What’s new in Hair – April 2019 | Dr. Sergio Vañó-Galván

Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

Nat Commun. 2019 Mar 8;10(1):1150. doi: 10.1038/s41467-019-09117-w. PMID: 30895660
Tziotzios C, Petridis C, Dand N, Ainali C, Saklatvala JR, Pullabhatla V, Onoufriadis A, Pramanik R, Baudry D, Lee SH, Wood K, Liu L, Seegobin S, Michelotti GA, Lwin SM, Christou EAA, Curtis CJ, de Rinaldis E, Saxena A, Holmes S, Harries M, Palamaras I, Cunningham F, Parkins G, Kaur M, Farrant P, McDonagh A, Messenger A, Jones J, Jolliffe V, Ali I, Ardern-Jones M, Mitchell C, Burrows N, Atkar R, Banfield C, Alexandroff A, Champagne C, Cooper HL, Vañó-Galván S, Molina-Ruiz AM, Perez NO, Patel GK, Macbeth A, Page M, Bryden A, Mowbray M, Wahie S, Armstrong K, Cooke N, Goodfield M, Man I, de Berker D, Dunnill G, Takwale A, Rao A, Siah TW, Sinclair R, Wade MS, Dlova NC, Setterfield J, Lewis F, Bhargava K, Kirkpatrick N, Estivill X, Stefanato CM, Flohr C, Spector T, Watt FM, Smith CH, Barker JN, Fenton DA, Simpson MA, McGrath JA.

This is a very interesting article about the genetics of frontal fibrosing alopecia (FFA). In this collaborative study, the research group of Dr. Christos Tziotzios and Dr. John McGrath from the United Kingdom performed a genome wide association study in an English and Spanish cohort of 1016 FFA patients and 4145 controls. They observed genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicated that the association is driven by the HLAB*07:02 allele. At 2p22.1, they implicated a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlighted overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02. As a conclusion, this study supports the autoimmune and hormonal mechanisms in the pathogenesis of FFA.

 

Variant PADI3 in Central Centrifugal Cicatricial Alopecia

N Engl J Med. 2019 Feb 28;380(9):833-841. doi: 10.1056/NEJMoa1816614.
Malki L, Sarig O, Romano MT, Méchin MC, Peled A, Pavlovsky M, Warshauer E, Samuelov L, Uwakwe L, Briskin V, Mohamad J, Gat A, Isakov O, Rabinowitz T, Shomron N, Adir N, Simon M, McMichael A, Dlova NC, Betz RC, Sprecher E.

In this article published in the prestigious New England Journal of Medicine, the authors demonstrate the genetic basis of central centrifugal cicatricial alopecia (CCCA). CCCA is the most common form of scarring alopecia among women of African ancestry. The disease is occasionally observed to affect women in families in a manner that suggests an autosomal dominant trait and usually manifests clinically after intense hair grooming. The authors used exome sequencing in a group of women with alopecia (discovery set), compared the results with those in a public repository, and applied other filtering criteria to identify candidate genes. They then performed direct sequencing to identify disease-associated DNA variations and RNA sequencing, protein modelling, immunofluorescence staining, immunoblotting, and an enzymatic assay to evaluate the consequences of potential etiologic mutations. They used a replication set that consisted of women with CCCA to confirm the data obtained with the discovery set.

In the discovery set, which included 16 patients, they identified one splice site and three heterozygous missense mutations in PADI3 in 5 patients (31%). PADI3 encodes peptidyl arginine deiminase, type III (PADI3), an enzyme that post-translationally modifies other proteins that are essential to hair-shaft formation. They then directly sequenced PADI3 in an additional 42 patients (replication set) and observed genetic variants in 9 of them. A post-hoc analysis of the combined data sets showed that the prevalence of PADI3 mutation was higher among patients with CCCA than in a control cohort of women of African ancestry. In conclusion, mutations in PADI3, which encodes a protein that is essential to proper hair-shaft formation, were associated with CCCA.

 

The efficacy and safety of dutasteride compared with finasteride in treating men with androgenetic alopecia: a systematic review and meta-analysis.

Clin Interv Aging. 2019 Feb 20;14:399-406. doi: 10.2147/CIA.S192435. PMID: 30863034
Zhou Z, Song S, Gao Z, Wu J, Ma J, Cui Y.

Oral 5α-reductase inhibitors, including finasteride and dutasteride, are the preferred and most efficacious treatment modalities for male androgenetic alopecia (male pattern baldness). Despite their promising efficacy on hair regrowth, there is debate about the potential adverse effects of these drugs on sexual function. In this systematic review and meta-analysis, Zhou et al. investigated the risk of adverse sexual effects due to treatment of androgenetic alopecia in male patients with finasteride, 1 mg/day, or dutasteride, 0.5 mg/day. Fifteen randomized double-blinded placebo-controlled trials (4,495 subjects) were meta-analysed. Use of 5α-reductase inhibitors carried a 1.57-fold risk of sexual dysfunction [95% confidence interval (95% CI) 1.19–2.08]. The relative risk was 1.66 (95% CI 1.20–2.30) for finasteride and 1.37 (95% CI 0.81–2.32) for dutasteride. In conclusion, both drugs were associated with a slightly increased risk for sexual dysfunction, although the increase was not statistically significant for dutasteride.

 

“Normal-appearing” scalp areas are also affected in lichen planopilaris and frontal fibrosing alopecia: An observational histopathologic study of 40 patients

Exp Dermatol. 2018 Nov 7. doi: 10.1111/exd.13834. PMID: 30403306
Doche I, Romiti R, Hordinsky MK, Valente NS.

This is an interesting study about the potential histological involvement of clinically unaffected areas in lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA). In this study, Dr. Doche et al. assessed histopathologic changes in affected and unaffected scalp in both diseases and healthy control subjects and compared these findings with clinical signs and scalp symptoms. They demonstrated in a cohort of 40 patients that “normal-appearing” scalp that was devoid of clinical lesions of LPP and FFA showed lymphocytic perifollicular inflammation around the isthmus/infundibulum areas in 65% of biopsy specimens, perifollicular fibrosis in 15% and mucin deposits in 7.5% of the cases. None of these findings were found in control samples. No direct correlation was found between the degree of histopathological inflammation, scalp symptoms and clinical lesions in the corresponding affected scalp areas. In conclusion, the results of this study suggest that both diseases may be more generalized processes which affect the scalp and therefore might need systemic or total scalp therapy.

 

Low-dose daily aspirin reduces topical minoxidil efficacy in androgenetic alopecia patients

Dermatol Ther. 2018 Nov;31(6):e12741. doi: 10.1111/dth.12741.PMID: 30226287
Goren A, Sharma A, Dhurat R, Shapiro J, Sinclair R, Situm M, Kovacevic M, Lukinovic Skudar V, Goldust M, Lotti T, McCoy J.

In this study, Dr. Goren et al. reported the inhibitory effect of low dose daily aspirin use on the efficacy of topical minoxidil. Previously, this research group demonstrated that sulfotransferase activity in hair follicles predicts response to topical minoxidil in the treatment of androgenetic alopecia. In the present study, the authors determined the follicular sulfotransferase enzymatic activity following 14 days of oral aspirin administration in a cohort of 24 subjects. In these patients, 50% were initially predicted to be responders to minoxidil. However, following 14 days of aspirin administration, only 27% of the subjects were predicted to respond to topical minoxidil. In conclusion, dermatologists should be aware that the use of low dose daily aspirin may decrease the effectiveness of topical minoxidil.

 

Frequency of the Types of Alopecia at Twenty-Two Specialist Hair Clinics: A Multicenter Study

Skin Appendage Disorders. https://doi.org/10.1159/000496708
Vañó-Galván S, Saceda-Corralo D, Blume-Peytavi U, Cucchía J, Dlova N.C., Gavazzoni Dias M.F.R., Grimalt R., Guzmán-Sánchez D, Harries M, Ho A, Holmes S, Larrondo J, Mosam A, Oliveira-Soares R, Pinto G.M, Piraccini B.M, Pirmez R, De la Rosa Carrillo D, Rudnicka L, Shapiro J, Sinclair R, Tosti A, Trüeb R.M, Vogt A, Miteva M.

In this collaborative multicentre study of 22 centers, the authors aimed to analyse the frequency of the types of alopecia of patients coming for consultation in specialist hair clinics (SHCs) and to assess for global variations. SHCs from Europe, America, Africa and Australia participated in the study. A total of 2,835 patients (72.7% females and 27.3% males) with 3,133 diagnoses of alopecia were included (73% were non-cicatricial and 27% were cicatricial alopecias). In all, 57 different types of alopecia were characterized. The most frequent type was androgenetic alopecia (AGA) (37.7%), followed by alopecia areata (AA) (18.2%), telogen effluvium (TE) (11.3%), frontal fibrosing alopecia (FFA) (10.8%), lichen planopilaris (LPP) (7.6%), folliculitis decalvans (FD) (2.8%), discoid lupus (1.9%) and fibrosing alopecia in a pattern distribution (FAPD) (1.8%). There was a male predominance in patients with acne keloidalis nuchae, dissecting cellulitis and FD, and female predominance in traction alopecia, central centrifugal cicatricial alopecia, FFA, TE, FAPD and LPP. The authors conclude that AGA, followed by AA and TE, were the most frequent cause of non-cicatricial alopecia, while FFA was the most frequent cause of cicatricial alopecia in SHCs in all studied geographical areas.

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