The epidemiology of alopecia areata: a population-based cohort study in UK primary care.

BACKGROUND: There is a lack of population-based information on the disease burden and management of alopecia areata (AA). OBJECTIVES: To describe the epidemiology of AA, focusing on incidence, demographics and patterns of healthcare utilization. METHODS: Population-based cohort study of 4·16 million adults and children, using UK electronic primary care records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database, 2009-2018. The incidence and point prevalence of AA were estimated. Variation in AA incidence by age, sex, deprivation, geographical distribution and ethnicity was examined. Patterns of healthcare utilization were evaluated in people with incident AA. RESULTS: The AA incidence rate was 0·26 per 1000 person-years. AA point prevalence in 2018 was 0·58% in adults. AA onset peaked at age 25-29 years for both sexes, although the peak was broader in females. People of nonwhite ethnicity were more likely to present with AA, especially those of Asian ethnicity [incidence rate ratio (IRR) 3·32 (95% confidence interval 3·11-3·55)]. Higher AA incidence was associated with social deprivation [IRR most vs. least deprived quintile 1·47 (1·37-1·59)] and urban living [IRR 1·23 (1·14-1·32)]. People of higher social deprivation were less likely to be referred for specialist dermatology review. CONCLUSIONS: By providing the first large-scale estimates of the incidence and point prevalence of AA, our study helps to understand the burden of AA on the population. Understanding the variation in AA onset between different population groups may give insight into the pathogenesis of AA and its management.

Establishing and prioritizing research questions for the treatment of alopecia areata: the Alopecia Areata Priority Setting Partnership.

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.

The importance of mindfulness in psychosocial distress and quality of life in dermatology patients.

BACKGROUND: Mindfulness, defined as purposively and nonjudgementally paying attention in the present moment, could be used within psychosocial interventions to reduce the distress associated with social anxiety and avoidance found in many skin conditions. However, little is known about the relationship between naturally occurring levels of mindfulness and distress in dermatology patients. OBJECTIVES: To examine the relationship between mindfulness and psychosocial distress in a dermatological population. It was hypothesized that higher levels of mindfulness would be associated with lower levels of social anxiety, anxiety, depression and skin shame, and with better quality of life. METHODS: Adult dermatology outpatients (n = 120) from one hospital completed items assessing subjective severity, skin shame, fear of negative evaluation, anxiety and depression, quality of life, and levels of mindfulness. RESULTS: Considering depression, 14% reported mild, 5% moderate and 2·5% severe symptoms. For anxiety, 22% reported mild, 23% moderate and 6% severe symptoms. In addition, 33·4% reported clinically significant social anxiety. After controlling for subjective severity, mindfulness explained an additional 19% of the variance in depression, 39% in anxiety, 41% in social anxiety, 13% in skin shame and 6% in dermatological quality of life. One specific facet of mindfulness (acting with awareness) was found to be the most consistent predictor of distress. CONCLUSIONS: The findings indicate that higher levels of mindfulness are associated with lower distress. This suggests that facilitating mindfulness may be helpful in reducing distress in dermatology patients, and the use of mindfulness techniques warrants further investigation.

Frontal fibrosing alopecia: possible association with leave-on facial skin care products and sunscreens; a questionnaire study.

BACKGROUND: Since its first description in 1994, frontal fibrosing alopecia (FFA) has become increasingly common, suggesting that environmental factors are involved in the aetiology. OBJECTIVES: To identify possible causative environmental factors in FFA. METHODS: A questionnaire enquiring about exposure to a wide range of lifestyle, social and medical factors was completed by 105 women with FFA and 100 age- and sex-matched control subjects. A subcohort of women with FFA was patch tested to an extended British standard series of allergens. RESULTS: The use of sunscreens was significantly greater in the FFA group compared with controls. Subjects with FFA also showed a trend towards more frequent use of facial moisturizers and foundations but, compared with controls, the difference in frequencies just failed to reach statistical significance. The frequency of hair shampooing, oral contraceptive use, hair colouring and facial hair removal were significantly lower in the FFA group than in controls. Thyroid disease was more common in subjects with FFA than controls and there was a high frequency of positive patch tests in women with FFA, mainly to fragrances. CONCLUSIONS: Our findings suggest an association between FFA and the use of facial skin care products. The high frequency of sunscreen use in patients with FFA, and the fact that many facial skin care products now contain sunscreens, raises the possibility of a causative role for sunscreen chemicals. The high frequency of positive patch tests in women with FFA and the association with thyroid disease may indicate a predisposition to immune-mediated disease.

What women want - quantifying the perception of hair amount: an analysis of hair diameter and density changes with age in caucasian women.

BACKGROUND: It has long been known that women lose satisfaction with their hair with ageing. Our data show that caucasian women perceive a decrease in hair amount in their mid 40s with a further decrease in the mid to late 50s, which leads to this dissatisfaction. Neither loss of density (hairs per cm(2) ) nor shaft diameter alone can fully account for this perception. A new metric, 'hair amount', is proposed as a quantitative metric combining the impact of both density and diameter on the perception of hair loss. OBJECTIVES: Creation of a single parameter combining the contribution of diameter and density to perception of female age-related hair loss. METHODS: In total, 1099 caucasian women (ages 18-66 years) with self-perceived hair loss and 315 caucasian women (ages 17-86 years) with no complaint of hair loss were evaluated. Scalp hair diameter was measured using optical fibre diameter and image analysis. Scalp hair density was measured by phototrichogram with manual or automated counting. RESULTS: Parietal scalp hair diameter increased from ages 20 to 40-45 years, then decreased. Hair density was highest in the youngest group, age 20-30 years, and decreased thereafter with increasing rate. In women self-perceiving hair loss, the rate of decrease in density was significantly faster than for women with no self-perception of hair loss. The combined metric 'hair amount' was relatively constant at younger ages, increasing very slightly to age 35 years, then decreasing significantly. CONCLUSIONS: Increasing hair shaft diameter offsets decreasing hair density through the mid 30s. After that, a lower rate of diameter increase combined with the decrease in density begins to significantly impact the perception of hair amount so that thinning becomes increasingly more noticeable in the mid 40s to the mid to late 50s. Quantitative determination of hair amount is a useful tool to combine the contributions of hair density and diameter to women's perception of age-related hair loss.

Investigation of the male pattern baldness major genetic susceptibility loci AR/EDA2R and 20p11 in female pattern hair loss.

BACKGROUND: The aetiology of female pattern hair loss (FPHL) is largely unknown. However, it is hypothesized that FPHL and male pattern baldness (AGA) share common susceptibility alleles. The two major susceptibility loci for AGA are the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X-chromosome, and a locus on chromosome 20p11, for which no candidate gene has yet been identified. OBJECTIVES: To examine the role of the AR/EDA2R and 20p11 loci in the development of FPHL using 145 U.K. and 85 German patients with FPHL, 179 U.K. supercontrols and 150 German blood donors. METHODS: Patients and controls were genotyped for 25 single nucleotide polymorphisms (SNPs) at the AR/EDA2R locus and five SNPs at the 20p11 locus. RESULTS: Analysis of the AR/EDA2R locus revealed no significant association in the German sample. However, a nominally significant association for a single SNP (rs1397631) was found in the U.K. sample. Subgroup analysis of the U.K. patients revealed significant association for seven markers in patients with an early onset (P = 0·047 after adjustment for the testing of multiple SNPs by Monte Carlo simulation). No significant association was obtained for the five 20p11 variants, either in the overall samples or in the analysis of subgroups. CONCLUSIONS: The observed association suggests that the AR/EDA2R locus confers susceptibility to early-onset FHPL. Our results do not implicate the 20p11 locus in the aetiology of FPHL.

Improvement in scalp hair growth in androgen-deficient women treated with testosterone: a questionnaire study.

BACKGROUND: Androgens are thought to have an adverse effect on female scalp hair growth. However, our clinical experience of androgen replacement therapy in women with androgen deficiency, in which hair loss was seldom reported, led us to question this concept. OBJECTIVES: To evaluate the effect of subcutaneous testosterone therapy on scalp hair growth in female patients. METHODS: A total of 285 women, treated for a minimum of 1year with subcutaneous testosterone implants for symptoms of androgen deficiency, were asked to complete a survey that included questions on scalp and facial hair. Age, body mass index (BMI) and serum testosterone levels were examined. RESULTS: Out of the 285 patients, 76 (27%) reported hair thinning prior to treatment; 48 of these patients (63%) reported hair regrowth on testosterone therapy (responders). Nonresponders (i.e. no reported hair regrowth on therapy) had significantly higher BMIs than responders (P=0·05). Baseline serum testosterone levels were significantly lower in women reporting hair loss prior to therapy than in those who did not (P=0·0001). There was no significant difference in serum testosterone levels, measured 4weeks after testosterone implantation, between responders and nonresponders. No patient in this cohort reported scalp hair loss on testosterone therapy. A total of 262 women (92%) reported some increase in facial hair growth. CONCLUSIONS: Subcutaneous testosterone therapy was found to have a beneficial effect on scalp hair growth in female patients treated for symptoms of androgen deficiency. We propose this is due to an anabolic effect of testosterone on hair growth. The fact that no subject complained of hair loss as a result of treatment casts doubt on the presumed role of testosterone in driving female scalp hair loss. These results need to be confirmed by formal measurements of hair growth.

Hair through the female life cycle.

At a population level female scalp hair growth shows features of regression with chronological ageing, although there is wide interindividual variation in timing and degree. The subjective assessment of hair loss is classically determined by hair density but it is apparent that other factors contribute to the clinical picture. Changes can occur in hair cycling, hair density, hair diameter and pigmentation, and possibly in structural qualities of the hair fibre. These changes are most pronounced in female pattern hair loss. Although conventionally considered as the female counterpart of male androgenetic alopecia the evidence that female pattern hair loss is androgen dependent is less clear cut than in men and it probably has a multifactorial basis. The emerging evidence implicating environmental factors is of particular interest as, unlike genes, such factors may be amenable to intervention. The clinical signs in women complaining of hair loss may be variable. In evaluating the patient complaining of hair loss, while true pathology must always be considered, the clinician needs to be aware of how age affects hair growth. These changes form the focus of this article.

How not to get scar(r)ed: pointers to the correct diagnosis in patients with suspected primary cicatricial alopecia.

Primary cicatricial alopecias (PCAs) are a rare, but important, group of disorders that cause irreversible damage to hair follicles resulting in scarring and permanent hair loss. They may also signify an underlying systemic disease. Thus, it is of paramount importance that clinicians who manage patients with hair loss are able to diagnose these disorders accurately. Unfortunately, PCAs are notoriously difficult conditions to diagnose and treat. The aim of this review is to present a rational and pragmatic guide to help clinicians in the professional assessment, investigation and diagnosis of patients with PCA. Illustrating typical clinical and histopathological presentations of key PCA entities we show how dermatoscopy can be profitably used for clinical diagnosis. Further, we advocate the search for loss of follicular ostia as a clinical hallmark of PCA, and suggest pragmatic strategies that allow rapid formulation of a working diagnosis.

Frontal fibrosing alopecia: clinical presentations and prognosis.

BACKGROUND: Frontal fibrosing alopecia is an uncommon condition characterized by progressive frontotemporal recession due to inflammatory destruction of hair follicles. Little is known about the natural history of this disease. OBJECTIVES: To determine the clinical features and natural history of frontal fibrosing alopecia. METHODS: We studied the cases notes of patients diagnosed with frontal fibrosing alopecia from 1993 to 2008 at the Royal Hallamshire Hospital, Sheffield. RESULTS: There were 18 patients aged between 34 and 71 years. Three were premenopausal. All had frontotemporal recession with scarring. This was associated with partial or complete loss of eyebrows in 15 patients while four had hair loss at other sites. One had keratosis pilaris-like papules on the face, and one had follicular erythema on the cheeks. Three patients had oral lichen planus, of whom two also had cutaneous lichen planus affecting other sites of the body. Treatments given included intralesional triamcinolone acetonide, 0.1% tacrolimus ointment and oral hydroxychloroquine. Progression of frontotemporal recession was seen in some patients, but not all. In one patient the hair line receded by 30 mm over 72 months, whereas in another patient there was no positional change in the hair line after 15 years. CONCLUSIONS: Frontal fibrosing alopecia is more common in postmenopausal women, but it can occur in younger women. It may be associated with mucocutaneous lichen planus. Recession of the hair line may progress inexorably over many years but this is not inevitable. It is not clear whether or not treatment alters the natural history of the disease - the disease stabilized with time in most of the patients with or without continuing treatment.

The autoimmune regulator gene (AIRE) is strongly associated with vitiligo.

BACKGROUND: Vitiligo is an autoimmune disorder that occurs with greatly increased frequency in the rare recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. We have previously detected an association between alopecia areata and single nucleotide polymorphisms (SNPs) in the AIRE gene. OBJECTIVES: To report the findings of an extended study including haplotype analysis on six AIRE polymorphisms (AIRE C-103T, C4144G, T5238C, G6528A, T7215C and T11787C) in vitiligo, another APECED-associated disease. METHODS: A case-control analysis was performed. RESULTS: Results showed a strong association between AIRE 7215C and vitiligo [P = 1.36 x 10(-5), odds ratio (OR) 3.12, 95% confidence interval (CI) 1.87-5.46]. We found no significant association with the other polymorphisms individually. However, haplotype analysis revealed that the AIRE haplotype CCTGCC showed a highly significant association with vitiligo (P = 4.14 x 10(-4), OR 3.00, 95% CI 1.70-5.28). To select the most informative minimal haplotypes, we tagged the polymorphisms using SNP tag software. Using AIRE C-103T, G6528A, T7215C and T11787C as tag SNPs, the haplotype AIRE CGCC was associated with vitiligo (P = 0.003, OR 2.49, 95% CI 1.45-4.26). CONCLUSIONS: The link between vitiligo and AIRE raises the possibility that defective skin peripheral antigen selection in the thymus is involved in the changes that result in melanocyte destruction in this disorder.

Genetic analysis of autoimmune regulator haplotypes in alopecia areata.

Alopecia areata is an immune-mediated disorder, occurring with the highest observed frequency in the rare recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. We have previously detected association between alopecia areata and a single nucleotide polymorphism (SNP) in the AIRE gene in patients without APECED, and we now report the findings of an extended examination of the association of alopecia areata with haplotype analysis including six SNPs in the AIRE gene: C-103T, C4144G, T5238C, G6528A, T7215C and T11787C. In Caucasian groups of 295 patients and 363 controls, we found strong association between the AIRE 7215C allele and AA [P = 3.8 x 10(-8), OR (95% CI): 2.69 (1.8-4.0)]. The previously reported association between AA and the AIRE 4144G allele was no longer significant on correction for multiple testing. The AIRE haplotypes CCTGCT and CGTGCC showed a highly significant association with AA [P = 6.05 x 10(-6), 9.47 (2.91-30.8) and P = 0.001, 3.51 (1.55-7.95), respectively]. To select the haplotypes most informative for analysis, we tagged the polymorphisms using SNPTag software. Employing AIRE C-103T, G6528A, T7215C and T11787C as tag SNPs, two haplotypes were associated with AA; AIRE CGCT and AIRE CGCC [P = 3.84 x 10(-7), 11.40 (3.53-36.9) and P = 3.94 x 10(-4), 2.13 (1.39-3.24) respectively]. The AIRE risk haplotypes identified in this study potentially account for a major component of the genetic risk of developing alopecia areata.