Frontal fibrosing alopecia: a descriptive cross‐sectional study of 711 cases in female patients from the UK

Frontal fibrosing alopecia (FFA) is an inflammatory primary scarring alopecia of uncertain aetiology that represents a variant of lichen planopilaris.1 It predominantly, although not exclusively, affects post-menopausal women.2 Its pathogenesis is characterised by immune-mediated follicular destruction at the level of the hair bulge, which leads to a clinical phenotype of progressive fronto-temporal hair and eyebrow loss that is often preceded by widespread body hair loss.

Frontal fibrosing alopecia: a descriptive cross-sectional study of 711 cases in female patients from the UK DOI: 10.1111/bjd.19399 DEAR EDITOR, Frontal fibrosing alopecia (FFA) is an inflammatory primary scarring alopecia of uncertain aetiology that represents a variant of lichen planopilaris. 1 It predominantly, although not exclusively, affects postmenopausal women. 2 Its pathogenesis is characterized by immune-mediated follicular destruction at the level of the hair bulge, which leads to a clinical phenotype of progressive frontotemporal hair and eyebrow loss that is often preceded by widespread body-hair loss. 2 Histologically, a lichenoid inflammatory infiltrate surrounds the isthmus and infundibulum of the hair follicle, and this progresses to follicular scarring and dropout in advanced disease. 2 We recently completed the first genome-wide association study (GWAS) in FFA coupled with transcriptomic and metabolomic analyses, which have provided important insights into its pathogenesis. 3 We have conducted and herein present a descriptive cross-sectional study of the clinical phenotype in women from the FFA UK GWAS Cohort.
Ethical approval was obtained from the Northampton NRES Committee, UK (REC 15/EM/0273). Patients with a formal diagnosis of FFA made by a consultant dermatologist from 20 secondary care dermatology departments across the UK were eligible for inclusion. A diagnosis of FFA was made based on clinical criteria, with histological confirmation if required. 2 Each patient was assessed for multiple clinical variables based on a standardized pro forma. Analysis was limited to female participants of Eurasian ancestry in line with our previous GWAS. 3 Statistical analysis was descriptive and exploratory, estimating frequencies and measures of centrality and spread, and participants for whom data were missing for a given variable were excluded from the analysis. All analyses were conducted using Stata version 15 (StataCorp, College Station, TX, USA).
Phenotypic data were available for 711 UK women with FFA among a total of 1044 participants in the GWAS cohort. Their median age was 66 (interquartile range 59-72) and the median duration of scalp hair loss was 7 years (interquartile range 5-10). In 485 of 663 (73Á2%) participants with available data, frontotemporal hairline recession occurred following menopause. Other clinical characteristics and comorbidities are summarized in Table 1. Perifollicular erythema was present in 77Á3% and hyperkeratosis in 26Á0% of participants. In addition to frontotemporal recession, concomitant occipital recession was noted in 26Á0%. Eyebrow loss was noted in 90Á6% and eyelash loss in 44Á5%. Limb hair loss was also documented in 77Á5% and most commonly affected both arms and legs, while concomitant axillary or pubic hair loss was reported in 67Á0%. Concurrent multifocal involvement suggesting coexistence of classic lichen planopilaris (14Á7%) and nail changes of any type (23Á7%) were noted in a smaller proportion of participants. Other forms of lichen planus were seen in 9Á5% of participants, with oral (5Á1%) and vulval disease (3Á5%) being most prevalent.
In keeping with the immune-mediated pathogenesis of FFA, 20Á7% of participants reported at least one comorbid autoimmune disease ( Table 1). The most common was autoimmune thyroid disease (12Á9%), followed by coeliac disease (1Á5%) and pernicious anaemia (1Á2%). As hormonal aberrations have been implicated in the pathogenesis of FFA, we also examined whether certain endocrine disorders were prevalent in this cohort. 2 A history of oestrogen deficiency secondary to oophorectomy or primary ovarian insufficiency was present in 5Á6% of women, while 2Á3% reported exposure to selective oestrogen receptor modulators (tamoxifen or clomiphene). With regard to exogenous hormone use, the oral contraceptive pill was used for > 6 months by 71Á2% of women.
In summary, this descriptive study outlines the clinical characteristics and treatment modalities in a cohort of 711 women with FFA, recapitulating findings described by other international studies. 4 Analysis of comorbidities revealed that autoimmune disease, thyroid hormone abnormalities and oestrogen deficiency were more prevalent than in the general population, while the frequency of oral contraceptive use was similar. [5][6][7] These findings accord with other epidemiological studies and the results of our genetic investigation, which implicated causal genetic variation related to antigen presentation and hormone or xenobiotic metabolism in FFA pathogenesis. 3,8 This investigation is limited by its cross-sectional design, the absence of a control group, and missing data for certain clinical features. Therefore, further detailed clinical and experimental investigations are required to dissect the roles of autoimmunity and hormone metabolism in FFA pathogenesis.

Supporting Information
Additional Supporting Information may be found in the online version of this article at the publisher's website: Appendix S1 Full list of authors and affiliations.
Sustained improvement of surgical scar appearance 1 year after early intervention with nonablative fractional laser treatment: a randomized controlled split-wound trial DOI: 10.1111/bjd.19400 DEAR EDITOR, Early laser treatment during wound healing has increasingly gained focus to improve scar formation. 1 The majority of trials addressing early laser intervention for improving scar formation present short follow-up times of 1-3 months. 2 Considering the pathophysiology of scar formation, a scar is not mature until a year after injury. Thus, the effect of early laser treatment should be evaluated at least 1 year after scar intervention, and knowledge about long-term effect is lacking. [3][4][5][6][7] In 2018 our study group presented the 3-month follow-up data of a clinical trial on nonablative fractional laser (NAFL) treatment in early wound healing for improvement of scar formation. 8 This paper provides long-term data at the 1-year followup.
The clinical trial has previously been described in detail. 8 In short, this was a randomized, controlled, intraindividual splitsurgical wound study, comparing 1540-nm erbium-glass NAFL-treated scar halves vs. untreated control halves. Three NAFL treatments were applied on the randomized scar halves using two handpieces, sequentially distributing energy (40-50 mJ per microbeam) deeply and more superficially in the skin before excision, at suture removal and 6 weeks after surgery. Each surgical wound's central 0Á5-cm section was excluded from evaluation to prevent a NAFL bystander effect on the untreated control half.
Clinical evaluations at the 1-year follow-up were blinded and based on the Patient Observer Scar Assessment Scale (POSAS) as the primary outcome and the Vancouver Scar Scale (VSS) as the secondary outcome. Descriptive statistics were used to report characteristics accordingly. Outcomes lacked normal distribution and thus a nonparametric test of paired data was applied (Wilcoxon signed-rank test). P-values < 0Á05 were considered statistically significant. Stata v.14Á2 was used (StataCorp, College Station, TX, USA).
Among the 30 patients who completed the 3-month follow-up, 24 completed 1-year follow-up. The results are presented in Table 1. Fifteen men and nine women were included, and the median age was 63 years [interquartile range (IQR) 49-79]. Scars were located on the thorax (n = 14), upper and lower extremities (n = 3 and n = 4) and the head and neck area (n = 3). The mean length of included scars was 4Á6 cm (range 2Á5-7Á0). Neither sex, age nor scar length differed significantly between the patients who completed 1year follow-up and those who did not. However, the localization of scars was significantly different, as only patients with head and neck scars were lost to follow-up. Among the six patients who were lost to follow-up, four (67%) had a better POSAS-total score for NAFL-treated scar halves, one patient had a better score for the control half, and one patient had no score difference at the 3-month evaluation.
The primary outcome, POSAS-total, showed significant improvement in the NAFL-treated scar halves with a median of 11 (IQR 8Á5-13Á5), compared with the control halves, with a median of 12 (IQR 10Á5-15; P = 0Á037). The variation in POSAS-total was distributed as follows: 46% of the scars had a better score for the NAFL-treated scar halves with a range of 1-7 points; in 17% the control scar halves had a better score