Natalie Garcia Bartels

Follow-Up Study of the First Genome-Wide Association Scan in Alopecia Areata: IL13 and KIAA0350 as Susceptibility Loci Supported with Genome-Wide Significance

Recently, the first genome-wide association study (GWAS) of alopecia areata (AA) was conducted in a North-American sample, and this identified eight susceptibility loci surpassing genome-wide significance. The aim of the present follow-up association analysis was to confirm five of these eight loci (single-nucleotide polymorphisms (SNPs) from the CTLA4, IL-2RA, and HLA regions were not included due to previous own findings) and test 12 other loci from the GWAS, which did not surpass the threshold for genome-wide significance. Twenty-three SNPs from the 17 loci were investigated using a sample of 1,702 Central European AA patients and 1,723 controls. Of the five loci with previously reported genome-wide significance, association was confirmed for all of these: ULBP3/ULBP6, PRDX5, IL-2/IL-21, STX17, and IKZF4/ERBB3 (P-value <0.05). To detect robust evidence for association among the 12 other loci, a meta-analysis of the present association data and the data of the recent GWAS was performed. Genome-wide significant association was found for rs20541 (P(comb)=7.52 × 10(-10); odds ratio (OR)=1.30 (1.23-1.38)) and rs998592 (P(comb)=1.11 × 10(-11); OR=1.28 (1.21-1.36)), thus establishing IL-13 and KIAA0350/CLEC16A as susceptibility loci for AA. Interestingly, IL-13 and KIAA0350/CLEC16A are susceptibility loci for other autoimmune diseases, supporting the hypothesis of shared pathways of autoimmune susceptibility.

Follicular and percutaneous penetration pathways of topically applied minoxidil foam

In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances. This study investigates a selective closure technique of hair follicle orifices in vivo assessing interfollicular and follicular absorption rates of topical minoxidil foam in humans. In delimited skin area, single hair orifices or interfollicular skin were blocked with a microdrop of special varnish-wax-mixture in vivo. Minoxidil foam (5%) was topically applied, and transcutaneous absorption was measured by a new surface ionization mass spectrometry technique in serum. Different settings (open, closed or none of both) enabled to clearly distinguish between interfollicular and follicular penetration of the topically applied minoxidil foam. Five minutes after topical application, minoxidil was detected in blood samples when follicles remained open, whereas with closed follicles 30 min were needed. Highest levels were found first when both pathways were open, followed by open follicles and subsequently by closed follicles. These results demonstrate the high importance of the follicular penetration pathway. Hair follicles are surrounded by a dense network of blood capillaries and dendritic cells and have stem cells in their immediate vicinity, making them ideal targets for drug delivery.

A randomized double-blind placebo-controlled pilot study to assess the efficacy of a 24-week topical treatment by latanoprost 0.1% on hair growth and pigmentation in healthy volunteers with androgenetic alopecia

BACKGROUND Latanoprost is a prostaglandin analogue used to treat glaucoma. It can cause adverse effects, such as iridial and periocular hyperpigmentation, and eyelash changes including pigmentation and increased thickness, length, and number. Latanoprost has been used to treat eyelash alopecia, but knowledge on its effects on human scalp hair growth is not available. OBJECTIVE The primary objectives were to assess the efficacy of latanoprost on hair growth and pigmentation. The secondary objectives were to assess the effect on scalp pigmentation; investigate the treatment duration needed to affect hair growth, hair pigmentation, and scalp pigmentation; and assess safety of latanoprost. METHODS Sixteen men with mild androgenetic alopecia (Hamilton II-III) were included. Latanoprost 0.1% and placebo were applied daily for 24 weeks on two minizones on the scalp. Measurements on hair growth, density, diameter, pigmentation, and anagen/telogen ratio were performed throughout the study. RESULTS At 24 weeks, an increased hair density on the latanoprost-treated site was observed compared with baseline (n = 16, P < .001) and placebo-treated site (P = .0004). LIMITATIONS Only young men with mild androgenetic alopecia were included. The results may not be applicable to other patient groups. Choice of investigational site may have affected the results. CONCLUSIONS Latanoprost significantly increased hair density (terminal and vellus hairs) at 24 weeks compared with baseline and the placebo-treated area. Latanoprost could be useful in stimulating hair follicle activity and treating hair loss.

Comparison of the efficacy and safety of topical minoxidil and topical alfatradiol in the treatment of androgenetic alopecia in women

Background: Two drugs which are approved for the treatment of androgenetic alopecia in women in Germany were compared with regard to their influence on hair growth.

Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata

Alopecia areata (AA) is a common hair loss disorder, which is thought to be a tissue-specific autoimmune disease. Previous research has identified a few AA susceptibility genes, most of which are implicated in autoimmunity. To identify new genetic variants and further elucidate the genetic basis of AA, we performed a genome-wide association study using the strategy of pooled DNA genotyping (729 cases, 656 controls). The strongest association was for variants in the HLA region, which confirms the validity of the pooling strategy. The selected top 61 single-nucleotide polymorphisms (SNPs) were analyzed in an independent replication sample (454 cases, 1364 controls). Only one SNP outside of the HLA region (rs304650) showed significant association. This SNP was then analyzed in a second independent replication sample (537 cases, 657 controls). The finding was not replicated on a significant level, but showed the same tendency. A combined analysis of the two replication samples was then performed, and the SNP rs304650 showed significant association with P=3.43 × 10−4 (OR=1.24 (1.10–1.39)). This SNP maps to an intronic region of the SPATA5 (spermatogenesis-associated protein 5) gene on chromosome 4. The results therefore suggest the SPATA5 locus is a new susceptibility locus for AA.

Comparison of two in vivo measurements for skin surface topography

Non‐contact methods for quantifying skin surface topography in vivo are common in skin research. The surface evaluation of living skin (SELS) and the phaseshift rapid in vivo measurement of skin (PRIMOS) are two approaches to measure skin surface roughness and wrinkling via optical methods. The aim of this study was to compare the reliability and interrelatedness of the parameters obtained by both technologies.

Effect of baby swimming and baby lotion on the skin barrier of infants aged 3–6 months

Background: Skin care is important especially in infancy as the skin barrier matures during the first year of life. We studied the effects of baby swimming and baby lotion on the skin barrier function of infants.

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

Do Repeated Skin Barrier Measurements Influence Each Other's Results? An Explorative Study

Background: Biophysical skin measurement techniques are widely used to quantify the skin barrier function. In clinical research usually several parameters are subsequently measured in the same skin areas. In this study, possible interfering effects of subsequent measurement procedures on transepidermal water loss (TEWL), stratum corneum hydration (SCH) and skin surface pH were investigated. Methods: An exploratory study was conducted. Twelve young (mean age 32.9 ± 7.2 years) and 12 elderly (mean age 68.3 ± 2.5 years) subjects without any skin diseases were enrolled. The parameters TEWL, skin surface pH, SCH, sebum content, and surface evaluation of living skin were obtained successively in pairs from 4 contralateral volar forearm skin areas. Results: SCH and skin surface pH seemed to be unaffected by previous measurement procedures. TEWL was systematically increased after pH and systematically decreased after stratum corneum measurements. Conclusions: Measurements per se might interact with the skin, thus changing its characteristics. If several skin barrier function parameters need to be assessed subsequently in the same skin areas, we recommend that TEWL should be measured first followed by all others.

Children with Dry Skin and Atopic Predisposition: Daily Use of Emollients in a Participant-Blinded, Randomized, Prospective Trial

Background: Dry skin reflects a skin barrier defect which can lead to atopic dermatitis. Little is known about the distinct effects of emollient use in children with dry skin and atopic predisposition. Objectives: We investigated the effects of daily application of pressed ice plant juice (PIPJ)-based emollients and petrolatum-based emollients. Methods: Children aged 2-6 years with dry skin and atopic predisposition were randomized into 2 groups: group 1 received emollients containing PIPJ and natural lipids, while group 2 received petrolatum-based emollients. Skin condition and biophysical properties of the skin barrier were assessed at inclusion and weeks 4, 12 and 16. Results: Skin condition improved significantly in all children. Comparing the groups, children treated with emollients containing PIPJ showed significantly higher stratum corneum hydration values and significantly lower transepidermal water loss values at week 16 on the forearm and forehead. A significant decrease in skin pH was noted in group 2 on the forearm and forehead; group 1 showed a stable course. Conclusion: Early intervention with emollients in children with dry skin condition and atopic predisposition may improve their skin condition during daily emollient application. PIPJ-based formulations may be helpful to maintain skin barrier integrity.