Editor's Highlights - August 2024.

Pigmentary and hair disorders have a significant cosmetic and psychological impact. In the August issue of the Journal, we highlight the use of reflectance confocal microscopy in diagnosing and monitoring treatment responses in patients with melasma. We will also discuss new therapeutic approaches involving oral melatonin and a combination of glutathione and resveratrol for melasma. Additionally, the ongoing revolution in alopecia treatment with oral low-dose minoxidil will be spotlighted, including the circumstances under which media attention has contributed to the growing interest in oral minoxidil prescriptions.

Comparison of Efficacy of Autologous Platelet Rich Plasma Therapy With 5% Topical Minoxidil Spray in Treating Alopecia Areata: A Head-to-Head Assessment of Novel Approaches.

BACKGROUND: Alopecia areata (AA) remains one of the most challenging afflictions encountered in dermatology clinics. It is characterized by an autoimmune-mediated inflammatory process of and around hair follicles, causing reversible, non-scarring hair loss. With the ongoing search for optimal treatment strategies, the potentially positive role of autologous platelet-rich plasma (PRP) therapy as well as minoxidil has been reported in various studies; however, the comparison of the two treatment modalities is largely underexplored. This research aims to compare and assess the effectiveness of intralesional PRP with topical minoxidil therapy in AA to identify efficacious management options amongst the newly described treatment modalities. METHODOLOGY: The research work was conducted over four months and included 40 (31 males and 9 females) patients suffering from alopecia areata. They were divided into Group A, which was administered monthly autologous PRP injections, while Group B was given daily topical 5% minoxidil therapy. In group A, four treatments of PRP were given, each one month apart. While in group B, daily topical minoxidil spray was administered for the same duration. The alopecia areata severity grade was recorded by employing the "Severity of Alopecia Tool" (SALT) scoring system. The pre- and post-treatment SALT scores were noted and compared at each monthly visit. RESULTS: The study comprised nine (22.5%) female and 31 (77.5%) male patients. At the beginning of the study and after one month of treatment, the difference in the SALT score was not statistically significant between the two groups, suggesting that both interventions had similar effects during the early stages of the treatment. At two months, a statistically significant difference emerged (p-value 0.037), indicating that a more significant fall in the SALT score was observed with autologous PRP treatment compared to topical minoxidil. After four months, a highly significant difference was noted between the two groups (p-value <0.0001), implying that intralesional PRP therapy led to a far more significant decrease in the SALT score compared to topical minoxidil therapy. CONCLUSION: Monthly intralesional autologous PRP therapy for four months manifests better outcomes in alopecia areata than daily 5% topical minoxidil therapy.

A bibliometric analysis of alternative drug therapy options in the treatment of androgenetic alopecia.

BACKGROUND: Oral finasteride and topical minoxidil formulations are the only FDA-approved drug therapies for androgenetic alopecia (AGA). Research into dutasteride, topical finasteride, and nontopical minoxidil (low-dose oral and sublingual) formulations in the treatment of AGA has spiked within recent years. Early findings show that these alternative drug therapies may have similar to improved efficacy and safety profiles relative to the conventional treatment options. AIMS: Conducting a bibliometric analysis, compare trends in publications on these alternative drug therapies, identify key contributors, evaluate major findings from top-cited articles, and elucidate gaps in evidence. METHODS: A search was conducted on the Web of Science database for publications on the use of alternative drug therapies in the treatment of AGA. A total of 95 publications, published between January 2003-March 2024, and their citation metadata were included in the analysis. RESULTS: Dutasteride showed the greatest (n = 37) and longest (20+ years) history of publications, as well as the highest cumulative citations (n = 914); however, nontopical minoxidil showed a burst in research activity within the last 5 years (n = 33 publications since 2019). A relatively low number of randomized control trials (n = 3) for nontopical minoxidil suggests a need for higher-quality evidence. CONCLUSIONS: Our analysis reveals major trends, contributors, and gaps in evidence for alternative drug therapies for AGA, which can help inform researchers on their future projects in this growing field of study. There is enthusiasm for exploring off-label formulations: nontopical forms of minoxidil (oral and sublingual), topical finasteride, and mesotherapy.

Stimulation of hair regrowth in an animal model of androgenic alopecia using 2-deoxy-D-ribose.

Androgenic alopecia (AGA) affects both men and women worldwide. New blood vessel formation can restore blood supply and stimulate the hair regrowth cycle. Recently, our group reported that 2-deoxy-D-ribose (2dDR) is 80%-90% as effective as VEGF in the stimulation of neovascularization in in vitro models and in a chick bioassay. In this study, we aimed to assess the effect of 2dDR on hair growth. We prepared an alginate gel containing 2dDR, polypropylene glycol, and phenoxyethanol. AGA was developed in C57BL6 mice by intraperitoneally injecting testosterone (TE). A dihydrotestosterone (DHT)-treated group was used as a negative control, a minoxidil group was used as a positive control, and we included groups treated with 2dDR gel and a combination of 2dDR and minoxidil. Each treatment was applied for 20 days. Both groups treated with 2dDR gel and minoxidil stimulated the morphogenesis of hair follicles. H&E-stained skin sections of C57BL/6 mice demonstrated an increase in length, diameter, hair follicle density, anagen/telogen ratio, diameter of hair follicles, area of the hair bulb covered in melanin, and an increase in the number of blood vessels. Masson's trichrome staining showed an increase in the area of the hair bulb covered in melanin. The effects of the FDA-approved drug (minoxidil) on hair growth were similar to those of 2dDR (80%-90%). No significant benefit were observed by applying a combination of minoxidil with 2dDR. We conclude that 2dDR gel has potential for the treatment of androgenic alopecia and possibly other alopecia conditions where stimulation of hair regrowth is desirable, such as after chemotherapy. The mechanism of activity of 2dDR remains to be established.

Real-world effectiveness and safety of tofacitinib for alopecia areata: A retrospective cohort study of 202 patients.

BACKGROUND: Alopecia areata (AA) is an autoimmune hair loss disorder characterised by collapse of hair follicle immune privilege and mediated by autoreactive CD8+ T lymphocytes and natural killer cells. Treatment is often unsatisfactory. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is implicated in the pathogenesis of AA and Janus Kinase inhibitor (JAKi) medications are promising emerging treatments for AA. OBJECTIVES: We evaluated the safety and effectiveness of tofacitinib in a real-world setting over 18 months of treatment. METHODS: A retrospective cohort study of all patients with scalp AA commenced on tofacitinib between 1 November 2016 and 31 May 2019. The primary endpoint was the percent change in Severity of Alopecia Tool (SALT) score at 18 months. RESULTS: Two hundred and two patients were included. After 18 months of treatment, 55.9%, 42.6% and 29.2% achieved 50%, 75% and 90% reductions in their SALT scores respectively. Increased duration of AA was a negative predictor of hair regrowth. Males and patients with baseline SALT ≥90 were slower to respond to treatment in the first 12 months. One hundred and twenty-four patients and 168 patients received concomitant systemic corticosteroids or low-dose oral minoxidil during tofacitinib therapy respectively. There were no serious adverse events. CONCLUSION: Tofacitinib was a safe and effective treatment for patients with moderate-to-severe AA. Further randomised controlled studies are needed to establish the optimal treatment regimen.

Management of androgenic alopecia: a systematic review of the literature.

We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.

Mesotherapy as a Promising Alternative to Minoxidil for Androgenetic Alopecia: A Systematic Review.

Patterned hair loss (PHL) is a severe hair condition that affects both sexes. Mesotherapy is a treatment that involves microinjecting medications and/or vitamins into the middle layer of the skin. Mesotherapy reduces systemic adverse effects by delivering drugs directly to the hair follicle, increasing local bioavailability while lowering systemic exposure. Local side effects and reactions may develop due to mesotherapy. This study systematically evaluated the safety and efficacy of mesotherapy to minoxidil 5%, as well as addressing its limitations, dosing, and technique, with the intent of providing valuable trials and insights for clinicians and patients considering mesotherapy for improved androgenetic alopecia (AGA) outcomes. The literature search carried out by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria yielded 11 relevant studies from an initial pool of 18 articles. These studies covered various aspects of the role of mesotherapy and minoxidil in AGA, including techniques, complications, limitations, and outcomes. In conclusion, available trials and research on mesotherapy and minoxidil demonstrated excellent statistical significance and a high patient satisfaction rate, with the exception of two publications that took into account certain uncommon adverse effects of mesotherapy. However, recent research suggests that a mesotherapy method for alopecia with a low risk of side effects is effective.

Evaluation of the Safety and Effectiveness of Oral Minoxidil in Children: A Systematic Review.

The minimal adverse-effect profile and positive clinical response of low-dose oral minoxidil (LDOM) have recently caused the drug to gain popularity for the treatment of hair disorders in adults. However, in the pediatric population, hesitancy still surrounds the use of oral minoxidil given the wide profile of potential side effects the drug offers. This review aims to characterize the safety and use of oral minoxidil in children for the treatment of all disorders to equip physicians with ample knowledge when prescribing oral minoxidil in the pediatric population. A total of 41 studies (19 case reports, 10 cohort studies, 7 retrospective chart reviews, and 5 case series) that reported data on 442 pediatric patients for whom oral minoxidil was used for treatment were included. Conditions for which treatment with minoxidil was described were hair disorders (83.9%, 371/442) and hypertension (11.3%, 50/442); accidental usage (4.8%, 21/442) was also noted in the literature and included in this review. This review is broken down by dosage and describes the safety and efficacy of oral minoxidil in pediatric patients aged 0 to 18 years old for the treatment of hair disorders. This review found that LDOM may represent a safe option for the treatment of hair disorders in children. This study also suggests moderate and high doses of oral minoxidil may not be safe for use in children. Additional studies are needed to further understand this drug's efficacy and safety in children.

Split-scalp pilot study to evaluate effectiveness of Minoxidil 0,5% MMP® versus Topical Minoxidil 5% in the treatment of Female Pattern Hair Loss.

Female Pattern Hair Loss (FPHL) is a common form of non-scaring hair loss that occurs in adult women. Although several treatments have already been proposed for FPHL, only Topical Minoxidil accumulated an adequate level of evidence. This study aimed to evaluate the therapeutic response of MMP® (intradermal infiltration) of Minoxidil formulation in the frontal-parietal-vertex regions compared with the gold-standard home administration of Minoxidil 5% Capillary Solution. This self-controlled comparative study evaluated 16 FPHL patients, without treatment for at least 6 months, confirmed by trichoscopy with TrichoLAB® software. They received 4 monthly sessions of MMP® with Minoxidil 0,5% on the right side of the scalp (frontal-parietal-vertex areas), followed by occlusion with plastic film for 12 h and prescription of Minoxidil 5% Solution for home use once a day, on both scalp sides, starting 72 h after the procedure. The reassessment trichoscopy was 6 weeks after the last session and they answered a "self-assessment" questionnaire. Treated scalp areas were compared and showed both treatments, in general, were effective, with no difference between them. If they were analyzed separately by treated areas, there were signs of better response in the parietal-vertex regions with treatment by MMP® with Minoxidil, while clinical treatment indicated a better response in the other regions. When patients were divided into more and less advanced cases, a better response in parietal-vertex regions treated by MMP® with Minoxidil in less advanced patients was confirmed. MMP® with Minoxidil showed a better response in the parietal-vertex regions in less advanced FPHL patients. It represents yet another resource to improve quality of life of these suffering patients.

DNA Microarray and Bioinformatic Analysis Reveals the Potential of Whale Oil in Enhancing Hair Growth in a C57BL/6 Mice Dorsal Skin Model.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through a high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% whale oil) were topically applied to the dorsal skin of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained dorsal skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptome analysis also confirmed increases for 20% WO in filaggrin (Flg), a gene related to skin barrier function; fibroblast growth factor 21 (Fgf21), which is involved in hair follicle development; and cysteine-rich secretory protein 1 (Crisp1), a candidate gene for alopecia areata. Furthermore, the results of KEGG pathway analysis indicated that 20% WO may have lower stress and inflammatory responses than 3% MXD. Therefore, WO is expected to be a safe hair growth agent.

Combating "dread shed": The impact of overlapping topical and oral minoxidil on temporary hair shedding during oral minoxidil initiation.

Background: Low dose oral minoxidil (LDOM) is a preferred treatment for alopecia due to ease of use and efficacy. While LDOM is typically well tolerated, patients may experience a temporary increase in hair shedding starting treatment, colloquially regarded as "dread shed". One proposed method to combat this is to overlap therapies by maintaining use of topical minoxidil when initiating LDOM. Objective: To evaluate the impact of maintaining topical minoxidil when initiating LDOM on "dread shed". Methods: We performed a retrospective chart review of patients seen at New York University Langone Health Dermatology from January 1, 2008 to August 1, 2023 prescribed LDOM. Results: A total of 115 patients met inclusion criteria, of whom 37 maintained use of topical minoxidil when initiating LDOM. Six patients experienced "dread shed" when initiating LDOM, 2 of whom overlapped therapies. We did not find that overlapping therapies had a significant impact on decreasing rates of "dread shed". Limitations: Limitations include retrospective design, sample size, and subjective patient-reported assessment of hair shedding. Conclusions: A total of 5.2% of patients experienced dread shed, which is lower than previously reported in literature. Maintaining topical minoxidil during LDOM initiation does not significantly impact "dread shed". This remains a significant side effect deserving of further research.

Congenital Triangular Alopecia: A Case of Effective Response with 5% Topical Minoxidil in a Male Adolescent.

Congenital triangular alopecia (CTA) is a rare entity of non-cicatricial alopecia characterized by triangular or oval-shaped alopecia patches on the frontotemporal region of the scalp. Few therapeutic options exist, and there is currently no effective treatment except for hair transplantation. We report the case of an adolescent boy with CTA who was treated with 5% topical minoxidil solution. During therapy, the patient showed improvement in the form of the appearance of terminal hairs, which started to show after two months of treatment. After eight months of treatment, the affected area was fully covered with dense terminal hairs. The patient did not report any adverse reactions/side effects.

Meta-Analysis of Efficacy of Platelet-Rich Plasma Combined with Minoxidil for Androgenetic Alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is a prevalent type of hair loss that impacts individuals of both genders. Platelet-rich plasma (PRP) and minoxidil have been employed as therapeutic interventions for AGA, yet the efficacy of their concurrent use remains ambiguous. OBJECTIVE: To perform a comprehensive review and meta-analysis aimed at evaluating the effectiveness of platelet-rich plasma (PRP) in combination with minoxidil for the treatment of androgenetic alopecia (AGA). METHODS: We conducted a comprehensive search of the databases PubMed, Embase, Web of Science, and Cochrane Library, encompassing their complete records up until December 2023. Eligible studies were randomized controlled trials that compared the combination of PRP and minoxidil with minoxidil or PRP alone in patients with AGA. The primary outcome measure was the change in hair growth as assessed by the hair density or hair thickness. Secondary outcome measures included patient satisfaction, and global photographic assessment. RESULTS: A total of 6 studies involving 343 participants were included in this meta-analysis. The results showed that PRP combined with minoxidil significantly improved hair growth compared to minoxidil or PRP alone. The pooled analysis demonstrated a significant increase in hair density (weighted mean difference [WMD] = 9.14; 95% confidence interval [CI]: 6.57-11.70) and hair diameter (WMD = 4.72; 95% CI 3.21-6.23) in the PRP combined with minoxidil group. Moreover, patients receiving PRP combined with minoxidil reported higher satisfaction rates compared to those using minoxidil or PRP alone. CONCLUSIONS: This meta-analysis suggests that PRP combined with minoxidil is an effective treatment for AGA, providing significant improvement in hair growth and patient satisfaction. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Trilayer dissolving microneedle for transdermal delivery of minoxidil: a proof-of-concept study.

Alopecia areata (AA) is a chronic autoimmune disease characterized by bald patches in certain areas of the body, especially the scalp. Minoxidil (MNX), as a first-line treatment of AA, effectively induces hair growth. However, oral and topical administration pose problems, including low bioavailability, risk of uncontrolled hair growth, and local side effects such as burning hair loss, and scalp irritation. In the latest research, MNX was delivered to the skin via microneedle (MN) transdermally. The MNX concentration was distributed throughout the needle so that drug penetration was reduced and had the potential to irritate. In this study, we formulated MNX into three-layer dissolving microneedles (TDMN) to increase drug penetration and avoid irritation. Physicochemical evaluation, parafilm, was used to evaluate the mechanical strength of TDMN and showed that TDMN could penetrate the stratum corneum. The ex-vivo permeation test showed that the highest average permeation result was obtained for TDMN2, namely 165.28 ± 31.87 ug/cm2, while for Minoxidil cream it was 46.03 ± 8.5 ug/cm2. The results of ex vivo and in vivo dermatokinetic tests showed that the amount of drug concentration remaining in the skin from the TDMN2 formula was higher compared to the cream preparation. The formula developed has no potential for irritation and toxicity based on the HET-CAM test and hemolysis test. TDMN is a promising alternative to administering MNX to overcome MNX problems and increase the effectiveness of AA therapy.

Patient-reported outcomes of topical finasteride/minoxidil treatment for male androgenetic alopecia: A retrospective study using telemedical data.

BACKGROUND: Oral finasteride and topical minoxidil are the current standard of care for male androgenetic alopecia and a combination of the two treatments can be considered for greater efficacy. Clinical trials of topical finasteride have also yielded promising results, but routine care data are lacking. AIMS: To examine patient-reported outcomes of men with androgenetic alopecia who received topical finasteride admixed with minoxidil compared to the current standard of care (oral finasteride). METHODS: Retrospective, cross-sectional study with data from a German direct-to-consumer teledermatology platform between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided after 6 weeks on topical finasteride/minoxidil or oral finasteride treatment. RESULTS: A total of 1545 patients who received topical finasteride/minoxidil treatment were included; 238 (15.4%) participated in the follow-up questionnaire. At week six, 62.2% (148/238) reported positive changes in their hair appearance, and 44.1% (105/238) reported an improvement of self-esteem. Treatment-related adverse events were reported in 11.8% (28/238). Full treatment adherence was observed in 74.4% (177/238). Comparing the topical treatment group to those receiving oral finasteride, lower treatment adherence was reported, along with higher rates of local adverse events; no difference was found in the incidence of sexual adverse events. CONCLUSION: Based on patient-reported outcomes, topical finasteride/minoxidil seems to be effective and well tolerated, but not superior to oral finasteride. Lower treatment adherence for topical usage must be considered when considering treatment options. Additional real-world data are needed to further evaluate the efficacy and safety of topical finasteride/minoxidil.