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British Journal of Dermatology 05/2012; 166(5):916-26. · 3.67 Impact Factor
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S Redler,
F F Brockschmidt,
R Tazi-Ahnini,
D Drichel,
M P Birch,
K Dobson,
K A Giehl,
S Herms,
M Refke,
N Kluck,
R Kruse,
G Lutz,
H Wolff,
M Böhm,
T Becker,
M M Nöthen, A G Messenger,
R C Betz
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ABSTRACT: The aetiology of female pattern hair loss (FPHL) is largely unknown. However, it is hypothesized that FPHL and male pattern baldness (AGA) share common susceptibility alleles. The two major susceptibility loci for AGA are the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X-chromosome, and a locus on chromosome 20p11, for which no candidate gene has yet been identified.
To examine the role of the AR/EDA2R and 20p11 loci in the development of FPHL using 145 U.K. and 85 German patients with FPHL, 179 U.K. supercontrols and 150 German blood donors.
Patients and controls were genotyped for 25 single nucleotide polymorphisms (SNPs) at the AR/EDA2R locus and five SNPs at the 20p11 locus.
Analysis of the AR/EDA2R locus revealed no significant association in the German sample. However, a nominally significant association for a single SNP (rs1397631) was found in the U.K. sample. Subgroup analysis of the U.K. patients revealed significant association for seven markers in patients with an early onset (P = 0·047 after adjustment for the testing of multiple SNPs by Monte Carlo simulation). No significant association was obtained for the five 20p11 variants, either in the overall samples or in the analysis of subgroups.
The observed association suggests that the AR/EDA2R locus confers susceptibility to early-onset FHPL. Our results do not implicate the 20p11 locus in the aetiology of FPHL.
British Journal of Dermatology 02/2012; 166(6):1314-8. · 3.67 Impact Factor
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A G Messenger
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ABSTRACT: At a population level female scalp hair growth shows features of regression with chronological ageing, although there is wide interindividual variation in timing and degree. The subjective assessment of hair loss is classically determined by hair density but it is apparent that other factors contribute to the clinical picture. Changes can occur in hair cycling, hair density, hair diameter and pigmentation, and possibly in structural qualities of the hair fibre. These changes are most pronounced in female pattern hair loss. Although conventionally considered as the female counterpart of male androgenetic alopecia the evidence that female pattern hair loss is androgen dependent is less clear cut than in men and it probably has a multifactorial basis. The emerging evidence implicating environmental factors is of particular interest as, unlike genes, such factors may be amenable to intervention. The clinical signs in women complaining of hair loss may be variable. In evaluating the patient complaining of hair loss, while true pathology must always be considered, the clinician needs to be aware of how age affects hair growth. These changes form the focus of this article.
British Journal of Dermatology 12/2011; 165 Suppl 3:2-6. · 3.67 Impact Factor
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S Redler,
M P Birch,
D Drichel,
K Dobson,
F F Brockschmidt,
R Tazi-Ahnini,
K A Giehl,
N Kluck,
R Kruse,
G Lutz,
H Wolff,
T Becker,
M M Nöthen, A G Messenger,
R C Betz
British Journal of Dermatology 06/2011; 165(3):703-5. · 3.67 Impact Factor
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ABSTRACT: Primary cicatricial alopecias (PCAs) are a rare, but important, group of disorders that cause irreversible damage to hair follicles resulting in scarring and permanent hair loss. They may also signify an underlying systemic disease. Thus, it is of paramount importance that clinicians who manage patients with hair loss are able to diagnose these disorders accurately. Unfortunately, PCAs are notoriously difficult conditions to diagnose and treat. The aim of this review is to present a rational and pragmatic guide to help clinicians in the professional assessment, investigation and diagnosis of patients with PCA. Illustrating typical clinical and histopathological presentations of key PCA entities we show how dermatoscopy can be profitably used for clinical diagnosis. Further, we advocate the search for loss of follicular ostia as a clinical hallmark of PCA, and suggest pragmatic strategies that allow rapid formulation of a working diagnosis.
British Journal of Dermatology 02/2009; 160(3):482-501. · 3.67 Impact Factor
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ABSTRACT: Background Vitiligo is an autoimmune disorder that occurs with greatly increased frequency in the rare recessive autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy syndrome (APECED) caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22·3. We have previously detected an association between alopecia areata and single nucleotide polymorphisms (SNPs) in the AIRE gene.Objectives To report the findings of an extended study including haplotype analysis on six AIRE polymorphisms (AIRE C–103T, C4144G, T5238C, G6528A, T7215C and T11787C) in vitiligo, another APECED-associated disease.Methods A case–control analysis was performed.Results Results showed a strong association between AIRE 7215C and vitiligo [P = 1·36 × 10−5, odds ratio (OR) 3·12, 95% confidence interval (CI) 1·87–5·46]. We found no significant association with the other polymorphisms individually. However, haplotype analysis revealed that the AIRE haplotype CCTGCC showed a highly significant association with vitiligo (P = 4·14 × 10−4, OR 3·00, 95% CI 1·70–5·28). To select the most informative minimal haplotypes, we tagged the polymorphisms using SNP tag software. Using AIRE C–103T, G6528A, T7215C and T11787C as tag SNPs, the haplotype AIRE CGCC was associated with vitiligo (P = 0·003, OR 2·49, 95% CI 1·45–4·26).Conclusions The link between vitiligo and AIRE raises the possibility that defective skin peripheral antigen selection in the thymus is involved in the changes that result in melanocyte destruction in this disorder.
British Journal of Dermatology 08/2008; 159(3):591 - 596. · 3.67 Impact Factor
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ABSTRACT: Vitiligo is an autoimmune disorder that occurs with greatly increased frequency in the rare recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. We have previously detected an association between alopecia areata and single nucleotide polymorphisms (SNPs) in the AIRE gene.
To report the findings of an extended study including haplotype analysis on six AIRE polymorphisms (AIRE C-103T, C4144G, T5238C, G6528A, T7215C and T11787C) in vitiligo, another APECED-associated disease.
A case-control analysis was performed.
Results showed a strong association between AIRE 7215C and vitiligo [P = 1.36 x 10(-5), odds ratio (OR) 3.12, 95% confidence interval (CI) 1.87-5.46]. We found no significant association with the other polymorphisms individually. However, haplotype analysis revealed that the AIRE haplotype CCTGCC showed a highly significant association with vitiligo (P = 4.14 x 10(-4), OR 3.00, 95% CI 1.70-5.28). To select the most informative minimal haplotypes, we tagged the polymorphisms using SNP tag software. Using AIRE C-103T, G6528A, T7215C and T11787C as tag SNPs, the haplotype AIRE CGCC was associated with vitiligo (P = 0.003, OR 2.49, 95% CI 1.45-4.26).
The link between vitiligo and AIRE raises the possibility that defective skin peripheral antigen selection in the thymus is involved in the changes that result in melanocyte destruction in this disorder.
British Journal of Dermatology 08/2008; 159(3):591-6. · 3.67 Impact Factor
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ABSTRACT: Zusammenfassung: Haarausfall vom weiblichen Typ ist hufig und durch eine Reduktion der Haardichte im Bereich des Scheitels und der vorderen Kopfhaut bei Erhalt des Haaransatzes gekennzeichnet. Mit höherem Lebensalter steigt die Prvalenz. Im Allgemeinen wird diese Form des Effluviums als weibliches Pendant der mnnlichen Glatzenbildung betrachtet und auch als weibliche androgenetische Alopezie bezeichnet. Allerdings ist die Bedeutung der Androgene nicht vollstndig geklrt. Ohne Zweifel kann der Verlust der Kopfhaare ein Merkmal von Hyperandrogenismus bei Frauen sein, doch findet man bei vielen Frauen mit einem Haarausfall vom weiblichen Typ keine anderen klinischen oder biochemischen Hinweise für einen Androgenüberschuss. Haarausfall vom weiblichen Typ ist wahrscheinlich ein multifaktorielles, genetisch determiniertes Geschehen, und es ist möglich, dass sowohl Androgen-abhngige und Androgen-unabhngige Mechanismen zum Phnotyp beitragen. Im Umgang mit Patientinnen, die unter Haarausfall vom weiblichen Typ leiden, muss der Arzt sich immer bewusst sein, dass die unerwünschten Wirkungen auf die Lebensqualitt als sehr gravierend empfunden werden können und nicht unbedingt mit dem tatschlichen Haarverlust korrelieren müssen. Die gegenwrtig verfügbaren Behandlungsoptionen sind im Prinzip unbefriedigend, bewirken aber bei einigen Frauen durchaus eine leichte Verbesserung der Haardichte.Summary: Female pattern hair loss is a common condition characterised by a diffuse reduction in hair density over the crown and frontal scalp with retention of the frontal hairline. The prevalence increases with advancing age. It has been widely thought to be the female counterpart of male balding and is often referred to as female androgenetic alopecia. However, the role of androgens is not fully established. Scalp hair loss is undoubtedly a feature of hyperandrogenism in women but many women with female pattern hair loss have no other clinical or biochemical evidence of androgen excess. Female pattern hair loss is probably a multifactorial genetically determined trait and it is possible that both androgen-dependent and androgen-independent mechanisms contribute to the phenotype. In managing patients with female pattern hair loss the physician should be aware that the adverse effects on quality of life can be quite severe and do not necessarily correlate with the objective degree of hair loss. The treatment options are currently limited but modest improvements in hair density are achievable in some women.
H& G Zeitschrift fur Hautkrankheiten 06/2008; 77(7‐8):342 - 347.
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ABSTRACT: Alopecia areata is an immune-mediated disorder, occurring with the highest observed frequency in the rare recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. We have previously detected association between alopecia areata and a single nucleotide polymorphism (SNP) in the AIRE gene in patients without APECED, and we now report the findings of an extended examination of the association of alopecia areata with haplotype analysis including six SNPs in the AIRE gene: C-103T, C4144G, T5238C, G6528A, T7215C and T11787C. In Caucasian groups of 295 patients and 363 controls, we found strong association between the AIRE 7215C allele and AA [P = 3.8 x 10(-8), OR (95% CI): 2.69 (1.8-4.0)]. The previously reported association between AA and the AIRE 4144G allele was no longer significant on correction for multiple testing. The AIRE haplotypes CCTGCT and CGTGCC showed a highly significant association with AA [P = 6.05 x 10(-6), 9.47 (2.91-30.8) and P = 0.001, 3.51 (1.55-7.95), respectively]. To select the haplotypes most informative for analysis, we tagged the polymorphisms using SNPTag software. Employing AIRE C-103T, G6528A, T7215C and T11787C as tag SNPs, two haplotypes were associated with AA; AIRE CGCT and AIRE CGCC [P = 3.84 x 10(-7), 11.40 (3.53-36.9) and P = 3.94 x 10(-4), 2.13 (1.39-3.24) respectively]. The AIRE risk haplotypes identified in this study potentially account for a major component of the genetic risk of developing alopecia areata.
Tissue Antigens 04/2008; 71(3):206-12. · 2.59 Impact Factor
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02/2008: pages 3199 - 3318; , ISBN: 9780470750520
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ABSTRACT: The pathology of female pattern hair loss (FPHL) is characterized by an increase in the proportion of vellus follicles, manifest as a low terminal/vellus ratio. This is conventionally thought to be due to a progressive miniaturization of terminal hair follicles. There is also a prolongation of the latent period of the hair cycle (kenogen) in both male pattern hair loss and FPHL and follicles in kenogen may be difficult to classify histologically. Therefore, a low terminal/vellus ratio could be due to a preferential increase in the number of terminal follicles in kenogen rather than to a true increase in the number of vellus follicles.
To establish whether there is an increase in the absolute number of vellus follicles during the progression of FPHL, indicating a process of follicular miniaturization.
We studied 42 women complaining of hair loss. The severity of the hair loss was graded clinically on a five-point scale from 1 (no obvious hair loss) to 5 (severe hair loss). Three 4-mm punch biopsies were taken from the frontal scalp of each patient, sectioned horizontally and stained with haematoxylin and eosin. Two levels were studied on each biopsy: through the mid-infundibular region and through the mid-isthmus. The following were counted: total follicles, terminal follicles, vellus follicles, anagen and telogen/catagen follicles. The results from the three biopsies from each subject were averaged and statistical evaluations performed on the mean values.
There was a progressive decline in mean total follicle count with increasing grade of hair loss (grade 1, 317 cm(-2); grade 5, 243 cm(-2)) and a more pronounced reduction in terminal follicle counts (grade 1, 263 cm(-2); grade 5, 96 cm(-2)). The absolute number of vellus follicles increased from 33 cm(-2) (grade 1) to 71 cm(-2) (grade 4), declining to 51 cm(-2) at grade 5. The terminal/vellus ratio fell from 12.8 (grade 1) to 2.3 (grade 4) and remained at this level thereafter. The proportion of follicles in telogen increased from 13.7% (grade 1) to 31.4% (grade 5).
Our results show that there is an increase in vellus follicle numbers with increasing severity of hair loss in women with FPHL, suggesting that terminal follicles do indeed miniaturize. It is possible that there is also an increase in the number of follicles in a latent stage of telogen but this was difficult to assess from our data. The fall in total follicle counts with stabilizing of the terminal/vellus ratio in severe hair loss suggests that miniaturization does not stop with a vellus follicle but progresses to follicular deletion.
British Journal of Dermatology 12/2006; 155(5):926-30. · 3.67 Impact Factor
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ABSTRACT: Background The pathology of female pattern hair loss (FPHL) is characterized by an increase in the proportion of vellus follicles, manifest as a low terminal/vellus ratio. This is conventionally thought to be due to a progressive miniaturization of terminal hair follicles. There is also a prolongation of the latent period of the hair cycle (kenogen) in both male pattern hair loss and FPHL and follicles in kenogen may be difficult to classify histologically. Therefore, a low terminal/vellus ratio could be due to a preferential increase in the number of terminal follicles in kenogen rather than to a true increase in the number of vellus follicles.Objectives To establish whether there is an increase in the absolute number of vellus follicles during the progression of FPHL, indicating a process of follicular miniaturization.Methods We studied 42 women complaining of hair loss. The severity of the hair loss was graded clinically on a five-point scale from 1 (no obvious hair loss) to 5 (severe hair loss). Three 4-mm punch biopsies were taken from the frontal scalp of each patient, sectioned horizontally and stained with haematoxylin and eosin. Two levels were studied on each biopsy: through the mid-infundibular region and through the mid-isthmus. The following were counted: total follicles, terminal follicles, vellus follicles, anagen and telogen/catagen follicles. The results from the three biopsies from each subject were averaged and statistical evaluations performed on the mean values.Results There was a progressive decline in mean total follicle count with increasing grade of hair loss (grade 1, 317 cm−2; grade 5, 243 cm−2) and a more pronounced reduction in terminal follicle counts (grade 1, 263 cm−2; grade 5, 96 cm−2). The absolute number of vellus follicles increased from 33 cm−2 (grade 1) to 71 cm−2 (grade 4), declining to 51 cm−2 at grade 5. The terminal/vellus ratio fell from 12·8 (grade 1) to 2·3 (grade 4) and remained at this level thereafter. The proportion of follicles in telogen increased from 13·7% (grade 1) to 31·4% (grade 5).Conclusions Our results show that there is an increase in vellus follicle numbers with increasing severity of hair loss in women with FPHL, suggesting that terminal follicles do indeed miniaturize. It is possible that there is also an increase in the number of follicles in a latent stage of telogen but this was difficult to assess from our data. The fall in total follicle counts with stabilizing of the terminal/vellus ratio in severe hair loss suggests that miniaturization does not stop with a vellus follicle but progresses to follicular deletion.
British Journal of Dermatology 10/2006; 155(5):926 - 930. · 3.67 Impact Factor
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ABSTRACT: Although female pattern hair loss can be a feature of hyperandrogenism, many women with hair loss show no clinical or biochemical features of androgen excess. It is possible that hair loss in nonhyperandrogenic women is due to a high level of response to androgens by scalp hair follicles. In this study we explored this idea using sebum excretion as a marker of the cutaneous end-organ response to androgens.
To test the hypothesis that hair loss in nonhyperandrogenic women is due to an increased cutaneous end-organ response to androgens.
We studied 100 women, 41 with female pattern hair loss (without hirsutism), 29 with hirsutism (with and without scalp hair loss) and 30 subjects without hair problems. We measured hair density on the frontal scalp, forehead sebum excretion, serum free androgen index (FAI), and body mass index (BMI).
The mean FAI was significantly raised in hirsute women compared with nonhirsute women (P < 0.001), but there was no difference in FAI levels between nonhirsute women with and without hair loss. The mean BMI was also significantly elevated in hirsute women (P < 0.01) but there was no difference in BMI between nonhirsute women with and without hair loss. The mean sebum excretion was higher in hirsute women than nonhirsute women but the difference was not statistically significant. There was no difference in sebum excretion between nonhirsute women with and without hair loss. There was no correlation between hair density and sebum excretion.
Our results show that sebum excretion is not elevated in women with female pattern hair loss. This may indicate that different androgen-response pathways operate in controlling hair growth and sebum excretion. The alternative explanation is that nonandrogenic mechanisms are involved in mediating hair loss in some women.
British Journal of Dermatology 01/2006; 154(1):85-9. · 3.67 Impact Factor
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British Journal of Dermatology 06/2005; 152(5):1086-7. · 3.67 Impact Factor
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British Journal of Dermatology 05/2005; 152(5):1086 - 1087. · 3.67 Impact Factor
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ABSTRACT: We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.
British Journal of Dermatology 03/2004; 150(2):186-94. · 3.67 Impact Factor
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ABSTRACT: We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.
British Journal of Dermatology 01/2004; 150(2):186 - 194. · 3.67 Impact Factor
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British Journal of Dermatology 11/2003; 149(4):692-9. · 3.67 Impact Factor
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ABSTRACT: These guidelines for management of alopecia areata have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.
British Journal of Dermatology 09/2003; 149(4):692 - 699. · 3.67 Impact Factor
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ABSTRACT: Oestrogens play a major role in non-classic target tissues in both sexes, yet there have been few studies on estrogens and skin. Recently a second oestrogen receptor (ERbeta) has been discovered. Therefore, we have compared the expression of oestrogen receptor alpha (ERalpha), beta (ERbeta), the androgen receptor (AR) and a cell proliferation marker in male and female non-balding scalp skin. ERbeta was the major steroid receptor expressed in human skin. It was highly expressed in epidermis, blood vessels and dermal fibroblasts, in contrast to ERalpha and AR. In the hair follicle, ERbeta expression was localized to nuclei of outer root sheath, epithelial matrix and dermal papilla cells, in contrast to ERalpha, and the AR, which was only expressed in dermal papilla cells. Serial sections also showed strong nuclear expression of ERbeta in the cells of the bulge, while neither ERalpha nor AR was expressed. In the sebaceous gland, ERbeta was expressed in both basal and partially differentiated sebocytes. ERalpha exhibited a similar pattern of expression, while the AR was expressed in the basal and very early differentiated sebocytes. There was no obvious difference in the expression of either oestrogen receptor in male or female skin. The wide distribution of ERbeta in human skin suggests that oestrogens may play an important role in the maintenance of skin and in the regulation of the pilosebaceous unit, and provides further evidence for oestrogen action in non-classic target tissues. The differential expression of ERalpha, ERbeta and AR in human skin suggests that the mechanisms by which steroid hormones mediate their effects may be more complex than previously thought.
Experimental Dermatology 05/2003; 12(2):181-90. · 3.54 Impact Factor
