Spironolactone in adolescent acne vulgaris.

Acne vulgaris (AV) is the most common skin condition affecting adolescents, most likely due to elevated androgen levels during puberty. Androgens stimulate and enlarge the sebaceous glands and keratinocytes, resulting in increased production of sebum and abnormal hyperproliferation of keratinocytes which lead to the formation of acne lesions. Current standard of care for AV includes topical therapies for mild cases and antibiotics or oral retinoids for severe cases. In recent years, spironolactone, an aldosterone antagonist and diuretic, has been applied to the treatment of AV due to its anti-androgen effects. Spironolactone is currently recommended in women who use oral contraceptives, are refractory to or contraindicated for standard treatment, show clinical signs of hyperandrogenism, or present with late-onset or persistent-recurrent AV past the teenage years. It is not prescribed to adolescents due to potential side effects; however, current data studying adults indicate that most side effects are mild, and that potential associations with hyperkalemia and increased risk of cancer are not sufficiently supported. Hence, we believe that spironolactone may be a safe and effective therapy for adolescent AV.

Vemurafenib and cobimetinib-induced toxic epidermal necrolysis in a patient with metastatic melanoma.

Combination therapy in the treatment of metastatic melanoma has been associated with more durable response rate compared to monotherapy. However, previous studies have shown that combined target therapy commonly causes a wide spectrum of adverse events. These adverse reactions are usually manageable, however, it is always necessary to compare drug efficacy with its potential adverse effects. Toxic epidermal necrolysis represents severe mucocutaneous reaction, usually triggered by medications and characterized by extensive necrosis and detachment of the epidermis. Here we present a first case of toxic epidermal necrolysis induced by combined target therapy (vemurafenib plus cobimetinib). The case was observed in a young patient with BRAF mutant melanoma who was started on first-line metastatic immunotherapy with pembrolisumab.

Allergic contact dermatitis in patients with frontal fibrosing alopecia: An international multi-center study.

Frontal fibrosing alopecia (FFA) mainly affects the anterior hairline and eyebrows and its etiology and associated factors remain obscure. The aim of this study was to evaluate the allergic contact dermatitis with patch test in patients with FFA. In this prospective study, 20 patients with FFA and 24 age and sex-matched healthy individuals were evaluated with patch testing. Diagnosis was made histologically, clinically and based on dermoscopic findings. Demographic data, age of onset, disease duration and FFA severity index are evaluated in all patients. Positive patch test reaction to one or more allergen was observed in 65% of patients while it was 37.5% in control group (P = .003). There was a significant difference between age (P = .006) and positive patch test results. No statistical significant difference was observed in the results of patch testing and disease duration (P = .519), menopausal status (P = .085), and FFA severity index (P = .573). Our findings suggest an association between FFA and allergic contact dermatitis. The utility of patch testing in FFA patients can explore the role of allergic etiology and may have an enormous impact on the diagnostic potential and quality of life of these patients.

Efficacy of topical latanoprost in the treatment of eyelid vitiligo: A randomized, double-blind clinical trial study.

Numerous studies have demonstrated that the pigmentation of iris and around the eyelid is a common side effect of latanoprost, a prostaglandin F2alpha analogue used in the treatment of glaucoma. Hence, the authors decided to study the effectiveness of topical latanoprost on vitiligo patches around the eyelid. In this randomized, double-blind, clinical trial study, 31 patients with vitiligo vulgaris and focal vitiligo involving the eyelids were evaluated. Patients were randomly divided into two groups. First group received topical latanoprost gel twice daily for 12 weeks, whereas the second group received placebo with the same protocol. To evaluate severity of the disease the VIDA rating system was used. Serial photos of the patches were taken to compare and evaluate the repigmentation percentage of the patches. The patients in both groups had almost similar VIDA score (p > .05). First group showed improved pigmentation, whereas participants in the second group did not show any improvement in the pigmentation. The group treated with latanoprost showed significant reduction in the symptoms of the disease, whereas those treated with placebo did not show any alteration (p > .05). No significant complications were observed in either groups. Latanoprost proved effective in treating vitiligo disease involving eyelids.

Low-level laser therapy and narrative review of other treatment modalities in androgenetic alopecia.

Androgenetic alopecia (AGA), also termed as androgenic alopecia or common baldness, is a condition where there is androgen mediated conversion of susceptible terminal hair into vellus hair. Although it is reported more commonly in males, it also affects females but the incidence is relatively unknown. AGA tremendously affects the psychology of the patient due to its chronicity of treatment and cosmetic implications. There are numerous treatment options available for AGA but the choice of treatment has to often be tailored according to the patient's needs, affordability, and compliance. This review focusses on the various treatment options available, with special emphasis on the role of low-level laser therapy (LLLT) in the management of AGA. The literature research considered published journal articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) and reference lists of respective articles. Only articles available in English were considered for this review.

Androgen sensitivity gateway to COVID-19 disease severity.

In this communication, we present arguments for androgen sensitivity as a likely determinant of COVID-19 disease severity. The androgen sensitivity model explains why males are more likely to develop severe symptoms while children are ostensibly resistant to infection. Further, the model explains the difference in COVID-19 mortality rates among different ethnicities. Androgen sensitivity is determined by genetic variants of the androgen receptor. The androgen receptor regulates transcription of the transmembrane protease, serine 2 (TMPRSS2), which is required for SARS-CoV-2 infectivity. TMPRSS2 primes the Spike protein of the virus, which has two consequences: diminishing viral recognition by neutralizing antibodies and activating SARS-CoV-2 for virus-cell fusion. Genetic variants that have been associated with androgenetic alopecia, prostate cancer, benign prostatic hyperplasia and polycystic ovary syndrome could be associated with host susceptibility. In addition to theoretical epidemiological and molecular mechanisms, there are reports of high rates of androgenetic alopecia of from hospitalized COVID-19 patients due to severe symptoms. Androgen sensitivity is a likely determinant of COVID-19 disease severity. We believe that the evidence presented in this communication warrants the initiation of trials using anti-androgen agents.

Mission impossible: Dermal delivery of growth factors via microneedling.

The clinical application of transdermal delivery has been limited to lipophilic drugs with a molecular weight of less than 500 Da. The development of polymeric microneedles enabled the transdermal delivery of larger proteins and drugs. Extensive research has been conducted on the molecular size, solubility, pH, concentration, and polarity of transdermal delivery; however, the maximal molecular weight for transdermal microneedle delivery has not been established. Clinicians often use simple microneedles to deliver high molecular weight growth factors of platelet-rich plasma across the skin; thus, we set out to explore the feasibility of delivering growth factors through microneedling. In this communication, we present histological evidence that microneedling do not enhance transdermal delivery of growth factors and thus provide no clinical benefit.

Frontal pattern hair loss among Chinese women is frequently associated with ponytail hairstyle.

Female alopecia patients in China often present with a frontal pattern hair loss. This feature is seen less frequently in western women. Women in China frequently style their hair in a ponytail. Thus, we hypothesized that the high prevalence of frontal pattern hair loss in Chinese women is due to traction alopecia. To better understand this, we studied 43 women presenting frontal alopecia at a hair clinic. Among the women presenting frontal alopecia, 79% reported styling their hair in a ponytail four or more days per week for an average period of 10 years. To our knowledge, this is the first study to elucidate the cause of frequent frontal alopecia in Chinese women. Although cultural style changes are difficult to change, we believe that awareness of the medical implications of frequent ponytail styling will reduce the rate of frontal alopecia among Chinese women.

Platelet rich plasma in androgenetic alopecia: A systematic review.

In recent years, dozens of manufacturers and clinics have been promoting the use of platelet rich plasma (PRP) procedures for skin and hair regeneration. Well-designed randomized controlled studies for these procedures are lacking. In this communication, we review the efficacy and safety of PRP procedures for androgenetic alopecia from multiple published peer-reviewed studies. The conclusion of our analysis is that until the present moment there is not enough evidence for the use of PRP procedures in the treatment of androgenetic alopecia. We hope that this review will help practitioners and patients to make better-informed treatment decisions.

Tretinoin enhances minoxidil response in androgenetic alopecia patients by upregulating follicular sulfotransferase enzymes.

Minoxidil sulfate is the active metabolite required to exert the vasodilatory and hair growing effects of minoxidil. For hair growth, sulfotransferase enzymes expressed in outer root sheath of the hair follicle sulfonate minoxidil. The large intra-subject variability in follicular sulfotransferase was found to predict minoxidil response and thus explain the low response rate to topical minoxidil in the treatment of androgenetic alopecia. A method to increase minoxidil response would be of significant clinical utility. Retinoids have been reported to increase minoxidil response. The purported mechanism of action was retinoid modulation of skin permeation to minoxidil; however, evidence to the contrary supports retinoids increase dermal thickness. In order to elucidate the effect of topical retinoids on minoxidil response, we studied the effect of topical tretinoin on follicular sulfotransferase. In this study, we demonstrate that topical tretinoin application influences the expression of follicular sulfotransferase. Of clinical significance, in our cohort, 43% of subjects initially predicted to be nonresponders to minoxidil were converted to responders following 5 days of topical tretinoin application. To the best of our knowledge, this is the first study to elucidate the interaction mechanism between topical minoxidil and retinoids and thus provides a pathway for the development of future androgenetic alopecia treatments.

Minoxidil in the treatment of androgenetic alopecia.

The National Institutes of Health (US NIH, 2018) estimates that in the US approximately 50 million men and 30 million women suffer from AGA (also known as pattern hair loss). Minoxidil is the only topical drug for the treatment of both female and male pattern hair loss. In the US, minoxidil is approved over-the-counter (OTC) at a maximum concentration of 5%. In this review, we summarize the findings of the pivotal studies used in support of the drug's approval as well as recent discoveries and novel developments in the use of minoxidil for the treatment of AGA.

Styling without shedding: Novel topical formula reduces hair shedding by contracting the arrector pili muscle.

Approximately 40% of women experience excessive hair shedding during styling (e.g., hair brushing). Previously, we demonstrated that topically applied phenylephrine, a potent α1 adrenergic receptor agonist, can be used to contract the arrector pili muscle of the follicular unit; thus, increasing the force required to pluck hair and reducing shedding during brushing. While demonstrating efficacy, phenylephrine has several drawbacks when applied to the scalp, including the possibility cardiovascular events. We hypothesized that a high concentration of a weak α1 agonist would allow for: (a) rapid penetration through the stratum corneum eliciting a quick response; (b) a low probability of cardiac adverse events owing to the low receptor binding affinity; and (c) an efficacy of the weak α1 agonist similar to that of phenylephrine at the local site of application. Accordingly, we developed a novel topical solution, AB-102, containing a high concentration of a weak α1 agonist. Several studies were conducted to test the safety and efficacy of AB-102. In a dose escalating safety study, utilizing a wearable holter monitor, we observed no cardiac or hemodynamic adverse events. In addition, in a controlled efficacy study, AB-102 reduced the number of hairs shed during brushing by up to 77% (average of 38%).

Anterior, frontal congenital triangular alopecia, redundancy in therapy without improvement.

Congenital triangular alopecia (CTA) is a benign noncicatricial localized pattern of hair loss with unknown etiology. Although referred to as "congenital," CTA may develop in adulthood. It is believed that many cases of CTA are never diagnosed or are misdiagnosed; causing the incidence to be underestimated. The present study evaluates a case of 20-year-old woman presenting with a single circular to oval area of hair-loss in the mid-frontal region of her scalp. To date, about 170 cases of CTA have been reported and we present the first case in which the alopecic patch is located in the mid-frontal region of the scalp. We present this case not only to challenge the preconceived notion that all CTAs are frontotemporal, but also to inform other practitioners about this rare condition and prevent redundant medical treatment.

Characterization of follicular minoxidil sulfotransferase activity in a cohort of pattern hair loss patients from the Indian Subcontinent.

Several studies have established that sulfotransferase enzyme activity in the outer root sheath of plucked hair follicles predicts response to topical minoxidil in the treatment of pattern hair loss. However, the prevalence of this enzyme activity among Indian patients has not been studied. Additionally, no reports in the literature characterize sulfotransferase activity based on sex, age, duration of hair loss, grade of hair loss, and family history. In this study we utilized a sulfotransferase activity assay first reported by Goren et al. We characterize the follicular sulfotransferase activity of 120 pattern hair loss patients visiting a dermatology outpatient clinic in India. Overall, 40.8% of patients with pattern hair loss had low levels of sulfotransferase. Surprisingly, 49.3% of men had low levels of sulfotransferase compared to 26.6% of women. No correlation was found between sulfotransferase activity and age, duration of hair loss, grade of hair loss, or family history. A sub-analysis of patient reported outcomes (PRO) validated previous findings that sulfotransferase enzyme activity is a predictive marker for minoxidil response in pattern hair loss patients.

Prevalence of hair shedding among women.

Hair shedding in female patients is a frequent complaint in dermatological, endocrinological, and gynecological consults. Previously, the Sinclair Hair Shedding Scale was developed to assess normal versus excessive hair shedding in female pattern hair loss (FPHL) subjects. However, the prevalence of hair shedding in females not suffering from FPHL is unknown. To gain better understanding of hair shedding in the general population, we recruited 300 subjects visiting a public hospital for conditions other than alopecia. Of the 300 subjects recruited, 263 did not suffer from FPHL. Among those subjects, approximately 40% reported experiencing excessive hair shedding (as defined by the Sinclair Hair Shedding Scale) on hair washing days. In comparison, in our subject population, approximately 60% of subjects with FPHL reported excessive hair shedding on hair washing days. To best of our knowledge, this is the first study to quantify the prevalence of hair shedding in women. While, no treatment currently exists for this condition, we hope that this study would encourage physicians and researchers to address this frequent concern.

α1 -AR agonist induced piloerection protects against the development of traction alopecia.

Traction alopecia is hair loss that occurs after persistent pulling (e.g., during cosmetic procedures) on the roots of hair over time. Unlike plucking, which is painful, persistent pulling may go unnoticed until a patient presents with either bald spots or diffuse telogen shedding. Each hair follicle in the scalp contains an arrector pili muscle that, when contracted, erects the hair. The smooth muscle in the arrector pili expresses α1 adrenergic receptors (α1 -AR). As such, we hypothesized that contraction of the arrector pili muscle via an α1 -AR agonist would increase the threshold of force required to pluck hair during cosmetic procedures. Female subjects, ages 18-40, were recruited to study the effect of topically applied phenylephrine, a selective α1 -AR agonist, on epilation force and hair shedding during cosmetic procedures. In our blinded study, 80% of subjects demonstrated reduced shedding on days using phenylephrine compared to days using a placebo solution. The average reduction in hair loss was approximately 42%. In addition, the force threshold required for epilation increased by approximately 172% following topical phenylephrine application. To our knowledge this is the first study demonstrating the utility of α1 -AR agonists in the treatment of traction alopecia and hair shedding during cosmetic procedures.