Phase 2 randomized, dose-ranging trial of CTP-543, a selective Janus Kinase inhibitor, in moderate-to-severe alopecia areata.

BACKGROUND: Janus kinase (JAK) activation is suggested to have a pathological role in alopecia areata (AA). CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2, is being developed as an oral treatment for AA. OBJECTIVE: To assess the safety and efficacy of a 24-week regimen of CTP-543 in patients with chronic, moderate-to-severe AA. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, sequential-design trial, patients were randomized to receive CTP-543 (4 mg, 8 mg, or 12 mg) or placebo every 12 hours for 24 weeks. RESULTS: A dose-related increase was observed in the percentage of patients with ≥50% relative reduction in Severity of Alopecia Tool scores from baseline at week 24 (9% placebo, 21% 4 mg twice daily, 47% 8 mg twice daily, and 58% 12 mg twice daily), with statistical significance versus placebo (P < .001) observed for the 8-mg twice daily and 12-mg twice daily groups, with differences from placebo noted as early as 12 weeks after the initiation of treatment. Safety results were consistent with the known safety profiles of JAK inhibitors. LIMITATIONS: These initial findings are from a relatively small controlled trial, and additional studies are needed to fully characterize the safety and efficacy of CTP-543 in adult patients with AA. CONCLUSIONS: Patients treated with CTP-543 (8 or 12 mg, twice daily) had a significant reduction in the severity of AA.

Development of the alopecia areata scale for clinical use: Results of an academic-industry collaborative effort.

BACKGROUND: The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. OBJECTIVE: To develop an AA severity scale based on expert experience. METHODS: A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. RESULTS: Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. LIMITATIONS: The scale is a static assessment intended to be used in clinical practice and not clinical trials. CONCLUSION: The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease.

The Alopecia Areata Consensus of Experts (ACE) study part II: Results of an international expert opinion on diagnosis and laboratory evaluation for alopecia areata.

BACKGROUND: We previously reported the Alopecia Areata Consensus of Experts study, which presented results of an international expert opinion on treatments for alopecia areata. OBJECTIVE: To report the results of the Alopecia Areata Consensus of Experts international expert opinion on diagnosis and laboratory evaluation for alopecia areata. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Consensus threshold was set at greater than or equal to 66%. RESULTS: Of 148 questions, expert consensus was achieved in 82 (55%). Round 1 consensus was achieved in 10 of 148 questions (7%). Round 2 achieved consensus in 47 of 77 questions (61%). The final face-to-face achieved consensus in 25 of 32 questions (78%). Consensus was greatest for laboratory evaluation (12 of 14 questions [86%]), followed by diagnosis (11 of 14 questions [79%]) of alopecia areata. Overall, etiopathogenesis achieved the least category consensus (31 of 68 questions [46%]). LIMITATIONS: The study had low representation from Africa, South America, and Asia. CONCLUSION: There is expert consensus on aspects of epidemiology, etiopathogenesis, clinical features, diagnosis, laboratory evaluation, and prognostic indicators of alopecia areata. The study also highlights areas where future clinical research could be directed to address unresolved hypotheses in alopecia areata patient care.

Burden of Illness in Alopecia Areata: A Cross-Sectional Online Survey Study.

Previous QOL and disease burden studies have not captured all relevant aspects of living with alopecia areata (AA). To better understand the burden and everyday experience of living with moderate-to-severe AA, a cross-sectional, online, quantitative-qualitative survey was developed to assess symptoms, relationships, productivity, treatments, and financial burden. Adult patients were recruited from the National Alopecia Areata Foundation database. Data were analyzed descriptively. A total of 216 patients completed the survey. Most were female (83%), aged ≥45 years (59%), and white (78%). Nearly 2 of 3 respondents (62%) made different major life decisions (regarding relationships, education, or career) owing to AA. Most respondents (85%) stated coping with AA as a daily challenge, citing mental health issues, concealing hair loss, and others' reactions; 47% reported anxiety and/or depression. Many patients (75%) persistently concealed hair loss (mean time spent, 10.3 h/wk). Treatment discontinuation was common owing to lack of efficacy, side effects, and cost. Associated expenditures included buying wigs or hairpieces and psychotherapy (mean ∼$2,000/y each). Survey respondents comprised a self-selected sample, which may not reflect the entire population. The impact of AA extends beyond cosmetic concerns and carries a considerable psychosocial burden. Efficacious, less burdensome AA treatments are needed to regrow hair and alleviate psychosocial sequelae.

The Alopecia Areata Consensus of Experts (ACE) study: Results of an international expert opinion on treatments for alopecia areata.

BACKGROUND: A systematic review failed to identify any systemic therapy used in alopecia areata (AA) where use is supported by robust evidence from high-quality randomized controlled trials. OBJECTIVE: To produce an international consensus statement on the use and utility of various treatments for AA. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Agreement of 66% or greater was considered consensus. RESULTS: In the first round, consensus was achieved in 22 of 423 (5%) questions. After a face-to-face meeting in round 3, overall, consensus was achieved for only 130 (33%) treatment-specific questions. There was greater consensus for intralesional treatment of AA (19 [68%]) followed by topical treatment (25 [43%]). Consensus was achieved in 45 (36%) questions pertaining to systemic therapies in AA. The categories with the least consensus were phototherapy and nonprescription therapies. LIMITATIONS: The study included a comprehensive list of systemic treatments for AA but not all treatments used. CONCLUSION: Despite divergent opinions among experts, consensus was achieved on a number of pertinent questions. The concluding statement also highlights areas where expert consensus is lacking and where an international patient registry could enable further research.

Gram-negative infections in patients with folliculitis decalvans: a subset of patients requiring alternative treatment.

Background Folliculitis decalvans is a neutrophilic cicatricial alopecia whose etiology remains unknown. It is frequently associated with staphylococcal infections. We aimed to determine the rate of gram-negative infections in patients with folliculitis decalvans. Methods A retrospective chart review was performed of patients with biopsy-proven folliculitis decalvans seen at a tertiary hair referral center. The results of bacterial cultures were evaluated. Subjects were determined to have no infection, gram-positive infections, gram-negative infections, or mixed infections. Results Thirty-nine subjects were included in the study. Ninety-three cultures were performed. The majority of cultures were positive for staphylococci. Eleven patients (28%) had gram-negative infections of the scalp. Gram-negative infections comprised one-third of all cultures (33%). Conclusion We present the largest cohort of folliculitis decalvans patients with gram-negative infections, suggesting the need for routine bacterial cultures in patients who are not responsive to standard anti-staphylococcal antibiotics. Awareness of the incidence of these infections may lead to better therapeutic outcomes.

Frontal fibrosing alopecia with involvement of the central hair part: distribution of hair loss corresponding to areas of sunscreen application.

Frontal fibrosing alopecia (FFA) typically presents with band-like scarring alopecia in the frontal and temporal hairline along with eyebrow loss. Although this type of hair loss is being seen with increased frequency worldwide, the etiology of the condition is unknown. Studies have suggested a potential environmental role with moisturizers and sunscreens being possible triggers. Herein, we present a 42-year-old woman with a biopsy-proven diagnosis of frontal fibrosing alopecia. In addition to the typical pattern, she also had a striking linear patch of hair loss along her central part. This was an area where she regularly applied sunscreen for many years. Although a causative role for sunscreen ingredients in the development of FFA has not been proven, the evidence accumulated thus far, including our suggestive case, substantiates the need for further study. Additionally, increasing awareness of this potential effect leading to appropriate counseling regarding cessation of possible triggers may be critical for the prevention of further hair loss.

Cutaneous manifestations of COVID-19: a systematic review and analysis of individual patient-level data.

Distinctive patterns in the cutaneous manifestations of COVID-19 have been recently reported. We conducted a systematic review to identify case reports and case series characterizing cutaneous manifestations of confirmed COVID-19. Key demographic and clinical data from each case were extracted and analyzed. The primary outcome measure was risk factor analysis of skin related outcomes for severe COVID-19 disease. Seventy-one case reports and series comprising 144 cases of cutaneous involvement in COVID-19 were included. The most frequently occurring morphologies were: morbilliform (30.6%), varicelliform (18.8%), urticarial (13.2%), chilblains-like (12.5%), and acro-ischemic (9%). The median age of patients was 51 years (mean: 45.9, range: 0 to 91). Patients with chilblains-like eruptions had lower frequencies of extracutaneous COVID-19 symptoms (5/18, 27.8%, P<0.05) and were less likely to have severe COVID-19 disease (2/18, 11%, 95% CI 1.4% to 34.7%, P=0.02). Patients with livedoid and acro-ischemic morphologies had severe COVID-19 more frequently than those with other morphologies (17/21, 81%, 95% CI 58.0% to 94.5%, P<0.0001). The most frequently observed cutaneous manifestations of COVID-19 (morbilliform, varicelliform, and urticarial) are well-described patterns of viral exanthems. However, chilblains-like, livedoid, and acro-ischemic morphologies are not traditionally associated with viral infections and were significantly associated with severity of COVID-19 disease.

Objective outcome measures: Collecting meaningful data on alopecia areata.

BACKGROUND: Although alopecia areata is a common disorder, it has no US Food and Drug Administration-approved treatment and evidence-based therapeutic data are lacking. OBJECTIVE: To develop guidelines for the diagnosis, evaluation, assessment, response criteria, and end points for alopecia areata. METHODS: Literature review and expert opinion of a group of dermatologists specializing in hair disorders. RESULTS: Standardized methods of assessing and tracking hair loss and growth, including new scoring techniques, response criteria, and end points in alopecia areata are presented. LIMITATIONS: The additional time to perform the assessments is the primary limitation to use of the methodology in clinical practice. CONCLUSION: Use of these measures will facilitate collection of standardized outcome data on therapeutic agents used in alopecia areata both in clinical practice and in clinical trials.

Vitamin D Deficiency in an Alopecia Referral Clinic During a 3-Month Period: The Need to Pursue Systemic Screening.

Alopecia is typically viewed as a localized process, and comorbidities are not usually analyzed. The authors examine the prevalence of vitamin D deficiency among patients attending an alopecia clinic during a 3-month period. The data showed that 79% of patients had vitamin D deficiency, and the average value of low vitamin D was 19.1 mg/mL in patients. Vitamin D levels have not been examined extensively in skin disorders, and it is not clear whether vitamin D levels are correlative or causative in alopecia. The co-occurrence of both findings at such a dramatic level suggests the need for evaluation of this laboratory value in the alopecia population.

Hormones and clocks: do they disrupt the locks? Fluctuating estrogen levels during menopausal transition may influence clock genes and trigger chronic telogen effluvium.

Chronic telogen effluvium describes the clinical condition noted mostly in middle-aged women of increased, diffuse scalp hair shedding that is prolonged and often presents with a fluctuating course that may continue for years but does not lead to visible hair thinning. Despite its description almost 20 years ago, the underlying pathologic cause of CTE is yet to be identified. However the culmination of research in the field of hair biology and the burgeoning field of chronobiology may lead to exciting breakthroughs in our understanding of CTE. In this paper the current literature on CTE is reviewed and a hypothesis is put forth that CTE may be triggered by hormonal fluctuations and alterations in circadian control genes.

Skin disorders associated with obesity in children and adolescents: a population-based study.

Obesity in children is a major public health concern in the United States. The objectives of the current study were to determine the prevalence of various groups of cutaneous disorders in obese children and adolescents and to compare the use of dermatology services in obese subjects with that those with a normal body mass index (BMI). This was a retrospective, population-based study at the Kaiser Permanente Northern California Managed Healthcare System. The main outcome measures were the relative risk of cutaneous disorders associated with insulin resistance, androgen excess, bacterial infection, fungal infection, viral infection, inflammation, mechanical changes, and other skin conditions (hidradenitis, hyperhidrosis) in three weight groups (normal, overweight, obese) and the number of dermatology visits. A total of 248,775 subjects were included. Bivariate analyses showed a higher proportion of insulin resistance disorders, bacterial infection, fungal infection, inflammatory disorders, mechanical changes, and other skin conditions in obese subjects than in subjects with a normal BMI (p < 0.001). Disorders of androgen excess and viral infection were significantly less common in obese subjects (p < 0.001). Obese subjects had significantly lower odds of having at least one dermatology encounter than subjects with a normal BMI (odds ratio = 0.92, 95% confidence interval 0.88, 0.96, p = 0.003). Early onset obesity is associated with cutaneous disorders characterized by hyperproliferation, inflammation, bacterial and fungal infection, and mechanical changes but lower rates of disorders of androgen excess and viral infection. The use of dermatology services was not greater in obese patients. Heightened recognition and further analysis of adipose tissue as an endocrine organ that is capable of affecting the skin is warranted.

The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity.

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. Objective: To 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 Review: A 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. Findings: Of 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 Relevance: This 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.

Epidemiologic trends in pediatric tinea capitis: a population-based study from Kaiser Permanente Northern California.

BACKGROUND: Epidemic levels of tinea capitis (TC) have previously been reported in children. OBJECTIVE: We sought to determine new epidemiologic trends for TC among northern California children from 1998 through 2007. METHODS: Annual incidence of TC was based on diagnosis code or first-time antifungal prescriptions in all children up to age 15 years at Kaiser Permanente Northern California. RESULTS: An average of 672,373 children/y met the inclusion criteria. Trend analyses showed decreases in TC by diagnosis code and by prescriptions (73.7% and 23.7%, respectively). Girls had lower incidence rates than boys by diagnosis (111.9 vs 146.4, P < .001 for 1998, and 27.9 vs 39.9, P < .001 for 2007). African Americans had the highest incidence rates by diagnosis (447.3 in 1998 and 184.1 in 2007) compared with other ethnic groups. Trichophyton tonsurans was the predominant organism (89.4% of all positive fungal cultures in 1998 and 91.8% in 2007). Prescriptions for griseofulvin declined, whereas the prescriptions for other antifungals increased. LIMITATIONS: This was a retrospective study. CONCLUSIONS: In this cohort, there was a significant decrease in incidence of TC over the study period. Trichophyton tonsurans continued to be the predominant organism. These trends may be a result of improved education, recognition, diagnosis, and treatment of TC and increased use of new oral antifungals.

Elastin staining patterns in primary cicatricial alopecia.

BACKGROUND: Most biopsy specimens of cicatricial (scarring) alopecia can be readily subclassified as lymphocytic versus neutrophilic, but specific diagnosis remains difficult, particularly when a late stage of the disease is sampled. OBJECTIVE: We sought to document patterns of scarring highlighted by elastic tissue staining in primary cicatricial alopecia. METHODS: We documented Verhoeff elastic van Gieson staining patterns in 58 routinely embedded (vertical) biopsy specimens of cicatricial alopecia. Patterns of fibrosis included perifollicular (wedge-shaped vs broad tree trunk-shaped) and diffuse. The patterns were compared against the diagnosis obtained by independent expert clinical review, including central centrifugal cicatricial alopecia (CCCA), lichen planopilaris, traction alopecia, frontal fibrosing alopecia, discoid lupus erythematosus, and tufted folliculitis. RESULTS: Wedge-shaped perifollicular fibrosis was seen in lichen planopilaris but also in CCCA. Broad tree trunk-shaped perifollicular fibrosis was most commonly encountered in CCCA. LIMITATIONS: The retrospective nature of the study precluded temporal staging of the disease process. CONCLUSIONS: Patterns of fibrosis highlighted by elastin staining in primary cicatricial alopecia appear to be disease specific. Superficial wedge-shaped perifollicular fibrosis is associated with but may not be specific for lichen planopilaris. Broad tree trunk-like perifollicular fibrosis is specific for CCCA but not present in many cases. Elastin staining represents a useful ancillary study for the evaluation of late-stage scarring alopecia in routinely oriented punch biopsy specimens.

Transversely sectioned biopsies in the diagnosis of end-stage traction alopecia.

The pathogenesis of scarring alopecia in African American women remains poorly understood. Furthermore, the overlapping clinical and histological features present diagnostic challenges. The diagnosis of end stage traction alopecia secondary to traumatic hair styling practices can sometimes present particular challenges. We present a young African American woman with a scarring alopecia. As we describe, a scalp biopsy processed by transverse sections enabled rapid diagnosis and presented advantages over a biopsy processed with vertical sections.

Protein profiling of forehead epidermal corneocytes distinguishes frontal fibrosing from androgenetic alopecia.

Protein profiling offers an effective approach to characterizing how far epidermis departs from normal in disease states. The present pilot investigation tested the hypothesis that protein expression in epidermal corneocytes is perturbed in the forehead of subjects exhibiting frontal fibrosing alopecia. To this end, samples were collected by tape stripping from subjects diagnosed with this condition and compared to those from asymptomatic control subjects and from those exhibiting androgenetic alopecia. Unlike the latter, which exhibited only 3 proteins significantly different from controls in expression level, forehead samples from frontal fibrosing alopecia subjects displayed 72 proteins significantly different from controls, nearly two-thirds having lower expression. The results demonstrate frontal fibrosing alopecia exhibits altered corneocyte protein expression in epidermis beyond the scalp, indicative of a systemic condition. They also provide a basis for quantitative measures of departure from normal by assaying forehead epidermis, useful in monitoring response to treatment while avoiding invasive biopsy.