a multicentre prevalence study

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

their role in diagnostics and therapy

Um die Vergleichbarkeit für zukünftige Studien zu gewährleisten, eröffnet sich durch die neue Modelle und Methoden ein breites Spektrum zur gezielten Bestimmung trichologischer Parameter. Dies wird in den aktuellen Studien durch die praktische Anwendung verdeutlicht. Die Methoden eignen sich, um gezielt die verschiedenen trichologischen Parameter nicht nur in kleinen Kollektiven sondern auch in großen, multizentrischen Studien zu untersuchen. Die Untersuchung der Wirkweise von Substanzen auf das Haarwachstum setzt die Kenntnis der verschiedenen Methoden und deren Zielparameter voraus. Wichtig ist es gerade bei langfristigen Studien, welche beim Wirkungsnachweis in der Trichologie aufgrund des langsamen Haarzyklus sinnvoll sind, einfach und gut reproduzierbare Methoden anzuwenden. Diese sollten, je nach Fragestellung, die Unterscheidung von Vellus- und Terminalhaaren, von Anagen- und Telogenhaaren sowie die Berechnung der Haardichte zulassen. Hierfür bieten sich die TrichoScan- und die Hair Metrix-Methode in vergleichbarer Weise an. Daneben sollten zusätzlich standardisierte, makroskopische Beurteilungen des Haarvolumens und der Haarfarbe erfolgen, um die gemessenen Parameter in Relation zum sichtbaren Effekt setzen zu können. Zusätzlich spielt die Patientenzufriedenheit gerade in Behandlung von Haarerkrankungen eine wichtige Rolle, da ein längerfristiges Effluvium und die daraus resultierende Alopezie bei den Betroffenen häufig zu großem Leidensdruck und deutlichen psychosozialen Konflikten führen. Daher erscheint es sinnvoll, neben der Beurteilung durch den Untersucher auch die Bewertung des Probanden in die Methodik einzubinden. Für die Generierung von neuen Substanzen zur Behandlung von Haarerkrankungen ist es sinnvoll, diese zunächst an kleinen Kollektiven zu untersuchen. Hierfür eignet sich die erstmalig, an der behaarten Kopfhaut, vorgestellte Minizonen-Technik, welche die Ermittlung von trichologischen Parametern unter Anwendung von Verum und Placebo an einem Probanden ermöglicht. Auf diese Weise erscheint die intraindividuelle Testung von Kandidatenmolekülen in der Therapie von Haarerkrankungen zukünftig besser möglich. Gerade für die Ermittlung von trichologischen Daten auf einer kleinen Fläche und an einem kleinen Probandenkollektiv ist die Auswahl einer Messmethode wichtig, welche wie die TrichoScan- oder Hair Metrix-Methode reproduzierbare Ergebnisse liefern, um möglichst exakt die notwendigen Ziel- Parameter zu ermitteln. Ein weiterer Vorteil der in den Studien verwendeten Modelle ist, dass die Methoden zur Ermittlung der Vielzahl an trichologischen Parameter nicht-invasiv sind. Dies ist nicht nur wichtig für die Compliance der Probanden sondern implementiert auch ihre zukünftige, routinemäßige Anwendung in der Diagnostik und der Kontrolle des Therapieverlaufs während der ambulanten Behandlung in standardisiert festgelegten, vergleichbaren Untersuchungsarealen.In order to enable the comparability of future studies, new trichologic methods and models open a wide array for a targeted determination of trichologic parameters. These methods are suitable for specifically examining the various trichologic parameters, not only in small collectives but also in large multicentric studies. This methodology should facilitate the differentiation of vellus and terminal hairs, of anagen and telogen hairs as well as the determination of the hair density. For this purpose, TrichoScan®- and Hair Metrix™-Method present themselves as likewise applicable. In parallel standardized macroscopic evaluations of the hair volume and hair color should additionally be applied in order to be able to set the measured parameters in relation to the visible effects. Furthermore, as a long-term effluvium leading to alopecia frequently results in great suffering and clear psychosocial conflicts of the afflicted person, patient satisfaction plays an important role. It seems therefore sensible to not only include the evaluation by the examining physician, but also the subject’s estimate into the method. For the development of new agents, the minizone-method has proven to be suitable. It allows the determination of trichologic parameters by means of using verum and placebo on the same subject. The intra-individual testing of candidate molecules in the future treatment of hair disorders seems to yield better results with this method. The selection of the measuring method is especially important for the collection of trichologic data from a small area and a small collective of subjects. Methods such as TrichoScan® and Hair Metrix™ provide reproducible results and allow detecting the necessary target parameters of ultimate accuracy

Genome-Wide MicroRNA Analysis Implicates miR-30b/d in the Etiology of Alopecia Areata

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 strategie

Assessment of the Genetic Spectrum of Uncombable Hair Syndrome in a Cohort of 107 Individuals

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

Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome

International audienceUncombable hair syndrome (UHS), also known as “spun glass hair syndrome,” “pili trianguli et canaliculi,” or “cheveux incoiffables” is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and familial UHS-affected case subjects with autosomal-dominant as well as -recessive inheritance have been reported. However, none of these case subjects were linked to a molecular genetic cause. Here, we report the identification of UHS-causative mutations located in the three genes PADI3 (peptidylarginine deiminase 3), TGM3 (transglutaminase 3), and TCHH (trichohyalin) in a total of 11 children. All of these individuals carry homozygous or compound heterozygous mutations in one of these three genes, indicating an autosomal-recessive inheritance pattern in the majority of UHS case subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational protein modifications, and their target structural protein TCHH are all involved in hair shaft formation. Elucidation of the molecular outcomes of the disease-causing mutations by cell culture experiments and tridimensional protein models demonstrated clear differences in the structural organization and activity of mutant and wild-type proteins. Scanning electron microscopy observations revealed morphological alterations in hair coat of Padi3 knockout mice. All together, these findings elucidate the molecular genetic causes of UHS and shed light on its pathophysiology and hair physiology in general