Skin diseases in hospitalized geriatrics:a 9-year analysis from a University Dermatology Center in Germany

The demographic trend of an ageing society is mirrored in the rising number of hospitalized geriatric patients in Germany. However, there is still a wide gap of knowledge regarding the dermatological diseases, comorbidities and performed procedures within this growingly important group of patients. The study was conducted as a retrospective monocentric data analysis of all patients 65 years or older from the Department of Dermatology, Medical Center-University of Freiburg, Germany. In total, 10,009 individual hospitalisations were included from 2009 to 2017, and there was a notable increase of geriatric patients in the study period. This study illustrates the following: leading major diagnoses included malignant neoplasm of the head and neck, ulcerated and non-ulcerated inflammatory spectrum of chronic venous insufficiency, whereas angina pectoris, type 2 diabetes and cardiac diseases were noted most frequently as secondary diagnoses. Patients with venous diseases had considerably more often cardiopulmonary minor diagnoses, whereas endocrine diagnoses peaked in the cohort of patients with psoriasis and psychiatric and muscululoskeletal disorders in patients with bullous dieseases. Moh's surgery, dressings and multimodal dermatological treatments were the most often encoded procedures

Use and importance of different information sources among patients with rare diseases and their relatives over time: a qualitative study

Background: Finding reliable information on one of more than 7000 rare diseases is a major challenge for those affected. Since rare diseases are defined only by the prevalence criterion, a multitude of heterogeneous diseases are included. Common to all, however, are difficulties regarding information access. Even though various quantitative studies have analyzed the use of different information sources for specific rare diseases, little is known about the use of information sources for different rare diseases, how users rate these information sources based on their experiences, and how the use and importance of these information sources change over time. Methods: Fifty-five patients with a variety of rare diseases and 13 close relatives participated in qualitative interviews. For these interviews, a semi-structured guideline was developed, piloted, and revised. Data analysis involved a qualitative content analysis developed by Philipp Mayring. Results: The participants considered internet as the most important and widespread information source, especially for early information. Although patients have difficulty dealing with information obtained online, they consider online searching a quick and practical option to gather information. During the course of the disease, personal contact partners, especially self-help associations and specialized doctors, become more important. This is also because information provided online is sometimes insufficiently detailed to answer their information needs, which can be complemented by information from doctors and self-help. Conclusions: People rarely use just one type of source, but rather refer to different sources and informants. The source used depends on the type of information sought as well as other person-related factors such as preexisting knowledge and the disease stage. To improve people’s information searching and connect them with medical specialists in rare diseases, a central information portal on rare diseases might be a suitable access point to provide free and quality assured information for patients, caregivers, and physicians. This would allow not only patients but also doctors to find quality assured information on symptoms and therapies as well as patient associations and specialized doctors

Bullous pemphigoid in infants: characteristics, diagnosis and treatment

BACKGROUND: Bullous pemphigoid (BP) in infants is a rare but increasingly reported autoimmune blistering skin disease. Autoantibody reactivity is usually poorly characterized. Current guidelines do not address specific aspects of the infantile form of BP. The objectives of this study are to define clinical and diagnostic characteristics of infantile BP and develop a treatment algorithm. METHODS: Detailed characterization of a current case series of five infants with BP from our departments. Comprehensive analysis of all reported cases (1-12 months) with respect to clinical and laboratory characteristics, treatment and outcome. RESULTS: In total 81 cases were identified (including our own). The mean age was 4.5 months. Moderately severe and severe disease was seen in 84% of cases. Involvement of hands and feet was present in all cases. Immunofluorescence microscopy was comparable with BP in adults. Where analyzed, the NC16A domain of bullous pemphigoid 180 kDa antigen/collagen XVII (BP180) was identified as the major target antigen. BP180 NC16A ELISA values in our cohort were significantly higher than in a control cohort of 28 newly diagnosed adult patients. 50% of patients were treated with systemic corticosteroids, 20% with a combination of systemic corticosteroids and dapsone or sulfapyridine and 10% with topical corticosteroids alone. 14% of patients needed a combination of multiple immunosuppressants. All but one patient reached remission. Relapses were rare. CONCLUSIONS: Presentation of infantile BP is often severe with blistering of hands and feet present in all cases. Pathogenesis and diagnostic criteria are comparable to adult BP, yet BP180 NC16A ELISA levels seem to be significantly higher in infants. The overall disease outcome is favorable. Based on the results of this study we propose a treatment algorithm for infantile BP

Hemidesmosomal Reactivity and Treatment Recommendations in Immune Checkpoint Inhibitor-Induced Bullous Pemphigoid—A Retrospective, Monocentric Study

Immune checkpoint inhibitors (ICI) induce T-cell-mediated antitumour responses. While ICI were initially successfully applied in metastasized melanoma, they are now approved for several tumour entities. Numerous autoimmune disorders have been reported to occur as adverse events of the treatment, among them bullous pemphigoid (BP), with less than 1% of the patients experiencing ICI-induced BP. This number is higher than the estimated prevalence of autoimmune bullous diseases in the general population of Germany, which lies around 0.05%. We here describe our cohort of eight patients, who developed a bullous pemphigoid under or shortly after ICI treatment. Half of them had a severe subtype (as shown by BPDAI >57) and showed a median onset of ICI-BP after 10 months of ICI initiation. Six patients had a palmar and/or plantar involvement, while oral involvement occurred in one case. All patients had linear epidermal IgG depositions in split skin in the indirect immunofluorescence. In four out of five biopsies available for direct immunofluorescence, linear IgG and C3 depositions were detected at the basement membrane, while one patient showed linear IgM staining. Moderate to high levels of FLBP180 autoantibodies were found in seven of eight cases. The disease can still be active after ICI discontinuation, while rituximab might be required for remission. Finally, four tumour samples were stained histochemically for collagen XVII (BP180), but no enhanced expression was found

Evaluation of Nomacopan for Treatment of Bullous Pemphigoid:A Phase 2a Nonrandomized Controlled Trial

Importance: Bullous pemphigoid is a difficult-to-treat autoimmune blistering skin disease that predominantly affects older adults and is associated with an increased mortality rate. Objective: To examine the safety and therapeutic potential of nomacopan, an inhibitor of leukotriene B4and complement C5, in patients with bullous pemphigoid. Design, Setting, and Participants: This multicenter, single-group, phase 2a nonrandomized controlled trial was conducted in the dermatology departments of universities in the Netherlands and Germany. Participants were enrolled between September 2018 and April 2020. Older adult patients (aged ≥55 years) with mild to moderate, new-onset or relapsing bullous pemphigoid were recruited into the study. Interventions: Patients received nomacopan, 90 mg, subcutaneously on day 1 and 30 mg subcutaneously daily until day 42. Main Outcomes and Measures: The primary end point was the proportion of patients with grade 3 to 5 (severe) adverse events associated or possibly associated with nomacopan. Secondary end points included mean absolute and percentage changes in the Bullous Pemphigoid Disease Area Index (BPDAI) activity score, the BPDAI pruritus score, and the patient-reported outcome measures Dermatology Life Quality Index (DLQI) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL). Results: A total of 9 patients (median [range] age, 75 [55-85] years) with bullous pemphigoid were included in the trial, of whom 5 were women (55.6%). No serious adverse events associated with nomacopan were found. The mean (90% CI) BPDAI activity score decreased from 32.0 (8.7) points on day 1 to 19.6 (9.0) points on day 42. Seven of 9 patients (77.8%) responded to nomacopan with a reduction in the BPDAI activity score of at least 8 points between days 1 and 42; in 3 responders, the reduction was 80% or greater. On day 42, the mean (90% CI) BPDAI pruritus score had decreased by 6.8 (4.6) points from 17.6 (4.0) points on day 1. The mean (90% CI) DLQI score decreased from 11.3 (4.2) points at baseline to 6.4 (3.8) points by day 42, and the mean (90% CI) TABQOL score decreased from 14.6 (5.4) points at baseline to 10.3 (5.0) points on day 42. Conclusions and Relevance: Results of this nonrandomized controlled trial suggest that nomacopan can be well tolerated in older patients with bullous pemphigoid and may have therapeutic benefits for suppressing acute flares of this disease. A larger, placebo-controlled randomized clinical trial is warranted to confirm this safety profile and to establish nomacopan as a new therapeutic option for bullous pemphigoid. Trial Registration: ClinicalTrials.gov Identifier: NCT04035733

Adopting Quality Criteria for Websites Providing Medical Information About Rare Diseases

BACKGROUND: The European Union considers diseases to be rare when they affect less than 5 in 10,000 people. It is estimated that there are between 5000 and 8000 different rare diseases. Consistent with this diversity, the quality of information available on the Web varies considerably. Thus, quality criteria for websites about rare diseases are needed. OBJECTIVE: The objective of this study was to generate a catalog of quality criteria suitable for rare diseases. METHODS: First, relevant certificates and quality recommendations for health information websites were identified through a comprehensive Web search. Second, all considered quality criteria of each certification program and catalog were examined, extracted into an overview table, and analyzed by thematic content. Finally, an interdisciplinary expert group verified the relevant quality criteria. RESULTS: We identified 9 quality certificates and criteria catalogs for health information websites with 304 single criteria items. Through this, we aggregated 163 various quality criteria, each assigned to one of the following categories: thematic, technical, service, content, and legal. Finally, a consensus about 13 quality criteria for websites offering medical information on rare diseases was determined. Of these categories, 4 (data protection concept, imprint, creation and updating date, and possibility to contact the website provider) were identified as being the most important for publishing medical information about rare diseases. CONCLUSIONS: The large number of different quality criteria appearing within a relatively small number of criteria catalogs shows that the opinion of what is important in the quality of health information differs. In addition, to define useful quality criteria for websites about rare diseases, which are an essential source of information for many patients, a trade-off is necessary between the high standard of quality criteria for health information websites in general and the limited provision of information about some rare diseases. Finally, transparently presented quality assessments can help people to find reliable information and to assess its quality

Adopting Quality Criteria for Websites Providing Medical Information About Rare Diseases

BACKGROUND: The European Union considers diseases to be rare when they affect less than 5 in 10,000 people. It is estimated that there are between 5000 and 8000 different rare diseases. Consistent with this diversity, the quality of information available on the Web varies considerably. Thus, quality criteria for websites about rare diseases are needed. OBJECTIVE: The objective of this study was to generate a catalog of quality criteria suitable for rare diseases. METHODS: First, relevant certificates and quality recommendations for health information websites were identified through a comprehensive Web search. Second, all considered quality criteria of each certification program and catalog were examined, extracted into an overview table, and analyzed by thematic content. Finally, an interdisciplinary expert group verified the relevant quality criteria. RESULTS: We identified 9 quality certificates and criteria catalogs for health information websites with 304 single criteria items. Through this, we aggregated 163 various quality criteria, each assigned to one of the following categories: thematic, technical, service, content, and legal. Finally, a consensus about 13 quality criteria for websites offering medical information on rare diseases was determined. Of these categories, 4 (data protection concept, imprint, creation and updating date, and possibility to contact the website provider) were identified as being the most important for publishing medical information about rare diseases. CONCLUSIONS: The large number of different quality criteria appearing within a relatively small number of criteria catalogs shows that the opinion of what is important in the quality of health information differs. In addition, to define useful quality criteria for websites about rare diseases, which are an essential source of information for many patients, a trade-off is necessary between the high standard of quality criteria for health information websites in general and the limited provision of information about some rare diseases. Finally, transparently presented quality assessments can help people to find reliable information and to assess its quality

Ethos im Lehrberuf

Dieses Manual soll es angehenden Lehrer*innen in der ersten Phase der Lehrkräfteausbildung ermöglichen, mit dem Thema ‚Ethos‘ in Kontakt zu treten und es als ein wichtiges Feld der professionellen Entwicklung kennen zu lernen. Das Manual ist für den Einsatz in der Lehrer*innenbildung an Hochschulen konzipiert und richtet sich vornehmlich an Dozierende in diesen Lehrbereichen. Darüber hinaus kann es aber auch von Lehrer*innen in der zweiten und dritten Phase für Fort- und Weiterbildung genutzt werden. Dazu finden sich im Manual einführende Texte zu den Themen Ethos (Kapitel 1), zur professionstheoretischen Verortung des pädagogischen Ethos in einem Domänenmodell der Professionalität (EPIK-Domänen, Kapitel 2) und zur praktischen Anwendung des Manuals in der Hochschullehre (Kapitel 3). Neben diesen einführenden Kapiteln besteht das ‚Herzstück‘ des Manuals in einer Sammlung von 24 Beispielen aus der schulischen Praxis (Kapitel 4). Sie alle stammen aus den Praktikumsreflexionen angehender Lehrer*innen, sie alle beschreiben herausfordernde Situationen, in denen Ethos gefragt ist oder sich zeigt – wir nennen dies eine Situation, die sich durch ethische Ambiguität auszeichnet. So führen die Beispiele ein in eine Praxis der Stellungnahme und des Fällens von (ethischen) Urteilen, eine Form der Übung, die zur Herausbildung eines Ethos beiträgt.This manual is intended to enable prospective teachers in the first phase of teacher education to get in touch with the topic of 'ethos' and to get to know it as an important field of professional development. The manual is designed for use in teacher education at universities and is primarily aimed at lecturers in these teaching areas. However, it can also be used by teachers in the second and third phase for further education and training. For this purpose, the manual contains introductory texts on the topics of ethos (chapter 1), on the professional-theoretical location of the pedagogical ethos in a domain model of professionalism (EPIK domains, chapter 2), and on the practical application of the manual in university teaching (chapter 3). In addition to these introductory chapters, the 'heart' of the manual is a collection of 24 examples from school-based practice (Chapter 4). They all come from the internship reflections of prospective teachers, they all describe challenging situations in which ethos is required or manifests itself - we call this a situation characterized by ethical ambiguity. Thus, the examples introduce a practice of taking a stand and making (ethical) judgments, a form of exercise that contributes to the formation of an ethos.Not Reviewe

Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans

Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology

Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa

BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and lifethreatening inherited skin fragility disorder that comes about due to a lack of functional type VII collagen, for which no effective therapy exists. ABCB5+ dermal mesenchymal stem cells (ABCB5+ MSCs) possess immunomodulatory, inflammation-dampening, and tissue-healing capacities. In a Col7a1-/-mouse model of RDEB, treatment with ABCB5+ MSCs markedly extended the animals\u27 lifespans. METHODS. In this international, multicentric, single-arm, phase I/IIa clinical trial, 16 patients (aged 4-36 years) enrolled into 4 age cohorts received 3 i.v. infusions of 2 × 106ABCB5+ MSCs/kg on days 0, 17, and 35. Patients were followed up for 12 weeks regarding efficacy and 12 months regarding safety. RESULTS. At 12 weeks, statistically significant median (IQR) reductions in the Epidermolysis Bullosa Disease Activity and Scarring Index activity (EBDASI activity) score of 13.0% (2.9%-30%; P = 0.049) and the Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa clinician (iscorEB-c) score of 18.2% (1.9%-39.8%; P = 0.037) were observed. Reductions in itch and pain numerical rating scale scores were greatest on day 35, amounting to 37.5% (0.0%-42.9%; P = 0.033) and 25.0% (-8.4% to 46.4%; P = 0.168), respectively. Three adverse events were considered related to the cell product: 1 mild lymphadenopathy and 2 hypersensitivity reactions. The latter 2 were serious but resolved without sequelae shortly after withdrawal of treatment. CONCLUSION. This trial demonstrates good tolerability, manageable safety, and potential efficacy of i.v. ABCB5+ MSCs as a readily available disease-modifying therapy for RDEB and provides a rationale for further clinical evaluation