K. Dobson

Nickel skin levels in different occupations and an estimate of the threshold for reacting to a single open application of nickel in nickel-allergic subjects.

Background  Nickel is a frequent allergen throughout the world. However, the extent to which nickel is relevant as an occupational contact allergen as opposed to being simply a reflection of jewellery exposure has been unclear. Some thresholds for cutaneous nickel exposure to induce a dermatitis reaction in nickel‐allergic individuals have been defined. Over recent years it has become possible to measure accurately the quantity of nickel on the skin of individuals in a number of occupations.

Frontal fibrosing alopecia: possible association with leave-on facial skin care products and sunscreens; a questionnaire study†

Since its first description in 1994, frontal fibrosing alopecia (FFA) has become increasingly common, suggesting that environmental factors are involved in the aetiology.

Investigation of the male pattern baldness major genetic susceptibility loci AR/EDA2R and 20p11 in female pattern hair loss

Background  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.

Selected variants of the steroid-5-alpha-reductase isoforms SRD5A1 and SRD5A2 and the sex steroid hormone receptors ESR1, ESR2 and PGR: no association with female pattern hair loss identified.

Abstract:  Female pattern hair loss (FPHL) is a common disorder with a complex mode of inheritance. Although understanding of its etiopathogenesis is incomplete, an interaction between genetic and hormonal factors is assumed to be important. The involvement of an androgen‐dependent pathway and sex steroid hormones is the most likely hypothesis. We therefore selected a total of 21 variants from the steroid‐5‐alpha‐reductase isoforms SRD5A1 and SRD5A2, the sex steroid hormone receptors ESR1, ESR2 (oestrogen receptor) and PGR (progesterone receptor) and genotyped these in a case–control sample of 198 patients (145 UK; 53 German patients) and 329 controls (179 UK; 150 German). None of these variants showed any significant association, either in the overall UK and German samples or in the subgroup analyses. In summary, the present results, while based on a limited selection of gene variants, do not point to the involvement of SRD5A1, SRD5A2, ESR1, ESR2 or PGR in FPHL.

Investigation of six novel susceptibility loci for male androgenetic alopecia in women with female pattern hair loss

Androgenetic alopecia is the most frequent hair loss disorder in both sexes, termed male-pattern baldness (AGA) in men, and female pattern hair loss (FPHL) in women. The aetiopathogenesis of FPHL is poorly understood; however, reports of familial cases and the occurrence of both FPHL and AGA in some families point to genetic factors and a shared genetic background [1,2]. The likely hypothesis of shared common disease-causing mechanisms is further supported by the presence of elevated androgen levels and male pattern hair loss in some affected women, and the identical histology of FPHL and AGA [3,4]. Our own recent findings could not demonstrate involvement of the well-established AGA susceptibility locus on chromosome 20p11 in FPHL, but suggested that the major AGA locus, the X-chromosomal locus containing the androgen receptor (AR) and the ectodysplasin A2 receptor (EDA2R) genes, may be specifically involved in the pathogenesis of earlyonset FPHL [5]. This finding underpins the assumption of shared susceptibility loci in FPHL and AGA. Recently, a large-scale meta-analysis of seven genome-wide association studies (GWAS) of males with early-onset AGA was published [6]. Genome-wide significance was obtained for six

Frontal fibrosing alopecia in men: an association with facial moisturizers and sunscreens

Frontal fibrosing alopecia (FFA) was first described by Kossard in 1994 in 6 postmenopausal women.(1) FFA remained rare during the 1990s but in the last 10-15 years it has become increasingly common, a phenomenon observed worldwide. The recent onset and apparent rising incidence of FFA suggest involvement of an environmental factor(s) in the aetiology. We previously reported a questionnaire study in women with FFA that asked about a wide range of medical, social and environmental exposures. This article is protected by copyright. All rights reserved.

Investigation of variants of the aromatase gene (CYP19A1) in female pattern hair loss

alterations in melanoma. N Engl J Med 2005; 353:2135–47. 4 Husain EA, Mein C, Pozo L et al. Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi. Mod Pathol 2011; 24:471–86. 5 Lee JH, Choi JW, Kim YS. Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis. Br J Dermatol 2011; 164:776–84. 6 Guo Y, Feng Y, Trivedi NS, Huang S. Medusa structure of the gene regulatory network: dominance of transcription factors in cancer subtype classification. Exp Biol Med (Maywood) 2011; 236:628–36. 7 Diaz-Cano SJ. General morphological and biological features of neoplasms: integration of molecular findings. Histopathology 2008; 53:1–19. 8 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646–74.

Investigation of four novel male androgenetic alopecia susceptibility loci: no association with female pattern hair loss

Female pattern hair loss (FPHL) is a common hair loss disorder in women and has a complex mode of inheritance. The etiopathogenesis of FPHL is largely unknown; however, it is hypothesized that FPHL and male pattern baldness [androgenetic alopecia (AGA)] share common genetic susceptibility alleles. Our recent findings indicate that the major AGA locus, an X-chromosome region containing the androgen receptor and the ectodysplasin A2 receptor (EDA2R) genes, may represent a common genetic factor underlying both early-onset FPHL and AGA. This gives further support for the widespread assumption of shared susceptibility loci for FPHL and AGA. However, we could not demonstrate association of further AGA risk loci, including 20p11, 1p36.22, 2q37.3, 7p21.1, 7q11.22, 17q21.31, and 18q21.1, with FPHL. Interestingly, a recent study identified four novel AGA risk loci in chromosomal regions 2q35, 3q25.1, 5q33.3, and 12p12.1. In particular, the 2q35 locus and its gene WNT10A point to an as-yet unknown involvement of the WNT signaling pathway in AGA. We hypothesized that the novel loci and thus also the WNT signaling may have a role in the etiopathogenesis of FPHL and therefore examined the role of these novel AGA risk loci in our FPHL samples comprising 440 German and 145 UK affected patients, 500 German unselected controls (blood donors), and 179 UK supercontrols. Patients and controls were genotyped for the top two single nucleotide polymorphisms at each of the four AGA loci. However, none of the genotyped variants displayed any significant association. In conclusion, the results of this study provide no support for the hypothesis that the novel AGA loci influence susceptibility to FPHL.

Selected variants of the melanocortin 4 receptor gene (MC4R) do not confer susceptibility to female pattern hair loss

Female pattern hair loss (FPHL) is a common hair loss disorder in women with a complex mode of inheritance. Its etiopathogenesis is poorly understood. Widespread assumptions of overlapping susceptibility variants between FPHL and male pattern baldness (androgenetic alopecia) and a crucial role of androgens or distinct sexual steroid hormones in the development of FPHL could neither be clearly demonstrated nor completely excluded at the molecular level up to date. Interestingly, recent studies suggested an association of metabolic syndrome—including obesity, hyperlipidaemia, hypertension and diabetes mellitus type 2 or abnormally high fasting blood glucose—with FPHL. Of note, mutations in the melanocortin 4 receptor gene (MC4R) have been identified in patients with morbid obesity. Interestingly, this neuropeptide receptor has been detected amongst others in the dermal papilla of the hair follicle. As almost half of our FPHL patients of German origin present with adipositas and/or obesity, we hypothesized as to whether FPHL could be associated with variants of the MC4R gene. Thus, we genotyped a total of six variants from MC4R in our case–control sample comprising 245 UK patients of German and UK origin. However, based on our present study none of the genotyped MC4R variants displayed any significant association, neither in the overall UK and German samples nor in any subgroup analyses. In summary, these results do not point to an involvement of MC4R in FPHL.

Frontal fibrosing alopecia: there is no statistically significant association with leave-on facial skin care products and sunscreens: reply from the authors.

We did not perform a matched one-to-one comparison between FFA subjects and controls, we compared two groups with similar ages. The only continuous variable was age. The responses to the questions posed were categorical. We therefore maintain that a Fishers exact test rather than a McNemars test was an appropriate method for analyzing the results.