Publications by authors named "Hans F Merk"

105 Publications

Practical recommendations for the allergological risk assessment of the COVID-19 vaccination - a harmonized statement of allergy centers in Germany.

Allergol Select 2021 26;5:72-76. Epub 2021 Jan 26.

Allergy and Asthma Center Westend, Berlin, Germany.

Severe allergic reactions to vaccines are very rare. Single severe reactions have occurred worldwide after vaccination with the new mRNA-based COVID-19 vaccines. PEG2000 is discussed as a possible trigger. We provide guidance on risk assessment regarding COVID-19 vaccination in patients with allergic diseases and suggest a standardized, resource-oriented diagnostic and therapeutic procedure. Reports of severe allergic reactions in the context of COVID-19 vaccination can be made via www.anaphylaxie.net using an online questionnaire.
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http://dx.doi.org/10.5414/ALX02225EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841415PMC
January 2021

[Laudation commemorating the 65th birthday of Prof. Dr. Alexander Kapp].

Hautarzt 2020 Dec;71(12):917-918

IUF - Leibniz-Institut für Umweltmedizinische Forschung, Düsseldorf, Deutschland.

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http://dx.doi.org/10.1007/s00105-020-04722-zDOI Listing
December 2020

False-positive test results in diagnosing allergy to glatiramer acetate: Case report and a systematic literature review.

Immun Inflamm Dis 2020 12 5;8(4):847-853. Epub 2020 Oct 5.

Department of Dermatology and Allergology, University Hospital of RWTH Aachen, Aachen, Germany.

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http://dx.doi.org/10.1002/iid3.357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654405PMC
December 2020

Thanks to Prof. Dr. Michael Meurer : Editors and publisher thank the long-serving editor of the journal Der Hautarzt. English version.

Hautarzt 2020 Dec;71(Suppl 2):82-83

 Klinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität München, Munich, Germany.

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http://dx.doi.org/10.1007/s00105-020-04701-4DOI Listing
December 2020

[Thanks to Prof. Dr. Michael Meurer : Editors and publisher thank the long-serving editor of the journal Der Hautarzt].

Hautarzt 2020 Oct;71(10):737-738

Klinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität München, München, Deutschland.

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http://dx.doi.org/10.1007/s00105-020-04690-4DOI Listing
October 2020

Inter-α-Trypsin Inhibitor Heavy Chain 5 (ITIH5) Is a Natural Stabilizer of Hyaluronan That Modulates Biological Processes in the Skin.

Skin Pharmacol Physiol 2020 14;33(4):198-206. Epub 2020 Aug 14.

Department of Dermatology and Allergology, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Introduction: Hyaluronan (HA) is a major component of the skin that exerts a variety of biological functions. Inter-α-trypsin inhibitor heavy chain (ITIH) proteins comprise a family of hyaladherins of which ITIH5 has recently been described in skin, where it plays a functional role in skin morphology and inflammatory skin diseases including allergic contact dermatitis (ACD).

Objective: The current study focused on the ITIH5-HA interaction and its potential clinical and functional impact in extracellular matrix (ECM) stabilization.

Methods: Studying the molecular effects of ITIH5 in skin, we established skin models comprising murine skin cells of Itih5 knockout mice and corresponding wild-type controls. In addition, human dermal fibroblasts with an ITIH5 knockdown as well as a murine recombinant Itih5 protein were established to examine the interaction between ITIH5 and HA using in vitro adhesion and HA degradation assays. To understand more precisely the role of ITIH5 in inflammatory skin diseases such as ACD, we generated ITIH5 knockout cells of the KeratinoSens® cell line.

Results: Using murine skin models, ITIH5 knockdown fibroblasts, and a reactive oxygen species (ROS)-mediated HA degradation assay, we proved that ITIH5 binds to HA, thereby acting as a stabilizer of HA. Moreover, microarray profiling revealed the impact of ITIH5 on biological processes such as skin development and ECM homeostasis. Performing the in vitro KeratinoSens skin sensitization assay, we detected that ITIH5 decreases the sensitizing potential of moderate and strong contact sensitizers.

Conclusion: Taken together, our experiments revealed that ITIH5 forms complexes with HA, thereby on the one hand stabilizing HA and facilitating the formation of ECM structures and on the other hand modulating inflammatory responses.
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http://dx.doi.org/10.1159/000509371DOI Listing
August 2020

Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Society of Allergology (AeDA), German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Austrian Society for Allergology and Immunology (ÖGAI), and the Paul-Ehrlich Society for Chemotherapy (PEG).

Allergol Select 2020 28;4:11-43. Epub 2020 May 28.

Department of Dermatology and Allergology am Biederstein, School of Medicine, Technical University of Munich, Munich, Germany.

This guideline on diagnostic procedures for suspected beta-lactam antibiotic (BLA) hypersensitivity was written by the German and Austrian professional associations for allergology, and the Paul-Ehrlich Society for Chemotherapy in a consensus procedure according to the criteria of the German Association of Scientific Medical Societies. BLA such as penicillins and cephalosporins represent the drug group that most frequently triggers drug allergies. However, the frequency of reports of suspected allergy in patient histories clearly exceeds the number of confirmed cases. The large number of suspected BLA allergies has a significant impact on, e.g., the quality of treatment received by the individual patient and the costs to society as a whole. Allergies to BLA are based on different immunological mechanisms and often manifest as maculopapular exanthema, as well as anaphylaxis; and there are also a number of less frequent special clinical manifestations of drug allergic reactions. All BLA have a beta-lactam ring. BLA are categorized into different classes: penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors with different chemical structures. Knowledge of possible cross-reactivity is of considerable clinical significance. Whereas allergy to the common beta-lactam ring occurs in only a small percentage of all BLA allergic patients, cross-reactivity due to side chain similarities, such as aminopenicillins and aminocephalosporins, and even methoxyimino cephalosporins, are more common. However, the overall picture is complex and its elucidation may require further research. Diagnostic procedures used in BLA allergy are usually made up of four components: patient history, laboratory diagnostics, skin testing (which is particularly important), and drug provocation testing. The diagnostic approach - even in cases where the need to administer a BLA is acute - is guided by patient history and risk - benefit ratio in the individual case. Here again, further studies are required to extend the present state of knowledge. Performing allergy testing for suspected BLA hypersensitivity is urgently recommended not only in the interests of providing the patient with good medical care, but also due to the immense impact of putative BLA allergies on society as a whole.
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http://dx.doi.org/10.5414/ALX02104EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304290PMC
May 2020

"New" inhalant plant allergens.

Allergol Select 2020 23;4:1-10. Epub 2020 Apr 23.

Department of Dermatology and Allergology, University Hospital of RWTH Aachen, Aachen.

Specific IgE measurements obtained from patients suffering from respiratory allergy (n = 952) show that, despite similar climatic conditions, there are clear regional differences in pollen sensitization between North Rhine-Westphalia and Bavaria. The data on sensitization levels and pollen concentration was taken from the research and development project Ufoplan 3710 61 228 of the German Environment Agency for North Rhine-Westphalia and Bavaria (2011 - 2014). Most poly-sensitized patients have already shown sensitization, both in the form of cross-reactivity and species-specific sensitization, to "new" pollen allergens, such as Bermuda grass and olive tree. These plants are currently not common in Germany, but may become considerably more widespread due to the increase in average yearly temperatures caused by the global warming. The other "new" aeroallergens discussed here are plants that can be found throughout Germany, such as nettle, cypress, and pine. Their current sensitization levels are higher than 8%; however, their clinical impact appears to be underestimated. For clinical practice it is important to identify when patients' symptoms are typically severe and which regional plants might be responsible for the patients' complaints in this period of time, as this affects further diagnostic strategy. Allergens having an immune effect can then be targeted by specific immunotherapies. The information on complaints of the patients should be regularly recorded in symptom diaries. Recording this information for at least 1 year may allow to discover a correlation between specific types of pollen and allergy symptoms.
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http://dx.doi.org/10.5414/ALX02066EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189803PMC
April 2020

The CD63 basophil activation test as a diagnostic tool for assessing autoimmunity in patients with chronic spontaneous urticaria.

Eur J Dermatol 2019 Dec;29(6):614-618

Department of Dermatology and Allergology, University Hospital of RWTH Aachen, Aachen,, Department of Dermatology and Allergology, University Hospital of Bonn, Bonn, Germany.

Background: Over the past years, it has become widely recognized that a proportion of chronic spontaneous urticaria (CSU) cases is of autoimmune origin, however, the search for reliable diagnostic tools to confirm underlying autoimmune pathophysiology is ongoing. The CD63 basophil activation test (CD63 BAT) has recently become useful for diagnosing autoimmune CSU.

Objectives: To analyse the correlation between positive CD63 BAT results, total IgE antibody levels, and the presence of autoimmune thyroiditis as a comorbidity in patients diagnosed with CSU.

Materials And Methods: We performed a retrospective analysis of CD63 BAT results obtained from 87 CSU and 20 non-CSU patients. The information extracted from the patients' records included age, gender, total IgE levels, clinical history of autoimmune thyroiditis (AT), and the presence of anti-thyroid autoantibodies.

Results: Positive CD63 BAT results were significantly more frequent in CSU patients compared with non-CSU subjects (p=0.045). Furthermore, we found a strong significant negative correlation between the stimulation index (SI) value for CD63 BAT and total IgE levels in CD63 BAT-positive CSU patients (p=0.004; Spearman's rank correlation coefficient ρ=-0.322), meaning that higher SI values corresponded to lower total IgE values, and vice versa.

Conclusion: The current standard set of diagnostic tools cannot be reliably used to determine when CSU is caused by autoimmune mechanisms. There is evidence that CD63 BAT represents a helpful diagnostic tool for detecting underlying autoimmunity. We show that high SI values in CD63 BAT-positive CSU patients correlate negatively with their total IgE levels. The clinical relevance of this effect needs to be investigated further.
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http://dx.doi.org/10.1684/ejd.2019.3680DOI Listing
December 2019

[Current developments in dermatopharmacology].

Hautarzt 2019 12;70(12):924-925

Universitätsklinik und Poliklinik für Dermatologie und Venerologie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Str. 40, 06097, Halle (Saale), Deutschland.

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http://dx.doi.org/10.1007/s00105-019-04508-yDOI Listing
December 2019

[The aryl hydrocarbon receptor as the target structure for new drugs in psoriasis and atopic dermatitis].

Authors:
Hans F Merk

Hautarzt 2019 Dec;70(12):942-947

Klinik für Dermatologie und Allergologie - Hautklinik, Universitätsklinikum Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland.

Coal tar therapy was used for centuries to treat skin disorders characterised by inflammation and skin barrier damage. It has been shown that the aryl hydrocarbon receptor (AhR) is the key target structure for these pharmacological effects of coal tar. Since coal tar has been used less and less because of the carcinogenicity of many ingredients of coal tar, other ligands of AhR were studied. Tapinarof is such a ligand and proved to be a promising new drug to treat psoriasis and atopic dermatitis. Since many endogenous and exogenous ligands of AhR are known, it may be that this "tar-smart" product is a first example of a new drug family with which dermatologists can treat skin disorders that are characterized by inflammation and skin barrier damage.
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http://dx.doi.org/10.1007/s00105-019-04503-3DOI Listing
December 2019

Altered Gene Expression in Dioxin-Like and Non-Dioxin-Like PCB Exposed Peripheral Blood Mononuclear Cells.

Int J Environ Res Public Health 2019 06 13;16(12). Epub 2019 Jun 13.

Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany.

Polychlorinated biphenyls (PCBs) are well known carcinogenic persistent environmental pollutants and endocrine disruptors. Our aim was to identify the possible dysregulation of genes in PCB exposed peripheral blood mononuclear cells (PBMCs) in order to give more insight into the differential pathophysiological effects of PCB congeners and mixtures, with an emphasis on immunological effects and oxidative stress. The PBMCs of a healthy volunteer (male, 56 years old) were exposed to a mixture of dioxin-like (DL)-PCBs (PCB 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189, 250 µg/L resp.) or non-dioxin-like (NDL)-PCBs (PCB 28, 52, 101, 138, 153, 180, 250 µg/L resp.) or single PCB congener (no.28, 138, 153, 180, 250 µg/L resp.). After an incubation period of 24 h, a microarray gene expression screening was performed, and the results were compared to gene expression in control samples (PBMCs treated with the vehicle iso-octane). Treatment of PBMCs with the DL-PCB mixture resulted in the largest number of differentially regulated genes (181 upregulated genes >2-fold, 173 downregulated >2-fold). Treatment with the NDL-PCB mix resulted in 32 upregulated genes >2-fold and 12 downregulated genes >2-fold. A gene set enrichment analysis (GSEA) on DL-PCB treated PBMCs resulted in an upregulation of 125 gene sets and a downregulation of 76 gene sets. Predominantly downregulated gene sets were involved in immunological pathways (such as response to virus, innate immune response, defense response). An upregulation of pathways related to oxidative stress could be observed for all PCB congeners except PCB-28; the latter congener dysregulated the least number of genes. Our experiment augments the information known about immunological and cellular stress responses following DL- as well as NDL-PCB exposure and provides new information on PCB 28. Further studies should be performed to evaluate how disruption of these pathways contributes to the development of autoimmune diseases and cancer.
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http://dx.doi.org/10.3390/ijerph16122090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617415PMC
June 2019

A EAACI drug allergy interest group survey on how European allergy specialists deal with β-lactam allergy.

Allergy 2019 06 17;74(6):1052-1062. Epub 2019 Feb 17.

Allergy Unit, Presidio Columbus, Rome, Italy.

An accurate diagnosis of β-lactam (BL) allergy can reduce patient morbidity and mortality. Our aim was to investigate the availability of BL reagents, their use and test procedures in different parts of Europe, as well as any differences in the diagnostic workups for evaluating subjects with BL hypersensitivity. A survey was emailed to all members of the EAACI Drug Allergy Interest Group (DAIG) between February and April 2016, and the questionnaire was meant to study the management of suspected BL hypersensitivity. The questionnaire was emailed to 82 DAIG centres and answered by 57. Amoxicillin alone or combined to clavulanic acid were the most commonly involved BL except in the Danish centre, where penicillin V was the most frequently suspected BL. All centres performed an allergy workup in subjects with histories of hypersensitivity to BL: 53 centres (93%) followed DAIG guidelines, two national guidelines and two local guidelines. However, there were deviations from DAIG recommendations concerning allergy tests, especially drug provocation tests. A significant heterogeneity exists in current practice not only among countries, but also among centres within the same country. This suggests the need to re-evaluate, update and standardize protocols on the management of patients with suspected BL allergy.
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http://dx.doi.org/10.1111/all.13721DOI Listing
June 2019

Expression of CYP1A1, CYP1B1 and IL-1β in PBMCs and skin samples of PCB exposed individuals.

Sci Total Environ 2018 Nov 22;642:1429-1438. Epub 2018 Jun 22.

Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany.

Polychlorinated biphenyls (PCBs) are well- known man-made persistent environmental pollutants and endocrine disruptors. As a result of mass production in the past, background levels of these compounds can be measured in human blood worldwide. In 2010 high internal levels of PCBs were discovered in workers of a transformer-recycling company in Germany. Our aim was to measure, whether the expression of CYP1A1, CYP1B1, and IL-1β is dysregulated in peripheral blood mononuclear cells (PBMCs) of the exposed individuals (n = max 308). Further, we measured the regulation of CYP1A1, CYP1B1, AHRR (aromatic hydrocarbon receptor repressor) and IL-1β in skin samples of 25 workers with elevated plasma PCB levels using quantitative PCR (q-RT-PCR). We found a significant correlation between the regulation of IL-1β in skin samples and lipid adjusted PCB levels. In the PBMCs, the expression levels of CYP1A1, CYP1B1 and IL-1β decreased over time with decreasing PCB plasma levels. The upregulation of the cytokine IL-1β in exposed individuals with higher PCB plasma levels warrants further investigation in order to examine its role in the pathophysiology of autoimmune disorders and tumor promotion.
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http://dx.doi.org/10.1016/j.scitotenv.2018.06.136DOI Listing
November 2018

Commentary on the "Evidence- and Consensus-Based (S3) Guidelines for the Treatment of Actinic Keratosis" Published by the International League of Dermatological Societies in Cooperation with the European Dermatology Forum.

Skin Pharmacol Physiol 2018 3;31(3):144-146. Epub 2018 Apr 3.

Department of Dermatology and Allergology, Clinic Vest, Recklinghausen, Germany.

In 2015, the International League of Dermatological Societies and the European Dermatology Forum published a guideline for the treatment of actinic keratosis, which is classified as an evidence- and consensus-based S3 guideline. From the point of view of the GD Task Force "Licht.Hautkrebs.Prävention," an interdisciplinary expert panel of the Society for Dermopharmacy for the prevention and treatment of skin cancer, this guideline reveals strengths and weaknesses but, in summary, does not meet the claim for an evidence- and consensus-based S3 guideline.
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http://dx.doi.org/10.1159/000486687DOI Listing
September 2018

Impact of increasing treatment rates on cost-effectiveness of subcutaneous immunotherapy (SCIT) in respiratory allergy: a decision analytic modelling approach.

Eur J Health Econ 2018 Dec 24;19(9):1229-1242. Epub 2018 Mar 24.

Institute for Health Care Management and Research, University of Duisburg-Essen, Thea-Leymann-Str. 9, 45127, Essen, Germany.

Background: Specific immunotherapy is the only causal treatment in respiratory allergy. Due to high treatment cost and possible severe side effects subcutaneous immunotherapy (SCIT) is not indicated in all patients. Nevertheless, reported treatment rates seem to be low. This study aims to analyze the effects of increasing treatment rates of SCIT in respiratory allergy in terms of costs and quality-adjusted life years (QALYs).

Methods: A state-transition Markov model simulates the course of disease of patients with allergic rhinitis, allergic asthma and both diseases over 10 years including a symptom-free state and death. Treatment comprises symptomatic pharmacotherapy alone or combined with SCIT. The model compares two strategies of increased and status quo treatment rates. Transition probabilities are based on routine data. Costs are calculated from the societal perspective applying German unit costs to literature-derived resource consumption. QALYs are determined by translating the mean change in non-preference-based quality of life scores to a change in utility. Key parameters are subjected to deterministic sensitivity analyses.

Results: Increasing treatment rates is a cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of 3484€/QALY compared to the status quo. The most influential parameters are SCIT discontinuation rates, treatment effects on the transition probabilities and cost of SCIT. Across all parameter variations, the best case leads to dominance of increased treatment rates while the worst case ICER is 34,315€/QALY. Excluding indirect cost leads to a twofold increase in the ICER.

Conclusions: Measures to increase SCIT initiation rates should be implemented and also address improving adherence.
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http://dx.doi.org/10.1007/s10198-018-0970-6DOI Listing
December 2018

Individual risk assessment in the diagnosis of immediate type drug hypersensitivity reactions to betalactam and non-betalactam antibiotics using basophil activation test: a single center experience.

Cutan Ocul Toxicol 2018 Dec 22;37(4):309-318. Epub 2018 Mar 22.

b Department of Dermatology and Allergology , University Hospital of RWTH Aachen , Aachen , Germany.

Background: Drug hypersensitivity reactions of immediate type pose a challenging problem, especially, if standard diagnostic procedures do not lead to conclusive results. The aim of this investigation is to identify, whether basophil activation test (BAT) is able to provide additional benefit in the diagnostic evaluation of immediate type drug hypersensitivity reactions to antibiotics in comparison with the routine allergological diagnostic methods.

Materials And Methods: We investigated patients, who presented to the Department of Dermatology and Allergology of the University Hospital of RWTH Aachen in Germany for diagnostic workup of type I allergic reactions to antibiotics during the period from 2009 to 2012. The analysis was performed retrospectively based on patient records. The inclusion criteria were performed standard allergological in vivo diagnostic and a BAT as a part of diagnostic workup.

Results: Eighty-two diagnostic investigations were performed in 52 patients. BAT was positive in 9 of 12 cases with a positive clinical history but negative skin test results. Furthermore, all patients who reported severe drug hypersensitivity reactions (anaphylactic reaction grade 2 and above) showed positive BAT (5/5), while only three of these five cases demonstrated a positive skin testing that led to the conclusion of possible immediate type drug hypersensitivity.

Conclusions: Although skin tests remain the most important part of the primary diagnostic investigation, BAT is an additional valuable and sensitive in vitro test in the diagnostic procedure of immediate type allergic reactions to antibiotics. However, further standardized investigations are needed in order to calculate exact sensitivity and specificity of this diagnostic tool in both, adult and pediatric populations.
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http://dx.doi.org/10.1080/15569527.2018.1448990DOI Listing
December 2018

Hyperpigmentation and higher incidence of cutaneous malignancies in moderate-high PCB- and dioxin exposed individuals.

Environ Res 2018 07 20;164:221-228. Epub 2018 Mar 20.

Department of Dermatology and Allergology, RWTH Aachen University, Pauwelstrasse 30, 52074 Aachen, Germany.

Polychlorinated biphenyls (PCB) are well known persistent and toxic environmental pollutants. Our aim was to identify effects of moderate-high exposure to dioxin-like (dl) and non-dioxin-like (ndl)-PCBs on the skin in order to provide more insight in the pathophysiological effects of these compounds. We performed a dermatological examination on 92 former workers from a transformer recycling company with known elevated serum PCB and/or dioxin (polychlorinated dibenzo-p-dioxin/polychlorinated dibenzo-p-furan (PCDD/F)) levels. In addition, we performed a skin cancer screening over a period of seven years (2010-2016) on resp. 268, 271, 210, 149, 92, 129 and 79 participants. We found a higher incidence of acne and malignancies of the skin (malignant melanoma, basal cell carcinoma and mycosis fungoides) in the workers compared to normal population. The probability of having hyperpigmentation on the skin was statistically significantly higher in workers with higher sumPCBs- (OR:1.09(1.12-2.17)), dioxin-like (dl)-PCBs- (OR:1.56(1.12-2.17)) and dioxin (PCDD/Fs) (OR:1.09(1.02-1.16)) levels. Age was a confounding factor in this model. Formation of hyperpigmentation could be an indicator for (moderate-high) exposure to toxic compounds like PCBs. The higher incidence of cutaneous malignancies found in the workers might be associated with PCB- and dioxin exposure, warranting further investigation on larger cohorts.
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http://dx.doi.org/10.1016/j.envres.2018.02.002DOI Listing
July 2018

RIS-1/psoriasin expression in epithelial skin cells indicates their selective role in innate immunity and in inflammatory skin diseases including acne.

Dermatoendocrinol 2017 4;9(1):e1338993. Epub 2017 Oct 4.

Department of Dermatology and Allergology, RWTH Aachen University, Aachen, Germany.

Objective: RIS-1/psoriasin/S100A7 is an epithelial antimicrobial peptide, whose expression is upregulated in inflammatory skin diseases and is induced by retinoids. Its molecular expression was investigated in skin cell cultures and in skin specimens to better understand its role in inflammatory procedures of the pilosebaceous unit.

Methods: rtPCR and northern blotting of RIS-1/psoriasin and the retinoid-metabolizing genes CYP26AI and CRABP-II were performed in cells cultures (keratinocytes, sebocytes, fibroblasts, endothelial cells, melanocytes, lymphocytes and prostate cells; native and treated with retinoids) and in situ hybridization in normal and inflamed skin (acne, psoriasis).

Results: a) RIS-1/psoriasin is expressed in keratinocytes and fibroblasts and in keratinocytes of the stratum granulosum . Retinoids and inflammatory conditions increase the levels of RIS-1/psoriasin in keratinocytes (both), sebocytes (inflammation only) and fibroblasts (retinoids). Sebocytes and fibroblasts are the metabolically most active skin cells, since they can upregulate the expression of CRABP-II and CYP26AI, genes responsible for retinoid metabolism. Inflammation modifies the compartmentation of RIS-1/psoriasin in sebaceous glands and the follicular root sheaths.

Conclusion: The present data indicate that anti-inflammatory treatment targeting the epithelial compartments of the skin, including such with antibacterial peptides, may be promising for inflammatory skin diseases.
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http://dx.doi.org/10.1080/19381980.2017.1338993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821165PMC
October 2017

Cutaneous allergic drug reactions: update on pathophysiology, diagnostic procedures and differential diagnosic.

Cutan Ocul Toxicol 2017 Dec 27;36(4):307-316. Epub 2017 Apr 27.

a Department of Dermatology and Allergology , RWTH Aachen University , Aachen , Germany.

Important changes in the understanding and management of drug hypersensitivity reactions during the last years result from the increasing importance of biologics in medical practice, which differ in their spectrum of adverse drug reactions (ADRs) from the classical covalent drugs. With regard to covalent drugs, ampicillin and amoxicillin as well as clavulanic acid play an increasing role among ADRs to betalactam antibiotics. Fluoroquinolones are mainly the cause of anaphylactic and photosensitivity reactions. Especially in allergic reactions to NSAIDs, pseudoallergic reactions should be considered in the differential diagnosis. In opposite to the main cutaneous allergic drug reactions such as urticaria or maculopapular skin rash, in which antibiotics are the main culprits, in severe drug allergic reactions such as SJS (Stevens-Johnson Syndrome), TEN (Toxic Epidermal Necrolysis), or DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) Syndrome, compounds like allopurinol and anticonvulsants are the main causes. Similar mutations in the IL36R gene, which were found in both patients with an AGEP (Acute Generalized Exanthematous Pustulosis) and pustular psoriasis, make the differential diagnosis more difficult and raise the question whether there is a difference between these diseases or whether AGEP is not just a drug induced pustular psoriasis. Finally, some special aspects of side effects of biologics and targeted therapies respectively are discussed.
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http://dx.doi.org/10.1080/15569527.2017.1319379DOI Listing
December 2017

Omalizumab is effective in cold urticaria-results of a randomized placebo-controlled trial.

J Allergy Clin Immunol 2017 09 4;140(3):864-867.e5. Epub 2017 Apr 4.

Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2017.01.043DOI Listing
September 2017

Prospective, Randomized Study on the Efficacy and Safety of Local UV-Free Blue Light Treatment of Eczema.

Dermatology 2016 19;232(4):496-502. Epub 2016 Aug 19.

Department of Dermatology and Allergology, University Hospital, RWTH Aachen University, Aachen, Germany.

Background: Blue light was shown to reduce the activation of T cells and modulate cytokine release in vitro. Therefore, we investigated the efficacy of blue light in the treatment of eczema.

Methods: A sample of 21 patients with mild to moderate eczema were locally treated with blue LED light (light-emitting diode, emission maximum: 453 nm). They received light treatment 3 times per week for 4 weeks. A contralateral control lesion remained untreated.

Results: A total of 20 patients completed the trial with a compliance rate of 100%. The blue light treatment was safe with no adverse events and no side effects. The primary end point change from baseline in the mean sum score of the local Eczema Severity Index (local ESI) was more pronounced for the treated area than for the control area (-1.9 ± 2.02 vs. -1.3 ± 2.24). The treatment difference was statistically significant (p = 0.0152, paired t test, two-sided).

Conclusion: In this study UV-free blue light was safe and effective in the reduction of eczema lesions.
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http://dx.doi.org/10.1159/000448000DOI Listing
July 2017

Potential health risk of allergenic pollen with climate change associated spreading capacity: Ragweed and olive sensitization in two German federal states.

Int J Hyg Environ Health 2016 May 1;219(3):252-60. Epub 2016 Feb 1.

Department of Dermatology and Allergology, University Hospital of Aachen, Aachen, Germany.

Background: Global climate changes may influence the geographical spread of allergenic plants thus causing new allergen challenges.

Objective: Allergy patients from two German federal states were compared for their status quo sensitization to ragweed, an establishing allergen, olive, a non-established allergen, and the native allergens birch, mugwort, and ash.

Methods: Between 2011 and 2013, 476 adult allergy patients per region were recruited. Patients completed a questionnaire, participated in a medical interview, and underwent skin prick testing and blood withdrawal for analysis of specific IgE to allergen components (ISAC technology). Data on regional pollen load from 2006 to 2011 were acquired from the German Pollen Information Service Foundation.

Results: Prick test reactivity to ragweed and ash, respectively, was lower in Bavaria than in NRW (ragweed: p=0.001, aOR=0.54; ash: p=0.001, aOR=0.59), whereas prick test reactivity to olive was higher (p=0.000, aOR=3.09). Prick test reactivity to birch and mugwort, respectively, did not significantly differ. 1% (1/127) of patients with prick test reactivity to ragweed showed sIgE to Amb a 1, and 65% (86/132) of olive-but-not-ash reactive patients showed sIgE to Ole e 1 (NRW: 67%, Bavaria: 65%; p=0.823, OR=0.91). Regional differences in sensitization pattern were neither explainable by cross-reactivity to pollen pan-allergens nor non-exposure variables nor by reported plant population or pollen data.

Conclusions: Spread of ragweed and particularly olive may result in prompt occurrence of allergic symptoms. Early identification of invasive allergens due to climate change does need time and spatial close meshed measurement of respective indicator allergens and sensitization pattern.
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http://dx.doi.org/10.1016/j.ijheh.2016.01.007DOI Listing
May 2016

Interferon Alpha Signalling and Its Relevance for the Upregulatory Effect of Transporter Proteins Associated with Antigen Processing (TAP) in Patients with Malignant Melanoma.

PLoS One 2016 6;11(1):e0146325. Epub 2016 Jan 6.

Department of Dermatology and Allergology, RWTH Aachen University, Aachen, Germany.

Introduction: Interferon alpha (IFNα) is routinely used in the clinical practice for adjuvant systemic melanoma therapy. Understanding the molecular mechanism of IFNα effects and prediction of response in the IFNα therapy regime allows initiation and continuation of IFNα treatment for responder and exclusion of non-responder to avoid therapy inefficacy and side-effects. The transporter protein associated with antigen processing-1 (TAP1) is part of the MHC class I peptide-loading complex, and important for antigen presentation in tumor and antigen presenting cells. In the context of personalized medicine, we address this potential biomarker TAP1 as a target of IFNα signalling.

Results: We could show that IFNα upregulates TAP1 expression in peripheral blood mononuclear cells (PBMCs) of patients with malignant melanoma receiving adjuvant high-dose immunotherapy. IFNα also induced expression of TAP1 in mouse blood and tumor tissue and suppressed the formation of melanoma metastasis in an in vivo B16 tumor model. Besides its expression, TAP binding affinity and transport activity is induced by IFNα in human monocytic THP1 cells. Furthermore, our data revealed that IFNα clearly activates phosphorylation of STAT1 and STAT3 in THP1 and A375 melanoma cells. Inhibition of Janus kinases abrogates the IFNα-induced TAP1 expression. These results suggest that the JAK/STAT pathway is a crucial mediator for TAP1 expression elicited by IFNα treatment.

Conclusion: We suppose that silencing of TAP1 expression provides tumor cells with a mechanism to escape cytotoxic T-lymphocyte recognition. The observed benefit of IFNα treatment could be mediated by the shown dual effect of TAP1 upregulation in antigen presenting cells on the one hand, and of TAP1 upregulation in 'silent' metastatic melanoma cells on the other hand. In conclusion, this work contributes to a better understanding of the mode of action of IFNα which is essential to identify markers to predict, assess and monitor therapeutic response of IFNα treatment in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146325PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703378PMC
July 2016

Myeloid human cell lines lack functional regulation of aryl hydrocarbon receptor-dependent phase I genes.

ALTEX 2016 19;33(1):37-46. Epub 2015 Nov 19.

Department of Dermatology and Allergology, University Hospital of the RWTH Aachen University, Aachen, Germany.

Primary dendritic cells and myeloid cell lines are used to assess the skin sensitization hazard in in vitro approaches. The aryl hydrocarbon receptor (AhR) modulates expression of CYP enzymes which play a significant role in the bioactivation of various xenobiotics. These studies revealed a strong constitutive expression of the AhR in primary human monocytes, monocyte-derived immature dendritic cells (iDC) and cord blood-derived Langerhans cells (LC). In contrast, mRNA and protein expression of AhR was hardly detectable in the cell lines THP-1 and MUTZ-3. U937 cells and MUTZ-3-derived dendritic (MUTZ-DC) or Langerhans cells (MUTZ-LC) showed about half the expression of AhR compared to iDC. Incubation of cells with the specific AhR-inducer benzo[a]anthracene resulted in an upregulation of CYP and IL-1β mRNA expression in primary monocytes and iDC. CYP1A1 but not CYP1B1 and IL-1β expression was increased by benzo[a]anthracene in these cell lines except for U937 cells. AhR-independent CYP genes were not regulated by benzo[a]anthracene. Constitutive mRNA expression of other non AhR-dependent CYP enzymes was higher in some of the cell lines compared to the corresponding primary cells. This study demonstrates significant differences in expression and regulation of phase I genes in cell lines currently used for in vitro skin sensitization hazard assessment compared to primary cells. Additional studies are required regarding the combination of cutaneous xenobiotic metabolizing enzymes and APC-sensitization for the development of valid in vitro models for skin sensitization assessment.
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http://dx.doi.org/10.14573/altex.1502041DOI Listing
October 2016

Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM).

Allergo J Int 2015;24(3):94-105

Department of Dermatology and Allergology, RTWH Aachen, Aachen, Germany.

Drug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1-6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of allergies. The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks-6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an "allergy passport" in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.
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http://dx.doi.org/10.1007/s40629-015-0052-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479479PMC
January 2015

Retinoid treatment of skin diseases.

Eur J Dermatol 2015 Sep-Oct;25(5):384-91

Department of Dermatology, SLK Hospital Heilbronn, Am Gesundbrunnen 20 -26, 74078 Heilbronn, Germany, Department of Dermatology and Allergology, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany.

Retinoids (vitamin A and its metabolites) are potent natural regulators of cellular activities, including cell growth and differentiation, and they mediate many essential regulatory functions, especially in the skin. Biologically active retinoids exert their effects by binding to nuclear retinoic acid receptors and retinoid-X-receptors. The group of pharmacologically used retinoids include naturally occurring and chemically synthesised vitamin A derivatives. Due to their influence on keratinocyte proliferation, epidermal differentiation and keratinisation, retinoids are commonly used in the field of dermatopharmacology. For safe administration of retinoids, in-depth information about adverse effects and comprehensive information of the patient are important. This article gives an overview on the effects, use, and side-effects of topical and systemic retinoids in dermatology.
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http://dx.doi.org/10.1684/ejd.2015.2544DOI Listing
October 2016