Paradoxical Hypertrichosis Associated with Laser and Light Therapy for Hair Removal: A Systematic Review and Meta-analysis.

BACKGROUND: Paradoxical hypertrichosis (PH) is an uncommon, poorly understood adverse effect associated with laser or intense pulsed light treatment for hair removal. OBJECTIVE: The objective of this study was to conduct a systematic review and meta-analysis to determine PH prevalence and associated risk factors. METHODS: We conducted a systematic review and meta-analysis of studies evaluating hair removal with lasers or intense pulsed light. Primary outcome was PH prevalence. Meta-regression and subgroup analysis were used to investigate associations among treatment modality, patients' characteristics, and PH. RESULTS: Included were 9733 patients in two randomized controlled trials and 20 cohort studies (three prospective and 17 retrospective). Pooled PH prevalence was 3% (95% confidence interval 1-6; I2 = 97%). Paradoxical hypertrichosis was associated with a face or neck anatomic location, and occurred in only 0.08% of non-facial/neck cases. Treatment modality and interval between treatments had no effect on the PH rate. There were insufficient data to determine the association between sex and skin type to PH. In three out of four studies, PH gradually improved with continued therapy. CONCLUSIONS: Based primarily on cohort studies, PH occurs in 3% of patients undergoing hair removal with lasers or intense pulsed light, yet rarely outside the facial/neck areas. Treatment modality does not seem to be a contributing factor. Continuation of treatment in areas with PH may be the most appropriate treatment.

Single-cell transcriptomic analysis of small and large wounds reveals the distinct spatial organization of regenerative fibroblasts.

Wound-induced hair follicle neogenesis (WIHN) has been an important model to study hair follicle regeneration during wound repair. However, the cellular and molecular components of the dermis that make large wounds more regenerative are not fully understood. Here, we compare and contrast recently published scRNA-seq data of small scarring wounds to wounds that regenerate in hope to elucidate the role of fibroblasts lineages in WIHN. Our analysis revealed an over-representation of the newly identified upper wound fibroblasts in regenerative wound conditions, which express the retinoic acid binding protein Crabp1. This regenerative cell type shares a similar gene signature to the murine papillary fibroblast lineage, which are necessary to support hair follicle morphogenesis and homeostasis. RNA velocity analysis comparing scarring and regenerating wounds revealed the divergent trajectories towards upper and lower wound fibroblasts and that the upper populations were closely associated with the specialized dermal papilla. We also provide analyses and explanation reconciling the inconsistency between the histological lineage tracing and the scRNA-seq data from recent reports investigating large wounds. Finally, we performed a computational test to map the spatial location of upper wound fibroblasts in large wounds which revealed that upper peripheral fibroblasts might harbour equivalent regenerative competence as those in the centre. Overall, our scRNA-seq reanalysis combining multiple samples suggests that upper wound fibroblasts are required for hair follicle regeneration and that papillary fibroblasts may migrate from the wound periphery to the centre during wound re-epithelialization. Moreover, data from this publication are made available on our searchable web resource: https://skinregeneration.org/.

Getting under the skin of hair aging: the impact of the hair follicle environment.

Like the skin, our hair shows striking changes with age, producing hairs with altered diameter, lustre and texture. The biology of hair aging has focused predominately on various aspects of the hair cycle, follicle size and the fibre produced, but surprisingly the impact of the aging scalp dermal environment on the hair follicle and fibre has been generally overlooked. Hair loss affects both sexes with incidence increasing with age. In men, male pattern-balding (androgenetic alopecia) is driven by androgens and follows a specific pattern of frontotemporal and vertex regression. Women also experience female pattern hair loss (FPHL), presenting as more general, diffuse hair thinning. Hair thinning in women is commonly associated with the menopause, corresponding with other age-related changes in skin. The rapidly growing hair follicle undergoes continued renewal throughout the life span of an individual, where it is exposed to a substantial number of extrinsic and intrinsic stressors. As the hair follicle sits deep within the dermis with its bulb residing in the hypodermis, detrimental age-related changes in the surrounding scalp skin may likely disrupt the hair follicle machinery. The impacts of these changes are unknown, but evidence suggests that scalp skin aging and hair follicle aging go hand-in-hand. Herein, we summarize the evidence that the age-related changes observed in sun-exposed human skin also occur in scalp skin and that these changes are likely to play a contributing role in the aging hair phenotype.

Functional complexity of hair follicle stem cell niche and therapeutic targeting of niche dysfunction for hair regeneration.

Stem cell activity is subject to non-cell-autonomous regulation from the local microenvironment, or niche. In adaption to varying physiological conditions and the ever-changing external environment, the stem cell niche has evolved with multifunctionality that enables stem cells to detect these changes and to communicate with remote cells/tissues to tailor their activity for organismal needs. The cyclic growth of hair follicles is powered by hair follicle stem cells (HFSCs). Using HFSCs as a model, we categorize niche cells into 3 functional modules, including signaling, sensing and message-relaying. Signaling modules, such as dermal papilla cells, immune cells and adipocytes, regulate HFSC activity through short-range cell-cell contact or paracrine effects. Macrophages capacitate the HFSC niche to sense tissue injury and mechanical cues and adipocytes seem to modulate HFSC activity in response to systemic nutritional states. Sympathetic nerves implement the message-relaying function by transmitting external light signals through an ipRGC-SCN-sympathetic circuit to facilitate hair regeneration. Hair growth can be disrupted by niche pathology, e.g. dysfunction of dermal papilla cells in androgenetic alopecia and influx of auto-reacting T cells in alopecia areata and lichen planopilaris. Understanding the functions and pathological changes of the HFSC niche can provide new insight for the treatment of hair loss.

Seventy-MHz Ultrasound Detection of Early Signs Linked to the Severity, Patterns of Keratin Fragmentation, and Mechanisms of Generation of Collections and Tunnels in Hidradenitis Suppurativa.

OBJECTIVES: To test the capability of 70-MHz ultrasound for detecting initial ultrasound signs of hidradenitis suppurativa (HS) linked to severity. METHODS: A cross-sectional study of the ultrasound images of patients with HS was conducted and compared with a healthy control group. Detection and identification of early subclinical ultrasound signs in the lesional and perilesional areas of the HS cases in comparison with the control group were performed. Statistical analyses included mean, dispersion measures, the Kruskal-Wallis test, and bivariate and multivariate ordered logistic regression studies. Significance was assessed at P < .05. RESULTS: A total of 139 patients with HS met the criteria and showed abnormalities of the hair follicles such as a curved shape, ballooning, and protrusion into pseudocysts, collections, or tunnels (donor of keratin sign). Significant increases in the sizes of the hair follicles and hair shafts were found in HS cases. The following ultrasound signs were significantly linked to severity: a connecting band between the base of adjacent hair follicles (bridge sign), a fragment of the hair shaft extruding through a dilated hair follicle (sword sign), and retained cylindrical fragments of keratin in the dermis. Two patterns of fragmentation of the keratin were detected: multifragment and cylindrical. CONCLUSIONS: Ultrasound can detect early HS signs that are significantly linked to severity and 2 types of fragmentation of the keratin, which could support the generation and perpetuation of the fluid collections and tunnels. These ultrasound signs can help prompt diagnosis and management, the development and testing of medications, and the measure of treatment outcomes in HS.

Self-Activated Electrical Stimulation for Effective Hair Regeneration via a Wearable Omnidirectional Pulse Generator.

Hair loss, a common and distressing symptom, has been plaguing humans. Various pharmacological and nonpharmacological treatments have been widely studied to achieve the desired effect for hair regeneration. As a nonpharmacological physical approach, physiologically appropriate alternating electric field plays a key role in the field of regenerative tissue engineering. Here, a universal motion-activated and wearable electric stimulation device that can effectively promote hair regeneration via random body motions was designed. Significantly facilitated hair regeneration results were obtained from Sprague-Dawley rats and nude mice. Higher hair follicle density and longer hair shaft length were observed on Sprague-Dawley rats when the device was employed compared to conventional pharmacological treatments. The device can also improve the secretion of vascular endothelial growth factor and keratinocyte growth factor and thereby alleviate hair keratin disorder, increase the number of hair follicles, and promote hair regeneration on genetically defective nude mice. This work provides an effective hair regeneration strategy in the context of a nonpharmacological self-powered wearable electronic device.

Review of Human Hair Follicle Biology: Dynamics of Niches and Stem Cell Regulation for Possible Therapeutic Hair Stimulation for Plastic Surgeons.

Plastic surgeons are frequently asked to manage male- and female-pattern hair loss in their practice. This article discusses the epidemiology, pathophysiology, and current management of androgenetic alopecia and emphasizes more recent knowledge of stem cell niches in hair follicles that drive hair cycling, alopecia, and its treatment. The many treatment programs available for hair loss include newer strategies that involve the usage of growth factors, platelet-rich plasma, and fat to stimulate follicle growth. Future research may clarify novel biomolecular mechanisms that target specific cells that promote hair regeneration.Level of Evidence V 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 .

Human long-term deregulated circadian rhythm alters regenerative properties of skin and hair precursor cells.

In mammals, desynchronized circadian rhythm leads to various biological symptoms. In skin and hair, human epidermal stem cell function in vitro is regulated by circadian oscillations, and thus contributes to tissue aging when deregulated. In mice, circadian arrhythmia of hair follicle stem cells contributes to age-related hair follicle cycling defects. Despite the well-described impact of circadian oscillations through a feedback loop involving the clock pathway on hair and skin stem cell function in vitro, little is known about the change in characteristics or regenerative properties of hHF (human hair follicle keratinocytes), hEpi (human interfollicular epidermal keratinocytes), and hHFDP (hair follicle dermal papilla stem cells) after long-term alteration of circadian rhythm in vivo. The present study was designed to asses hHF, hEpi, and hHFDP precursors and stem cell properties in response to clock pathway alteration due to long-term deregulated circadian rhythm in vivo. A clinical study protocol was designed to include two groups of women: diurnal workers (control) and shift workers (deregulated). After informed consent, two 3-mm fresh punch biopsies were taken from the occipital region of each donor (10 donors/group). Cell culture characterization, measurement of colony area, culture medium analysis, and RT-qPCR analysis were carried out. Long-term circadian rhythm deregulation affected clock pathway protein expression and correlated with alterations in hHF, hEpi, and hHFDP properties. This study provides, for the first time in humans, evidence that in vivo deregulation of the clock pathway affects regenerative properties of human skin and hair precursor cells.

Embryonic-like regenerative phenomenon: wound-induced hair follicle neogenesis.

Wound-induced hair follicle neogenesis (WIHN) is a regenerative phenomenon that occurs widely in the skin of adult mammalians. A fully functional follicle can regenerate in the center of a full-thickness wound with a large enough size. The cellular origin of this process is similar to embryonic process. Many growth and development-related pathways are involved in WIHN. Studying WIHN can deeply explore the mechanism of biological growth, development and regeneration, and can identify new treatments for hair-related disorders. Our review aims to enlighten future study by summarizing the clinical manifestation of WIHN, as well as the cellular and molecular mechanism of WIHN in recent studies.

Thermal modelling of controlled scalp hypothermia using a thermoelectric cooling cap.

This study presents a novel, thermoelectric cryotherapy cap that aims to provide effective and controlled scalp cooling to prevent hair loss for chemotherapy patients. The cap's design consists of multiple thermoelectric coolers (TECs) evenly spaced and bonded to a soft thermal interface material, tightly fitted to a patient's head. A numerical model is developed to assess the performance of alternative cap designs in relation to their ability to achieve hair follicle hypothermia. Under ideal conditions, 26.5 W of heat removal from the scalp is required to achieve the clinically-significant follicle temperature target of 22 °C. Temperature maps of the subcutaneous tissue are generated to visualise the development of hypothermic follicles, and thereby assess the effectiveness of the cap design. Transient studies show that cooling to the therapeutic temperature can be achieved within 40 min. To avoid the possibility of cold-induced tissue damage, individual thermoelectric cooling modules should not be operated at a cooling flux beyond approximately 3175 W/m2. This may be achieved with 38 modules evenly spaced in a checkerboard arrangement, each providing 0.7 W of cooling to the scalp.

Decorin promotes proliferation and migration of ORS keratinocytes and maintains hair anagen in mice.

DECORIN is a prototypical member of the small leucine-rich proteoglycan (SLRP) family that plays important roles in numerous biological processes and cellular biological pathways. We previously showed that Decorin expression was highly enhanced in mouse dorsal hair follicles (HFs) during the anagen phase and was reduced during the catagen and telogen phases, suggesting that Decorin might modulate follicular cycling and morphogenesis. In this study, to further clarify the effects of DECORIN on hair cells and the cycling transition, an in vitro overexpression strategy and Decorin-null (Dcn-/- ) mice were used to investigate the effects of DECORIN on outer root sheath (ORS) keratinocytes. DECORIN overexpression significantly enhanced proliferation and migration in ORS keratinocytes in vitro. Moreover, DECORIN overexpression upregulated the mRNA and protein expression levels of WNT10b, ß-CATENIN and LEF1. The DECORIN overexpression-induced increase in the proliferation and migration of ORS keratinocytes was partially inhibited by a Wnt/ß-catenin inhibitor. Furthermore, Dcn-/- mice had a shortened anagen phase and lower levels of ß-catenin expression than were observed in wild-type mice in imaging and histological analyses. Taken together, these findings suggest that DECORIN promotes the proliferation and migration of ORS keratinocytes in vitro and maintains hair anagen in mice.

Pathogenesis and treatment options for chemotherapy-induced alopecia: a systematic review.

Chemotherapy-induced alopecia (CIA) is one of the most troubling long-lasting side effects of cancer treatment. An estimated 65% of patients undergoing classic chemotherapy will experience hair loss, which is an extremely upsetting adverse event for many. CIA has been traditionally considered to be a diffuse, nonscarring alopecia; however, there are increasing reports of permanent hair loss post chemotherapy. Despite its large impact on patients, there are few proven treatments for CIA. Recent advancements in understanding the pathogenesis of hair loss are promising novel preventative and therapeutic strategies. Currently, scalp cooling during chemotherapy is the most effective preventive intervention with response rates ranging from 50 to 80%. To avoid patient morbidity, clinicians should be aware of the pathogenesis of CIA, characteristic patterns of hair loss associated with specific drug regimens, preventive measures that may be taken, and therapeutic options post chemotherapy. The following represents an updated systematic review of CIA, including characteristic clinical patterns, pathophysiology of the disease, therapeutic approaches, as well as a cost-effective analysis to assess the significance of this toxicity.

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%).

New Insight Into the Pathophysiology of Hair Loss Trigger a Paradigm Shift in the Treatment Approach.

Hair loss affects millions of men and women of all ages and ethnicities, impacting appearance, social interactions, and psycho-emotional well-being. Although a number of options are available, they are limited, carry a potential risk of side effects, and none have proven to be comprehensive for treatment of hair loss. Across the spectrum of hair loss disorders, there has long been a segmentation into distinct mechanisms, driving the main trend in current therapeutics to focus on targeting single molecules or pathways. However, research points to similar dysregulation of intrinsic signaling pathways within follicle physiology that span the hair loss disorder spectrum - with a common inflammatory component identified in most hair loss pathogenesis, including that of androgenetic alopecia (AGA).

J Drugs Dermatol. 2017;16(11 Suppl):s135-140.

Effects of two chronic stresses on mental state and hair follicle melanogenesis in mice.

Growing bodies of data show that psychological stress can be associated with hair loss and vitiligo. Researchers have revealed that stress could indeed inhibit hair growth in vivo, but the relationship between chronic stress and melanogenesis remains unknown. In this study, we established two types of stress models, chronic restraint stress (CRS) and chronic unpredicted mild stress (CUMS) mice models, and explored the possible role of stress in mice hair follicle melanogenesis. We found that stress changed hippocampal morphology, decreased 5-HT level in brain and skin and down-regulated 5-HT1A receptor expression in hippocampal CA1 region and skin. The alterations of 5-HT and 5-HT1A receptor might be a threshold of central stress to associate with the behaviour changes. Both two stresses caused cellular damage of melanocytes and inhibition of keratinocytes proliferation in HF, which made the synthetic pigment loss. CRS which was considered primarily as a "psychological" stressor had the lower melanin production in HF, as well as the level of 5-HT in skin was down-regulated more than those in CUMS group.

Higher plasma leptin is associated with higher risk of androgenetic alopecia in men.

In addition to genetics and androgens, novel factors could play a role in androgenetic alopecia (AGA). This study aims to investigate the association between plasma leptin level with the risk and severity of AGA in men. Forty-eight subjects were enrolled including 29 AGA and 19 non-AGA subjects. The plasma leptin level was significantly higher in AGA subjects, compared to non-AGA subjects (4.45 vs 2.76 ng/mL, P<.05). A higher plasma leptin levels were positively correlated with the risk of developing AGA in multivariate logistic analysis (odds ratio=2.77, P<.05). Leptin from the circulation might impact the development of AGA.