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Background: Female pattern hair loss (FPHL) is women's most common form of alopecia. The study aimed to evaluate the efficacy of extracorporeal shock waves for hair growth and regeneration in women with FPHL., Methods: A prospective single-center noncontrolled study was conducted in patients with FPHL who underwent eight treatment sessions with C-Actor, a shock wave applicator. Outcome measures included total hair count, number of follicular units (FUs)-single FUs, double FUs, triple and bigger FUs-the average thickness, cumulative hair thickness, and changes in the Derived Sinclair scale, assessed with Tricholab (Fotofinder System). Patients completed a survey to assess their subjective perceptions of hair improvement regarding softness, hair loss, quality, and volume., Results: Twenty women were included with a mean age of 43 (SD = 5.65). The mean increase in total hair count was 8.9% (p < 0.00001), in number of FUs 4.6% (p = 0.00031), in number of triple and bigger FUs 18.4% (p = 0.0004), in cumulative hair thickness 8.0% (p < 0.00001), with a decrease of 5.7% in mean Derived Sinclair scale value by 2.2-2.1 (p < 0.0001). After 3 months, 85% of patients perceived improvement in hair volume., Conclusion: Extracorporeal shock waves for hair growth and capillary regeneration in women with FPHL showed statistically significant outcomes, and all patients reported an improvement in hair characteristics., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

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; I 2 = 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., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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/., (© 2020 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

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., (© 2020 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

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., (© 2019 by the American Institute of Ultrasound in Medicine.)

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.

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.

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 .

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., (© 2018 The International Society of Dermatology.)

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, β-CATENIN and LEF1. The DECORIN overexpression-induced increase in the proliferation and migration of ORS keratinocytes was partially inhibited by a Wnt/β-catenin inhibitor. Furthermore, Dcn -/- mice had a shortened anagen phase and lower levels of β-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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

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/m 2 . This may be achieved with 38 modules evenly spaced in a checkerboard arrangement, each providing 0.7 W of cooling to the scalp., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.

Approximately 40% of women experience excessive hair shedding during styling (e.g., hair brushing). Previously, we demonstrated that topically applied phenylephrine, a potent α 1 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 α 1 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 α 1 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 α 1 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%)., (© 2017 Wiley Periodicals, Inc.)

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.

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., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The hair follicle is a mini-organ endowed with a unique structure and cyclic behaviour. Despite the intense research efforts which have been devoted at deciphering the hair follicle biology over the past 70 years, one must admit that hair follicle remains an enigma. In this brief review, various aspects of hair follicle biology will be addressed, and more importantly, unsolved questions and new possible research tracks will be highlighted, including hair follicle glycobiology and exosome-mediated cell-cell interactions. Even though bricks of knowledge are solidly being acquired, an integrative picture remains to emerge. One can predict that computer science, algorithms and bioinformatics will assist in fostering our understanding hair biology., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Alopecia areata (AA) affects anagen hair follicles, resulting in non-scarring hair loss. Since introduced by Huang et al., superficial cryotherapy has been accepted as a considerable primary therapeutic modality for AA. The aim of this study was to objectively clarify the therapeutic efficacy and safety of superficial hypothermic cryotherapy for treatment of AA. Medical records of 353 patients from 1993 to 2014 were retrospectively analyzed. According to the response to the superficial cryotherapy, patients were categorized into four groups: "marked", "partial", "poor" and "no recovery". The marked and partial recovery groups were considered as responders. The proportions of the responders among patient subgroups which were defined by various patients, disease, and treatment factors were compared. Of the patients, 60.9% were classified as responders after 3 months of superficial hypothermic cryotherapy. The proportion of the responders were higher when the treatment interval was 2 weeks or less and in the incipient disease stage, with statistical significance. No severe side-effects other than mild pain and pruritus were reported. In conclusion, superficial cryotherapy is an effective and safe therapeutic modality for AA. Especially when the treatment interval is 2 weeks or less and in the first occurrence of the disease, the therapeutic outcome is superior., (© 2016 Japanese Dermatological Association.)

Intense pulsed light (IPL) has been used for years in hair reduction; however, no previous studies discussed quantitative histological and immunohistochemical changes of hair follicles after IPL. Accordingly, this study aims to objectively quantify histological and immunohistochemical changes of hair follicles after IPL hair reduction. Right axillae of 21 volunteers were subjected to 6 IPL sessions using Quanta system IPL and evaluated at 1 week and 1 month after last session (i.e., 3 and 4 months from the start of treatment, respectively) in comparison to baseline and left control axillae. Using hair count, histological and immunohistochemical assessment of vertical and serial transverse sections coupled with computerized morphometric analysis, determination of hair reduction percentage, measurement of hair shaft (HS) diameter, calculation of percentage of hair follicle types and quantitative evaluation of PCNA, Ki67 and P53 markers were performed. After IPL, there was significant decrease of hair count, HS diameter, percentage of terminal anagen follicles, terminal/vellus (T/V) ratio, anagen/telogen (A/T) ratio and expression of PCNA and Ki67; however, significant increase of percentage of terminal telogen and total vellus follicles with vellus-like type and P53 expression was identified. So, reduction of hair number and thickness occurred after IPL by induction of telogenesis and miniaturization through decreased hair follicle proliferation and increase in DNA damage that could favor apoptosis.

Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair-bearing sites. Patchy alopecia areata affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in the anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models have shown that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified to be associated with signalling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.

Type 2 Diabetes mellitus (DM2) includes a continuum of metabolic disorders characterized by hyperglycemia that causes several chronic long-term complications such as coronary artery disease, peripheral arterial disease, nephropathy, and neuropathy. The hair follicle could reveal signs of early vascular impairment, yet its relationship to early metabolic injuries has been largely ignored. We propose that in earlier stages of the continuum of DM2-related metabolic disorders, a group of susceptible patients who do not yet meet the diagnostic criteria to be considered as persons with DM2 may present chronic vascular impairment and end organ damage, including hair follicle damage, which can be evaluated to identify an early risk marker. This hypothesis is based in the association found between insulin resistance and alopecia in non-diabetic persons, and the hair loss on the lower limbs as a manifestation of long-term peripheral arterial disease among subjects with DM2. In order to test this hypothesis, studies are required to evaluate if hair follicle characteristics are related to and can predict hyperglycemic complications, and if they do so, which feature of the hair follicle, such as hair growth, best characterizes such DM2-related conditions. If this hypothesis were proven to be true, significant advances towards a personalized approach for early prevention strategies and management of DM2 would be made. By focusing on the hair follicles, early stages of metabolic-related organ damage could be identified using non-invasive low-cost techniques. In so doing, this approach could provide early identification of DM2-susceptible individuals and lead to the early initiation of adequate primary prevention strategies to reduce or avoid the onset of large internal organ damage., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Amputees may suffer from dermatoses such as folliculitis and pilonidal sinus caused by pressure on the stump in hairy parts of the skin. These conditions commonly cause pain and need treatment that result in abandonment of prosthesis use and disrupt the patient's daily living activities. We believe these conditions may be easily, effectively and cheaply prevented with the use of intense pulsed light technology, which is produced for home epilation. The use of this kind of epilator in the early period post-amputation may prevent the development of folliculitis and pilonidal sinus. This application may also be cost-effective in long term., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aiming to decipher immunological mechanisms of the autoimmune disorder alopecia areata (AA), we hypothesized that interleukin-6 (IL-6) might be associated with juvenile-onset AA, for which there is currently no experimental model. Upon intramuscular transgenesis to overexpress IL-6 in pregnant female C57BL/6 (B6) mice, we found that the offspring displayed an initial normal and complete juvenile hair growth cycle, but developed alopecia around postnatal day 18. This alopecia was patchy and reversible (non-scarring) and was associated with upregulation of Ulbp1 expression, the only mouse homolog of the human AA-associated ULBP3 gene. Alopecia was also associated with inflammatory infiltration of hair follicles by lymphocytes, including alpha-beta T cells, which contributed to surface hair loss. Despite these apparently shared traits with AA, lesions were dominated by follicular dystrophy that was atypical of human AA disease, sharing some traits consistent with B6 alopecia and dermatitis. Additionally, juvenile-onset alopecia was followed by complete, spontaneous recovery of surface hair, without recurrence of hair loss. Prolonging exposure to IL-6 prolonged the time to recovery, but once recovered, repeating high-dose IL-6 exposure de novo did not re-induce alopecia. These data suggest that although substantial molecular and cellular pathways may be shared, functionally similar alopecia disorders can occur via distinct pathological mechanisms., (© 2015 The Authors. Experimental Dermatology Published by John Wiley & Sons Ltd.)

Alopecia areata (AA) is a T-cell-mediated hair loss disorder but the exact cause is unknown. In this report we describe patterns of onset, regrowth and relapse in AA and propose potential underlying mechanisms. We believe that these aspects of AA require integration into modern theories of AA pathogenesis., (© 2014 The Australasian College of Dermatologists.)

Acne vulgaris is a chronic inflammatory disease - rather than a natural part of the life cycle as colloquially viewed - of the pilosebaceous unit (comprising the hair follicle, hair shaft and sebaceous gland) and is among the most common dermatological conditions worldwide. Some of the key mechanisms involved in the development of acne include disturbed sebaceous gland activity associated with hyperseborrhoea (that is, increased sebum production) and alterations in sebum fatty acid composition, dysregulation of the hormone microenvironment, interaction with neuropeptides, follicular hyperkeratinization, induction of inflammation and dysfunction of the innate and adaptive immunity. Grading of acne involves lesion counting and photographic methods. However, there is a lack of consensus on the exact grading criteria, which hampers the conduction and comparison of randomized controlled clinical trials evaluating treatments. Prevention of acne relies on the successful management of modifiable risk factors, such as underlying systemic diseases and lifestyle factors. Several treatments are available, but guidelines suffer from a lack of data to make evidence-based recommendations. In addition, the complex combination treatment regimens required to target different aspects of acne pathophysiology lead to poor adherence, which undermines treatment success. Acne commonly causes scarring and reduces the quality of life of patients. New treatment options with a shift towards targeting the early processes involved in acne development instead of suppressing the effects of end products will enhance our ability to improve the outcomes for patients with acne.

Female Pattern Hair Loss or female androgenetic alopecia is the main cause of hair loss in adult women and has a major impact on patients' quality of life. It evolves from the progressive miniaturization of follicles that lead to a subsequent decrease of the hair density, leading to a non-scarring diffuse alopecia, with characteristic clinical, dermoscopic and histological patterns. In spite of the high frequency of the disease and the relevance of its psychological impact, its pathogenesis is not yet fully understood, being influenced by genetic, hormonal and environmental factors. In addition, response to treatment is variable. In this article, authors discuss the main clinical, epidemiological and pathophysiological aspects of female pattern hair loss.

Eyebrows, eyelashes, and eyelids are cosmetically and functionally important periocular landmarks that offer insights into a patient's emotional state. Several pathologies exist with respect to the eyebrows, eyelashes, and eyelids. Madarosis refers to loss of the eyebrows or eyelashes; milphosis refers specifically to eyelash loss. Excess growth of eyelash hair is termed trichomegaly. Excess skin in the upper or lower eyelids is called dermatochalasis. Pathology of these important structures can be reflective of important local and systemic disease processes., (Copyright © 2015. Published by Elsevier Inc.)

Clinicians have long reported that hair-bearing areas tend to heal more rapidly than those lacking hair follicles. In the past decade, numerous scientific studies have corroborated clinical evidence, showing a direct nexus between the human hair follicle and the wound healing process. The migration of epithelial follicular stem cells to the skin surface to help in the wound re-epithelialization and the effect of the hair cycle on the wound healing rate underline the influence of the hair follicle in the healing process. In clinical practice, non-healing wounds are pathologies of high prevalence with significant associated burden costs for the healthcare system. As the population ages, the prevalence of this pathology is expected to increase in future years. The recent advances in understanding the biology of hair follicle stem cells have created the challenges of using this newly acquired knowledge in practical therapeutic applications. Chronic leg ulcers are an example of the targeted pathologies that urgently need better therapies. In this essay, our aim is to raise interest in this question, reviewing what is known in relation to the connections between hair follicles and wound healing, and elaborating on future directions that the field might take, including implications for clinical practice., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The infundibulum is the funnel-shaped, uppermost epithelial segment of the hair follicle. Thus, as the infundibulum represents a major interface zone of mammalian skin epithelium with the environment and harbors a rich residential microflora, it is not surprising that this area is endowed with a specialized immune system and innate immune defenses. Clinically, the infundibulum is quite important, as it becomes prominently involved in many skin diseases such as acne, infundibular folliculitis and cysts, hidradenitis suppurativa, keratosis pilaris, Fox-Fordyce disease, and a subtype of basal cell carcinoma. Nevertheless, the biology of the infundibulum is only poorly understood, and it remains largely unknown how exactly the infundibulum contributes to skin disease, and how it might be targeted effectively for treating important skin diseases. Several recent studies in mouse models have identified new potential infundibular markers, shed light upon infundibular development and homeostasis, identified infundibular epithelial stem cells, and have implicated the infundibulum in the pathogenesis of additional skin disorders. These recent insights encourage one to systematically re-visit the biology and pathology of the infundibulum, one of the most important, yet least-studied frontiers in mammalian epithelial physiology.

Background: Lichen planopilaris (LPP) is a lymphocyte-mediated cicatricial alopecia mostly involving the bulge region of the hair follicle. The origin of LPP is unknown. Therapy for LPP often does not prevent disease progression. We describe histologic and immunohistologic features that aid in diagnosis and provide an explanation for disease progression in LPP., Objective: We sought to demonstrate a decrease in the number of catagen-/telogen-phase follicles and to confirm the loss of cytokeratin 15 (CK15) expression in the stem cells of LPP-affected follicles., Methods: In all, 144 LPP cases were retrieved; 55 cases were stained immunohistochemically, targeting the CK15 antigen with 40 cases ultimately analyzed for CK15 expression., Results: Catagen/telogen phase was significantly decreased or absent in all cases of LPP, a novel clue useful in histologic diagnostics. The loss of CK15+ stem cells in most affected follicles in LPP was also confirmed, with unaffected follicles retaining CK15+ stem cells., Limitations: Limited tissue for analysis remained in the clinical sample tissue blocks., Conclusion: Damaged follicles that have lost their CK15+ stem cells disappear when they enter catagen phase. CK15+ stem cell loss explains the clinical observation that LPP progresses despite immunosuppressive therapies. Finally, the absence of catagen/telogen hair follicles is a helpful diagnostic clue for LPP., (Published by Elsevier Inc.)

Facial bacterial infections are most commonly caused by infections of the hair follicles. Wherever pilosebaceous units are found folliculitis can occur, with the most frequent bacterial culprit being Staphylococcus aureus. We review different origins of facial folliculitis, distinguishing bacterial forms from other infectious and non-infectious mimickers. We distinguish folliculitis from pseudofolliculitis and perifolliculitis. Clinical features, etiology, pathology, and management options are also discussed., (Copyright © 2014. Published by Elsevier Inc.)

This paper reviews the recent literature on the diseases of the hair and pilosebaceous unit that may cause a red face. We discuss the epidemiology, clinicals, pathogenesis, and therapy of lichen planopilaris with its variants, discoid lupus erythematosus, folliculitis decalvans, dissecting folliculitis, acne keloidalis nuchae, pseudofolliculitis barbae, tinea capitis, tinea barbae, folliculitis of diverse causative factors and inflammatory follicular keratotic syndromes, ulerythema ophryogenes, atrophoderma vermiculatum, keratosis follicularis spinulosa decalvans, and folliculitis spinulosa decalvans., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The recently discovered leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6+) epithelial stem cell located within the follicular bulge of the adnexal compartment is capable of producing all cellular lineages of the skin. In this study, the authors sought to determine whether these cells can be transplanted for use as a type of cellular therapy for the repair of full-thickness wounds in which the native stem cell niche has been obliterated., Methods: Full-thickness murine skin was harvested and LGR6(+GFP) epithelial stem cells were isolated using fluorescence-activated cell sorting. This enriched epithelial stem cell population was then transplanted by means of local injection into wound beds on the dorsum of nude mice. Viability, migration, healing, the development of nascent hair follicles, and gene and proteomic expression studies were performed to determine whether the engraftment of LGR6(+GFP) epithelial stem cells enhanced healing when compared with controls., Results: Wound beds receiving LGR6(+GFP) epithelial stem cells showed enhanced healing; nascent follicle growth; and augmentation of the Wnt, vascular endothelial growth factor, epidermal growth factor, and platelet-derived growth factor pathways when compared with controls., Conclusions: The LGR6+ epithelial stem cells appear to hold great promise for the development of a clinically useful stem cell–based therapy for the repair of full-thickness wounds and hair regeneration. These results indicate that transplantation of LGR6+ epithelial stem cells promotes epithelialization, hair growth, and angiogenesis in tissues destined for scar formation.

Telogen effluvium (TE) is heterogeneous disorder. It can be classified into three main categories: the premature teloptosis, the collective teloptosis and the premature entry into telogen. The last category can be divided in three types: the drug induced TE, TE due to dietary deficiencies and the "autoimmune" TE. Despite this heterogeneity, the large majority of TE that arrive at the dermatologist's observation pertain to the autoimmune type, featuring a standard presentation. The typical patient is a woman claiming to have always had a "full head of hair" and reporting her hair to come out suddenly "by the handful". Usually, she is accurate about the date of onset of her shedding. She is in good health, without signs of anorexia nor nutrient deficiencies. She admits to having been in an anxious state for some months, and felt, occasionally or not, a painful or burning sensation at the scalp (trichodynia). Usually, the course of the disorder is chronic but intermittent, with apparent remissions being irregularly intermitted by relapses. The shed hairs do not exhibit telogen roots, but mostly exogen ones. This distinct entity, shares some analogies with alopecia areata, including the triggering role of emotional stress, trichodynia and the frequent association with Hashimoto's thyroiditis. Methods to assess its severity and to monitor treatment are described. In the absence of a documented etiopathogenesis, no treatment can be endorsed, but a course of topical corticosteroids could be tried.

Background: Discovery of leucine-rich repeat-containing G-protein-coupled receptors 5 and 6 (LGR5 and LGR6) as markers of adult epithelial stem cells of the skin and intestine permits researchers to draw on the intrinsic cellular fundamentals of wound healing and proliferation dynamics of epithelial surfaces. In this study, the authors use the intestine-derived human alpha defensin 5 to stimulate epithelial proliferation, bacterial reduction, and hair production in burn wound beds to provide the field with initial insight on augmenting wound healing in tissues devoid of adnexal stem cells., Methods: Murine third-degree burn wound beds were treated with (1) intestine-derived human alpha defensin 5, (2) skin-derived human beta defensin 1, and (3) sulfadiazine to determine their roles in wound healing, bacterial reduction, and hair growth., Results: The human alpha defensin 5 peptide significantly enhanced wound healing and reduced basal bacterial load compared with human beta defensin 1 and sulfadiazine. Human alpha defensin 5 was the only therapy to induce LGR stem cell migration into the wound bed. In addition, gene heat mapping showed significant mRNA up-regulation of key wound healing and Wnt pathway transcripts such as Wnt1 and Wisp1. Ex vivo studies showed enhanced cell migration in human alpha defensin 5-treated wounds compared with controls., Conclusions: Application of human alpha defensin 5 increases LGR stem cell migration into wound beds, leading to enhanced healing, bacterial reduction, and hair production through the augmentation of key Wnt and wound healing transcripts. These findings can be used to derive gut protein-based therapeutics in wound healing.

Anecdotical experiences indicate that Koebner phenomenon (KP) can also be observed in alopecia areata (AA). The present short report gives an account of what has been observed in some patients with remitting-relapsing AA in multiple patches, in whom the phenomenon was accidentally caused by perilesional Trichogram. The almost immediate appearance of relapses of the disease (1-7 days) and their evolution can be useful to understand the physiopathology of AA and and emphasize the compelling need for a rapid and appropriate diagnosis and treatment in the acute phase of AA, even with the active participation of the patient adequately trained. The method of trichogram should be reserved for cases in which non-invasive methods such as the Pull Test or Trichoscopy are not sufficient to verify the activity of the disease.

Hair is considered one of the most defining aspects of human appearance. Hair loss, or alopecia in women is often met with significant emotional distress and anxiety. In midlife, women may encounter various hormonal and age-related physiologic changes that can lead to alterations in hair texture and growth. The most significant hormonal alteration is the onset of menopause in which there is a cessation of ovarian estrogen production. This decrease in estrogen is known to have deleterious effects on the skin and cutaneous appendages. As our understanding of the molecular and hormonal controls on the hair follicle has grown, there has been increased interest in the various modulators of hair growth, including the potential role of estrogen. Further study of hair changes in midlife women provides an important opportunity for identification of the complex regulation of hair growth as well as identification of treatment targets that may specifically benefit women. In this review, management of hair loss in midlife women is discussed with a focus on three most commonly encountered clinical conditions: female pattern hair loss, hair shaft alterations due to hair care, and telogen effluvium., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Human hair disorders comprise a number of different types of alopecia, atrichia, hypotrichosis, distinct hair shaft disorders as well as hirsutism and hypertrichosis. Their causes vary from genodermatoses (e.g. hypotrichoses) via immunological disorders (e.g. alopecia areata, autoimmune cicatrical alopecias) to hormone-dependent abnormalities (e.g. androgenetic alopecia). A large number of spontaneous mouse mutants and genetically engineered mice develop abnormalities in hair follicle morphogenesis, cycling, and/or hair shaft formation, whose analysis has proven invaluable to define the molecular regulation of hair growth, ranging from hair follicle development, and cycling to hair shaft formation and stem cell biology. Also, the accumulating reports on hair phenotypes of mouse strains provide important pointers to better understand the molecular mechanisms underlying human hair growth disorders. Since numerous new mouse mutants with a hair phenotype have been reported since the publication of our earlier review on this matter a decade ago, we present here an updated, tabulated mini-review. The updated annotated tables list a wide selection of mouse mutants with hair growth abnormalities, classified into four categories: Mutations that affect hair follicle (1) morphogenesis, (2) cycling, (3) structure, and (4) mutations that induce extrafollicular events (for example immune system defects) resulting in secondary hair growth abnormalities. This synthesis is intended to provide a useful source of reference when studying the molecular controls of hair follicle growth and differentiation, and whenever the hair phenotypes of a newly generated mouse mutant need to be compared with existing ones., (Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

The identification of causative genes carries the promise of new and innovative therapeutic strategies for both inherited and acquired hair disorders. Moreover, the delineation of the relationships between similar phenotypes, resulting from mutations affecting seemingly distinct regulatory pathways, paves the way to improved diagnosis and treatment. Finally, understanding the biological processes governing HF development and maintenance may have implications for more general disease processes in the skin, such as inflammation and cancer.