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Journal of the European Academy of... Jun 2024Alopecia areata (AA) carries a psychological burden for patients beyond hair loss. However, quality-of-life measurement tools such as EQ-5D used in clinical trials may...
IMPORTANCE
Alopecia areata (AA) carries a psychological burden for patients beyond hair loss. However, quality-of-life measurement tools such as EQ-5D used in clinical trials may not adequately capture the burden of AA, the perceived stigmatization or the psychosocial impact of AA.
OBJECTIVE
To investigate the potential association between disease severity and the degree of social isolation, perceived stigmatization, anxiety and depression, alcohol consumption and work absenteeism using multiple PRO measures in patients with AA.
DESIGN, SETTING AND PARTICIPANTS
Using the Danish Skin Cohort, the study included adult patients diagnosed with AA. The study included multiple PRO measures, including Skindex-16, EQ-5D-5L, Work Productivity and Activity Impairment (WPAI), Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and the Alopecia Areata Symptom Impact Scale (AASIS). The questionnaires were dispatched to the patients in January 2023. The severity of AA was determined based on scalp involvement using a modified Alopecia Areata Scale. Multiple multivariate linear regressions were conducted using Skindex-16, AASIS and WPAI, while multivariate logistic regressions were applied to HADS, AUDIT-C and EQ-5D-5L.
RESULTS
A total of 376 patients were included, of which 177 (47%) had severe disease, 41 (11%) had moderate disease, 94 (25%) had mild disease, and 64 (17%) were in remission. The median age of patients was 55 (IQR, 47-66 years) and most were female (70%). Skindex-16 and AASIS were the only PRO measures able to distinguish between severity. For these scores, moderate and severe diseases, female sex, and involvement of eyebrows increased the score and negatively impacted patient quality of life.
CONCLUSION AND RELEVANCE
The results indicate the importance of using the proper tool for the intended measurement of quality of life and that factors such as the severity of AA, as well as female sex and involvement of the eyebrows, may potentially increase the psychosocial burden of AA.
PubMed: 38940661
DOI: 10.1111/jdv.20211 -
The Journal of Investigative Dermatology Jun 2024
PubMed: 38936767
DOI: 10.1016/j.jid.2024.05.022 -
Journal of Controlled Release :... Jun 2024Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant...
Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8NKG2DT cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.
PubMed: 38936744
DOI: 10.1016/j.jconrel.2024.06.060 -
Dermatology (Basel, Switzerland) Jun 2024Patients with alopecia areata (AA) report high levels of dissatisfaction with commonly used treatments. Patient-reported outcomes are essential to understanding...
INTRODUCTION
Patients with alopecia areata (AA) report high levels of dissatisfaction with commonly used treatments. Patient-reported outcomes are essential to understanding patients' experiences with AA treatments. The objective of this study was to evaluate patient-reported satisfaction with hair growth among patients with AA receiving ritlecitinib or placebo and the correlation between clinician-assessed efficacy and patient-reported satisfaction.
METHODS
In the ALLEGRO-2b/3 (NCT03732807) trial, patients with AA and ≥50% scalp hair loss were randomized to daily ritlecitinib or placebo for 24 weeks, with a 24-week extension of continued ritlecitinib or switch from placebo to ritlecitinib. The Patient Satisfaction with Hair Growth (P-Sat) measure evaluated patients' satisfaction with hair growth in 3 domains: amount, quality, and overall satisfaction with hair growth. The pre-specified analysis evaluated the proportion of patients who were slightly, moderately, or very satisfied with hair growth. Several post-hoc analyses assessed the proportion of patients who were moderately/very satisfied and moderately/very dissatisfied and calculated polyserial correlations between change from baseline (CFB) in Severity of Alopecia Tool (SALT) and P-Sat scores at Weeks 24 and 48.
RESULTS
At Week 24, the proportion of patients (N=718) reporting satisfaction (slightly, moderately, or very satisfied) overall with their hair growth ranged from 36.4% in the ritlecitinib 10-mg group (evaluated for dose ranging only) to 67.5% in the 200/50-mg group vs 22.6% in the placebo groups. In patients randomized to ritlecitinib, the proportion who were satisfied increased or was maintained at Week 48. A substantially greater proportion of placebo patients who switched to ritlecitinib reported satisfaction at Week 48 than at Week 24. Similar results were observed for patient satisfaction with the amount and quality of hair growth. In the post hoc analyses defining satisfaction as moderately/very satisfied and dissatisfaction as moderately/very dissatisfied, the benefit of ritlecitinib was also observed. All P-Sat domain scores strongly correlated with CFB-SALT scores at Weeks 24 (range 0.73-0.76; P<0.05) and 48 (0.74-0.77; P<0.05).
CONCLUSIONS
Patients receiving active ritlecitinib doses reported favorable results vs placebo in satisfaction with hair growth up to Week 48. High concordance was observed between improvement in scalp hair growth evaluated by clinicians and patient-reported satisfaction.
TRIAL REGISTRATION
Clinicaltrials.gov NCT0373280.
PubMed: 38934147
DOI: 10.1159/000539536 -
Actas Dermo-sifiliograficas Jun 2024
PubMed: 38925452
DOI: 10.1016/j.ad.2024.06.004 -
Current Opinion in Allergy and Clinical... Jun 2024This review summarizes recent advances in identifying genetic risk factors for atopic dermatitis and how these genetic associations are being used to explore the causal...
PURPOSE OF REVIEW
This review summarizes recent advances in identifying genetic risk factors for atopic dermatitis and how these genetic associations are being used to explore the causal relationships between atopic dermatitis and potential risk factors and downstream outcomes.
RECENT FINDINGS
A recent large-scale GWAS meta-analysis has identified 91 genetic loci associated with atopic dermatitis. Rare variant studies have also identified new gain-of-function or loss-of-function variants implicated in atopic dermatitis, particularly for FLG and STAT6/JAK1. Finally, there has been a surge in utilizing genetic association data to investigate the causal relationships between atopic dermatitis and other traits. Mendelian randomization studies have found that various metabolites and gut microbiota are causal for atopic dermatitis and have causally implicate atopic dermatitis in the development of alopecia areata, diabetes, vascular dementia and some cancers.
SUMMARY
The past year has seen a huge increase in the genes implicated for atopic dermatitis and in the use of genetics to explore causal relationships. The latter requires caution in implementation and interpretation, but is a promising area of research. In the coming years, increasing the ethnic diversity of atopic dermatitis genetic studies would be very welcome and the translation of current genetic findings into new drugs will be an exciting area of development.
PubMed: 38920356
DOI: 10.1097/ACI.0000000000001005 -
Clinical Reviews in Allergy & Immunology Jun 2024Down syndrome is the most common genetic cause of intellectual disability and has previously been associated with a variety of autoimmune disorders affecting multiple... (Review)
Review
Down syndrome is the most common genetic cause of intellectual disability and has previously been associated with a variety of autoimmune disorders affecting multiple organ systems. The high prevalence of autoimmune disease, in conjunction with other inflammatory and infectious diseases, in this population suggests an intrinsic immune dysregulation associated with triplication of chromosome 21. Emerging data on the role of chromosome 21 in interferon activation, cytokine production, and activation of B-cell mediated autoimmunity are emerging hypotheses that may explain the elevated prevalence of autoimmune thyroid disease, celiac disease, type I diabetes, autoimmune skin disease, and a variety of autoimmune neurologic conditions. As the life expectancy for individuals with Down syndrome increases, knowledge of the epidemiology, clinical features, management and underlying causes of these conditions will become increasingly important. Disorders such as Hashimoto's thyroiditis are prevalent in between 13 and 34% of individuals with Down syndrome but only 3% of the neurotypical population, a pattern similarly recognized in individuals with Celiac Disease (5.8% v 0.5-2%), alopecia areata (27.7% v. 2%), and vitiligo (4.4% v. 0.05-1.55%), respectively. Given the chronicity of autoimmune conditions, early identification and management can significantly impact the quality of life of individuals with Down syndrome. This comprehensive review will highlight common clinical autoimmune conditions observed in individuals with Down syndrome and explore our current understanding of the mechanisms of disease in this population.
PubMed: 38913142
DOI: 10.1007/s12016-024-08996-2 -
European Journal of Dermatology : EJD Apr 2024Alopecia areata (AA) is a chronic autoimmune disease that causes non-scarring hair loss. Data are lacking on the epidemiology and clinical and economic burden of AA in... (Observational Study)
Observational Study
Alopecia areata (AA) is a chronic autoimmune disease that causes non-scarring hair loss. Data are lacking on the epidemiology and clinical and economic burden of AA in Spain. To estimate the prevalence and incidence of AA in Spain and describe sociodemographic and clinical characteristics, treatment patterns, healthcare resource utilization (HCRU) and associated costs. This was an observational, retrospective, descriptive study based on the Health Improvement Network (THIN®) database (Cegedim Health Data, Spain). Patients with ICD9-Code 704.01 for AA, registered between 2014 and 2021, were identified. Prevalence (%) and incidence rates per 1,000 patient-years (IR) of AA were calculated and clinical characteristics, treatment characteristics and HCRU/costs were assessed. A total of 5,488 patients with AA were identified. The point prevalence of AA in 2021 was 0.44 (95% confidence interval [CI]: 0.43-0.45) overall, 0.48 (0.47-0.49) in adults, and 0.23 (0.21-0.26) in children ≤12 years. The 2021 IR for AA in adults was 0.55 (0.51-0.60). Of 3,351 adults with AA, 53.4% were female, mean (standard deviation [SD]) age was 43.1 (14.7) years, and 41.6% experienced comorbidities. Among adults, 2.7% used systemic treatment (0.5% immunosuppressants, 2.5% oral corticosteroids, 0.3% both). Laboratory tests and health care professional visits were the principal drivers of cost, which was €821.2 (1065.6)/patient in the first year after diagnosis. The epidemiology of AA in Spain is comparable with that reported for other countries, being more prevalent among adults. There is a significant burden of comorbidities and cost for patients, with limited use of systemic treatments, suggesting an unmet treatment need in this population.
Topics: Humans; Spain; Alopecia Areata; Retrospective Studies; Female; Male; Adult; Prevalence; Cost of Illness; Child; Health Care Costs; Incidence; Middle Aged; Adolescent; Young Adult; Child, Preschool; Immunosuppressive Agents; Aged
PubMed: 38907547
DOI: 10.1684/ejd.2024.4654 -
Dermatology and Therapy Jun 2024Alopecia areata (AA) is an autoimmune disease associated with high rates of emotional and psychosocial distress. The analysis reported here describes the evolution of...
Improvement in Measures of Quality of Life and Symptoms of Anxiety and Depression in Patients with Severe Alopecia Areata Achieving Sustained Scalp Hair Regrowth with Baricitinib.
INTRODUCTION
Alopecia areata (AA) is an autoimmune disease associated with high rates of emotional and psychosocial distress. The analysis reported here describes the evolution of measures assessing health-related quality of life (HRQoL) and symptoms of anxiety and depression up to week 104 in patients who achieved sustained scalp hair regrowth during treatment with baricitinib in the BRAVE-AA phase III trials.
METHODS
This post-hoc analysis included data from the double-blind, parallel-group, randomized, placebo-controlled phase III trials BRAVE-AA1 (ClinicalTrials.gov number: NCT03570749) and BRAVE-AA2 (ClinicalTrials.gov number: NCT03899259). Adults with severe AA (defined as a Severity of Alopecia Tool [SALT] score ≥ 50) randomized to baricitinib 4 mg or baricitinib 2 mg at baseline who achieved SALT score ≤ 20 by week 36 and maintained SALT score ≤ 20 through week 104 on the same dose of baricitinib were included in this analysis of integrated data. Scalp hair regrowth (SALT score) and improvements in Skindex-16 AA Scale and Hospital Anxiety and Depression Scale (HADS) domain scores were analyzed over the 104-week period using descriptive statistics.
RESULTS
In total, 131 patients (88 on baricitinib 4 mg and 43 on baricitinib 2 mg) were included in this analysis. Across the two groups, the mean age (standard deviation) was 37.2 years (12.7), and 84 (64.1%) patients were female. The interquartile range) for time to achieve a SALT score ≤ 20 for patients treated with baricitinib 4 mg and baricitinib 2 mg was 13.1 and 19.6 weeks, respectively. By week 104, 91% (baricitinib 2 mg) and 96% (baricitinib 4 mg) of patients had achieved a SALT score ≤ 10 on baricitinib treatment. In both groups, progressive improvements in the Skindex-16 AA and HADS domain scores were observed up to week 104.
CONCLUSION
This analysis of adults with severe AA treated with baricitinib revealed that achievement of sustained clinically meaningful scalp hair regrowth (SALT score ≤ 20) was associated with improvements in both measures of HRQoL and symptoms of anxiety and depression up to week 104.
PubMed: 38904749
DOI: 10.1007/s13555-024-01208-x -
Frontiers in Immunology 2024An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the...
An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the features of active stage alopecia areata, with a Severity of Alopecia Tool (SALT) score of 70%. The diagnosis was severe alopecia areata. The patient had a history of atopic dermatitis since infancy, with recurrent episodes of scattered papules and pruritus for 8 years. Initial treatment involved subcutaneous injections of dupilumab 300mg every 2 weeks for 6 months, resulting in a reduction of SALT score to 20% and improvement of atopic dermatitis symptoms. Discontinuation of Dupilumab and initiation of daily oral Baricitinib at a dose of 2mg for a duration of 5 months. According to the SALT score evaluation, the severity of hair loss was less than 10% and there was significant regrowth of hair. No significant adverse reactions were observed during the treatment period.
Topics: Humans; Alopecia Areata; Dermatitis, Atopic; Female; Purines; Child; Azetidines; Pyrazoles; Sulfonamides; Antibodies, Monoclonal, Humanized; Treatment Outcome; Severity of Illness Index; Drug Therapy, Combination
PubMed: 38903518
DOI: 10.3389/fimmu.2024.1395288