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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., Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.

OBJECTIVE: To investigate the prevalence of autoimmune disease and circulating autoantibodies in women with lichen sclerosus (LS) and erosive lichen planus (LP) of the vulva and to compare these with a control population. DESIGN: Age- and sex-matched controlled study. SETTING: The vulval clinics in Oxfordshire, England, for patients with LS and LP. Healthy controls were recruited from the hospital and community. PATIENTS: A total of 190 women with the typical features of adult-onset LS of the vulva, 126 women with adult-onset erosive LP of the vulva, and 922 female controls (of whom 230 were examined). INTERVENTIONS: Personal history of autoimmune disorder for patients and controls, family history of autoimmune disorder for vulval LS and LP cohorts, and an autoantibody screen. MAIN OUTCOME MEASURES: The presence or absence of a personal or family history of autoimmune disorder, and the presence or absence of 1 or more circulating autoantibodies. RESULTS: The mean ages of patients with LS, patients with erosive LP, and control patients were 63, 61, and 61 years, respectively. The mean age of the 230 controls examined (including those who had serum autoantibodies assayed) was 62 years. Autoimmune disorders were more frequent in patients with erosive LP compared with controls (29% vs 9%; P < .001) and in those with LS compared with controls (28% vs 9%; P < .001). Circulating autoantibodies were more frequent in those with erosive LP compared with controls (41% vs 20%; P < .001). Conclusion This study demonstrates an association of autoimmune disorder and autoantibodies with erosive LP of the vulva and confirms the autoimmune associations of vulval LS.

Autoantibodies to basement membrane proteins BP180 and BP230 are characteristic of bullous pemphigoid and other subepidermal immunobullous disorders. These antibodies are, however, reported in other pruritic dermatoses, non-bullous disorders and non-cutaneous disease. Few studies have assessed basement membrane antibodies in normal subjects; antibody prevalence in this population is not clear. This study aims to examine basement membrane zone antibodies in normal middle-aged to elderly subjects. Sera from 61 healthy subjects (majority age 50-70 years) were assessed by immunoblot, indirect immunofluorescence and enzyme-linked immunosorbent assay. Ninety-one bullous pemphigoid patients acted as positive controls. Antigenic target, antibody class and titre were examined; sera binding BP180 were assessed for reactivity to the non-collagenous 16A (NC16A) domain. Thirty-six normal subjects (59%) had antibodies to either BP180 or BP230 on immunoblot analysis. BP180 was the commonest target antigen, detected in 35 subjects; binding to the immunodominant NC16A domain was not detected. Immunofluorescence was positive in three subjects. Of the bullous pemphigoid sera, 88% were positive on immunoblot or immunofluorescence; a higher frequency had antibodies against BP230. In conclusion, significant numbers of normal healthy subjects have circulating autoantibodies to basement membrane proteins, chiefly BP180 detectable by immunoblot, but these do not bind the NC16A domain.

The aim of this study was to investigate whether increased oxidative stress occurs in erosive lichen planus of the vulva. Skin biopsies from six patients with untreated, histologically confirmed erosive lichen planus of the vulva were examined immunohistochemically using antibodies against antioxidant enzymes. The protein-bound lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenale (4-HNE) and the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated. Protein carbonyls as markers of protein oxidation were visualised using the dinitrophenylhydrazone (DNPH) method. Normal vulval tissues from 12 subjects served as controls. In vulval lichen planus tissue the enzymatic antioxidant defence was found to be significantly decreased in the epidermal layers. Furthermore, a significant increase of lipid peroxidation products and oxidative DNA damage was found within the epidermis. Protein oxidation occurred predominantly in the papillary dermis. This is the first study to demonstrate a decreased antioxidant defence and increased oxidative damage to lipids, DNA and proteins in lichen planus. These oxidative modifications point to pathophysiological alterations mainly within the basal cell layers of the epidermis and at the dermoepidermal junction. Further studies are warranted to investigate the potential role of oxidative stress in the development of autoimmunity in this disease.