Current Diagnostic and Therapeutic Practices in Alopecia Areata in Two Mediterranean Countries: A Survey-Based Study.

INTRODUCTION: Alopecia areata (AA) affects approximately 2% of the general population and is associated with significant psychosocial morbidity and poor health-related quality of life. Despite the high incidence of the disease the available clinical practice guidelines to help clinicians and improve patients' care are very poor and of a low methodological quality, as compared to other high-burden dermatoses. The aim of this survey is to capture the current clinical practice in AA management, as performed by dermatologists, in two Mediterranean countries to identify potential disparities and gaps in diagnosis and treatment. METHODS: A 50-item questionnaire was created in the English language and then translated into Greek and Italian language and sent to the Greek and Italian dermatologists via email. RESULTS: A total of 490 dermatologists from Italy and 234 from Greece participated in the survey. The diagnosis of AA is usually based on history and clinical examination, supported by trichoscopy. The rate of use of severity scores and scales to evaluate impact on quality of life by dermatologists was low. Treatment of patchy AA, in both adult and pediatric populations, is based on use of topical steroids as first-line treatment. Results on special site involvement (eyebrows, beard, and ophiasis), chronic cases, and the pediatric population highlight extreme heterogeneity in treatment approach. CONCLUSIONS: Our results highlight that management of AA, in terms of diagnosis and treatment, is still challenging.

Efficacy of the association of topical minoxidil and topical finasteride compared to their use in monotherapy in men with androgenetic alopecia: A prospective, randomized, controlled, assessor blinded, 3-arm, pilot trial.

PURPOSE: Topical minoxidil (MNX) 2%-5% and oral finasteride (F) 1 mg/day are the only two pharmacological treatments authorized for androgenetic alopecia (AGA). Recently, a 2.2 mg/mL topical formulation of F was developed to minimize the systemic adverse effects associated with the oral formula. MNX and F act through different mechanisms; therefore, their association could improve clinical efficacy. To evaluate the efficacy of the association of 5% MNX and 0.25% topical F compared to their use in monotherapy, a 6-month, prospective, randomized, assessor-blinded trial was conducted. PATIENTS AND METHODS: Forty-two males, mean age 24 ± 3 years, with AGA (I-VII of Norwood-Hamilton Grading Scale), treatment naive or free from any therapy for at least 6 months, were enrolled and randomly assigned to three arm treatment groups (2:1:1): group A (n = 19, the subjects applied 5% MNX in the morning and F spray in the evening), group B (n = 12, the subjects applied F spray in the evening), and group C (n = 11, the subjects applied 5% MNX twice daily). The efficacy of treatments was evaluated at baseline and after 3 and 6 months using a global photography score (GPAS; from -3 to +3) and trichoscopy evaluation and assessed by an investigator unaware of treatment allocation. At baseline and after treatments, the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), and testosterone were also evaluated. RESULTS: All treatments resulted in an increase in hair density compared to baseline. However, this improvement was significant only for group A (MNX + F), both at three (+56 density/cm2 , p < 0.05) and six (+81 density/cm2 , p < 0.001) months. The mean change from baseline in hair density was higher for group A compared to other groups and statistically different compared to group B (F) (p < 0.01), both after 3 and 6 months. Group A showed a global photographic assessment score (GPAS) significantly higher compared to group B (p < 0.001) and group C (p < 0.05) both at 3 and 6 months (2.0 ± 0.7 vs. 0.6 ± 0.8 and 1.3 ± 0.6; respectively). A significantly greater percentage of subjects in Group A achieved a GPAS score of ≥2 in comparison with Groups B and C both after 3 and 6 months (79% vs. 8% and 41%, respectively). No significant differences were observed in mean hair diameter and hormonal levels between the three groups. Good tolerability was observed in all treated groups. CONCLUSION: The association of 5% MNX lotion and 0.25% F in spray formulation in patients with AGA showed a significantly higher clinical and instrumental efficacy compared to the monotherapies, with comparable tolerability and safety profile.

Sub-Hz Closed-Loop Electro-Optomechanical Oscillator with Gallium Phosphide Photonic Crystal Integrated on SoI Circuitry.

We report on a new approach of a low phase noise electro-optomechanical oscillator directly working in the GHz frequency range. The developed nanoscale oscillator is a one-dimensional photonic crystal made of gallium phosphide (GaP), heterogeneously integrated on silicon-on-insulator circuitry. Based on the strong interaction between the optical mode at the telecommunication wavelength and the mechanical mode in GHz, ultra-pure mechanical oscillations are enabled and directly imprinted on an optical carrier. Further stabilization is achieved with a delayed optoelectronic feedback loop using integrated electro-mechanical self-injection. We achieve a short-term stability of 0.7 Hz linewidth and a long-term stability with an Allan deviation below 10-7 Hz/Hz at 10 s averaging time, which represents an important step toward fully integrated optomechanical oscillators. Integrability and the low phase noise of this oscillator address some of the most important needs of optoelectronic oscillators and pave the way toward on-chip integrated microwave oscillators for microwave applications such as RADARs.

A Machine Learning Algorithm Applied to Trichoscopy for Androgenic Alopecia Staging and Severity Assessment.

INTRODUCTION: Androgenic alopecia (AGA) staging is still based on macroscopic scales, yet the introduction of trichoscopy is gradually bringing an important change, even though it remains an eye-based method. However, recently developed artificial intelligence-assisted programs can execute automated count of trichoscopic patterns. Nevertheless, to interpret data elaborated by these programs can be complex. Machine learning algorithms might represent an innovative solution. Among them, support vector machine (SVM) models are among the best methods for classification. OBJECTIVES: Our aim was to develop a SVM algorithm, based on three trichoscopic patterns, able to classify AGA patients and to calculate a severity index. METHODS: We retrospectively analyzed trichoscopic images from 200 AGA patients using Trichoscale Pro® software, calculating the number of vellus hair, empty follicles and single hair follicular units. Then, we elaborated a SVM model, based on these three patterns and on sex, able to classify patients as affected by mild AGA or moderate-severe AGA, and able to calculate the probability of the classification being correct, expressed as percentage (from 50% to 100%). This probability estimate is higher in patients with more AGA trichoscopic patterns and, thus, it might serve as a severity index. RESULTS: For training and test datasets, accuracy was 94.3% and 90.0% respectively, while the Area Under the Curve was 0.99 and 0.95 respectively. CONCLUSIONS: We believe our SVM model could be of great support for dermatologists in the management of AGA, especially in better assessing disease severity and, thus, in prescribing a more appropriate therapy.

Detection of novel therapies using a multi-national, multi-institutional registry of cutaneous immune-related adverse events and management.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) remain a prevalent and common sequelae of immune checkpoint inhibitor (ICI) therapy, often necessitating treatment interruption and prolonged immune suppression. Treatment algorithms are still poorly defined, based on single-institution case reports without adequate safety assessments, and subject to publication bias. METHODS: Data in this registry were collected through a standardized REDCap form distributed to dermatologists via email listserv. RESULTS: Ninety-seven cirAEs were reported from 13 institutions in this registry. Topical and systemic steroids were the most common treatments used; however, targeted treatment matched to disease morphology was identified at numerous sites. Novel cirAE therapy uses that to our knowledge have not been previously described were captured including tacrolimus for the treatment of follicular, bullous, and eczematous eruptions and phototherapy for eczematous eruptions. Moreover, further evidence of cirAE treatment applications sparsely described in literature were also captured in this study including dupilumab and rituximab for bullous eruptions, phototherapy for lichenoid and psoriasiform eruptions, and acitretin for psoriasiform eruptions, among others. No serious adverse events were reported. Numerous targeted therapeutics including dupilumab, rituximab, and psoriasis biologics, among others, were associated with a cirAE grade improvement of ≥2 grades in every patient treated. CONCLUSION: This study suggests that a multi-institutional registry of cirAEs and management is not only feasible but that the information collected can be used to detect, evaluate, and rigorously assess targeted treatments for cirAEs. Further expansion and modification to include treatment progression may allow for sufficient data for specific treatment recommendations to be made.

Noise investigation of CW and mode-locked harmonic cavity nanolasers.

We theoretically investigate the noise properties of harmonic cavity nanolasers by introducing a model of coupled equations of evolution of the modes, taking spontaneous emission into account. This model is used to predict the noise among the nanolaser Hermite-Gaussian modes, both in continuous wave and mode-locked regimes. In the first case, the laser noise is described in terms of noise modes, thus illustrating the role of the laser dynamics. In the latter case, this leads to the calculation of the fluctuations of the pulse train parameters. The influence of the different laser parameters, including the amount of saturated absorption and the Henry factors, on the noise of the mode-locked regime is discussed in details.

The Pathological Culprit of Neuropathic Skin Pain in Long COVID-19 Patients: A Case Series.

Cutaneous neurosensory symptoms have become increasingly reported findings in COVID-19; however, these virus-related manifestations are largely overlooked, and their pathology is poorly understood. Moreover, alterations of skin sensibility currently recognize no clear histopathology substrate. The purpose of this study was to provide pathology evidence of neurosensory skin system involvement in COVID-19 patients complaining of subjective neurological symptoms affecting the skin. Out of 142 patients, six long COVID-19 cases complaining of cutaneous subjective neurological symptoms assessed on an NTSS-6 questionnaire underwent histopathological and immunohistochemical analyses of skin areas affected by paroxysmal diffuse burning and itching sensations. Two patients also performed electroneurography examination. The histology investigation showed hypertrophic glomus vascular bodies with hypertrophic S100+ perineural sheath cells and adjacent hypertrophy of the nerve branches associated with increased basophil polysaccharide matrix. Electroneurography revealed disturbances of A-delta and C dermal neuronal fibers. The main limitation of this study consisted of a limited number of skin biopsy samples, requiring further investigation. Histopathology findings are consistent with hypertrophy of nerve endings, suggesting a condition such as "dermal hyperneury", a recently reported small nerve hypertrophy condition affecting sensory C fibers. Such a neuropathic basis could explain dysesthesia experienced by the patients, as previously described in postherpetic neuralgia.

Intermediate Hair Follicles from Patients with Female Pattern Hair Loss Are Associated with Nutrient Insufficiency and a Quiescent Metabolic Phenotype.

Female pattern hair loss (FPHL) is a non-scarring alopecia resulting from the progressive conversion of the terminal (t) scalp hair follicles (HFs) into intermediate/miniaturized (i/m) HFs. Although data supporting nutrient deficiency in FPHL HFs are lacking, therapeutic strategies are often associated with nutritional supplementation. Here, we show by metabolic analysis that selected nutrients important for hair growth such as essential amino acids and vitamins are indeed decreased in affected iHFs compared to tHFs in FPHL scalp skin, confirming nutrient insufficiency. iHFs also displayed a more quiescent metabolic phenotype, as indicated by altered metabolite abundance in freshly collected HFs and release/consumption during organ culture of products/substrates of TCA cycle, aerobic glycolysis, and glutaminolysis. Yet, as assessed by exogenous nutrient supplementation ex vivo, nutrient uptake mechanisms are not impaired in affected FPHL iHFs. Moreover, blood vessel density is not diminished in iHFs versus tHFs, despite differences in tHFs from different FPHL scalp locations or versus healthy scalp or changes in the expression of angiogenesis-associated growth factors. Thus, our data reveal that affected iHFs in FPHL display a relative nutrient insufficiency and dormant metabolism, but are still capable of absorbing nutrients, supporting the potential of nutritional supplementation as an adjunct therapy for FPHL.

Analysis of Pros and Cons in Using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007: Production, Costs, and PET/CT Applications in Patients with Prostate Cancer.

The aim of this work is to compare [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 PET/CT as imaging agents in patients with prostate cancer (PCa). Comparisons were made by evaluating times and costs of the radiolabeling process, imaging features including pharmacokinetics, and impact on patient management. The analysis of advantages and drawbacks of both radioligands might help to make a better choice based on firm data. For [68Ga]Ga-PSMA-11, the radiochemical yield (RCY) using a low starting activity (L, average activity of 596.55 ± 37.97 MBq) was of 80.98 ± 0.05%, while using a high one (H, average activity of 1436.27 ± 68.68 MBq), the RCY was 71.48 ± 0.04%. Thus, increased starting activities of [68Ga]-chloride negatively influenced the RCY. A similar scenario occurred for [18F]PSMA-1007. The rate of detection of PCa lesions by Positron Emission Tomography/Computed Tomography (PET/CT) was similar for both radioligands, while their distribution in normal organs significantly differed. Furthermore, similar patterns of biodistribution were found among [18F]PSMA-1007, [68Ga]Ga-PSMA-11, and [177Lu]Lu-PSMA-617, the most used agent for RLT. Moreover, the analysis of economical aspects for each single batch of production corrected for the number of allowed PET/CT examinations suggested major advantages of [18F]PSMA-1007 compared with [68Ga]Ga-PSMA-11. Data from this study should support the proper choice in the selection of the PSMA PET radioligand to use on the basis of the cases to study.

Clinical and Trichoscopic Graded Live Visual Scale for Androgenetic Alopecia.

Introduction: Currently, the mostly used classifications of androgenetic alopecia (AGA) only provide a macroscopic and subjective description of this disorder, without evaluating trichoscopic features. Objectives: The aim of this study is to elaborate a graded live visual AGA severity scale including macroscopic and microscopic (trichoscopic) pictures, and to determine the most frequent trichoscopic characteristics associated to each grade. Methods: A retrospective observational study was conducted on 122 patients (50 females and 72 males) affected by AGA. Macroscopic and trichoscopic photographs were taken at standardized scalp points. Results: Each picture was ranked from AGA stage I to VII, according to Hamilton scale for men and Sinclair scale for women, and the most representative images of each severity degree were collected to produce a graded live visual scale. In males, 2 live visual scales, 1 for the anterior and 1 for posterior region of the scalp were created. In females, only 1 scale of the anterior region was realized. For each stage of severity, the corresponding trichoscopic parameters were statistically analyzed. Conclusions: We realized new macroscopic and trichoscopic graded live visual scales for male and female patients affected by AGA, which could help physicians in giving an objective evaluation of the disease and in better managing it.

Efficacy of a new combination of a microemulsion and oral supplementation for androgenetic alopecia: an interventional multicentric study.

BACKGROUND: The aim of this study was to study new therapeutic options for the treatment of female and male androgenetic alopecia (AGA) and to assess the efficacy of a possible new coadjuvant oral and topical therapy, containing a complex of natural substances. METHODS: Sixty individuals affected by mild-to-moderate female and male AGA were enrolled in the study and underwent the oral and topical treatment with a microemulsion formulation for 6 months. At baseline and at 3- and 6-month follow-up, global photographs were taken and three expert operators evaluated photographs using the 7-point scale. On a subgroup of our sample, non-invasive phototrichograms with TrichoScan® HD at baseline and follow-ups were performed to collect the trichological parameters of total number of hairs, hair density/cm2, vellus hair density/cm2, terminal hair density/cm2 and hair thickness. One-way ANOVA and Unpaired Student t-test were performed to analyze the data. RESULTS: Using the 7-point scale, a clinically visible improvement of hair loss was observed after three and six months of treatment. A statistically significant increase of all TrichoScan® trichological parameters was observed at both 3- and 6 month-follow-up. CONCLUSIONS: The complex of natural and active substances tested in this work showed good efficacy in improving both male and female hair loss. These new products could represent a valid alternative or coadjuvant therapy of AGA, increasing the efficacy of conventional treatments such as minoxidil or finasteride.

Recommendations on trichological treatments during COVID-19 pandemic.

COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2, which rapidly spreads via respiratory droplets and is the cause of the current pandemic. In this alarming situation, it is a delicate matter how to visit patients safely and how to manage their chronic treatments. The aim of this paper is to examine in detail the potential impact on SARS-CoV-2 infection of treatments routinely used in trichology and to provide a useful guide for the therapeutic management of trichological patients in this new COVID-19 era.

A new combination of molecules for the treatment of androgenetic alopecia and telogen effluvium: a double-blind randomized, monocentric, placebo-controlled study.

BACKGROUND: Androgenetic alopecia (AGA) is the most frequent form of alopecia. Telogen effluvium (TE) is a common form of diffuse hair loss mainly observed in women. The aim of our study was to evaluate the efficacy of a topical trichological treatment containing a new combination of molecules for the treatment of AGA and TE. METHODS: In-vitro tests were performed analyzing different combinations and concentrations of arginine, zinc and a third enzymatically neutral substance called AA on human follicles dermal papillae cells. These tests evaluated the capability of inhibiting the 5α-reductase (5-AR) enzyme and the 5-AR gene expression. We also performed an in-vivo study. Forty individuals affected by AGA and TE were divided into two groups. One group was administered a combination of zinc and arginine (lotion A), whilst the other placebo (lotion B). Therapy duration was 23 consecutive weeks. Follow-up examinations and pull tests occurred at baseline, after 6 weeks and at the end of the therapy. On 20 randomly selected patients we also performed noninvasive phototrichograms. RESULTS: In-vitro tests showed that the combination had a strong statistically significant inhibitory activity on 5-AR of dermal papillae cells. Number of hairs removed by pull-test significantly decreased at T0, T1 and T2 in patient treated with lotion A. We also observed an increase in the percentage of anagen hair and a decrease in telogen hairs. Concerning phototrichograms, all objective parameters evaluated showed better results in the lotion A group when compared with the placebo group. CONCLUSIONS: Based on our results, the combination of arginine and zinc tested in our study could represent a good therapeutic option for the treatment of AGA and TE and it might represent a valid alternative to finasteride.

Recurrence of alopecia areata after covid-19 vaccination: A report of three cases in Italy.

BACKGROUND: Common COVID-19 vaccines side effects are pain at the injection site, muscle pain, fever, headaches, fatigue. Possible immune-related side effects in predisposed individuals have not been established so far. MATERIALS AND METHODS: We report three cases of recurrence of alopecia areata (AA) occurred after the first dose of COVID-19 vaccine. RESULTS: All patients had previous episodes of AA with total hair regrowth and stable remission during the months preceding the vaccination. Rapid hair loss occurred 2-3 weeks after BNT162b2 mRNA (patient 1) and AZD1222/ChAdOx1 vaccine (patient 2 and 3), with widespread hair loss in two cases and a single patch of the vertex in one case, with typical trichoscopic features of AA. DISCUSSION: Both BNT162b2 mRNA and AZD1222/ChAdOx1 vaccines share the same goal of inducing the immune system, with antibodies production and Th1 cells activation with release of pro-inflammatory cytokines. Thus, in patients with pre-existing inflammatory dysregulated pathways, the interaction between the immune system and vaccines may enhance other autoimmune mechanisms. In our cases, we speculate that vaccine may have induced the hair loss focusing on components having a key role in both COVID-19 vaccination and AA pathogenesis. CONCLUSION: This report may help to collect new data concerning possible immune-related effects of vaccines. Certainly, only three cases are not sufficient to draw conclusion, thus a large-scale study is necessary. Immune-mediated side effects remain a rare event, thus the benefits of COVID-19 vaccines outweigh the risk of disease flares and we strongly recommend it in all eligible patients with AA.

Cutaneous adverse reactions after COVID-19 vaccines in a cohort of 2740 Italian subjects: An observational study.

An in-depth characterization of the incidence, morphology, and onset of COVID-19-vaccines cutaneous adverse reactions is currently lacking. The existing literature on COVID-19 vaccination-related cutaneous adverse reactions largely focused on messenger RNA vaccines and mainly included type 1 hypersensitivity reactions, such as urticaria and angioedema. Other cutaneous manifestations are still poorly characterized and have been classified as delayed hypersensitivity rash. Our prospective observational study on a sample of 2740 subjects who underwent the COVID-19 vaccination aimed at defining the prevalence of cutaneous adverse reactions and at identifying their timing of onset and their correlation with the administered dose. Vaccine-related cutaneous adverse reactions occurred in 50 subjects. Patients were asked to complete a questionnaire on the type of COVID-19 vaccine received, the time of onset of cutaneous reactions, and the dates of administration. Out of 2740 individuals who received the COVID-19 vaccination, 50 were diagnosed with cutaneous adverse reactions to vaccine, after the first dose in 28 patients, after the second in 20, and after both in two. We reported localized injection site erythema in 12 patients and generalized cutaneous reactions in 38 patients. Our study shows that cutaneous adverse reactions to COVID-19 vaccination are not common and most often occur after the first dose, recurring infrequently after the second dose. These reactions are usually easily manageable and, even in severe generalized cases, oral antihistamines and corticosteroids were sufficient for resolution. Therefore, except for immediate hypersensitivity reactions, cutaneous adverse reactions do not represent a contraindication to the completion of the vaccination cycle.

Are dissecting cellulitis and hidradenitis suppurativa different diseases?

Although dissecting cellulitis (DC) and hidradenitis suppurativa (HS) are classified separately, they share many clinical, dermatoscopic, pathogenetic, and histologic aspects, as well as therapeutic options. The association between DC, HS, and acne conglobata represents the follicular occlusion triad or follicular occlusion tetrad, which may include a pilonidal sinus. DC, also known as "folliculitis et perifolliculitis capitis abscendes et suffoidens," is classified as a secondary cicatricial and neutrophilic alopecia. It occurs with perifolliculitis of the scalp, dermal abscesses, sinus tract development, and secondary scarring alopecia. HS, sometimes known as acne inversa, is a chronic relapsing inflammatory disease afflicting apocrine gland-rich areas of the body with painful nodules and abscesses, sinus tracts, and scarring. Given the overlap between the clinical features and the pathogenesis of DC and HS, it would be more appropriate to consider these conditions as two different localizations of the same disease rather than two different pathologies, being a follicular occlusion disease occurring on the scalp and on the apocrine gland-rich areas of the body.

Resident human dermal γδT-cells operate as stress-sentinels: Lessons from the hair follicle.

Murine γδT-cells have stress-surveillance functions and are implicated in autoimmunity. Yet, whether human γδT-cells are also stress sentinels and directly promote autoimmune responses in the skin is unknown. Using a novel (mini-)organ assay, we tested if human dermis resident γδT-cells can recognize stressed human scalp hair follicles (HFs) to promote an alopecia areata (AA)-like autoimmune response. Accordingly, we show that γδT-cells from healthy human scalp skin are activated (CD69+), up-regulate the expression of NKG2D and IFN-γ, and become cytotoxic when co-cultured with autologous stressed HFs ex vivo. These autologous γδT-cells induce HF immune privilege collapse, dystrophy, and premature catagen, i.e. three hallmarks of the human autoimmune HF disorder, AA. This is mediated by CXCL12, MICA, and in part by IFN-γ and CD1d. In conclusion, human dermal γδT-cells exert physiological stress-sentinel functions in human skin, where their excessive activity can promote autoimmunity towards stressed HFs that overexpress CD1d, CXCL12, and/or MICA.