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ImportanceCurrent measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact.ObjectiveTo explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI).Evidence reviewA total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022.FindingsOf all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss.Conclusions and relevanceThis eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.

What is this summary about?This is a summary of the results of the ALLEGRO phase 2b/3 clinical trial, originally published in The Lancet. ALLEGRO-2b/3 looked at how well and safely the study medicine, ritlecitinib, works in treating people with alopecia areata ('AA' for short). The immune system protects your body from outside invaders such as bacteria and viruses. AA is an autoimmune disease, meaning a disease in which one's immune system attacks healthy cells of the body by mistake. In AA, the immune system attacks hair follicles, causing hair to fall out. AA causes hair loss ranging from small bald patches to complete hair loss on the scalp, face, and/or body. Ritlecitinib is a medicine taken as a pill every day, by mouth, that is approved for the treatment of severe AA. It blocks processes that are known to play a role in causing hair loss in patients with AA.What were the results of the study?Adults and adolescents (12 years and older) took part in the ALLEGRO-2b/3 study. They either took ritlecitinib for 48 weeks or took a placebo (a pill with no medicine) for 24 weeks. Participants taking placebo later switched to taking ritlecitinib for 24 weeks. The study showed that participants taking ritlecitinib had more hair regrowth on their scalp after 24 weeks than those taking the placebo. Hair regrowth was also seen on the eyebrows and eyelashes in participants taking ritlecitinib. Hair regrowth continued to improve to week 48 with continued ritlecitinib treatment. In addition, more participants taking ritlecitinib reported that their AA had 'moderately' or 'greatly' improved after 24 weeks than those taking the placebo. Similar numbers of participants taking ritlecitinib or placebo had side effects after 24 weeks. Most side effects were mild or moderate.What do the results of the study mean?Ritlecitinib was an effective and well-tolerated treatment over 48 weeks for people with AA. Clinical Trial Registration: NCT03732807 (phase 2b/3 ALLEGRO study).

IntroductionThe physical impact of alopecia areata (AA) is visible, but the psychological and social consequences and emotional burden are often underrecognized.MethodsIn this cross-sectional study, 547 participants recruited via the National Alopecia Areata Foundation completed a survey encompassing demographics; AA illness characteristics; and five patient-reported outcome measures on anxiety and depression, perceived stress, psychological illness impact, stigma, and quality of life (QoL). Differences in disease severity subgroups were assessed via analysis of variance (ANOVA) and t tests.ResultsMean age was 44.6 years, and 76.6% were female. Participants with more severe hair loss tended to report longer duration of experiencing AA symptoms (P

BackgroundAlopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata.MethodsIn this randomised, double-blind, multicentre, phase 2b-3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata and at least 50% scalp hair loss were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose (50 mg, 30 mg, 10 mg, 200 mg loading dose followed by 50 mg, or 200 mg loading dose followed by 30 mg), followed by a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. Randomisation was done by use of an interactive response system and was stratified by baseline disease severity and age. The sponsor, patients, and investigators were masked to treatment, and all patients received the same number of tablets to maintain masking. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24. The primary endpoint was assessed in all assigned patients, regardless of whether they received treatment. This study was registered with ClinicalTrials.gov, NCT03732807.FindingsBetween Dec 3, 2018, and June 24, 2021, 1097 patients were screened and 718 were randomly assigned to receive ritlecitinib 200 mg + 50 mg (n=132), 200 mg + 30 mg (n=130), 50 mg (n=130), 30 mg (n=132), 10 mg (n=63), placebo to 50 mg (n=66), or placebo to 200 mg + 50 mg (n=65). 446 (62%) of 718 patients were female and 272 (38%) were male. 488 (68%) were White, 186 (26%) were Asian, and 27 (4%) were Black or African American. Of 718 patients randomly assigned, 104 patients discontinued treatment (34 withdrew, 19 adverse events [AEs], 12 physician decision, 12 lack of efficacy, 13 lost to follow up, five rolled over to long-term study transfer, four pregnancies, two protocol deviations, one declined to attend follow-up due to COVID-19, one attended last visit very late due to COVID-19, and one non-compliance). At week 24, 38 (31%) of 124 patients in the ritlecitinib 200 mg + 50 mg group, 27 (22%) of 121 patients in the 200 mg + 30 mg group, 29 (23%) of 124 patients in the 50 mg group, 17 (14%) of 119 patients in the 30 mg group, and two (2%) of 130 patients in the placebo group had a response based on SALT score 20 or less. The difference in response rate based on SALT score 20 or less between the placebo and the ritlecitinib 200 mg + 50 mg group was 29·1% (95% CI 21·2-37·9; p

IntroductionAlopecia areata (AA) is an autoimmune disease characterized by hair loss. Patients with AA experience a range of social and emotional impacts, and the lack of effective treatments and multiple affected locations can deepen the burden of illness. The objective of the current study was to assess health-related quality of life (HRQL) among patients with AA, and to evaluate the relationship between patient-reported AA severity, HRQL and treatment patterns.MethodsA web survey was completed by participants recruited through the National Alopecia Areata Foundation. The survey included questions on disease characteristics, burden and impact (evaluated by the Skindex-16 for AA and items on work/school and sexual relationships), healthcare utilization and treatment experience. Analyses were conducted for the overall sample and by key subgroups, including AA severity and disease duration.ResultsA total of 1327 participants with AA completed the survey. The mean age was 39.7 [standard deviation (SD) 12.3] years and 58.4% were female. On average, participants had experienced signs and symptoms of AA for 11.5 years (SD 12.5) and were diagnosed by a healthcare provider (HCP) 10.5 (SD 12.2) years ago. Participants reported a range of severity of current scalp hair loss, including 0% (2.6%), 1-20% (39.8%), 21-49% (26.2%), 50-94% (10.2%) and 95-100% (21.3%). Participants reporting 95-100% of scalp hair missing were less likely to be currently seeing an HCP and to currently be on treatments for AA. There was a non-linear relationship between HRQL and current AA severity. Participants with 1-20% to 50-94% of current scalp hair missing reported higher symptom, functioning and emotional impacts due to AA than participants with 0% missing scalp hair and/or 95-100% missing scalp hair. Similar findings were observed for current eyebrow and eyelash severity, except for emotional impacts.ConclusionSeverity of AA plays an important role in understanding the burden of illness and healthcare patterns of people living with AA.

Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss. As a clinically heterogeneous disease, various classification systems have evolved for defining its severity. In this high-level review of the literature, we discuss the traditional classification systems for AA severity and their strengths and weaknesses. Most recent classifications have focused on the extent of scalp hair loss as a defining feature, but additional clinical aspects of the disease, including location, pattern, and duration of hair loss as well as impact on the patient's quality of life, are also relevant. These various components have typically been used unidimensionally to classify patients. We propose a multidimensional framework to define AA severity that incorporates multiple patient- and illness-related domains. Using such a framework, dermatologists may better assess the severity of the disease for the individual patient beyond the extent of hair loss.

BackgroundThe cutaneous manifestations of COVID-19 may be useful disease markers and prognostic indicators. Recently, postinfectious telogen effluvium and trichodynia have also been reported.ObjectiveTo evaluate the presence of trichodynia and telogen effluvium in patients with COVID-19 and describe their characteristics in relation to the other signs and symptoms of the disease.MethodsPatients with a history of COVID-19 presenting to the clinics of a group of hair experts because of telogen effluvium and/or scalp symptoms were questioned about their hair signs and symptoms in relation to the severity of COVID-19 and associated symptoms.ResultsData from 128 patients were collected. Telogen effluvium was observed in 66.3% of the patients and trichodynia in 58.4%. Trichodynia was associated with telogen effluvium in 42.4% of the cases and anosmia and ageusia in 66.1% and 44.1% of the cases, respectively. In majority (62.5%) of the patients, the hair signs and symptoms started within the first month after COVID-19 diagnosis, and in 47.8% of the patients, these started after 12 weeks or more.LimitationsThe recruitment of patients in specialized hair clinics, lack of a control group, and lack of recording of patient comorbidities.ConclusionThe severity of postviral telogen effluvium observed in patients with a history of COVID-19 infection may be influenced by COVID-19 severity. We identified early-onset (12 weeks) telogen effluvium.

Background The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into type II pneumocytes is dependent on a modification of viral spike proteins by transmembrane protease serine 2 (TMPRSS2) expressed on the surface of human cells. TMPRSS2 is regulated by the androgen receptor, hence, SARS-CoV-2 infectivity is indirectly dependent on androgenic status and phenotype. Previously, we have reported that men affected by androgenetic alopecia (AGA) are overrepresented in severe coronavirus disease 2019 (COVID-19). Additionally, we have reported that men taking antiandrogenic drugs, e.g., 5-alpha-reductase inhibitors (5ARis), are less likely to have severe COVID-19. Here we aimed to test whether the androgen receptor antagonist, Proxalutamide, would be a beneficial treatment for subjects with SARS-CoV-2 infection. Methods Male and female subjects were recruited to a double-blinded, randomized, prospective, investigational study of Proxalutamide for the treatment of COVID-19. Mild to moderate, non-hospitalized subjects, who were confirmed positive for SARS-CoV-2, were treated with either Proxalutamide 200 mg/day or placebo. Endpoints for the study were remission time (days) and the percentage of subjects confirmed negative for SARS-CoV-2 on Day 7 after treatment. A negative SARS-CoV-2 test was defined by concentration-time (Ct)>40 determined by real-time reverse transcription-polymerase chain reaction (rtPCR). Results Two-hundred thirty-six (2360 subjects were included in the study (108 female, 128 male); 171 were randomized to the Proxalutamide arm and 65 were in the placebo group. On Day 7, SARS-CoV-2 became non-detectable with rtPCR (cT>40) in 82% of the subjects in the Proxalutamide group versus 31% in the placebo group (p < 0.001). The average clinical remission time for patients treated with Proxalutamide was 4.2 ±5.4 days versus 21.8 ±13.0 days in the placebo arm (p < 0.001). Conclusion Proxalutamide significantly accelerated viral clearance on Day 7 in mild to moderate COVID-19 patients versus placebo. Further, the time to clinical remission was significantly reduced in patients treated with Proxalutamide versus placebo.

A subset of basal cell carcinomas (BCCs) are directly derived from hair follicles (HFs). In some respects, HFs can be defined as 'ordered' skin appendage growths, while BCCs can be regarded as 'disordered' skin appendage growths. The aim of the present study was to examine HFs and BCCs to define the expression of common and unique signaling pathways in each skin appendage. Human nodular BCCs, along with HFs and non‑follicular skin epithelium from normal individuals, were examined using microarrays, qPCR, and immunohistochemistry. Subsequently, BCC cells and root sheath keratinocyte cells from HFs were cultured and treated with Notch signaling peptide Jagged1 (JAG1). Gene expression, protein levels, and cell apoptosis susceptibility were assessed using qPCR, immunoblotting, and flow cytometry, respectively. Specific molecular mechanisms were found to be involved in the process of cell self‑renewal in the HFs and BCCs, including Notch and Hedgehog signaling pathways. However, several key Notch signaling factors showed significant differential expression in BCCs compared with HFs. Stimulating Notch signaling with JAG1 induced apoptosis of BCC cells by increasing Fas ligand expression and downstream caspase-8 activation. The present study showed that Notch signaling pathway activity is suppressed in BCCs, and is highly expressed in HFs. Elements of the Notch pathway could, therefore, represent targets for the treatment of BCCs and potentially in hair follicle engineering.

This article provides a review of the use of Janus Kinase inhibitors (JAKi) in the treatment of various types of scarring alopecia. It discusses the potential benefits of JAKi therapy in improving symptoms and hair regrowth in patients with conditions such as lichen planopilaris, central centrifugal cicatricial alopecia, folliculitis decalvans, frontal fibrosing alopecia, and dissecting cellulitis of the scalp. The article acknowledges the need for further research to fully understand the effectiveness and potential side effects of JAKi in this context. Overall, JAKi therapy shows promise but more investigation is required. [Extracted from the article]

Alopecia areata (AA) is believed to be a cell-mediated autoimmune hair loss disease. Both CD4 and cytotoxic CD8 T cells (CTLs) are important for the onset and progression of AA. Hair follicle (HF) keratinocyte and/or melanocyte antigen epitopes are suspected potential targets of autoreactive CTLs, but the specific epitopes have not yet been identified. We investigated the potential for a panel of known epitopes, expressed by HF keratinocytes and melanocytes, to induce activation of CTL populations in peripheral blood mononuclear cells. Specific synthetic epitopes derived from HF antigens trichohyalin and tyrosinase-related protein-2 induced significantly higher frequencies of response in AA CTLs compared with healthy controls (IFN-gamma secretion). Apoptosis assays revealed conditioned media from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides elevated the expression of apoptosis markers in primary HF keratinocytes. A cytokine array revealed higher expression of IL-13 and chemokine ligand 5 (CCL5, RANTES) from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides compared with controls. The data indicate that AA affected subjects present with an increased frequency of CTLs responsive to epitopes originating from keratinocytes and melanocytes; the activated CTLs secreted soluble factors that induced apoptosis in HF keratinocytes. Potentially, CTL response to self-antigen epitopes, particularly trichohyalin epitopes, could be a prognostic marker for human AA.