Comparison of Different Anti-Demodex Strategies: A Systematic Review and Meta-Analysis.

BACKGROUND: Demodex mites are related to some inflammatory diseases such as rosacea and blepharitis and could be harmful in patients with immunodeficiency or immunosuppression, especially notable in patients using biologic like dupilumab. In order to have an objective observation of different anti-Demodex strategies, we conducted this study, based on interventional clinical evidence with quantified Demodex mite data. METHODS: We used the PubMed, Embase, ClinicalTrials.gov, Medline, and International Clinical Trials Registry Platform (ICTRP) as databases. To assess the risk of bias, the RoB2 and ROBINS-I tools were used. The certainty of evidence was assessed following the GRADE guideline. Furthermore, the effect sizes (ESs) of different strategies were compared in different time periods (0-1, 1-2, 2-3, >3 months), as well as Demodex decrease rates. RESULTS: 1,618 studies were identified in the databases, with 21 of which included in the final quantitative synthesis. Interventions in these studies included ivermectin, tea tree oil (TTO), permethrin, crotamiton, metronidazole, light therapies, combined therapies, and other therapies. During 0-1 month, the ES varied from 0.07 (cleanser) to 1.95 (systemic ivermectin-metronidazole). During 1-2 months, the ES varied from 0.88 (topical permethrin) to 4.40 (topical ivermectin). During 2-3 months, the ES varied from 0.79 (topical permethrin) to 8.37 (topical ivermectin). During the time of 3 months, the ES varied from 0.59 (topical permethrin) to 2.25 (intense pulsed light [IPL]). In terms of Demodex decrease rates, topical ivermectin, TTO, permethrin, IPL, and baby shampoo had achieved a nearly 100% decrease. The reported adverse events were mostly mild, without severe adverse events reported in any of the studies. CONCLUSIONS: We found ivermectin (topical and systemic), ivermectin-metronidazole (topical), and TTO (topical) are promising anti-Demodex interventions. In addition to traditional pharmacotherapy, light therapies, especially IPL and skin cleansing, could also be considered as effective methods to control Demodex mite infestation.

Kenntnisse bayerischer Schüler zu sexuell übertragbaren Infektionen: eine Querschnittsstudie.

HINTERGRUND UND ZIELE: Trotz zahlreicher Informationsquellen und Kampagnen zu sexuell übertragbaren Infektionen (STI) haben diese Krankheiten in Deutschland in den letzten Jahren zugenommen. Ziel war es, das Bewusstsein und den Wissensstand junger Schüler in Bayern zu sexuell übertragbaren Krankheiten (STI) mit Schwerpunkt auf humane Papillomaviren (HPV) zu bewerten. METHODEN: In einer vollständig irreversibel anonymisierten Querschnittsstudie wurden insgesamt 4100 bayerische Schüler im Alter zwischen 12 und 17 Jahren anhand eines Multiple-Choice-Fragebogens hierzu befragt. ERGEBNISSE: Insgesamt wurden 3834 Fragebögen in die Datenanalyse einbezogen. Interessanterweise ist der Bekanntheitsgrad von HPV im Vergleich zu anderen STI bemerkenswert geringer. Mädchen und Jugendliche, die bereits vorbeugende Jugendgesundheitsuntersuchungen absolviert hatten, zeigten im Durchschnitt ein größeres Wissen über STI. Darüber hinaus konnten wir zeigen, dass Jugendliche mit geringerem Bildungsniveau, wie Realschüler, über die geringsten Kenntnisse verfügten. SCHLUSSFOLGERUNGEN: Die Querschnittsstudie zeigt, dass viele junge Menschen noch unzureichend über STI informiert sind. Die Informationslücken unterstreichen die Notwendigkeit einer intensiven und langfristigen Aufklärungsarbeit.

3D-Druck- und Silikonmodelle der Primäreffloreszenzen für die dermatologische Lehre im Fernstudium.

Hintergrund und Ziele: Die Corona-Pandemie betrifft eine Fülle von verschiedenen Lebensaspekten - Herausforderungen in der medizinischen Behandlung sind hier unzweifelhaft von höchster Wichtigkeit. Allerdings muss auch, um die Ausbildung von Studierenden zu gewährleisten, fortlaufende medizinische Lehre stattfinden. Während eines Semesters mit Lockdown-Phasen und eingeschränktem Patientenkontakt für die Studierenden schickten wir jedem Studierenden ein Silikonmodell zu und baten um die Evaluation dieses Lernwerkzeugs. Methoden: Mittels zweier vollständig und irreversibel anonymisierter Online-Fragebögen befragten wir Studierende des Dermatologie-Semesters (n  =  222) an der Medizinischen Fakultät der Ludwig-Maximilians-Universität in München im Wintersemester 2020/2021 - anschließend an Online-Lehre - zu ihrem Verständnis und der Eigeneinschätzung zu Primäreffloreszenzen vor und nach Erhalt der Silikonübungsmodelle. Diese wurden durch Schichtung verschiedener Silikontypen in negative 3D-Polylactid-Formen hergestellt, um bestimmte Festigkeiten und Farben darzustellen. Ergebnisse: Insgesamt wurden Fragebögen von 211 (95,0 %) und 213 (95,9 %) der 222 Studierenden analysiert, jeweils vor und nach dem Erhalt der Silikonmodelle. Die Studierenden gaben eine statistisch signifikante Zunahme ihrer Fähigkeiten an (P < 0,001). Ein Großteil der Studierenden evaluierte die Silikonmodelle positiv und berichtete von einem besseren Verständnis und Lernen der Primäreffloreszenzen. Schlussfolgerungen: Diese Lehrstudie zeigt die Vorzüge der haptischen Erfahrung in der dermatologischen Lehre auf - nicht nur in Zeiten von COVID-19, sondern auch danach.

Evaluation of the knowledge of students concerning sexually transmitted infections in Bavaria/Germany (a cross-sectional study).

BACKGROUND AND OBJECTIVES: Despite numerous information sources and campaigns on sexually transmitted infections (STIs), there has been an increase in STIs in Germany in recent years. The aim was to evaluate the awareness and knowledge level among young students in Bavaria/Germany for STIs with a focus on human papilloma viruses (HPV). METHODS: In a cross-sectional survey rendered completely and irreversibly anonymous, a total of 4,100 students from Bavaria between the ages of 12 and 17 were interviewed using a multiple choice questionnaire about their knowledge and awareness of STI, on the basis of gender, school education and preventive youth health examinations that had taken place. RESULTS: A total of 3,834 questionnaires were included in the data analysis. Interestingly, the awareness level for HPV is remarkably lower compared to other STIs. Girls and adolescents who had already taken preventive youth health examinations showed a higher knowledge of STIs on average. Additionally, we could show that adolescents of lower educational levels, such as secondary school students, had the least knowledge. CONCLUSIONS: The cross-sectional study shows that many young people are still insufficiently informed about STIs. The gaps in information and lack of knowledge underline the necessity of intensive and long-term educational work.

3D printing and silicone models of primary skin lesions for dermatological education as remote learning tool.

BACKGROUND AND OBJECTIVES: The corona pandemic affects many aspects of life - with challenges in medical treatment undoubtedly of paramount importance. However, continuing medical education needs to be consistently provided. During a semester with lockdown-phases and limited student-to-patient-contact availability, we supplied silicone models of primary skin lesions to every student and asked them to evaluate this teaching tool. METHODS: In two anonymous online surveys, we asked students enrolled in dermatology (n = 222) at the Medical Facility of the Ludwig Maximilian University of Munich in the winter semester 2020/2021 - subsequent to online teaching - about their understanding and self-assessment of primary skin lesions before and after receiving silicone models for practice. The models were produced by layering different types of silicone into negative 3D printed molds made from polylactide to attain different degrees of hardness and colors. RESULTS: Data from 211 (95.0 %) and 213 (95.9 %) of the 222 students were analyzed before and after receiving the silicone models, respectively. In all questions the students stated a highly significant improvement in their skills (P < 0.001). The majority of students evaluated the silicone models positively and reported a better understanding and learning of primary skin lesions. CONCLUSIONS: This study demonstrates the benefit of haptic experience in dermatology teaching not only in the time of COVID-19, but also thereafter.

S2k guideline: Rosacea.

This updated and upgraded S2k guideline deals with the diagnosis and treatment of rosacea, which is a common, chronic inflammatory skin disease mostly affecting the face. Initially, rosacea is characterized by recurrent erythema, telangiectasia and flushing. Later, the inflammatory component predominates, with persistent erythema with follicular papules, papulopustules and pustules. The development of phyma, which usually occurs on the acral localizations, is the most severe manifestation. For the treatment of rosacea, the interdisciplinary guideline committee, with representatives of the German Dermatological Society (DDG), the Professional Association of German Dermatologists (BVDD), the German Opthalmological Society (DOG), the Society for Dermopharmacy (GD), the Swiss Society for Dermatology and Venereology (SGDV) and the German Rosacea Aid e. V., recommends the avoidance of trigger factors and topical applications of metronidazole, azelaic acid or ivermectin. For symptomatic treatment of persistent centrofacial erythema, the topical vasoconstrictors brimonidine or oxymetazoline can also be used. Systemic therapy is recommended for therapy-resistant and severe forms of rosacea papulopustulosa. The drug of choice is low-dose doxycycline. Alternatively, low-dose isotretinoin can be recommended. Ocular rosacea should be treated with lid margin hygiene. For topical treatment, ciclosporin eye drops, azithromycin, ivermectin or metronidazole are suggested.

Comparative analysis of the phototoxicity induced by BRAF inhibitors and alleviation through antioxidants.

BACKGROUND: Small molecules tackling mutated BRAF (BRAFi) are an important mainstay of targeted therapy in a variety of cancers including melanoma. Albeit commonly reported as side effect, the phototoxic potential of many BRAFi is poorly characterized. In this study, we evaluated the phototoxicity of 17 distinct agents and investigated whether BRAFi-induced phototoxicity can be alleviated by antioxidants. METHODS: The ultraviolet (UV) light absorbance of 17 BRAFi was determined. Their phototoxic potential was investigated independently with a reactive oxygen species (ROS) and the 3T3 neutral red uptake (NRU) assay in vitro. To test for a possible phototoxicity alleviation by antioxidants, vitamin C, vitamin E phosphate, trolox, and glutathione (GSH) were added to the 3T3 assay of selected inhibitors. RESULTS: The highest cumulative absorbance for both UVA and UVB was detected for vemurafenib. The formation of ROS was more pronounced for all compounds after irradiation with UVA than with UVB. In the 3T3 NRU assay, 8 agents were classified as phototoxic, including vemurafenib, dabrafenib, and encorafenib. There was a significant correlation between the formation of singlet oxygen (P = .026) and superoxide anion (P < .001) and the phototoxicity observed in the 3T3 NRU assay. The phototoxicity of vemurafenib was fully rescued in the 3T3 NRU assay after GSH was added at different concentrations. CONCLUSION: Our study confirms that most of the BRAF inhibitors exhibited a considerable phototoxic potential, predominantly after exposure to UVA. GSH may help treat and prevent the phototoxicity induced by vemurafenib.

Methods for extraction and ex-vivo experimentation with the most complex human commensal, Demodex spp.

Demodex spp. mites are the most complex organisms of the human skin microbiome and were discovered more than 175 years ago, yet only little basic research is published about them. As they can be pathophysiologically relevant ectoparasites associated with rosacea, pityriasis folliculorum, and other inflammatory skin diseases, more research should be encouraged. Being a large microorganism or a tiny animal, there are no established basic methods to handle these mites. Here, we describe techniques enabling the extraction of Demodex mites from human skin, their analysis in different ex-vivo settings, the lysis of their exoskeleton, their preservation by freezing, and observation microscopically using specific fluorescent dyes or their inherent autofluorescence. These procedures should facilitate future Demodex research and fuel further the generation of knowledge. Furthermore it is intended to ultimatively enable the mite's cultivation in vitro and reveal its pathophysiological mechanisms.

Rosacea and perioral dermatitis: a single-center retrospective analysis of the clinical presentation of 1032 patients.

BACKGROUND: Rosacea is a common chronic inflammatory cutaneous disorder affecting nearly 5.5 % of the adult population. Our aim was to evaluate the prevalence and epidemiology of rosacea and perioral dermatitis (POD) in an ambulatory care setting. METHODS: We retrospectively analyzed medical data of patients with a confirmed diagnosis of rosacea or perioral dermatitis (POD) presenting at our university hospital outpatient clinic during a 3-year period. RESULTS: Out of 1032 patients, 81.5 % were diagnosed with rosacea and 18.5 % with POD. Overall prevalence was 1.4 % for rosacea and 0.3 % for POD. 69.3 % of the analyzed patients were female. Overall mean age was 49.3 ± 7.7 (1-92) years; the women's average age was less than the men's. Patients with POD were younger and predominantly female, whereas patients with phymatous rosacea were older and predominantly male. The most common phenotypes were papulopustular rosacea (68.4 %), erythematotelangiectatic rosacea (22.5 %), and phymatous rosacea (8.0 %). Special forms of rosacea were diagnosed in 15.8 % of the patients; the most frequent were ocular rosacea (6.9 %) and steroid-induced rosacea (5.4 %). CONCLUSIONS: The large patient cohort analyzed in our study provides a good estimate of the frequency of the rosacea subtypes, special forms and of perioral dermatitis in a hospital-based outpatient care setting.

Dermocosmetics for Use in Rosacea: Guideline of the Society for Dermopharmacy.

Rosacea is a widespread inflammatory skin disease that is chronically recurrent and affects predominately the central parts of the face. Affected individuals typically react to numerous cosmetics with redness, burning, and/or worsening of the complexion. Consequently, there is a high demand for dermocosmetics that do not provoke such reactions and are suitable for use in rosacea. The present guideline of the Society for Dermopharmacy describes the requirements that dermocosmetics for use in rosacea should meet. They include, inter alia, methods to prove the efficacy of and tolerance to these cosmetics, as well as the product documentation that the manufacturer or the distributing company should make available to professionals, like dermatologists and pharmacists, counseling patients with rosacea.

Characteristics of Gut Microbiota in Rosacea Patients-A Cross-Sectional, Controlled Pilot Study.

BACKGROUND: Recent studies have suggested a possible connection between rosacea and patients' gut microbiota. OBJECTIVE: To investigate the differences in fecal microbial profiles between patients with rosacea and healthy controls. METHODS: Gut microbiota of 54 rosacea patients (RP) were analyzed using MiSeq 16S rRNA sequencing. Enterotypes, the Firmicutes/Bacteroides (F/B) ratio, the significance of alpha and beta diversity, and differential abundance analysis (DAA) were calculated and compared with age- and gender-matched controls (CP, n = 50). RESULTS: Significant changes in the enterotypes and F/B ratio were observed between the RP and CP (p = 0.017 and p = 0.002, respectively). The RP showed a decreased microbial richness and diversity compared to the CP (Shannon p = 0.012, inverse Simpson p = 0.034). Beta diversity also differed between both groups (PERMANOVA, p = 0.006). Fourteen significantly different taxa were detected according to DAA. Faecalibacterium prausnitzii (coef. -0.0800, p = 0.008), Lachnoospiraceae ND 3007 group sp. (coef. -0.073, p < 0.001), and Ruminococcaceae (coef. -0.072, p = 0.015) were significantly decreased; Oscillobacter sp. (coef. 0.023, p = 0.031), Flavonifractor plautii (coef. 0.011, p = 0.037), and Ruminococccaceae UBA 1819 (coef. 0.010, p = 0.031) were significantly increased in the RP compared to the CP. CONCLUSION: Significant alterations in gut microbiota were present in the RP. Taxonomic shifts and reduced richness and diversity were observed when compared to the CP. Larger prospective studies are needed to investigate correlations with clinical features and to translate these findings into future therapeutic approaches.

Relationship between α-genus human papillomavirus and non-genital seborrheic keratosis: Report of new cases and updated review.

BACKGROUND: Seborrheic keratoses (SK) are the most common acquired benign tumor that affects middle-aged or older adults with great cosmetic concern. Clinical and histopathological similarities of SK and common warts have been addressed by investigating the possible presence of human papillomavirus (HPV) DNA in SK. Previous studies suggested the association between α-genus HPV and SK located on genital skin, whereas the causal relationship between α-HPV and non-genital SK remains controversial. AIM: This study aimed to clarify the pathogenic involvement of α-HPV in the development of non-genital SK. METHODS: We analyzed α-HPV DNA prevalence and HPV genotypes using a PCR-based microarray on 51 skin samples presenting with histologically confirmed SK without any malignant changes. Correlation between the histological subtype of SK and their HPV DNA-positive reactivity was also evaluated. RESULTS: Of 51 non-genital SK, two (3.9%) skin samples were positive for α-HPV DNA; high-risk HPV 31 and low-risk HPV 42 were found. Evaluation of HPV prevalence in different histological types of SK showed that both HPV-positive cases were acanthotic type; 14.3% of acanthotic SK lesions were positive, while all of the other types were negative for α-HPV. CONCLUSIONS: This study demonstrates that α-HPV positivity is very rare in common non-genital SK. The rare α-HPV-positive SK lesions histologically belonged to the acanthotic type, implying a potential impact of HPV infection on epidermal hyperproliferation. Although a possible association cannot be excluded, our findings suggest that α-HPV is not a major causative factor for non-genital SK.

Silicone Models for Dermatological Education: Assessment of a New Teaching Tool by Dermatologists.

INTRODUCTION: The coronavirus pandemic forced universities to transfer academic curricula into the digital realm and calls for the introduction of new teaching methods to adequately compensate for the limited in-patient training. Especially in the field of dermatology, the use of 3D models presents an interesting opportunity to maintain the teaching of diagnostically essential sensory and haptic characteristics of primary lesions. OBJECTIVES: We developed a prototype silicone model and presented it to the medical service of the Department of Dermatology of the Ludwig-Maximilians University for evaluation. METHODS: Silicone models demonstrating primary skin lesions were produced by using negative 3D-printed molds and different types of silicone. An online survey obtained evaluations from a group of dermatologists regarding the quality of previously supplied silicone 3D models and their potential use in medical education. Data from 58 dermatologists were collected and analyzed. RESULTS: The majority of the participants rated the models overall as positive and innovative, providing constructive feedback for additional modifications, and recommended further implementation into the regular curriculum as an additional tool after the end of the pandemic. CONCLUSIONS: Our study underlined the possible advantages of using 3D models as a supplement in educational training even after the end of the SARS-CoV-2 pandemic.

Cutaneous T-cell Lymphomas: A Single-center Retrospective Analysis.

INTRODUCTION: Cutaneous T-cell lymphomas (CTCLs) are rare diseases characterized by infiltration of malignant T-cells into the skin. We evaluated the prevalence, epidemiology, and therapy of CTCLs, focusing on its most well-known subtypes, namely mycosis fungoides (MF) and Sézary syndrome (SS). PATIENTS AND METHODS: We retrospectively analyzed the medical data of patients with a histologically confirmed diagnosis of CTCL presenting to our outpatient department during a 5-year period from January 2015 to December 2019. RESULTS: We evaluated the files of 102 patients, of whom 67% were men and 33% women. The overall mean age was 59.1±14.1 (24-86) years. Ninety-two patients (90%) were diagnosed with MF and ten patients (10%) with SS. According to ISCL/EORTC, the majority of patients initially classified as stage IA (34%) and IB (45%). Disease frequency decreased at advanced stages (II: 4%; III: 7%; IV: 10%). Forty-five patients (44.1%) received only skin-directed therapy (SDT). Twenty patients (19.6%) progressed from SDT to systemic therapy (ST). Thirty-seven patients (36.3%) received ST combined with SDT (TS) from the start of treatment. Overall, fifty different therapeutic approaches of TS were initiated due to lack of response to therapy or disease progression. CONCLUSION: Management of CTCLs aims to maintain patient quality of life while minimizing side-effects. As CTCLs are usually incurable diseases, the focus of treatment is on symptom control and prevention of disease progression. Due to the large patient group and the long observation period, our study allows for a valid evaluation of the frequency and therapy of MF and SS in a university outpatient clinic in Germany. We favor topical therapies in early stages with more invasive therapies in advanced stages.

Clinical clues to identify patients with ocular rosacea - a Germany-wide epidemiologic analysis.

BACKGROUND AND OBJECTIVES: Ocular rosacea is a special manifestation of rosacea with unknown etiology. Eye involvement in rosacea patients is surprisingly common; however, it is often underdiagnosed, resulting in inappropriate treatment. We aimed to provide an updated epidemiologic perspective on ocular rosacea in Germany to improve patient care. PATIENTS AND METHODS: Data of 777 rosacea patients were assessed using a detailed online questionnaire regarding ocular and skin symptoms, previous dermatological and ophthalmological consults, presence of type 1 hypersensitivities, and Demodex testing. All data were statistically analyzed. RESULTS: Most patients reported ocular symptoms (399/777, 51.4%), including red eyes (179/399, 44.9%), itching (187/399, 46.9%), sty or chalazion (309/399, 77.4%), and dryness (108/399, 27.1%). Ocular rosacea was confirmed in 149/309 cases who consulted an ophthalmologist (45.3%). A total of 159/399 (39.8%) had no pre-existing allergies. Eye involvement was significantly associated with the presence of skin symptoms (P < 0.05), impacting patients' general well-being and overall treatment satisfaction. About half of Demodex-positive patients (21/45, 46.7%) showed ocular symptoms. CONCLUSIONS: Eye involvement in rosacea patients was common, often presenting with unspecific symptoms.

High-frequency devices effect in vitro: promissing approach in the treatment of acne vulgaris?

BACKGROUND: Acne vulgaris is an inflammatory skin disorder leading to an impairment of quality of life and is therefore not only a cosmetic issue. Its pathogenesis is multifactorial - of particular importance is the colonization with the bacterium Propionibacterium acnes. A wide range of different treatment options exists including topical and systemic treatments depending on severity. High Frequency (HF) therapy, historically developed in the 19th century, claims antimicrobial effects on acne skin, but solid data on its efficacy and mechanism of action is lacking. OBJECTIVES: The main objective of this study was to determine the efficacy of HF therapy on skin flora and P. acnes in vitro using a commercial device as well as to review studies on the mechanism of action. METHODS: The plasma source was investigated regarding electrical settings, heat, and ozone development. Bacterial skin flora, fungal isolates, and P. acnes were exposed to HF in vitro and compared to unexposed controls by evaluating the number of colonies on agar plates. To further analyze bacterial species from normal skin flora, 16S-sequencing was performed. Statistical analyses were carried out using row analysis and unpaired t-test. RESULTS: HF treatment led to a significant reduction of almost every bacterial and fungal species investigated in this study. Moreover, the number of colonies forming units was significantly decreased in P. acnes after HF treatment compared to controls in vitro. STUDY LIMITATIONS: The experiments were performed in vitro only. To assess clinical effects further in vivo experiments are necessary. CONCLUSIONS: The results collected in this study, although in vitro, provide a mechanistic basis for HF as a complementary treatment option for patients with acne. It might also have a beneficial effect on patients with superficial infectious skin of the skin.