Androgenetic Alopecia: A Review.

This study reviewed the current knowledge on the epidemiology, pathophysiology, clinical presentations, diagnosis, treatment, quality-of-life assessment and recent trends in androgenetic alopecia (AGA). Relevant articles on AGA from PubMed, Google Scholar, Medline and Scopus from 1950 to 2024 were obtained and scrutinized.. Key search words included each term like 'androgenetic alopecia', 'androgenic alopecia', 'pattern baldness' and 'pattern hair loss' AND each term like 'epidemiology', 'pathophysiology', 'genetics', 'hormones', 'micronutrient', 'stress and inflammation', 'growth factors', 'clinical features', 'staging', 'cardiovascular associations', 'diagnosis' and 'management' were used in the search. AGA is a non-scarring hair loss that is exemplified by a progressive decline of hair follicles, or non-functional or dead hair follicles in the scalp in a defined pattern. It is the most common hair loss, more common in men but can also present in younger age as premature AGA. Hormones, genetics, micronutrient deficiency, microinflammation and stress have been implicated, while psychosocial distress and cutaneous correlate of cardiovascular diseases have become sources of relentless research. AGA is a patterned hair loss that is more prevalent in Men. It results from the interactions between hormonal, genetic and other factors which determine the extent of hair loss and associated disorders (psychosocial and cardiovascular). As results of more research become available, the extent of AGA, its comorbidities as well as the full spectrum of their manifestations will continue to be sources of health education and more holistic examination by dermatologists and patients.

Novel splicing-site mutation in DCAF17 gene causing Woodhouse-Sakati syndrome in a large consanguineous family.

BACKGROUND: Woodhouse-Sakati syndrome is a rare autosomal recessive disease with endocrine and neuroectodermal aberrations with heterogeneous phenotypes and disease course. The most common phenotypes of the disease are progressive sensorineural hearing loss and alopecia, mild-to-moderate mental retardation and hypogonadism. The disease results from mutations in the DCAF17 gene. METHOD: Here, we reported a large consanguineous pedigree with multiple affected individuals with Woodhouse-Sakati syndrome phenotypes. Laboratory tests confirmed the endocrine perturbance in affected individuals. To find out the underlying genetic change, whole-exome sequencing was carried out. RESULT: Analysis of the exome data identified a splicing-site deletion NM_025000.3:c.1423-1_1425delGACA in DCAF17 gene. Sanger sequencing confirmed the co-segregation of the variant with the disease phenotypes in the family. CONCLUSION: The variant is predicted to cause aberrant splicing, i.e., exon skipping, resulting in the translation of a truncated functionless protein which results in appearance of typical phenotypic features and clinical laboratory findings of Woodhouse-Sakati syndrome in affected members of the family.

Perspectives on miRNAs Targeting DKK1 for Developing Hair Regeneration Therapy.

Androgenetic alopecia (AGA) remains an unsolved problem for the well-being of humankind, although multiple important involvements in hair growth have been discovered. Up until now, there is no ideal therapy in clinical practice in terms of efficacy and safety. Ultimately, there is a strong need for developing a feasible remedy for preventing and treating AGA. The Wnt/ß-catenin signaling pathway is critical in hair restoration. Thus, AGA treatment via modulating this pathway is rational, although challenging. Dickkopf-related protein 1 (DKK1) is distinctly identified as an inhibitor of canonical Wnt/ß-catenin signaling. Thus, in order to stimulate the Wnt/ß-catenin signaling pathway, inhibition of DKK1 is greatly demanding. Studying DKK1-targeting microRNAs (miRNAs) involved in the Wnt/ß-catenin signaling pathway may lay the groundwork for the promotion of hair growth. Bearing in mind that DKK1 inhibition in the balding scalp of AGA certainly makes sense, this review sheds light on the perspectives of miRNA-mediated hair growth for treating AGA via regulating DKK1 and, eventually, modulating Wnt/ß-catenin signaling. Consequently, certain miRNAs regulating the Wnt/ß-catenin signaling pathway via DKK1 inhibition might represent attractive candidates for further studies focusing on promoting hair growth and AGA therapy.

Oxidative stress and its impact on skin, scalp and hair.

Oxidative stress is an unbalanced condition in which the tissues of the body are not sufficiently able to counteract either exogenous or endogenous sources of reactive oxygen species. Oxidative stress is strongly associated with ageing, both local and systemic, as well as a wide range of local health conditions. This review focuses on the oxidative stress data known for skin, scalp and hair. This oxidative stress may be the 'currency' by which an unhealthy scalp leads to deleterious consequences to the hair. The ramifications of this scalp oxidative stress to normal hair elongation, retention and replacement are discussed.

Le stress oxydatif est une condition déséquilibrée dans laquelle les tissus du corps ne sont pas suffisamment capables de contrer la source exogène ou endogène d'espèces réactives de l'oxygène. Le stress oxydatif est fortement associé au vieillissement, à la fois local et systémique, ainsi qu'à un large éventail de problèmes de santé locaux. Cette revue se concentre sur les données de stress oxydatif connues pour la peau, le cuir chevelu et les cheveux. Ce stress oxydatif peut être la « devise ¼ par laquelle un cuir chevelu malsain entraîne des conséquences délétères pour les cheveux. Les ramifications de ce stress oxydatif du cuir chevelu sur l'allongement, la rétention et le remplacement normaux des cheveux sont discutées.

Systemic Sarcoidosis with Psoriasiform Plaques and Patchy Nonscarring Alopecia.

ABSTRACT: Cutaneous sarcoidosis occurs in about one-quarter of patients with systemic disease and presents with either specific or nonspecific signs. Psoriasiform sarcoidosis is an uncommon presentation. Herein, study authors report a rare case of systemic sarcoidosis that presented with psoriasiform plaques and patchy alopecia. The main patient complaint was disfigurement from skin lesions over different areas of his body, followed by scalp alopecia and uveitis. These lesions were well-defined plaques, some oozing and others scaly. Dermoscopic examination revealed yellow-orange globular structure. A biopsy was taken; the eventual diagnosis was sarcoidosis, for which the patient received treatment with systemic steroids, resulting in improvement of all of his lesions. Physicians should suspect sarcoidosis in any patient presenting with psoriasiform skin lesions not responding to traditional psoriasis treatment.

Trichoscopic Findings in Androgenetic Alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is an androgen-related condition that develops in genetically predisposed individuals. The condition is characterized by the progressive loss of terminal hairs on the scalp in a characteristic distribution. Trichoscopy represents the dermoscopy imaging of the scalp and hair. Structures which may be visualized by trichoscopy include hair shafts, hair follicle openings, perifollicular epidermis and cutaneous microvessels. OBJECTIVE: The aim of this prospective study was to identify the trichoscopic features of androgenetic alopecia. METHODS: Hundred-four patients with AGA and 80 healthy subjects were enrolled in this study. Data on age, gender, personal and family history, clinical type and duration of disease were collected and analyzed. Control group consisted of 80 generally healthy subjects. Trichoscopic examination was performed using either videodermatoscope or handheld dermatoskope. Trichoscopy results were obtained in frontal, occipital and both temporal areas of the scalp, including number of yellow dots and vellus hairs, number of hairs in one pilosebaceous unit and percentage of follicular ostia with perifollicular hyperpigmentation. The data were statistically evaluated. RESULTS: The number of yellow dots, pilosebaceous units with only one hair and with perifollicular hyperpigmentation was significantly increased in androgenetic alopecia (p<0.05). The percentage of thin hairs (<0.03 mm) in AGA was significantly higher than in healthy controls (p<0.05). CONCLUSION: Our study has shown the significances of trichoscopy of patients with AGA. Regular clinical and trichoscopical follow-ups are very important to monitor disease activity and treatment tolerance.

One Disease with two Faces: Semidominant Inheritance of a Novel HTRA1 Mutation in a Consanguineous Family.

OBJECTIVES: To identify the underlying genetic defect for a consanguineous family with an unusually high number of members affected by cerebral small vessel disease. MATERIALS AND METHODS: A total of 6 individuals, of whom 3 are severely affected, from the family were clinically and radiologically evaluated. SNP genotyping was performed in multiple members to demonstrate genome-wide runs-of-homozygosity. Coding variants in the most likely candidate gene, HTRA1 were explored by Sanger sequencing. Published HTRA1-related phenotypes were extensively reviewed to explore the effect of number of affected alleles on phenotypic expression. RESULTS: Genome-wide homozygosity mapping identified a 3.2 Mbp stretch on chromosome 10q26.3 where HTRA1 gene is located. HTRA1 sequencing revealed an evolutionarily conserved novel homozygous c.824C>T (p.Pro275Leu) mutation, affecting the serine protease domain of HtrA1. Early-onset of cognitive and motor deterioration in homozygotes are in consensus with CARASIL. However, there was a clear phenotypic variability between homozygotes which includes alopecia, a suggested hallmark of CARASIL. All heterozygotes, presenting as CADASIL type 2, had spinal disk degeneration and several neuroimaging findings, including leukoencephalopathy and microhemorrhage despite a lack of severe clinical presentation. CONCLUSION: Here, we clearly demonstrate that CARASIL and CADASIL type 2 are two clinical consequences of the same disorder with different severities thorough the evaluation of the largest collection of homozygotes and heterozygotes segregating in a family. Considering the semi-dominant inheritance of HTRA1-related phenotypes, genetic testing and clinical follow-up must be offered for all members of a family with HTRA1 mutations regardless of symptoms.

Obesity accelerates hair thinning by stem cell-centric converging mechanisms.

Obesity is a worldwide epidemic that predisposes individuals to many age-associated diseases, but its exact effects on organ dysfunction are largely unknown1. Hair follicles-mini-epithelial organs that grow hair-are miniaturized by ageing to cause hair loss through the depletion of hair follicle stem cells (HFSCs)2. Here we report that obesity-induced stress, such as that induced by a high-fat diet (HFD), targets HFSCs to accelerate hair thinning. Chronological gene expression analysis revealed that HFD feeding for four consecutive days in young mice directed activated HFSCs towards epidermal keratinization by generating excess reactive oxygen species, but did not reduce the pool of HFSCs. Integrative analysis using stem cell fate tracing, epigenetics and reverse genetics showed that further feeding with an HFD subsequently induced lipid droplets and NF-κB activation within HFSCs via autocrine and/or paracrine IL-1R signalling. These integrated factors converge on the marked inhibition of Sonic hedgehog (SHH) signal transduction in HFSCs, thereby further depleting lipid-laden HFSCs through their aberrant differentiation and inducing hair follicle miniaturization and eventual hair loss. Conversely, transgenic or pharmacological activation of SHH rescued HFD-induced hair loss. These data collectively demonstrate that stem cell inflammatory signals induced by obesity robustly represses organ regeneration signals to accelerate the miniaturization of mini-organs, and suggests the importance of daily prevention of organ dysfunction.

Scalp Biophysical Characteristics in Males with Androgenetic Alopecia: A Comparative Study with Healthy Controls.

BACKGROUND: Androgenetic alopecia (AGA) is the most common type of hair loss in men. Its prevalence increases with advancing age. Characteristics of hair loss in male AGA reveal the possibility of different biophysical and physiological profiles between androgen-sensitive (vertex) and androgen-insensitive (occipital) scalps. However, these variations have not been well investigated. OBJECTIVE: We aimed to evaluate and compare scalp biophysical and physiological characteristics in male AGA patients and healthy controls. METHODS: Scalp biophysiological profiles were evaluated by non-invasive measuring techniques, including skin surface lipids (SSL), transepidermal water loss (TEWL), and stratum corneum hydration (SCH) on both vertex and occipital areas. Values were compared between scalp areas and study groups. Participants with AGA were further categorized based on disease severity (Hamilton-Norwood classification) for subgroup analyses. Correlation coefficients were evaluated to determine the effects of AGA severity and age on each functional parameter. RESULTS: Participants were 31 AGA subjects and 31 healthy controls. The vertex scalp of AGA patients had significantly higher SSL (p = 0.03) and lower SCH (p = 0.02) compared to the occipital scalp. TEWL was not significantly different (p = 0.31). AGA group SSL showed a positive correlation with severity of hair loss (r = 0.61, p = 0.03). When compared to controls, the AGA group vertex scalp had significantly higher SSL (p = 0.03) and lower TEWL (p < 0.001). The occipital area showed no statistically significant differences. CONCLUSION: Male AGA presents with different biophysical and physiological characteristics in androgen-sensitive and androgen-insensitive areas, and with further differences from controls. These findings could direct further research and aid in the development of optimal hair and scalp treatments to improve scalp functional profiles in particular patients.

Cutaneous Manifestations of COVID-19.

Patients with coronavirus disease 2019 (COVID-19) present with multisystem signs and symptoms, including dermatologic manifestations. The recent literature has revealed that dermatologic manifestations of COVID-19 often are early onset and provide helpful cues to a timely diagnosis. We compiled the relevant emerging literature regarding the dermatologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) so that physicians can be aware of the various clinical cutaneous presentations in this time of high incidence of COVID-19.

Cell cycle regulation in human hair follicle dermal papilla cells using nonthermal atmospheric pressure plasma-activated medium.

ABSTRACT: Nonthermal atmospheric pressure (NAP) plasmas have recently been developed and have been used for wound healing, blood coagulation, and cancer therapy. NAP plasmas can induce either cell proliferation or cell death, depending on the dose. Due to their efficacy and application easily, plasma activated mediums (PAMs) have been used in human cells recently.In atmosphere, NAP plasmas react with molecular content of air such as N2, O2, H2O vapor, etc, and generate a variety of reactive oxygen and nitrogen species. High reactive oxygen species (ROS) levels promote damage of cellular DNA, proteins, and lipids. Such damage can lead to cell-cycle arrest, and cellular death. However, low levels of ROS have been caused an increase in cell cycle progression.Human skin is arranged in 3 layers, including (from top to bottom) the epidermis (and its appendages), the dermis, and the hypodermis. Human dermal papilla cells (DPCs) are located in the middle or even deep part of the dermis. DPCs play a key role in hair regeneration, and a lot of effort have been made to promote DPC hair formation ability. DPC is increased proliferation, delayed senescence, and enhanced hair by depending on the amount of ROS through the NAP-PAM treatment.In this study, we used NAP plasmas to the human hair follicle DPCs exposed from 0 to 20 minutes, so we were investigated the effects of PAM on cell proliferation and cell cycle progression. After NAP-PAM treatment for 24 hours, cell cycle was arrested in the G0/G1 phase. The NAP-PAM-treated human hair follicle DPCs recovered gradually after 48 hours of the treatment compared to the untreated cells.Therefore, this approach offers promising results for further application of NAP-PAM in clinical dermatology. In future, it can be applied clinically in the form of active water that can delay the progression of baldness and alopecia areata.

Severe primary hypothyroidism in an apparently asymptomatic 19-year-old woman: a case report.

BACKGROUND: Hypothyroidism is diagnosed on the basis of laboratory tests because of the lack of specificity of the typical clinical manifestations. There is conflicting evidence on screening for hypothyroidism. CASE PRESENTATION: We report a case of an apparently healthy 19-year-old Kuwaiti woman referred to our clinic with an incidental finding of extremely high thyroid-stimulating hormone (TSH), tested at the patient's insistence as she had a strong family history of hypothyroidism. Despite no stated complaints, the patient presented typical symptoms and signs of hypothyroidism on evaluation. Thyroid function testing was repeated by using different assays, with similar results; ultrasound imaging of the thyroid showed a typical picture of thyroiditis. Treatment with levothyroxine alleviated symptoms and the patient later became biochemically euthyroid on treatment. CONCLUSION: There is controversy regarding screening asymptomatic individuals for hypothyroidism; therefore, it is important to maintain a high index of suspicion when presented with mild signs and symptoms of hypothyroidism especially with certain ethnic groups, as they may be free of the classical symptoms of disease.

Clinical characteristics and outcomes of adult patients admitted with COVID-19 in East London: a retrospective cohort analysis.

BACKGROUND: Descriptions of clinical characteristics of patients hospitalised withCOVID-19, their clinical course and short-term inpatient and outpatient outcomes in deprived urban populations in the UK are still relatively sparse. We describe the epidemiology, clinical course, experience of non-invasive ventilation and intensive care, mortality and short-term sequelae of patients admitted to two large District General Hospitals across a large East London National Health Service Trust during the first wave of the pandemic. METHODS: A retrospective analysis was carried out on a cohort of 1946 patients with a clinical or laboratory diagnosis of COVID-19, including descriptive statistics and survival analysis. A more detailed analysis was undertaken of a subset of patients admitted across three respiratory units in the trust. RESULTS: Increasing age, male sex and Asian ethnicity were associated with worse outcomes. Increasing severity of chest X-ray abnormalities trended with mortality. Radiological changes persisted in over 50% of cases at early follow-up (6 weeks). Ongoing symptoms including hair loss, memory impairment, breathlessness, cough and fatigue were reported in 70% of survivors, with 39% of patients unable to return to work due to ongoing symptoms. CONCLUSIONS: Understanding the acute clinical features, course of illness and outcomes of COVID-19 will be crucial in understanding the effect of differences in risk, as well as the effectiveness of new interventions and vaccination between the successive waves of the pandemic.

Anti-androgenetic alopecia effect of policosanol from Chinese wax by regulating abnormal hormone levels to suppress premature hair follicle entry into the regression phase.

Previously, we have demonstrated that policosanol from Chinese wax suppressed testosterone(T)-induced alopecia in mice. However, the underlying mechanism remained to be determined. Herein, we investigated the mechanism of policosanol against androgenetic alopecia (AGA). AGA was induced in Kunming mice by subcutaneous administration of testosterone propionate for 60 d. Policosanol (0.5 %, 1% or 2%) was applied topically on the back of mice. Finasteride (2%) was applied topically as a positive control. The serum T and estradiol (E2) concentrations were determined by ELISA after 28 and 60 days of treatment. The cutaneous expression or activity of key mediators of hair growth, such as alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF), was measured. MTS assay was performed to evaluate cell proliferation in cultured human dermal papilla cells (DPCs) treated with dihydrotestosterone (DHT). Western blotting was performed to evaluate the protein expression of Bax, Bcl2, TGF-ß2, caspase-9, and caspase-3. We found lower T and T/E2 ratio in mice treated with policosanol than in the model group. Policosanol suppressed premature hair follicle entry into the regression phase, as shown by improving VEGF and EGF expression and ALP activity. The MTS assay showed that policosanol markedly inhibited the apoptosis of DHT-treated DPCs. Western blotting showed that policosanol significantly reduced the protein expression of TGF-ß2, cleaved caspese-9, cleaved caspase-3, and Bax, and increased that of Bcl2. The optimal effect was obtained with 12.50 g/mL policosanol. In conclusion, policosanol prevents androgenetic alopecia by regulating hormone levels and suppressing premature hair follicle entry into the regression phase.

Laboratory Testing in Telogen Effluvium.

Telogen effluvium (TE) – a common cause of non- scarring hair loss – is managed with varying clinical protocols given the paucity of evidence-based practices.

A Randomized, Double-Blind, Placebo-Controlled Study of a Nutraceutical Supplement for Promoting Hair Growth in Perimenopausal, Menopausal, and Postmenopausal Women With Thinning Hair.

Hair loss is a complex and multi-factorial problem that is associated with significant psychological morbidity in women. Menopausal women represent a significant percentage of those affected, since the menopausal hormonal transition can be a contributing factor. A novel nutraceutical supplement has been specifically formulated with phytoactives to improve hair growth and quality in menopausal women (Nutrafol® Women’s Balance Capsules). The objective of this 6-month, randomized, double-blind, placebo-controlled study was to assess the safety and efficacy of this oral supplement to promote hair growth in perimenopausal, menopausal, and postmenopausal women with self-perceived thinning. Subjects were randomized to the study supplement (n=40) or placebo (n=30). The primary endpoint was a statistically significant increase in the number of terminal and vellus hairs based on phototrichogram analysis. Daily intake of the nutraceutical supplement resulted in progressive and significant increase in terminal and total hair counts on days 90 (P<0.01) and 180 (P<0.01) compared to placebo. The vellus hair counts significantly increased for the active treatment group (P<0.05) by day 180 while significantly decreasing for the placebo group subjects. Hair shedding progressively and significantly decreased for the active group compared to placebo, culminating in a reduction of 32.41% by day 180 (P<0.01). The study supplement was well-tolerated. ClinicalTrials.gov Identifier: NCT04048031 J Drugs Dermatol. 2021;20(1):55-61. doi:10.36849/JDD.5701 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Dihydrotestosterone-induced hair regrowth inhibition by activating androgen receptor in C57BL6 mice simulates androgenetic alopecia.

Androgenic alopecia (AGA), also known as male pattern baldness, is one of the most common hair loss diseases worldwide. The main treatments of AGA include hair transplant surgery, oral medicines, and LDL laser irradiation, although no treatment to date can fully cure this disease. Animal models play important roles in the exploration of potential mechanisms of disease development and in assessing novel treatments. The present study describes androgen receptor (AR) in C57BL/6 mouse hair follicles that can be activated by dihydrotestosterone (DHT) and translocate to the nucleus. This led to the design of a mouse model of androgen-induced AGA in vivo and in vitro. DHT was found to induce early hair regression, hair miniaturization, hair density loss, and changes in hair morphology in male C57BL/6 mice. These effects of DHT could be partly reversed by the AR antagonist bicalutamide. DHT had similar effects in an ex vivo model of hair loss. Evaluation of histology, organ culture, and protein expression could explain the mechanism by which DHT delayed hair regrowth.

Severe metabolic disorders coexisting with Werner syndrome: a case report.

Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer. Werner syndrome is a segmental progeroid syndrome whose presentation resembles accelerated aging. The most common causes of death for WS patients are atherosclerosis and cancer. A 40-year-old female presented with short stature, bird-like facies, canities with alopecia, scleroderma-like skin changes, and non-healing foot ulcers. The patient reported a history of delayed puberty, abortion, hypertriglyceridemia, and juvenile cataracts. A clinical diagnosis of WS was made and subsequently confirmed. We discovered two WRN gene mutations in the patient, Variant 1 was the most common WRN mutation, nonsense mutation (c.1105C>T:p.R369Ter) in exon 9, which caused a premature termination codon (PTC) at position 369. Variant 2 was a frameshift mutation (c.1134delA:p.E379KfsTer5) in exon 9, which caused a PTC at position 383 and has no published reports describing. Patients with WS can show a wide variety of clinical and biological manifestations in endocrine-metabolic systems (DM, thyroid dysfunction, and hyperlipidemia). Doctors must be cognizant of early manifestations of WS and treatment options.