Exp Dermatol. 2010 Aug;19(8):e347-9.

An unexpected twist in alopecia areata pathogenesis: are NK cells protective and CD49b+ T cells pathogenic?

Kaufman G, et al

Abstract
Natural killer (NK) cells have become a recent focus of interest in alopecia areata (AA) research. To further investigate their role in an established mouse model of hair loss due to AA, lesional skin from older C3H/HeJ mice with AA was grafted to young C3H/HeJ female mice, and NK cells were depleted by continuous administration of rabbit anti-asialo GM1. As expected, this significantly reduced the number of pure NK cells in murine skin, as assessed by NKp46 quantitative immunohistochemistry. Quite unexpectedly, however, the onset of hair loss in C3H/HeJ mice was accelerated, rather than retarded. NK cell depletion was accompanied by a significant increase in the number of perifollicular CD49b+T cells in the alopecic skin of anti-asialo GM1-treated mice. These findings underscore the need to carefully distinguish in future AA research between pure NK cells and defined subsets of CD49b+ lymphocytes, as they may exert diametrically opposed functions in hair follicle immunology and immunopathology.

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Diagnostic defects and therapeutic set-backs in hair disorders

Piérard-Franchimont C, Quatresooz P, Piérard GE.

CHU du Sart Tilman et Sauvenière, Service de Dermatopathologie, Belgique.

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Abstract

Hair loss, also called hair effluvium is often considered as an ancillary complaint. However, this situation is quite common in both genders. It is part of numerous clinical presentations in internal medicine and dermatology. Obviously, any correlation between a biologic abnormality and hair loss does not prove a relationship of causality. In absence of pathogenic diagnosis and causality criteria, chances are low to control adequately hair effluvium by a treatment given by the whims of fate. In addition, the risk and frequency of therapeutic inertia are increased. When the hair loss is not controlled and/or compensated by regrowth of new hairs, several types of alopecia inexorably develop.

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Diagnostic defects and therapeutic set-backs in hair disorders

Piérard-Franchimont C, Quatresooz P, Piérard GE.

CHU du Sart Tilman et Sauvenière, Service de Dermatopathologie, Belgique.

Modisfied and edited for hai rloss blog

Abstract

Hair loss, also called hair effluvium is often considered as an ancillary complaint. However, this situation is quite common in both genders. It is part of numerous clinical presentations in internal medicine and dermatology. Obviously, any correlation between a biologic abnormality and hair loss does not prove a relationship of causality. In absence of pathogenic diagnosis and causality criteria, chances are low to control adequately hair effluvium by a treatment given by the whims of fate. In addition, the risk and frequency of therapeutic inertia are increased. When the hair loss is not controlled and/or compensated by regrowth of new hairs, several types of alopecia inexorably develop.

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A mouse model of androgenetic alopecia.
Crabtree JS,
Wyeth

Abstract
Androgenetic alopecia (AGA), commonly known as male pattern baldness, is a form of hair loss that occurs in both males and females. Although the exact cause of AGA is not known, it is associated with genetic predisposition through traits related to androgen synthesis/metabolism and androgen signaling mediated by the androgen receptor (AR). Current therapies for AGA show limited efficacy and are often associated with undesirable side effects. A major hurdle to developing new therapies for AGA is the lack of small animal models to support drug discovery research. Here, we report the first rodent model of AGA. Previous work demonstrating that the interaction between androgen-bound AR and beta-catenin can inhibit Wnt signaling led us to test the hypothesis that expression of AR in hair follicle cells could interfere with hair growth in an androgen-dependent manner. Transgenic mice overexpressing human AR in the skin under control of the keratin 5 promoter were generated. Keratin 5-human AR transgenic mice exposed to high levels of 5alpha-dihydrotestosterone showed delayed hair regeneration, mimicking the AGA scalp. This effect is AR mediated, because treatment with the AR antagonist hydroxyflutamide inhibited the effect of dihydrotestosterone on hair growth. These results support the hypothesis that androgen-mediated hair loss is AR dependent and suggest that AR and beta-catenin mediate this effect. These mice can now be used to test new therapeutic agents for the treatment of AGA, accelerating the drug discovery process.

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Androgenetic alopecia ( pattern hair loss ) and cardiovascular risk factors in men and women: A comparative study.
Arias-Santiago S, et al

Abstract
Numerous studies in recent decades have associated male androgenetic alopecia (AGA) or pattern hair loss with the risk of cardiovascular disease. However, only 3 studies have addressed this association in female patients. Most studies considered the risk of myocardial infarction or mortality as a result of heart disease, without analyzing cardiovascular risk factors. OBJECTIVES: The objectives of this study were to analyze the presence of cardiovascular risk factors included in the Adult Treatment Panel-III criteria for metabolic syndrome, the prevalence of carotid atheromatosis, hormonal (aldosterone, insulin, testosterone, and sex hormone-binding globulin) factors, and acute phase reactant (C-reactive protein, fibrinogen, D-dimers, erythrocyte sedimentation rate) variables in male and female patients with AGA and in a control group, and to analyze differences among the groups. METHODS: This case-control study included 154 participants, 77 with early-onset AGA (40 male and 37 female) and 77 healthy control subjects (40 male and 37 female) from the dermatology department at a university hospital in Granada, Spain. RESULTS: Metabolic syndrome was diagnosed in 60% of male patients with AGA (odds ratio [OR] = 10.5, 95% confidence interval [CI] 3.3-32.5), 48.6% of female patients with AGA (OR = 10.73, 95% CI 2.7-41.2), 12.5% of male control subjects, and 8.1% of female control subjects. Atheromatous plaques were observed in 32.5% of male patients with AGA (OR = 5.93, 95% CI 1.5-22.9) versus 7.5% of male control subjects (P = .005) and 27% of female patients with AGA (OR = 4.19, 95% CI 1.05-16.7) versus 8.1% of female control subjects (P = .032). Aldosterone and insulin levels were significantly higher in the male and female patients with AGA versus their respective control subjects. Mean values of fibrinogen were significantly higher in male patients with AGA, whereas values of fibrogen, C-reactive protein, and D-dimers were significantly higher in female patients with AGA versus their respective control subjects. LIMITATIONS: The study of a wider sample of patients with AGA would confirm these findings and allow a detailed analysis of the above factors as a function of the degree of alopecia or between menopausal and premenopausal women. CONCLUSION: The determination of metabolic syndrome and ultrasound study of the carotid arteries may be useful screening methods to detect risk of developing cardiovascular disease in male and female patients with early-onset AGA and signal a potential opportunity for early preventive treatment. Copyright © 2009 American Academy of Dermatology, Inc.

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Type 1 interferon signature in the scalp lesions of alopecia areata.
Ghoreishi M, et al

Summary Background: Auto-immune attack of the bulbar region of anagen phase hair follicles by CD8(+) T cells and Th-1 cytokines has been proposed to result in hair loss in alopecia areata. The initiating stimuli are unknown. As interferon alpha therapy may trigger hair loss due to alopecia areata, we propose that type 1 interferons are involved in the induction of disease. Objectives: To compare lesional scalp from patients with hair loss due to alopecia areata to scalp lesions of cutaneous diseases associated with local type 1 interferon related protein expression. Methods: Lesional scalp of patients with alopecia areata, discoid lupus erythematosus, lichen planopilaris and male pattern hair loss was examined by immunohistochemistry for expression of the type I interferon-inducible MxA, the chemokine receptor CXCR3, and the cytotoxic proteins granzyme B and TiA-1. Results: MxA was expressed in the intra-dermal and subcutaneous compartments of the hair follicle including sebaceous glands in inflammatory alopecia areata similar to lesions of cicatricial alopecia (discoid lupus erythematosus, lichen planopilaris) but not in the epidermal compartment of alopecia areata, and not at all in non-inflammatory alopecia areata or androgenetic alopecia. The location of CXCR3 expressing cells correlated with MXA expression. The inflammatory cells around the hair follicle in alopecia areata included a lower number of granzyme B(+) and TiA-1(+) cells compared to cicatricial alopecia and demonstrated predominant TiA-1(+) expression. Conclusions: We demonstrate the expression of type 1 interferon related proteins in the inflammatory lesions of AA. The distribution pattern of the interferon signature and cytotoxicity-associated proteins in hair loss due to alopecia areata differs from cicatricial alopecia.

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Laminin-511, inducer of hair regrowth, is down-regulated and its suppressor in hair growth, laminin-332 up-regulated in chemotherapy-induced alopecia
Hisayoshi Imanishi

Chemotherapy-induced alopecia (hair loss) occurs frequently in patients using anticancer agents [1]. For example, the incidence of CIA in patients treated with paclitaxel (PTX), docetaxel (TXT) and etoposide (VP-16) is 87.7, 78.4, and 75.7% respectively [2]. These chemotherapeutic drugs are known to lead to hair loss in anagen (anagen effuvium) by inducing apoptosis of hair matrix cells. Previous studies have identified two distinct chemotherapy-induced hair follicle dystrophies, termed the dystrophic catagen and the dystrophic anagen pathways. The dystrophic catagen pathway occurs in response to a higher dose of chemotherapeutic drugs than the dystrophic anagen pathway. Hair follicles that have progressed along the dystrophic catagen pathway exhibit abnormal distributions of melanin pigments. The hair roots in the affected follicles taper off and are without the typical club-shaped morphology. The dystrophic anagen pathway is triggered by lower doses of chemotherapeutic drugs and consequently results in a milder impairment in hair elongation. During the dystrophic anagen pathway the hair shaft is shed and the follicle undergoes a so-called “incomplete recovery”. The follicle regenerates but with a faulty hairshaft and then undergoes a complete catagen-telogen transition to enter a “secondary recovery” phase [9]. In the latter pathway, miniaturization of the hair, atrophy of hair matrix, and abnormality in the distribution of melanin pigments have been observed [8].A number of procedures and reagents have been used in attempts to ameliorate the effects of CIA. These include scalp tourniquets, scalp cooling, scalp hypothermia and treatment with tocopherol and minoxidil. Unfortunately, the success of these treatments is quite limited. Thus, there remains a need for new therapies for patients afflicted with CIA. The development of such new therapies would be facilitated by a better understanding of the molecular mechanisms that underlie hair loss in CIA. To this end we have analyzed the expression of certain extracellular matrix proteins in a mouse model of CIA. In our study, we focused on laminin-332 and -511 since there is accumulating evidence that these laminin heterotrimers are key regulators of hair growth [18]. Specifically, it has been reported that the skin of day 16.5 embryonic mice lacking the á5 subunit of laminin-511 contains fewer hair germs compared to wild type controls. In addition, Gao et al. have presented data indicating that laminin-511 is essential for the transduction of crucial morphogenetic signals that regulate ciliary function and dermal papilla cell maintenance during hair downgrowth. Moreover, we have presented evidence that laminin-511 supports hair growth while laminin-332 antagonizes such effects in an in vitro model [18]. The data we present here indicate that chemotherapeutic agents affect the dynamics of laminin-511 and -332 in the hair growth cycle. Furthermore, our data indicate that intradermal injection of laminin-511 may prevent CIA.

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Pattern hair loss and its treatment in males:
El-Domyati M, et al

Male pattern hair loss is a common disorder of hair, resulting from genetic, endocrine, and aging factors leading to follicular miniaturization. Inflammation is a potential player in this process. AIMS: To study the histopathological and ultrastructural changes occurring in male androgenetic alopecia (AGA) or pattern hair loss. Patients/methods Fifty-five subjects were included in this study. Skin biopsies were subjected to examination, staining for collagen I and ultrastructural study. The frontal balding area showed an increase in telogen hairs and a decrease in anagen/telogen ratio and terminal/vellus hair ratio. Follicular inflammation was almost a constant feature and showed a significant inverse correlation with perifollicular fibrosis. Follicular inflammation plays a role in pattern hair loss in early cases. Over time, thickening of perifollicular sheath takes place due to increased deposition of collagen. This produces fibrosis, and sometimes complete destruction of the affected follicles in advanced cases of hair loss.

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