Natalie Garcia Bartels’s research while affiliated with Charité Universitätsmedizin Berlin and other places

Importance: Uncombable hair syndrome (UHS) is a rare hair shaft anomaly that manifests during infancy and is characterized by dry, frizzy, and wiry hair that cannot be combed flat. Only about 100 known cases have been reported so far. Objective: To elucidate the genetic spectrum of UHS. Design, setting, and participants: This cohort study includes 107 unrelated index patients with a suspected diagnosis of UHS and family members who were recruited worldwide from January 2013 to December 2021. Participants of all ages, races, and ethnicities were recruited at referral centers or were enrolled on their own initiative following personal contact with the authors. Genetic analyses were conducted in Germany from January 2014 to December 2021. Main outcomes and measures: Clinical photographs, Sanger or whole-exome sequencing and array-based genotyping of DNA extracted from blood or saliva samples, and 3-dimensional protein modeling. Descriptive statistics, such as frequency counts, were used to describe the distribution of identified pathogenic variants and genotypes. Results: The genetic characteristics of patients with UHS were established in 80 of 107 (74.8%) index patients (82 [76.6%] female) who carried biallelic pathogenic variants in PADI3, TGM3, or TCHH (ie, genes that encode functionally related hair shaft proteins). Molecular genetic findings from 11 of these 80 individuals were previously published. In 76 (71.0%) individuals, the UHS phenotype were associated with pathogenic variants in PADI3. The 2 most commonly observed PADI3 variants account for 73 (48.0%) and 57 (37.5%) of the 152 variant PADI3 alleles in total, respectively. Two individuals carried pathogenic variants in TGM3, and 2 others carried pathogenic variants in TCHH. Haplotype analyses suggested a founder effect for the 4 most commonly observed pathogenic variants in the PADI3 gene. Conclusions and relevance: This cohort study extends and gives an overview of the genetic variant spectrum of UHS based on molecular genetic analyses of the largest worldwide collective of affected individuals, to our knowledge. Formerly, a diagnosis of UHS could only be made by physical examination of the patient and confirmed by microscopical examination of the hair shaft. The discovery of pathogenic variants in PADI3, TCHH, and TGM3 may open a new avenue for clinicians and affected individuals by introducing molecular diagnostics for UHS.

Background: Dry skin and the associated impaired epidermal barrier function are postulated to constitute a major element in the development of atopic dermatitis. Objective: The aim of this study was to evaluate the effect of two plant-based formulations on the epidermal barrier function in a defined cohort of infants with a predisposition for atopic dermatitis. Methods: Over a period of 16 weeks, 25 infants who were ages 3 to 12 months and had an atopic predisposition and dry skin received two emollients that contained pressed juice of the ice plant. The infants received both cream and lotion on the forearm, only cream on the face, and only lotion on the leg. Stratum corneum hydration (SCH), transepidermal water loss (TEWL), skin surface pH, and sebum were assessed on the infants’ forehead, leg, and forearm. The Scoring Atopic Dermatitis (SCORAD) index was used for the clinical assessment. Results: SCH significantly increased in all body regions that were assessed. The forearm and leg revealed stable levels of pH and TEWL, but a decline in pH (week 16) and TEWL (week 4) was noted on the forehead. At week 16, sebum levels were lower on the forehead compared with those at baseline. SCORAD scores improved significantly during the study. Conclusion: A daily application of both emollients was associated with increased SCH levels and a stable course of TEWL, pH, and sebum on the forehead except for the forehead when compared with the forearm and leg. Clinically, improved SCORAD scores were noted.

Alopecia areata (AA) is one of the most common forms of human hair loss. Although genetic studies have implicated autoimmune processes in AA etiology, understanding of the etiopathogenesis is incomplete. Recent research has implicated microRNAs, a class of small noncoding RNAs, in diverse autoimmune diseases. To our knowledge, no study has investigated the role of microRNAs in AA. In this study, gene-based analyses were performed for microRNAs using data of the largest genome-wide association meta-analysis of AA to date. Nominally, significant P-values were obtained for 78 of the 617 investigated microRNAs. After correction for multiple testing, three of the 78 microRNAs remained significant. Of these, miR-30b/d was the most significant microRNA for the follow-up analyses, which also showed lower expression in the hair follicle of AA patients. Target gene analyses for the three microRNAs showed 42 significantly associated target genes. These included IL2RA, TNXB, and ERBB3, which had been identified as susceptibility loci in previous genome-wide association studies. Using luciferase assay, site-specific miR-30b regulation of the AA risk genes IL2RA, STX17, and TNXB was validated. This study implicates microRNAs in the pathogenesis of AA. This finding may facilitate the development of future treatment strategies.

Objectives The aim of this study was to measure the prevalence of skin diseases in aged nursing home residents and to explore possible associations with demographic and medical characteristics. Design Descriptive multicentre prevalence study. Setting and participants The study was conducted in a random sample of ten institutional long-term care facilities in the federal state of Berlin, Germany. In total, n=223 residents were included. Results In total, 60 dermatological diseases were diagnosed. The most frequently diagnosed skin disease was xerosis cutis (99.1%, 95% CI 97.7% to 100.0%) followed by tinea ungium (62.3%, 95% CI 56.0% to 69.1%) and seborrheic keratosis (56.5%, 95% CI 50.2% to 63.0%). Only few bivariate associations have been detected between skin diseases and demographic and medical characteristics. Conclusion Study results indicate that almost every resident living in residential care has at least one dermatological diagnosis. Dermatological findings range from highly prevalent xerosis and cutaneous infection up to skin cancer. Not all conditions require immediate dermatological treatment and can be managed by targeted skin care interventions. Caregivers need knowledge and diagnostic skills to make appropriate clinical decisions. It is unlikely that specialised dermatological care will be delivered widely in the growing long-term care sector. Trial registration number This study is registered at https://clinicaltrials.gov/ct2/show/NCT02216526.

is missing (Short communication).

Background: Aged residents of institutional long-term care facilities are at high risk for developing skin and tissue diseases. Besides various common skin problems, dry skin (xerosis cutis) is one of the most frequent skin conditions in this setting. Objectives: To investigate the effectiveness of two structured skin care regimens in comparison to routine skin care on xerosis cutis in nursing home residents. Design: A multi-center, pragmatic, randomized, controlled, investigator blinded study with three parallel groups. Settings: The study was conducted in a random sample of ten out of 291 institutional long-term care facilities of the federal state of Berlin, Germany. Participants: Long-term care residents being 65+ years affected by dry skin were included. Methods: The residents were allocated into one of three study groups. Two interventional groups used standardized skin care regimens, consisting of a body wash and twice daily applications of leave-on products for eight weeks. The third control group performed skin care as usual. All participating residents were examined at baseline and after 4 and 8 weeks. Xerosis cutis was measured with the Overall Dry Skin score. Instrumental skin barrier measurements were performed at baseline and after 8 weeks. Diaries were used to document washing and skin care frequencies. Results: In total, 133 residents were included and allocated to one of the three groups. Mean age was 83.8 (SD 8.3) years, 65.4% were female and most residents had care levels I (42.9%) or II (42.9%) according to the German Social Code Book XI. Mean Barthel score was 46.8 (SD 24.2) and mean Braden score was 17.6 (SD 3.7). Leg skin areas were drier compared to arms and trunk areas. At the end of the study the Overall Dry Skin scores in the intervention groups were lower compared to the control group. There were statistically significant improvements of skin dryness in both intervention groups compared to the control group over time. Conclusions: The results of this pragmatic trial indicate that structured skin care regimens are effective in reducing skin dryness in aged nursing home residents within eight weeks. Trial registration: The study is registered at https://clinicaltrials.gov/ct2/show/NCT02216526.