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.

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 .

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.

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.

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.

Hair follicle changes following intense pulsed light axillary hair reduction: histometrical, histological and immunohistochemical evaluation.

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.

Home-applied IPL epilation may prevent the problems due to hair follicle in amputees.

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.

Maternal IL-6 can cause T-cell-mediated juvenile alopecia by non-scarring follicular dystrophy in mice.

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.

Female Pattern Hair Loss: a clinical and pathophysiological review

AbstractFemale 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.

Reflections on how wound healing-promoting effects of the hair follicle can be translated into clinical practice.

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.

Red face revisited: Disorders of hair growth and the pilosebaceous unit.

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.

Deciphering the functions of the hair follicle infundibulum in skin physiology and disease.

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.

Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous wounds results in enhanced healing, nascent hair follicle development, and augmentation of angiogenic analytes.

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 cell­based 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 revisited.

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.