Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe 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 indicates that the association is driven by the HLA-B*07: 02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1 , encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights 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.

Takedaall through his universities and none related to this study. W.S.C., W.R.G. and M.N. are employees of Pfizer Ltd. S.H. is principal investigator and C.T. is principal and (national) chief investigator on the Pfizer-funded ALLEGRO clinical trial in alopecia areata. M.H., A.E.M., S.H. and A.G.M. are members of the British Association of Dermatologists (BAD) guidelines group for alopecia areata.

Sequirus and Takedaall through his universities and none related to this study. W.S.C. is an employee of Pfizer Ltd. S.H. is principal investigator and C.T. is principal and (national) chief investigator on the Pfizer-funded ALLEGRO clinical trial in alopecia areata. M.H., A.E.M., S.H. and A.G.M. are members of the British Association of Dermatologists guidelines group for alopecia areata.

Summary Background Alopecia areata (AA) is a common hair loss disorder that results in patchy to complete hair loss. Many uncertainties exist around the most effective treatments for this condition. Objectives To identify uncertainties in AA management and treatment that are important to both service users (people with hair loss, carers and relatives) and healthcare professionals. Methods An AA priority setting partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in AA. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. Results In total, 2747 treatment uncertainties were submitted by 912 participants, of which 1012 uncertainties relating to AA (and variants) were analysed. Questions were combined into ‘indicative uncertainties’ following a structured format. A series of ranking exercises further reduced this list to a top 25 that were taken to a final prioritization workshop where the top 10 priorities were agreed. Conclusions We present the top 10 research priorities for AA to guide researchers and funding bodies to support studies important to both patients and clinicians.

Many emerging studies have implicated the Janus kinase/signal transducer and activator of transcription (JAK-STAT) cytokine signalling mechanism in disease pathogenesis. This signalling pathway is involved in haematopoiesis and immune development. Mutations in genes regulating JAK-STAT signalling can cause common inflammatory disorders and myeloproliferative disorders. JAK and STAT inhibitors are new management tools for disorders such as myelofibrosis and rheumatoid arthritis. Evidence suggests that the cytokine components of the JAK-STAT pathways play a crucial role in common skin disorders, including psoriasis and atopic dermatitis. We present an overview for the clinical dermatologist of the significance of these signalling pathways in various skin disorders, and introduce the potential application of JAK and STAT inhibition as a new therapeutic tool in dermatology.