/ddg.13075DOI Listing
July 2017

[Anesthesiological care of trauma patients in orthogeriatric co-management].

Anaesthesist 2017 May;66(5):375-392

Klinik für Anästhesiologie und Allgemeine Intensivmedizin, Medizinische Universität Innsbruck, Anichstr. 35, 6020, Innsbruck, Österreich.

Elderly patients increasingly need to undergo surgery under anesthesia, especially following trauma. A timely interdisciplinary approach to the perioperative management of these patients is decisive for the long-term outcome. Orthogeriatric co-management, which includes geriatricians and anesthesiologists from an early stage, is of great benefit for geriatric patients. Patient age, comorbidities and self-sufficiency in activities of daily life are decisive for an anesthesiological assessment of the state of health and preoperative risk stratification. If necessary additional investigations, such as echocardiography must be carried out, in order to guarantee optimal perioperative anesthesiological management. Certain medical factors can delay the initiation of anesthesia and it is absolutely necessary that these are taken into consideration for surgical management. Not every form of anesthesia is equally suitable for every geriatric patient.
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http://dx.doi.org/10.1007/s00101-017-0323-3DOI Listing
May 2017
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