Andrew G. Messenger

Background: In clinical trials for alopecia areata (AA) the treatment effect (percentage of hair loss) is estimated using the Severity of Alopecia Tool (SALT) score. Trials in patients with severe AA (≥50% hair loss) employed a “local” rating of the SALT score performed at trial sites by different investigators. However, in mild-to-moderate AA (≤50% hair loss) where SALT scores are lower, potential inter-rater variability and margin of error may compromise the results. Objectives: To compare Centralised and Local measurement of hair loss in mild-moderate AA. Methods: In a Phase 2 clinical trial a centralised measurement of hair loss was performed from photographic images taken using a standardised protocol and professional camera equipment. Local scoring was also undertaken at screening/baseline for eligibility. We assessed: the repeatability of the central system (screening vs baseline values), the reproducibility of the central versus the local rating system and the potential impact of each method on the endpoints using a Monte-Carlo simulation method. Results: There was good agreement and consistency of scoring with Central rating. This provided much smaller margins of error, 50% lower than Local rating. The simulations demonstrated that substituting Local rating for Central rating would result in a reduction of the likelihood of a statistically significant outcome by at least 50% depending on the SALT score defined clinical response endpoint. Conclusions: Central rating is most appropriate in the Phase 2 ‘learning’ stage of clinical development and provides an accurate representation of the quantity of hair loss, minimising error and ensuring consistency in measurements. ‘What is already known about this topic?: - Hair loss in alopecia areata (AA) multicentre clinical trials is measured using the SALT score - In severe AA (SALT 50-100) local ‘in-person’ assessment is recommended to monitor treatment effects but here margins of error for changes have a wide tolerance - In mild/moderate AA (SALT<50), where smaller changes are likely, measurement accuracy and precision are essential - Published standardised imaging processes supporting the use of Central rating lack the required numerical analysis support this report provides ‘What does this study add?: - Local rating is not appropriate as scoring lacks accuracy and precision required in the mild/moderate condition - The value of Central rating over Local assessment is confirmed

Background: There are no licensed treatments for patients with mild-to-moderate patchy alopecia areata (AA). Objectives: To evaluate the efficacy, safety and dose-response of STS01, a novel nanoparticle controlled-release, topical formulation of dithranol/Prosilic. Methods: In a phase 2, double-blind study, adult patients with mild-to-moderate AA (guideline ≥10% to ≤50% of scalp hair loss) were randomly assigned to STS01 at doses of 0.25%, 0.5%, 1%, 2% or placebo, daily for 6 months. The primary endpoints included the proportion of patients achieving a ≥30% improvement in Severity of Alopecia Tool (SALT) score, and percentage change from baseline in SALT score. This minimum level of improvement is generally accepted as an indicator of the population likely to progress to complete regrowth Results: A total of 155 patients were randomized and treated (placebo, n=32; STS01 groups, n=30–31). STS01 1% met the primary efficacy endpoint of ≥30% SALT score improvement compared to placebo: 75.9% (95% CI, 60.3–91.4%) vs 36.7% (95% CI, 19.4–53.9%) at 6 months; p=0.0037. The least squares (LS) mean percentage change in SALT score from baseline to end-of-treatment showed a clear dose response relationship; STS01 0.5% was the minimally effective dose and 2% the maximum tolerated dose, and there was a statistically significant improvement in the STS01 1% group (−55.0% vs +0.6% with placebo; p<0.01). Significant improvements (p<0.05) in LS mean percentage changes from baseline in SALT scores were demonstrated in the STS01 1% group at 2 months (−28.6% vs 12.8%), 4 months (−57.2% vs 1.5%), and 6 months (−67.0% vs 0.6%). Clinical Global Impression-improvement was reported in 72.0% of patients with STS01 1% vs 41.7% with placebo (p<0.05). The most commonly reported treatment-emergent adverse events were skin irritation reactions, but were mostly mild (STS01: 56.7%–71.0%; placebo: 21.9%) or moderate (STS01:13.3%–35.5%; placebo: 0%) and manageable by reduced frequency of application. There were 15 skin-related discontinuations with STS01 (12.2%) and 2 (6.3%) with placebo. Conclusions: STS01 demonstrated a clear dose response, with STS01 1% dose optimally more effective than placebo for hair regrowth with minimal tolerance concerns in mild-to-moderate patchy AA. Skin irritation reactions were generally manageable and there were no new safety signals. Further characterisation of the STS01 1% dose is planned in a phase 3 study. Lay summary: Alopecia areata (AA) is a specific form of hair loss that occurs when the immune system attacks hair follicles causing hair to fall out. It usually starts in small, round patches. AA is a distressing condition that has many negative psychological and social effects. While there are new treatments for people with severe AA, there are still few treatments for mild/moderate patchy AA. Dithranol is a treatment that has been used for AA. In a simple cream form it purposely irritates the skin to stimulate hair regrowth, but this also stains skin, hair and fabrics. In this study, we tested a more advanced form of dithranol, called STS01 targeting the immune system without causing irritation. STS01 has been specifically designed as a new type of cream, to reduce the irritation and staining but also improve immune response. Overall, 155 UK adults with mild/moderate patchy AA took part – one group of people were given cream that had no STS01 (placebo) and the other groups were given similar creams that contained different amounts of STS01. We found that more participants using STS01 had hair regrowth than those using the placebo cream. Skin irritation reactions were mostly mild or moderate. Unlike previous dithranol creams, STS01 does not need to be washed off after 30 minutes, making it more convenient. Staining of the skin occurred in very few participants. Hair regrowth was better with higher doses of STS01, but the 1% dose had fewer skin irritation reactions than the 2% dose. The 1% STS01 dose will now be tested in a larger number of people with AA to further confirm these promising results. What is already known about this topic?: There are no licensed treatments for patients with mild to moderate patchy alopecia areata (AA), the most common form of this auto-immune condition. Topical dithranol is recommended on British Association of Dermatology guidelines as an irritant treatment for AA. However, these standard preparations have administration issues due to rapid oxidation, skin irritation, and staining. STS01 is a novel nanoparticle controlled-release once-daily topical formulation of dithranol specifically targeting down regulation of the auto-immune response and reducing administration issues What does this study add?: This phase 2, placebo-controlled trial showed clinically relevant improvements in hair regrowth with all measures assessed. STS01 was generally well-tolerated with no serious adverse events; skin reactions were mostly of mild or moderate intensity. STS01 represents a convenient and effective approach to the treatment of mild to moderate AA. Graphical

A phase 2, randomised, double-blind, placebo-controlled trial has been conducted in mild-to-moderate patchy alopecia areata (AA). This demonstrated significant and dose-related improvements in hair regrowth with STS01, a controlled release, topical formulation of dithranol. Here we report the results of the Alopecia Areata Symptom Impact Scale (AASIS) that assesses the severity of symptoms, daily functioning and feelings. Similar to trials in severe AA, significant improvements in hair regrowth did not translate into significant health-related quality of life (HRQoL) improvements, even in patients with complete hair regrowth, although there was some treatment-related correlation between changes in AASIS scores from baseline and clinical assessment SALT scores. The use of current HRQoL methods or indeed new measures in development for future trials, will have considerable challenges: patients may not have a ‘true’ baseline at entry, may develop coping mechanisms, and there may be a delay between physical and psychological improvement. Learning points: Alopecia areata is an autoimmune disease that imposes a substantial psychosocial burden on individuals. Poor health-related quality of life (HRQoL) is not directly related to the severity of hair loss as measured by SALT score. Patients with mild to moderate AA (≤50% hair loss as measured by SALT score) are similarly affected to those with severe AA (SALT score >50) STS01 is a novel controlled release, topical formulation of dithranol that showed significant and dose-related improvements in hair regrowth compared to placebo in a phase 2 double-blind randomised clinical trial in patients with mild to moderate AA. However, similar to trials in severe AA, significant improvements in hair regrowth did not appear to translate into significant HRQoL improvements, as measured using the Alopecia Areata Quality of Life Questionnaire. There are substantial limitations in the current tools for measuring HRQoL in individuals with AA, highlighting the need for increased understanding of the impact and determinants of HRQoL to help address these challenges.

Lay Summary: Alopecia areata (AA) is a long-term condition that can occur in both children and adults. AA can appear as patches of baldness on the scalp. Sometimes, nail growth is also affected. Hair on other parts of the body may also fall out, such as the beard, eyebrows and eyelashes. Alopecia totalis is the name for total loss of scalp hair. Alopecia universalis is complete loss of scalp, facial and body hair. This is the second version of the guideline. The British Association of Dermatologists gathered a group of experts in managing people of all ages with AA. The group consisted of eight consultant dermatologists, one dermatology specialist registrar, one general practitioner, one psychologist, two people with AA and a team with expertise in preparing guidelines. This group of experts reviewed relevant studies published until 11 July 2025. Using the evidence, the group produced recommendations using rigorous standards for guideline development. The guideline development group produced 56 recommendations for management of people with AA. They also made 9 recommendations for future research and suggested 11 audit points for hospitals. Based on the guideline, a patient information leaflet is also available on the British Association of Dermatologists’ website (https://www.skinhealthinfo.org.uk/condition/alopecia-areata).

Background: Limited evidence exists on prevailing treatments, disease characteristics and real-world outcomes of patients with alopecia areata (AA), particularly for those with ≥ 50% scalp hair loss (SHL) managed in clinical settings outside the USA. Objective: To provide evidence on disease characteristics, clinical management and outcomes of patients with AA with ≥ 50% SHL from real-world practice settings in Europe. Methods: The Assessment of real-world Disease characteristics and outcomes in Alopecia Areata in a Global non-Interventional Observational cohort (ADAAGIO) study was a retrospective chart review study in the UK, France, Spain and Germany. Adults and adolescents with ≥ 50% SHL were included. The first clinical observation of ≥ 50% SHL defined the study index date (2015–2019). Patients had ≥ 6 months of follow-up from index. Analyses were descriptive. The primary endpoint was the absolute Severity of Alopecia Tool (SALT) score, assessed longitudinally. Other endpoints included change in SALT score from baseline, and sustained SALT ≤ 20, defined as time to achieving SALT ≤ 20 without regression to SALT > 30 within 6 months, and sustained SALT ≤ 20 was assessed via inverse probability of censoring weighting (IPCW)-adjusted Kaplan–Meier estimation. Results: In total, 741 patients were included [median age at index: 27 years (range 12–81); 52.6% (390/741) female]. The mean SALT score at index was 63.5 (SD 15.6); 80.2% (594/741) had patchy AA and 19.8% (147/741) had alopecia totalis or universalis. Topical corticosteroids were the most common treatment post-index, with 55.6% (412/741) receiving ≥ 1 course with a median cumulative exposure of 4 months. Systemic and intralesional corticosteroids [44.1% (327/741) and 22.5% (167/741), respectively], Systemic and intralesional corticosteroids [44.1% (327/741) and 22.5% (167/741), respectively], systemic were also common. The mean absolute SALT reduction at 12 months post-index was –44.6% (SD 37.3%). However, at 12 months, based on IPCW-adjusted estimation, few patients (10.6%) achieved SALT ≤ 20 that was sustained for ≥ 6 months. Conclusions: Although patients in this study experienced substantial absolute SALT score reductions, few achieved and sustained SALT ≤ 20. These findings highlight the potential suboptimal effectiveness of the varied treatments.

Background: As the incidence of frontal fibrosing alopecia (FFA) continues to rise, there is a need for an optimal treatment algorithm for FFA. Objectives: To produce an international consensus statement on the treatment modalities and prognostic indicators of FFA. Methods: Sixty‐nine hair experts from six continents were invited to participate in a three‐round Delphi process. The final stage was held as a virtual meeting facilitated via Zoom. The consensus threshold was set at ≥66%. Results: Of 365 questions, expert consensus was achieved in 204 (56%) questions following completion of the three rounds. Three additional questions were included at the final meeting. The category with the strongest consensus agreement was disease monitoring (9; 100%). Questions pertaining to physical therapies achieved the least category consensus (15; 40%), followed by systemic therapy (45; 43%). Limitations: The study lacked sufficient representation from Africa and South America. Conclusions: SOFFIA highlights areas of agreement and disagreement among experts. Robust research is warranted to provide evidence‐based treatment recommendations.

Introduction This study assessed Dermatology Life Quality Index (DLQI) scores of patients with alopecia areata (AA) and compared scores between adults and adolescents. Methods This was a retrospective chart review in France, Germany, Spain, and the UK. Patients with ≥ 50% scalp hair loss (SHL) due to AA and a DLQI score recorded at their index date (first date of ≥ 50% SHL) were included. The DLQI (scale 0–30; higher scores indicate greater impact) assesses the impact of AA on health-related quality of life (QOL). Multivariable linear regression was used to examine the effect of age on DLQI score, adjusting for covariates. Modified Poisson regression analysis was used to estimate relative risks (RRs) between age groups and DLQI categories (none to moderate effect, very large effect, and extremely large effect), adjusting for covariates, including baseline Severity of Alopecia Tool (SALT) score. Results Overall, 335 patients were included (249 adults, 86 adolescents). At index, adults had a higher mean (SD) SALT score than adolescents (63.7 [15.5] vs 60.4 [12.8]), whereas mean (SD) DLQI scores were higher in adolescents than adults (22.1 [5.3] vs 18.2 [7.5]). Most patients (84%) had DLQI scores indicating a very large or extremely large impact on their lives; this was more pronounced in adolescents than adults (98% vs 80%). In the multilinear model, adolescents had significantly higher DLQI scores than adults (β = 3.51; P < 0.001), indicating a 3.51-point increase in DLQI score associated with being an adolescent. The RR (95% CI) of a DLQI score indicating a very large effect (1.28 [1.07–1.53]) or extremely large effect (1.40 [1.21–1.61]) relative to no or moderate effect was significantly higher for adolescents vs adults. Conclusion This study demonstrates that, at the time of experiencing ≥ 50% SHL due to AA, both adults and adolescents reported significant impacts on their QOL, with a higher impact on adolescents.

In this review, we discuss recent developments in our understanding of frontal fibrosing alopecia, a disease that has become increasingly common and widespread since its first description in 1994. An inherited predisposition to frontal fibrosing alopecia, previously suspected from the occurrence of familial cases, has been confirmed through genetic studies. Nevertheless, the epidemiology continues to implicate environmental factors in the aetiology. The search has focussed mainly on personal skin care products such as facial moisturisers and UV filters, and there is also some evidence implicating exogenous oestrogens, but confirmation of direct causal links has so far proved elusive. The pathologic mechanisms underlying follicular deletion are being clarified, including the nature of the inflammatory component, the loss of follicular immune privilege in the bulge region and the role of epithelial-mesenchymal transition in the scarring process. Lichen planus pigmentosus, a common accompaniment to frontal fibrosing alopecia in those with darker skin, is probably a feature of the same pathology affecting interfollicular epidermis, rather than a co-morbidity, and may offer new clues to the aetiology. Treatment is still based largely on retrospective case series and variable endpoints. However, methods for assessing frontal fibrosing alopecia and monitoring treatment responses have been strengthened and randomised controlled trials with novel agents (e.g. Janus kinase inhibitors) are in progress. As the main aim of effective treatment is to prevent disease progression, early diagnosis will remain an important target, as will prevention in the longer term.

Lay Summary: Alopecia areata (AA) is a long-term condition that can occur in both children and adults. AA can appear as patches of baldness on the scalp. Sometimes, nail growth is also affected. Hair on other parts of the body may also fall out, such as the beard, eyebrows and eyelashes. Total loss of scalp hair is called alopecia totalis (AT). Complete loss of scalp, facial and body hair is called alopecia universalis (AU). The British Association of Dermatologists gathered a group of experts in managing people of all ages with AA. The group consisted of 11 dermatologists, 1 psychologist, 2 people with AA and a team with expertise in preparing guidelines. This group of experts reviewed relevant studies published until 19 October 2023. Using the evidence, the group produced recommendations using rigorous standards for guideline development. The guideline development group produced 49 recommendations for management of people with AA. They also made 7 recommendations for future research and suggested 11 audit points for hospitals. Based on the guideline, the group prepared an updated patient information leaflet. The leaflet is available on the British Association of Dermatologists’ website (https://www.skinhealthinfo.org.uk/condition/alopecia-areata).

Background: Alopecia areata (AA) is an immune-mediated form of hair loss that can occur at any age, often with a significant mental health burden. Objectives: We aimed to provide estimates of the lifetime incidence of AA, and the impacts on mental health, healthcare utilization and work-related outcomes, assessing variation across major sociodemographic subgroups. Methods: AA cases were identified in primary care from the UK population-based Oxford-Royal College of General Practitioners Research and Surveillance Centre database (2009–2018). Lifetime incidence of AA was estimated at age 80 years using modified time-to-event models with age as the timescale, overall and stratified by sex, ethnicity, deprivation and geography. Mental health, healthcare utilization and work-related outcomes were assessed in the 2 years after AA diagnosis compared with matched unaffected controls, and stratified by the same sociodemographic subgroups. Results: During the study period, 6961 people developed AA. Overall lifetime incidence of AA was 2.11% [95% confidence interval (CI) 2.06–2.16]. Females had a higher lifetime incidence (2.35%, 95% CI 2.28–2.43) than males (1.88%, 95% CI 1.81–1.94). Lifetime incidence was higher in those of Asian ethnicity (5.87%, 95% CI 5.51–6.24), Other (4.5%, 95% CI 3.63–5.31), Mixed (4.4%, 95% CI 3.50–5.37) and Black (3.0%, 95% CI 2.63–3.42) ethnicity, compared with White ethnicity (1.7%, 95% CI 1.68–1.80). Lifetime incidence was highest in those with the greatest deprivation: most-deprived quintile (2.92%, 95% CI 2.77–3.07) compared with least-deprived (1.68%, 95% CI 1.59–1.78). Across sociodemographic subgroups, people with AA of Black ethnicity were most likely to have anxiety (adjusted odds ratio vs. matched controls 2.92, 95% CI 1.71–4.91), and had the greatest risk of time off work (adjusted hazard ratio vs. matched controls 2.54, 95% CI 1.80–3.56). Conclusions: AA affects around 1 in 50 people over their lifetime. The incidence and impact of AA on mental health and work outcomes is highest in ethnic groups other than White. Clinicians should be aware of the marked heterogeneity in the incidence and impact of AA, and support targeted healthcare to groups at the highest risk of alopecia and its consequences.