Epidermolytic ichthyosis: Clinical spectrum and burden of disease in a large German cohort.

BACKGROUND: Keratinopathic ichthyoses are a group of hereditary skin disorders caused by pathogenic variants in keratin genes such as KRT1, KRT2 and KRT10, resulting in conditions such as epidermolytic ichthyosis (EI), autosomal-recessive EI, superficial EI and epidermal nevus. Case reports highlight the diversity of clinical manifestations, but only limited information exists regarding the quality of life and burden of disease. OBJECTIVES: The objective of this study was to assess the clinical spectrum, genotype-phenotype correlations and burden of disease in patients with epidermolytic ichthyosis in Germany. METHODS: We conducted an observational study involving 48 patients diagnosed with EI. Evaluations included the severity of skin involvement using the Investigator's Global Assessment (IGA), the modified Ichthyosis Area Severity Index (mIASI) and complications. The burden of disease was evaluated using the Dermatology Life Quality Index (DLQI) or the Children's Dermatology Life Quality Index (cDLQI). RESULTS: Based on clinical features, mIASI and IGA, EI can be categorized into localized, intermediate and severe forms. Patients with keratin 1 mutations tended to have severe EI, while the three forms were evenly distributed in those with keratin 10 mutations. The study highlights that around half of the patients with EI experienced itch and severe pain. Quality of life was affected, with daily life restrictions of 78% due to care and therapies. Reimbursement for moisturizing ointments by health insurance was insufficient for one-quarter of cases. CONCLUSIONS: The results emphasize the need for targeted interventions and comprehensive care strategies to enhance the quality of life for affected individuals.

Short anagen hair syndrome: association with mono- and biallelic variants in WNT10A and a genetic overlap with male pattern hair loss.

BACKGROUND: Short anagen hair (SAH) is a rare paediatric hair disorder characterized by a short anagen phase, an inability to grow long scalp hair and a negative psychological impact. The genetic basis of SAH is currently unknown. OBJECTIVES: To perform molecular genetic investigations in 48 individuals with a clinical phenotype suggestive of SAH to identify, if any, the genetic basis of this condition. METHODS: Exome sequencing was performed in 27 patients diagnosed with SAH or with a complaint of short, nongrowing hair. The cohort was screened for variants with a minor allele frequency (MAF) < 5% in the general population and a Combined Annotation Dependent Depletion (CADD) score > 15, to identify genes whose variants were enriched in this cohort. Sanger sequencing was used for variant validation and screening of 21 additional individuals with the same clinical diagnosis and their relatives. Genetic association testing of SAH-related variants for male pattern hair loss (MPHL) was performed using UK Biobank data. RESULTS: Analyses revealed that 20 individuals (42%) carried mono- or biallelic pathogenic variants in WNT10A. Rare WNT10A variants are associated with a phenotypic spectrum ranging from no clinical signs to severe ectodermal dysplasia. A significant association was found between WNT10A and SAH, and this was mostly observed in individuals with light-coloured hair and regression of the frontoparietal hairline. Notably, the most frequent variant in the cohort [c.682T>A;p.(Phe228Ile)] was in linkage disequilibrium with four common WNT10A variants, all of which have a known association with MPHL. Using UK Biobank data, our analyses showed that c.682T>A;p.(Phe228Ile) and one other variant identified in the SAH cohort are also associated with MPHL, and partially explain the known associations between WNT10A and MPHL. CONCLUSIONS: Our results suggest that WNT10A is associated with SAH and that SAH has a genetic overlap with the common phenotype MPHL. The presumed shared biologic effect of WNT10A variants in SAH and MPHL is a shortening of the anagen phase. Other factors, such as modifier genes and sex, may also play a role in the clinical manifestation of hair phenotypes associated with the WNT10A locus.

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.

Acral lamellar ichthyosis with amino acid substitution in the C-terminus of keratin 2.

BACKGROUND: Most cases of hereditary ichthyoses present with generalized scaling and skin dryness. However, in some cases skin involvement is restricted to particular body regions as in acral lamellar ichthyosis. OBJECTIVES: We report on the genetic basis of acral ichthyosis in two families presenting with a similar phenotype. METHODS: Genetic testing was performed by targeted next generation sequencing and whole-exome sequencing. For identity-by-descent analysis, the parents were genotyped and data analysis was performed with the Chromosome Analysis Suite Software. RT-PCR with RNA extracted from skin samples was used to analyse the effect of variants on splicing. RESULTS: Genetic testing identified a few heterozygous variants, but only the variant in KRT2 c.1912 T > C, p.Phe638Leu segregated with the disease and remained the strongest candidate. Pairwise identity-by-descent analysis revealed no indication of family relationship. Phenylalanine 638 is the second last amino acid upstream of the termination codon in the tail of K2, and substitution to leucine is predicted as probably damaging. Assessment of the variant is difficult, in part due to the lack of crystal structures of this region. CONCLUSIONS: Altogether, we show that a type of autosomal dominant acral ichthyosis is most probably caused by an amino acid substitution in the C-terminus of keratin 2.

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

Abstract 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. Objective: 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.

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.

Impact of allergic reactions and urticaria on mental health and quality of life.

BACKGROUND: Allergic diseases represent a major global health issue with more than one-third of the global population affected by at least one allergic condition. Allergic conditions can not only cause life-threatening anaphylactic reactions but also impact daily life with a significant influence on mental health and the quality of life (QoL). OBJECTIVES: This study aims to evaluate the health-related QoL and depression severity among patients presenting in a tertiary care allergy center. METHODS: A cross-sectional study was conducted among 596 patients presenting with allergic symptoms or previously diagnosed allergies between October 2018 and April 2019.Patients were screened for depression and the QoL impairment by using three validated scales: the Beck Depression Inventory (BDI), the Dermatologic Life Quality Index (DLQI), and the three-level version of the EuroQol 5-Dimensional (EQ-5D-3L) scale. RESULTS: One-third (34.8%) of the study population was male and two-thirds (65.2%) were female. About 73.7% (n = 427/579) of the patients suffered from at least one previously diagnosed allergic disease, most frequently to pollen (37.0%, n = 214/579) and food (27.3%, n = 158/579), and 20.0 % (n = 116/579) suffered from urticaria. About 19.3% of the total population suffered from depression. Urticaria, as well as insect venom, food/food additives, and drug allergies significantly affected the QoL and depression severity (p < 0.001), reflected by higher DLQI and BDI scores, and lower scores in the EQ5D-3L index. CONCLUSION: Our results provide evidence for a possible correlation of allergies (e.g. against insect venom, food/food additives, and drugs) and/or urticaria with a reduced QoL and a higher depression rate. Patients particularly indicated restrictions for the dimensions, pain/discomfort as well as anxiety/depression. It might be beneficial to implement a standardized questionnaire as a regular screening method for evaluating the mental health status of patients with allergies and/or urticaria.

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.

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.

Alitretinoin in the treatment of cutaneous T-cell lymphoma.

INTRODUCTION: In this survey, we analyzed data from patients suffering from the most common cutaneous T-cell lymphomas (CTCLs) subtypes mycosis fungoides (MF) and Sézary syndrome (SS), treated with the retinoid alitretinoin during a 7-year period at our outpatient department between 2015 and 2020. MATERIALS AND METHODS: We analyzed patient medical records including TNMB stage, side effects under therapy with alitretinoin, time to next treatment (TTNT), and previous photo documentation. RESULTS: A total of 35 patients with MF (n = 28) and SS (n = 7) were included in the study, of whom 69% were male and 31% were female. The mean age of onset was 56 ± 15 years in MF and 65.4 ± 10.8 years in SS with 51.4% having early stage (IA-IIA) and 48.6% having advanced stage (IIB-IVA) CTCL. Of these patients 37.2% responded to alitretinoin, 28.6% had a stable course, and 34.3% experienced progression. Alitretinoin was administered as a monotherapy (25.7%) or combined with five concomitant therapies (74.2%), most frequently with ECP (31.4%) and PUVA (11.4%). 63% did not report any side effects, most often hypertriglyceridemia (20%) was described. CONCLUSION: Considering that nearly two thirds of the CTCL patients treated with alitretinoin showed a response or stable disease, together with a low number of side effects and low cost compared to bexarotene, alitretinoin may be a potential alternative in the treatment of less advanced CTCLs. This survey represents the largest number of recorded therapies with the retinoid alitretinoin in CTCLs in a European patient collective.

Teledermatology in times of COVID-19.

Remote consultations are likely to grow in importance in the following years, especially if the coronavirus disease 2019 (COVID-19) pandemic continues. Patients' opinions on teledermatology have already been analyzed, but a current analysis during the COVID-19 pandemic is lacking. The purpose of this survey was to investigate the satisfaction of patients who had received dermatological advice via telephone during the COVID-19 pandemic and to analyze their general opinion about eHealth as well as possible limitations for a broad implementation. Ninety-one patients managed in the dermatology department using telephone consultation during the COVID-19 pandemic were interviewed. An anonymous questionnaire, including the established quality of life questionnaire (Dermatology Life Quality Index [DLQI]), was used. It was found that men were more satisfied with telephone consultations than women (p = 0.029), educational level and age did not correlate with satisfaction (p = 0.186 and 388, respectively), and the longer the waiting time for a telephone consultation, the lower the satisfaction (p = 0.001). Grouped analysis of all participants showed that the majority (54.0% n = 38/71) were "very happy" with the telephone consultation. Higher disease burden (DLQI) was associated with lower satisfaction (p = 0.042). The main stated reasons for using telemedicine were shorter waiting times (51.6% n = 47/91) and no travel requirement (57.1% n = 47/91). Almost one-quarter (23.1% n = 21/89) of patients would use teledermatology in the future, 17.6% (n = 16/89) would not, and 57.1% (n = 51/89) would only use it in addition to a traditional consultation with personal contact. In conclusion, most patients in the study group still preferred traditional face-to-face medical consultations to telephone consultations, but also desired an add-on telemedical tool. Dermatological care using more modern telemedicine technologies than telephone conferencing is needed to better address patients' desires, especially in times of the COVID-19 pandemic.