Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the Phase 3 randomized, controlled trial (THRIVE-AA1).

BACKGROUND: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. OBJECTIVE: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. METHODS: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg BID, deuruxolitinib 12 mg BID, or placebo for 24 weeks. The primary endpoint was percentage of patients achieving Severity of Alopecia Tool (SALT) score ≤20. A key secondary endpoint was percentage of satisfaction of hair patient-reported outcome (SPRO) responders. RESULTS: Significantly higher proportions of patients taking deuruxolitinib met the primary endpoint (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary endpoints versus placebo, including SPRO (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. LIMITATIONS: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. CONCLUSION: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.

Treatment modalities for lymphocytic and neutrophilic scarring alopecia.

Primary cicatricial alopecia can result in permanent hair loss from the destruction of hair follicles. Early intervention is key in controlling disease progression, reducing symptoms, and optimizing hair density. Treatment modalities range from topical and intralesional therapies to oral medications and light therapy.

Association between alopecia areata, anxiety, and depression: A systematic review and meta-analysis.

BACKGROUND: To date, there is no comprehensive meta-analysis analyzing the association between alopecia areata, anxiety, and depression. OBJECTIVE: We sought to analyze the existing literature to examine the association between alopecia areata, anxiety, and depression. METHODS: We extracted literature from 4 databases including MEDLINE, Embase, PsychINFO, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (ie, PRISMA) reporting guidelines to finalize a list of relevant articles to be included in our systematic review and meta-analysis. There were no restrictions placed on publication year or age of participants. RESULTS: Eight studies that included 6010 patients with AA and 20 961 control individuals were included in the quantitative analysis. These included 4 cross-sectional studies and 4 case-control studies. Analysis of these studies showed a positive association with anxiety (pooled odds ratio, 2.50; 95% confidence interval, 1.54-4.06) and depression (pooled odds ratio, 2.71; 95% confidence interval, 1.52-4.82). LIMITATIONS: Publication bias may be a limitation of the study. CONCLUSION: This study suggests that patients with AA are at higher risk of both anxiety and depression. Health care professionals must be cognizant of this higher risk and consider routine assessment of these conditions and referral to appropriate providers when indicated.

Complementary and alternative medicine for alopecia areata: A systematic review.

BACKGROUND: Despite high use of complementary and alternative medicine (CAM) for alopecia areata (AA), efficacy and safety remain unclear. OBJECTIVE: To identify all CAM therapies studied for treatment of AA. Outcomes of interest included disease course and psychologic well-being. METHODS: PubMed and Embase were searched to identify English articles containing original data investigating CAM in individuals with AA from 1950-2018. Quality was assessed with Oxford Centre for Evidence Based Medicine criteria. RESULTS: Of 1015 initial citations, 16 articles met inclusion criteria: 5 randomized controlled trials, 5 prospective controlled cohorts, 4 prospective noncontrolled cohorts, 1 retrospective cohort, and 1 case series. CAM therapies with best evidence and efficacy for hair growth in AA include essential oil aromatherapy, topical garlic, and oral glucosides of peony with compound glycyrrhizin. Hypnosis and mindfulness psychotherapy represent low-quality evidence for improvement of psychologic and quality of life outcomes. Adverse events were rare and mild for all therapies evaluated. LIMITATIONS: Inconsistent or poorly reported study methodology and nonstandardized outcomes limit the conclusions that can be made from these studies. CONCLUSIONS: This work serves to inform physician treatment of patients with AA seeking CAM while encouraging further investigation into these therapies to address some of the therapeutic challenges of AA.

Health Utility Measures Among Patients with Androgenetic Alopecia After Hair Transplant.

BACKGROUND: Hair loss causes significant psychosocial distress to patients. Health utility measurements offer an objective, quantitative assessment of health-related quality of life (QOL). METHODS: We performed a prospective cohort study on patients with hair loss between January 1, 2018 and December 31, 2020. Patient metrics were compared with layperson perception of alopecia, prospectively collected between August 1 and December 31, 2017. Health utility measures were quantified using the visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO) in quality-adjusted life-years (QALYs) and relative to the minimal clinically important difference (MCID). Bonferroni correction to the significance threshold was performed. RESULTS: Thirty-one patients with alopecia were compared with 237 laypeople. Patient metrics for female hair loss were all significantly lower than laypeople measures (VAS QALYs 0.65 ± 0.21 vs. 0.83 ± 0.18, p = 0.0001). Mean SG QALYs were lower for patients in the male alopecia state (0.86 ± 0.23 vs. 0.96 ± 0.12, p = 0.0278). Post-hair transplant improvement in TTO was significantly greater for patients (+ 0.08 ± 0.12 vs. + 0.02 ± 0.09, p = 0.0070) and significantly more often exceeded the MCID (45.2% vs. 16.9%, p = 0.0006). CONCLUSIONS: Alopecia negatively impacts QOL, and the true patient experience is more taxing than what is perceived by laypeople. Hair transplantation improves QOL more for male patients than common perception. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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.

Subcutaneous metastasis from an atypical pulmonary carcinoid tumor.

Pulmonary carcinoid tumors are uncommon neuroendocrine tumors that rarely metastasize to the skin. We report the case of a 71-year-old woman with a longstanding history of primary atypical pulmonary carcinoid tumor who presented with a new tender cutaneous nodule. Immunostaining of the nodule was consistent with metastatic atypical carcinoid tumor of the skin including positive staining for neuroendocrine markers chromogranin and synaptophysin. Dermatologists should consider cutaneous neuroendocrine metastasis when evaluating new nodules in patients with stable pulmonary carcinoid tumors or in those with concomitant concerning respiratory symptoms.

A Potential Role for IL-4 and IL-13 in an Alopecia Areata-Like Phenotype: A Clinical Perspective.

Although alopecia areata (AA) has been traditionally classified as a strictly T helper type 1-mediated process, the T helper type 2 (Th2) pathway may contribute to an AA-like phenotype in some individuals. Herein, we describe three clinical cases that support the potential role of Th2 activity through the upregulation of IL-4 and IL-13 in an AA-like phenotype.

Brigham Eyebrow Tool for Alopecia: A Reliable Assessment of Eyebrow Alopecia Areata.

There are no tools to evaluate eyebrow involvement in patients with alopecia areata. We developed and assessed the reliability of the Brigham Eyebrow Tool for Alopecia (BETA) as a quantitative evaluation of eyebrow alopecia areata. BETA uses facial landmarks of eyebrow anatomy and is calculated using surface area and density. A total of 50 eyebrow images with varying levels of hair loss were distributed to six board-certified dermatologists at three academic medical centers with standardized instructions and examples. Interrater and intrarater reliability were calculated using intraclass correlation coefficients (ICCs). BETA demonstrated high interrater (ICC = 0.88, confidence interval = 0.83-0.92 right eyebrow scores and ICC = 0.90, confidence interval = 0.85-0.94 left eyebrow scores) and intrarater (ICC = 0.90, confidence interval = 0.85-0.93 right eyebrow scores and ICC = 0.91, confidence interval = 0.87-0.94 left eyebrow scores) reliability. When measured in the same patient with varying degrees of hair loss over time, BETA demonstrated sensitivity to change. BETA is a simple and reliable objective assessment of eyebrow alopecia areata. BETA is easy-to-use and quick to calculate, making it feasible for a variety of clinical and research settings. Although developed for alopecia areata, we hope that BETA will be investigated in other etiologies of eyebrow alopecia to serve as a universal tool for monitoring disease progression, improvement, and response to treatment.

The effect of scalp cooling on CIA-related quality of life in breast cancer patients: a systematic review.

PURPOSE: Chemotherapy-induced alopecia (CIA) remains a distressing adverse event of cancer treatment but may be prevented by scalp cooling. The effectiveness of scalp cooling, however, is dependent on the chemotherapy regimen with successful hair preservation (i.e., < 50% hair loss) in 41-59% of women on taxane-based therapies in comparison to 16-36% on anthracycline-based therapies. Despite the potential utility, use of scalp cooling has shown a more equivocal impact on quality of life (QoL). In this review, we aim to evaluate the use of scalp cooling for CIA and quantitative QoL measures. METHODS: A systematic review of PubMed, Embase, Web of Science, and Cochrane databases for clinical studies on scalp cooling to prevent CIA published before October 29, 2018 was performed. Clinical studies with 5 or more patients that reported on a quantitative QoL measure were included and graded according to a modified five-point scale from the Oxford Centre for Evidence-Based Medicine. RESULTS: Studies meeting inclusion criteria included 4 randomized clinical trials (RCT), 8 cohort studies, and 1 cross-sectional study with 1282 unique patients. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30: 46%) and Breast Cancer Module (QLQ-BR23: 46%) represented the most commonly used QoL assessments. Overall, 4 (31%) of the 13 studies concluded that scalp cooling was associated with significant improvements in QoL measures; 8 (62%) determined that there was either non-significant or no improvements; and 1 (7.7%) provided a mixed conclusion. Although 2 (50%) RCT demonstrated that scalp cooling can effectively prevent CIA depending on the chemotherapy regimen, these studies did not show that successful hair preservation was associated with improved QoL measures. CONCLUSIONS: This review demonstrates that scalp cooling is not consistently associated with significant QoL improvements as assessed by EORTC QLQ-C30 and -BR23. Representing a critical limitation, more than one-third of the studies did not subcategorize QoL outcomes for successfully or unsuccessfully scalp-cooled patients but rather reported on QoL measures for all scalp-cooled patients in general. Failure to prevent hair loss in patients undergoing an expensive and potentially uncomfortable treatment likely contributes to decreased well-being, impacting the overall distribution of QoL measures in scalp cooling patients compared to controls. Future studies should incorporate validated QoL instruments specific to hair disease and classify QoL outcomes for scalp-cooled patients based on the degree of hair preservation.

Histologic and clinical cross-sectional study of chronic hair loss in patients with cutaneous chronic graft-versus-host disease.

BACKGROUND: While scalp alopecia represents a distinctive feature of chronic graft-versus-host disease (cGVHD), little is known about the clinical and histologic presentation of hair loss. OBJECTIVES: We sought to classify the clinical presentations and histologic findings of chronic hair loss in patients with cutaneous cGVHD. METHODS: A prospective cohort of 17 adult hematopoietic cell transplantation (HCT) recipients with cutaneous cGVHD was enrolled. Dermatologic examinations were performed, and punch biopsy specimens of the scalp were obtained. Biopsy specimens were analyzed with hematoxylin-eosin and immunohistochemical stains in all cases and fluorescence in situ hybridization analyses in specific cases. RESULTS: Clinically, 4 patterns of hair loss were described-patchy nonscarring (41.2%), diffuse nonscarring (11.8%), diffuse sclerotic (11.8%), and patchy sclerotic (5.9%). The location of the inflammatory infiltrate on hematoxylin-eosin-stained specimens correlated with the hair loss pattern patients had clinically, with cell populations around the bulb and bulge in nonscarring and sclerotic cases, respectively. Fluorescence in situ hybridization studies in female cGVHD patients with male donors demonstrated green Y chromosomes limited to the area of the hair follicle affected by inflammatory cells. CONCLUSION: This study describes the various clinical and histologic subtypes of long-standing alopecia in adult cGVHD patients and suggests that this alopecia may be a direct manifestation of cGVHD of the hair follicle.