What’s new in hair — June 2017 | Dr. Claire A. Higgins

The transcriptional landscape of seasonal coat colour moult in the snowshoe hare

Mol Ecol. 2017 May 13. doi: 10.1111/mec.14177. [Epub ahead of print]

Exogen, or hair shedding, is a key mechanism enabling animals to change their coat in respect to seasonal changes in the environment. Environmental cues, such as day length and temperature, result in changes not only in hair length, but hair type, hair density and hair colour. For example, the snowshoe hare has a white coat in the winter and a brown coat in the summer. Seasonal moulting in spring and autumn enables snowshoe hares to change their coats from white to brown after the winter season, and from brown to white at the end of summer. In addition, moulting occurs in a wave in an anterior to posterior direction, and so during the moulting period an animal may have mosaic patches of white, brown, or intermediate (white/brown) hair on their body. In this paper, Ferreira et al take advantage of this progressive moult to assess the transcriptional changes which occur in the skin during the spring moult of snowshoe hares. Three biopsies were taken from the dorsal coat of 5 snowshoe hares whose coats were actively moulting resulting in white, intermediate and brown patches of hair. Sequencing and subsequent analysis identified 766 genes as differentially expressed in at least one of the three pairwise comparisons. Clustering of samples revealed that “white” and “brown” skin biopsies clustered together regardless of which snowshoe hare the biopsy was taken from, while “intermediate” samples tended to separate into either “white” or “brown” clusters highlighting inter-hare differences. Gene Ontology (GO) analysis identified 54 Biological Processes significantly represented by genes in the “white” cluster, while only 1 Biological Process, ‘Collagen catabolic process’ was represented by genes in the “brown” cluster, corresponding with the end of the moult. This analysis will be of interest for hair follicle biologists wishing to identify genes associated with moulting patterns, coat colour, and transition through the hair cycle in wild animals.

 

Various Types of Minor Trauma to Hair Follicles During Follicular Unit Extraction for Hair Transplantation

Plast Reconstr Surg Glob Open. 2017 Mar 16;5(3):e1260. doi: 10.1097/GOX.0000000000001260. eCollection 2017 Mar.

Hair follicle transplantation is the relocation of follicles from the occipital scalp to the frontal scalp to combat Androgenetic alopecia, more commonly known as Male Pattern Baldness (MPB). Traditionally, strip grafts were harvested from the occipital scalp and cut into follicular units for transplantation. However, this method of harvesting hair is becoming gradually replaced by follicular unit extraction (FUE), which is less invasive and results in minimal scarring at the donor site. Despite these advantages of FUE, follicle survival rate is reported to be lower after transplantation of FUE, compared to strip graft harvested hair follicles. In this study, Park and You examined 4200 1mm punches, harvested by FUE from 42 patients (100 per patient), to assess types of micro injury which may be occurring during FUE and contributing to a lowered follicle survival rate. Analysis of follicles under a microscope showed that 6.34% were transected, leaving just the upper follicle with no bulb, while paring (removal of the outer root sheath) was present in 9.07% of follicles. Injury to the dermal papilla or bulb region of the follicle occurred in 2.03% of follicles, while fracture of the hair shaft was observed in 1.95% of follicles collected. While it may seem that a large percentage of follicles were damaged by FUE, it would be interesting to analyse follicles harvested by strip graft for comparison. Presumably, there would be less damage of follicles harvested by strip grafting. In addition, how these different forms of micro injury affect survival rate of the follicle after transplantation remains to be elucidated.

 

Excellent response to tofacitinib in a patient with alopecia universalis

Acta Dermatovenerol Alp Pannonica Adriat. 2017 Jun;26(2):47-49.

Alopecia areata (AA) is an autoimmune disease which results in immune cell attack of the hair follicle and subsequently hair loss. There are various forms of AA; Patchy Alopecia (AAP) is characterised by circular patches of hair loss on the scalp, while Alopecia Universalis (AU) is complete loss of hair on the scalp and body. In the past few years, oral Janus kinase (JAK) inhibitors, specifically ruxolitinib and tofacitinib have been proposed as treatments for AA, and both of these drugs are currently being tested in clinical trials for AA in the United States. In this study, Erduran et al treated a 23 year old female in Turkey, who had developed AAP at the age of 14 and AU at 19, with oral tofacitinib. Initially the patient was treated with 5mg twice daily, but after 2 months this dose was increased to 10mg in the morning, and 5mg at night (15mg daily). After 6 months the patient had achieved complete hair regrowth, and intriguingly the photographs in the manuscript suggest that the patient transitioned from AU, to AAP, before complete regrowth was achieved. At 12 months the dose was lowered to 10mg daily, but the patient started transitioning back to AAP, and the dose was increased again to 15mg daily. At the time of this article, the patient had been on 15mg daily for 19 months, with no aberrant side effects. This study contributes to the growing body of evidence suggesting JAK inhibitors are effective treatments for AA.

 

A Case of Topical Ruxolitinib Treatment Failure in Alopecia Areata

J Cutan Med Surg. 2017 Jun 1:1203475417716363. doi: 10.1177/1203475417716363. [Epub ahead of print]

Alopecia areata (AA) is a form of nonscarring hair loss. Hair loss is initially caused as a result of an influx of cytotoxic T cells (CTCs) which attack the hair follicle, but these CTCs in turn increase in number as a result of signalling from the follicle. Thus, a feed forward loop exacerbates hair loss. Both sides of this feed forward loop are mediated by signalling through the Jak-Stat pathway, and thus Janus Kinase (JAK) inhibitors have been proposed as effective treatments for disease reversal. Oral JAK inhibitors (ruxolitinib and tofacitinib) are showing high efficacy in clinical trials for AA. One point to note is that oral delivery makes use of the circulatory system, and the high numbers of capillaries in the skin dermis, to deliver the inhibitors to the target tissue. While this may be beneficial for drug delivery, clinicians warn of numerous side effects which may be caused by systemic delivery. In this manuscript, Deeb and Beach trial a 66 year old woman in Canada presenting with a 4 year history of AA, with 0.6% ruxolitinib cream applied topically for 3.5 months. At the end of 3.5 months the trial was stopped due to the high monetary cost to the patient, and no improvement of AA. In human skin the follicle bulb, and target of ruxolitinib, is 3mm below the surface. It should be noted that this report focuses on just one patient, but it seems that topical ruxolitinib (0.6% cream) cannot penetrate deep enough into the skin to have a therapeutic effect, and thus other vehicles of delivery need to be investigated.

 

Planar cell polarity-dependent and independent functions in the emergence of tissue-scale hair follicle patterns

Dev Biol.2017 Jun 7. pii: S0012-1606(17)30220-8. doi: 10.1016/j.ydbio.2017.06.003. [Epub ahead of print]

Hair shaft exit is not perpendicular to the skin; rather, hair fibres exit the skin in a posterior direction. This is facilitated by the unidirectional tilt of hair follicles under the skin surface, which are orientated in an anterior to posterior manner. Several genes within the planar cell polarity (PCP) pathway, including Vangl2, Celsr1 and Fzd6 are expressed in an asymmetric pattern in the follicle during development and enable this follicular alignment. Indeed, loss of function of Vangl2 or Celsr1 results in growth of follicles perpendicular to the skin epidermis, while Fzd6 mutations cause follicles to grow at random orientations to one another. Despite a well-described role of PCP genes in follicle patterning during development, the role of Vangl2 or Celsr1 in postnatal follicle patterning has not been assessed as mutations in these genes are embryonic lethal. In this study, Cetera et al use a K14-Cre mouse to conditionally delete Vangl2 specifically in the skin epithelium, and investigate the role of Vangl2 in adult follicles. They found that while mice had disorganised hair follicle alignments at birth, follicles appeared to collectively rotate and globally align along the anterior to posterior axis shortly after birth. Comparatively, when the authors ablated both Vangl1 and Vangl2 (core PCP genes), collective rotation of follicles still occurred resulting in the development of local patterns and whorls, but this was not relative to the body axis. Thus, the authors demonstrate that while collective rotation of follicles is independent of the PCP pathway, global alignment of follicles along the body axis requires PCP function.

 

Common Allergens Identified Based on Patch Test Results in Patients with Suspected Contact Dermatitis of the Scalp

Skin Appendage Disord. 2017 Mar;3(1):7-14. doi: 10.1159/000453530. Epub 2016 Dec 17.

Contact dermatitis is an inflammatory condition which results in a compromised skin barrier and rashes or blisters in response to irritant or allergen exposure. Lesions are rarely observed on the scalp, but instead patients with scalp contact dermatitis present with chronic itch and hair loss. In this study, Aleid et al assessed patch test data from 226 patients presenting with scalp contact dermatitis to identify common allergens. Of the patients assessed, 85.8% presented with severe itching/burning, while 58.5% had hair shedding. Whilst in 45 patients no allergens were identified, in the remaining 181 patients the most common allergens were metals and fragrances. In the metal category, nickel elicited a positive allergen reaction in 23.8% of patients, while cobalt affected 21% of patients. With fragrances, balsam of Peru affected 18.2% individuals, while fragrance mix affected 14.4%. Nickel and cobalt are both commonly used in metal bristle hair brushes, hair clasps and pins, while fragrances are found in shampoos, conditioners and tonics. Intriguingly, of the 226 patients, only 21 were men; it would be interesting to see the breakdown of allergen response grouped by gender. Irrespective, this paper serves as a useful resource for clinicians to identify the possible source of allergen in their scalp contact dermatitis patients.

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