Tofacitinib in Pediatric Alopecia Areata Totalis and Alopecia Universalis: A Retrospective Analysis From India.

Alopecia areata totalis and universalis are disabling conditions and therapeutically challenging as they are refractory to conventional options. Tofacitinib is a Janus-kinase (JAK) inhibitor utilized to treat alopecia areata (AA) as an off-label drug. In India, FDA-approved JAK inhibitors such as baricitinib and ritlecitinib are not available. There are only a few case reports on tofacitinib in AA in the Indian population. We present the data of 9 pediatric cases of clinically and histologically proven alopecia areata totalis (AT) and alopecia universalis (AU), for whom oral tofacitinib was given after baseline investigations. The following parameters were analysed: Photographic image and severity of alopecia tool (SALT) score at baseline, 3 months and 6 months, and Children Dermatology Life Quality Index (cDLQI) at baseline and 6 months. The mean ± standard deviation (M ± SD) of the SALT score and cDLQI(M ± SD) at baseline were 95 ± 5 and 17 ± 2. At weeks 4 and weeks 12, the SALT (M ± SD) score was 92.7 ± 6.1 and 34.35 ± 11.16, respectively. At weeks 24, the SALT (M ± SD) score and cDLQI (M ± SD) were 3.33 ± 5 and 6 ± 2. The final reduction in SALT score from the baseline was 100% in 6/9 cases (66.67%), 75% to 99% in 3/9 (22.23%), and 50 to 75% in 1/9 (11.12%). We also observed minimal adverse effects (one child developed herpes zoster) with tofacitinib. Our study demonstrates that oral tofacitinib represents a viable modality in managing difficult-to-treat pediatric AA, such as AT and AU, with a good safety profile.

Effective management Alopecia totalis by Ayurveda - A case report.

Alopecia areata (AA) is a T-cell-mediated autoimmune illness characterized by intermittent, non-scarring hair loss, Alopecia totalis(AT) is a type of AA characterized by total hair loss on the face and scalp. Unfortunately, it is projected that 10-15 % of people with AA will advance to total hair loss on the scalp (AT) or hair loss on the scalp and body Alopecia Universalis (AU) only 10 % of patients with AT/AU recover completely. Treatment for severe AA is often unsatisfactory. The most popular AT/AU therapy techniques were topical steroid application and oral steroid administration. We present a case of Alopecia totalis that was treated with cupping therapy and ayurvedic treatments such as Punarnava Mandoor, manjistadi Kashaya, asanadi gana Kashaya, purnachandrodaya rasa, a churna combo, and Malatyadi and Dhurdhurapatradi taila for external application over scalp. The treatment's effectiveness is due to the synergistic action of all the herbs and the immunostimulant activity of cupping.

Synchronous pancreas and gallbladder cancer with concomitant alopecia totalis.

A 55-year-old female presented with history of pain in the right hypochondrium along with complete loss of facial and scalp hair over last two months. On evaluation, she was found to have locally advanced, synchronous malignancies of the gallbladder and head of the pancreas. Synchronous malignancy of gallbladder and pancreas is in itself very rare and less than 10 such cases have been reported in the world literature. Alopecia totalis has been classically associated with various autoimmune disorders. However, alopecia totalis as a presenting feature of any abdominal malignancy has never been reported in the medical literature. The present report describes a rare association of synchronous pancreatobiliary malignancies with strange clinical presentation.

Post-Traumatic Stress Disorder in Patients with Alopecia Areata: A Survey Study in the USA.

Introduction: Alopecia areata (AA) is an autoimmune condition that results in nonscarring hair loss. AA is comorbid with mental health disorders including anxiety and depression. This study aimed to evaluate the presence of post-traumatic stress disorder (PTSD) in relation to hair loss in patients with AA. Methods: A cross-sectional national survey was distributed using the National Alopecia Areata Foundation's (NAAF) email list. This study was approved by the Mass General Brigham Institutional Review Board. Participants were asked to complete the PTSD Checklist for the DSM-5 (PCL-5), a validated screening tool for PTSD in the context of their AA. Results: Of the 1,449 completed surveys (completion rate 79.6%), most respondents were female (83.8%) and white (76.6%) with an average age of 50.6 ± 15.6 years. Respondents had AA for an average of 17.7 ± 15.8 years, with 91.4% experiencing current active hair loss. A total of 33.9% of respondents screened positively for PTSD, with an average score of 48.8 ± 12.3 on the PCL-5 in participants who screened positively. Participants with alopecia totalis have the highest average PCL-5 score of 30.1 ± 19.2, followed by participants with alopecia universalis with an average score of 26.0 ± 19.9, and lastly patchy AA with an average score of 24.5 ± 18.3 (p = 0.003). Feelings of intrusion and avoidance were the predominant reported symptoms. Total PTSD scores were significantly higher in respondents who were younger and identified as Black or African American and Hispanic when compared to white and non-Hispanic respondents, respectively. Conclusion: These findings identify that one in 3 patients with AA in this cohort meet the screening criteria for PTSD specifically relating to their hair loss experience. These results further highlight the mental health comorbidities associated with AA and emphasize that these symptoms may persist even after hair regrowth. Limitations include the nonrandomized NAAF population with most participants being white females. Future studies should confirm these findings in other patient populations. Finally, respondent's baseline mental health was not assessed; therefore, a causal relationship between AA and PTSD cannot be deduced.

Alopecia areata: What's new in the epidemiology, comorbidities, and pathogenesis?

BACKGROUND: Alopecia areata (AA) is a common, acquired, and nonscarring type of hair loss that affects people of every generation and is intractable in severe and relapsing cases. Patients with AA, especially those with greater scalp involvement, have poor health-related quality-of-life scores. PURPOSE: Following our previous review article in the April 2017 issue of the Journal of Dermatological Science, we aim to provide a pair of review articles on recent progress in multidisciplinary approaches to AA. MAIN FINDINGS: We found more than 1800 publications on AA from July 2016 to December 2022. CONCLUSIONS: In this review, we focused on the latest information on the epidemiology, comorbidities, and pathogenesis of AA.

Efficacy of Baricitinib in Patients with Various Degrees of Alopecia Areata Severity: Post-Hoc Analysis from BRAVE AA1 and BRAVE AA2.

BACKGROUND: Baricitinib, an oral selective JAK1/JAK2 inhibitor, is approved for the treatment of adults with severe alopecia areata (AA). OBJECTIVE: To evaluate differences in response up to week 52 among subgroups based on the baseline severity of AA assessed with the Severity of Alopecia Tool (SALT) score. METHODS: Data were pooled from BRAVE-AA1 and BRAVE-AA2, two randomized, placebo-controlled, phase 3 trials, which enrolled adults with a SALT score ≥ 50. Patients were subdivided by the degree of AA severity at baseline. RESULTS: Among the 855 patients treated with baricitinib 2 mg and 4 mg, improvements in scalp hair growth continued through to week 52. A superior response was observed in patients with a SALT score of 50-94 versus a score of 95-100. Patients on baricitinib 4 mg had a faster and higher response rate compared to baricitinib 2 mg. CONCLUSION: Across all degrees of severity for baricitinib 2 mg and 4 mg doses, the proportion of patients responding was yet to plateau up to week 52. Response to treatment was longer for patients with a baseline SALT score 95-100. Further studies are needed to analyze other parameters that may impact observed response rates.

Janus kinase inhibitors for alopecia areata.

Janus kinase (JAK) inhibitors have ushered in a new era in alopecia areata (AA). Historically, moderate-to-severe AA was refractory to treatment. JAK inhibitors have changed that; now, treatment of moderate-to-severe AA is possible. Here, we briefly review the history of and rationale for JAK inhibitor treatment of AA, phase 3 clinical trial data, and considerations regarding differences among JAK inhibitors, safety, and patient selection.

Clinical and Genetic Aspects of Alopecia Areata: A Cutting Edge Review.

Alopecia areata (AA) is a chronic, non-scarring, immune-mediated skin disease that affects approximately 0.5-2% of the global population. The etiology of AA is complex and involves genetic and environmental factors, with significant advancements in genetic research occurring in recent years. In addition to well-known genes such as PTPN22, CTLA4, and IL2, which have been widely supported as being associated with AA, an increasing number of specific gene-related loci have been discovered through advances in genetic research. For instance, gene analysis of microRNAs can reveal the critical role of miRNAs in regulating gene expression, aiding in the understanding of cellular and organismal functional regulatory mechanisms. Furthermore, numerous studies have confirmed the existence of correlations between AA and other immune-related diseases. Examples include hyperthyroidism and rheumatoid arthritis. By understanding the interrelationships between AA and other immune diseases, we can further comprehend potential shared genetic foundations or pathogenic mechanisms among different diseases. Genetic research plays a crucial role in unraveling the pathogenesis of AA, as the identification of genetic variations associated with AA can assist in formulating more effective and targeted treatment strategies.

Incidence Rates of Infections, Malignancies, Thromboembolism, and Cardiovascular Events in an Alopecia Areata Cohort from a US Claims Database.

INTRODUCTION: Alopecia areata (AA) is an autoimmune disease with an underlying immuno-inflammatory pathogenesis. Treatments can include systemic corticosteroids and immunomodulators (such as Janus kinase inhibitors); these medications may be associated with a risk of some adverse events. However, large-scale observational studies of baseline incidence rates (IRs) of infection, cardiovascular disease, malignancy, and thromboembolism in US patients with AA, including those with alopecia totalis or alopecia universalis (AT/AU), are limited. This real-world, US claims-based study aimed to estimate the incidence of events in patients with AA compared with matched patients without AA. METHODS: Patients aged ≥ 12 years enrolled in the Optum Clinformatics Data Mart database from 1 October 2016 to 30 September 2020, with ≥ 2 AA diagnosis codes were included in the AA cohort. Patients without AA were age-, sex-, and race-matched 3:1 to patients with AA. Baseline comorbidities were evaluated during the 12-month period pre-index date. Incident cases of serious/herpes infections, malignancies, major adverse cardiovascular events (MACE), and thromboembolic events were evaluated post-index date. Data are presented using descriptive statistics, proportional percentages, frequencies, and IRs (calculated with 95% CI). RESULTS: Overall, 8784 patients with AA, 599 of whom had AT/AU, were matched to 26,352 patients without AA. IRs per 1000 person-years among the AA and non-AA cohorts, respectively, were 18.5 and 20.6 for serious infections, 19.5 and 9.7 for herpes simplex infections, 7.8 and 7.6 for herpes zoster infections, 12.5 and 11.6 for primary malignancies, 16.0 and 18.1 for MACE, and 4.9 and 6.1 for venous thromboembolisms. Compared with patients with non-AT/AU AA, patients with AT/AU largely had higher IRs for most baseline comorbidities and outcome events evaluated. CONCLUSION: Patients with AA had a higher IR of herpes simplex infection than the matched non-AA cohort. Patients with AT/AU generally had higher rates of outcome events than patients without AT/AU.

Allergen-specific immunotherapy improves alopecia totalis in a severe atopic dermatitis patient.

House dust mite (HDM) is the most common allergen exacerbating atopic dermatitis (AD), and allergen-specific immunotherapy (AIT) using HDM exhibited significant improvements in previous studies. Alopecia can occur as a complication of AD. Alopecia totalis (AT), a severe form of alopecia areata (AA), does not respond well to treatment and the chance of full recovery is less than 10%. For extensive hair loss, topical immunotherapy such as diphenylcyclopropenone (DPCP) is used as the first-line treatment. However, since DPCP is a kind of contact allergen, it has the potential to exacerbate AD. A 38-year-old man with AD and AA visited our clinic with symptoms worsening from 3 months ago. Although taking oral methylprednisolone (8 mg/day) and cyclosporine (100 mg/day) for 3 months, he has lost over 90% of his hair and the Eczema Area and Severity Index (EASI) was 43. Total serum immunoglobulin E (IgE) levels were 4454 kU/L (normal <100 kU/L) and the specific IgE levels for Dermatophagoides pteronyssinus and Dermatophagoides farinae following ImmunoCAP® were 20.8 and 37.4 kU/L, respectively. This patient did not respond well to previous treatment and was reluctant to use long-term steroids, so subcutaneous AIT using HDM was administered along with oral cyclosporine (100 mg/day). Topical tacrolimus was also applied to the AD lesions throughout the body. To reduce itching, nonsedative antihistamines were used if necessary. Hair loss was almost completely improved 1 year after the AIT initiation and the skin lesions of AD also improved (EASI 2.4). The specific IgE levels for D. pteronyssinus and D. farinae were 3.73 and 7.16 kU/L, respectively. Herein, we report a patient with promising results following AIT for AT with severe AD. In severe alopecic patients with AD refractory to conventional treatment, including immunosuppressants, AIT could be considered as a treatment option.

Assessing Patient's Values When Selecting Treatments for Alopecia Areata: A Cross-Sectional Survey Study.

Introduction: Alopecia areata (AA) is an autoimmune condition that results in nonscarring hair loss. There is currently only one Food and Drug Administration (FDA)-approved treatment for AA; as a result, a wide range of treatments are commonly administered. This study aimed to determine how patients with AA prioritize treatment characteristics when choosing a therapy. Methods: A cross-sectional national survey was distributed using the National Alopecia Areata Foundation's (NAAF) email list. This study was approved by the Mass General Brigham Institutional Review Board. Participants were asked to rank the importance of five treatment domains. Results: Of the 1,074 completed surveys (completion rate 77.4%), most respondents were female (85.4%) and white (77.8%) with an average age of 49.3 ± 15.4 years. Respondents had AA for an average of 17.7 ± 15.4 years, with 90.0% experiencing current active hair loss. 95.6% of respondents considered the treatment's ability to achieve hair regrowth as important, 93.9% listed the availability of information about the treatment (e.g., via doctor or online) as important, 89.1% ranked the treatment side effects as important, 75.7% the cost, and 68.0% the convenience of use. A sub-analysis was performed examining responses between respondents who identify as white versus nonwhite, which showed that while the order of importance was the same between groups, a significantly larger proportion of nonwhite respondents attributed higher importance to cost (white: 73.8%, nonwhite: 82.4%; p = 0.006) and convenience (white: 65.3%, nonwhite: 77.3%; p < 0.001) than their white counterparts. Discussion/Conclusion: These findings identify key domains that can serve as a starting point in shared decision-making between patients and physicians. This knowledge can streamline dermatologist delivery of key information and highlight areas of improvement for future therapeutics. Limitations include the nonrandomized NAAF population with most participants being white females. Future studies should confirm these findings in other patient populations.

A phase 2a randomized vehicle-controlled multi-center study of the safety and efficacy of delgocitinib in subjects with moderate-to-severe alopecia areata.

Alopecia areata/AA is an autoimmune cause of nonscarring hair loss. The pathogenesis of AA involves many immune axes, including Th1/Th2 pathways. Delgocitinib is a pan-Janus kinase/JAK inhibitor that broadly blocks pro-inflammatory cytokines and has been effective in other inflammatory skin conditions. Recent human studies/reports have shown that use of some systemic JAK inhibitors led to hair regrowth, suggesting this medication class as a potential therapy for AA. However, topical treatment is desirable due to potential systemic side effects. To assess the efficacy and safety of topical delgocitinib in AA, we conducted a double-blind, randomized, vehicle-controlled clinical trial in 31 moderate-to-severe AA patients that were randomized 2:1 to receive delgocitinib ointment 30 mg/g (n = 20) or ointment vehicle (n = 11) for 12 weeks. The primary endpoint was change in severity of Alopecia Tool/SALT score from baseline to week 12. The secondary endpoint included safety profile by reported adverse events. Twenty-three subjects completed the trial, with eight discontinuing mostly due to voluntary withdrawal. Ten patients receiving delgocitinib ointment and three patients receiving vehicle showed SALT score improvements after 12 weeks, but the mean percent SALT improvement at week 12 compared to baseline between the two arms was not significant (p = 0.92). Our study suggests that delgocitinib ointment is not effective in moderate-to-severe AA, likely due to its inability to penetrate sufficiently deeply into the dermis of the scalp, but larger studies are necessary to assess whether a different formulation of topical JAK inhibitors may be suitable to treat mild or more localized forms of AA.