Reduced rates of substance use disorder in patients with alopecia: An all of us case-control study.

Alopecia areata (AA), depression, anxiety, and decreased quality of life are highly associated in the literature. It has been noted that there is an increased risk of substance use in those with AA to help cope with the psychological burdens and perceived stigmatization. This study aims to explore the relationship between substance use disorder (SUD) and scarring/non-scarring alopecia using the All of Us database. Of the 9,385 patients with alopecia, 8.4% had SUD of any kind. Multivariable regression revealed that alopecia is a potential protective factor against SUD when controlling for other covariates of significance, with a decreased odds of 0.73. Substance use disorder prevalence was not different between scarring and non-scarring alopecia. This may be the result of patients fearing exacerbation of hair loss, or due to increased mental health and community support in patients with alopecia. Dermatologists and primary care providers should continue to promote psychotherapy and community support to patients whose diagnosis of alopecia has a negative psychosocial impact.

The Role of 5% Minoxidil versus Platelet-Rich Plasma in Treatment of Alopecia Areata.

OBJECTIVE: To compare the efficacy of topical minoxidil and platelet-rich plasma (PRP) in the treatment of alopecia areata (AA). STUDY DESIGN: Randomised control trial. Place and Duration of the Study: Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from December 2021 to June 2022. METHODOLOGY: The study included all the patients who visited JPMC Karachi during the study period. Permission from the ERB was obtained. The inclusion criteria were any gender and age 10 to 45 years. Topical minoxidil 5% solution was applied twice daily to Group A (six pubs/time), while PRP injections were administered to Group B at baseline and every four weeks for three months. Serial photos and the severity of alopecia tool (SALT) were used to determine the clinical assessment. When comparing the effectiveness between the two groups, a p-value of <0.05 was considered significant. SPSS version 23 was used to analyse the data. RESULTS: Mean age was 23.11 ± 8.9 years in 376 patients. PRP and Minoxidil groups had mean SALT scores at three months that were 1.48 and 1.54, respectively. Both treatments were shown to be efficacious. There was no statistically significant difference in efficacy between the minoxidil solution and PRP (p = 0.483). CONCLUSION: There is no apparent difference between PRP and topical minoxidil 5% solution in the management of AA. To verify the results, additional studies are needed with a larger sample size and a longer duration of follow-up. KEY WORDS: Minoxidil, Platelet-rich plasma, Alopecia areata, Severity of alopecia tool score.

Ruxolitinib 1.5% Topical Cream for the Treatment of Pediatric Alopecia Areata.

Alopecia areata (AA) is a common autoimmune disorder. Although its pathogenesis is not fully understood, AA involves CD8 T cell-mediated destruction of the hair follicle. Several treatment options exist; however, there is minimal evidence in the pediatric population. Currently, there are no curative treatments for AA. The literature suggests that Janus kinase (JAK) inhibitors may be an effective treat-ment for AA, but evidence in pediatric patients is limited. Here, we report a case of severe pediatric AA treated with topical ruxolitinib, a JAK inhibitor. J Drugs Dermatol. 2024;23(5):378-379. doi:10.36849/JDD.7782.

Italian National Registry of Alopecia Areata: an epidemiological study of 699 Italian patients.

BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA. METHODS: The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients. RESULTS: The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life. CONCLUSIONS: AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.

Hair growth-promoting effects of Enz_MoriL on human dermal papilla cells through modulation of the Wnt/ß-Catenin and JAK-STAT signaling pathways.

Enz_MoriL is a naturally occurring substance extracted from the leaves of Morus alba L. through enzymatic conversion. Historically, M. alba L. has been recognized for its potential to promote hair regrowth. However, the precise mechanism by which Enz_MoriL affects human hair follicle dermal papilla cells (hDPCs) remains unclear. The aim of this study was to investigate the molecular basis of Enz_MoriL's effect on hair growth in hDPCs. Interferon-gamma (IFN-γ) was used to examine the effects of Enz_MoriL on hDPCs during the anagen and catagen phases, as well as under conditions mimicking alopecia areata (AA). Enz_MoriL demonstrated the ability to promote cell proliferation in both anagen and catagen stages. It increased the levels of active ß-catenin in the catagen stage induced by IFN-γ, leading to its nuclear translocation. This effect was achieved by increasing the phosphorylation of GSK3ß and decreasing the expression of DKK-1. This stimulation induced proliferation in hDPCs and upregulated the expression of the Wnt family members 3a, 5a, and 7a at the transcript level. Additionally, Enz_MoriL suppressed JAK1 and STAT3 phosphorylation, contrasting with IFN-γ, which induced them in the catagen stage. In conclusion, Enz_MoriL directly induced signals for anagen re-entry into hDPCs by affecting the Wnt/ß-catenin pathway and enhancing the production of growth factors. Furthermore, Enz_MoriL attenuated and reversed the interferon-induced AA-like environment by blocking the JAK-STAT pathway in hDPCs.

Low rates of vaccination among atopic dermatitis, alopecia areata, psoriasis, and psoriatic arthritis patients on biologics.

Biologics and Janus kinase (JAK) inhibitors are immunomodulating and immunosuppressing medications utilized to treat atopic dermatitis (AD), psoriasis (PSO), psoriatic arthritis (PsA), and alopecia areata (AA). Special recommendations must be considered when prescribing vaccinations in this population, as the pneumococcal and herpes zoster vaccine are recommended to patients ≥ 19-years-old (rather than ≥ 65-years-old and ≥ 50-years-old as in the general population, respectively), along with a yearly influenza and up to date COVID-19 vaccination. Additionally, TNF-α and JAK-inhibitors may increase the risk of latent Hepatitis B virus (HBV) reactivation among high-risk patients. Prior to prescribing these medications, a quantitative HepB Surface Antibody (HepB SA) test is performed to determine immunity. This study utilized the SlicerDicer function on EPIC Medical Records to search for any patient ≥ 19-years-old prescribed a biologic or JAK inhibitor for AD, PSO, PsA, or AA between 10/2003 and 10/2023 at a large tertiary institution. Vaccination rates among patients on biologics and JAK inhibitors were low, with rates being significantly lower in patients 19-64 years-old, compared to those ≥ 65 years-old for most disease states (p < 0.01). Among AD, PSO/PsA, and AA patients, on average, 9.39% were vaccinated for influenza, 6.76% for herpes zoster, 16.56% for pneumococcal pneumonia, and 63.98% for COVID-19. Only 3.16% of patients were adequately vaccinated for HepB after an abnormal HepB SA test. Here, extremely low rates of vaccination among patients on biologics and JAK inhibitors at our institution were highlighted, emphasizing the imperative need for ensuring vaccination in this group.

Evaluating the sources and types of dietary and nutritional advice for patients with alopecia areata.

Although there are now two Food and Drug Administration (FDA)-approved treatments for severe alopecia areata (AA), many patients still resort to non-medical therapies and lifestyle modifications such as diet and nutrition. The goal of this study was to evaluate the sources and types of dietary and nutritional advice for patients with AA. We distributed a cross-sectional national survey using the National Alopecia Areata Foundation's email list-serv between August 2022 and January 2023. Most respondents were White (76.3%), employed (58.3%) females (84.4%) with a mean age of 52 years. 163 (19.1%) respondents reported receiving diet and/or nutritional advice and 418 (49.5%) respondents reported searching for diet and/or nutritional advice to help with their AA; the most common source of advice was online. The most common dietary changes were the use of vitamins or supplements (30.6%), adherence to diets (23.2%), and the addition of specific foods (21.4%). 209 (50.2%) respondents reported no change in their disease and 197 (47.4%) respondents reported no change in how they felt about their disease compared to before they tried the change. Many AA patients search for or receive unsolicited dietary and nutritional advice and subsequently modify their behavior to manage their disease. However, the efficacy of these changes is unclear. Providers should be mindful of the sources through which patients obtain treatment information as well as the lifestyle changes patients make to counsel patients with evidence-based information. Further investigation is needed to better characterize the direct and indirect costs of dietary and nutritional modification in the treatment of AA.

Evaluating the Cost Burden of Alopecia Areata Treatment: A Comprehensive Review for Dermatologists.

Alopecia areata (AA) is managed with prolonged medical treatments and cosmetic therapies, whose cost can be burdensome. We sought to identify the costs of AA treatment and consolidate the available data for the practicing dermatologist by performing a PubMed search of articles indexed for MEDLINE. Ten studies including approximately 16,000 patients with AA across a range of Oxford Centre for Evidence-Based Medicine Levels of Evidence were included. Studies showed that despite the limited efficacy of many AA therapies, patients incurred substantial expenses to manage their AA.

Elucidating the role of T-Reg related cytokines: serum transforming growth factor beta and interleukin-35 in alopecia areata.

Previous studies demonstrated that Th1 cytokines like IL-2, IL-12 and IFN-γ have initiatory role in alopecia areata (AA) and positive correlation with disease severity. They informed that serum levels of Th17 cytokines, IL-17, IL-22, IL-23 increased in active AA patients and corelated, particularly IL-17, with disease severity. In recent reports it was showed the balance between Th17 and Treg cells is crucial for maintaining tolerance to self-antigens, and an imbalance towards Th17 may contribute to the development of autoimmune diseases like AA. But research on serum Treg markers in AA is limited. It was aimed to investigate whether the Treg cells have a role in the pathogenesis of AA analyzing the serum levels of Treg cytokines IL-35 and TGF-ß in the patients with AA. 42 AA patients and 38 healthy controls were enrolled. Patient demographics, clinical data, disease severity assessed by Severity of Alopecia Tool (SALT) scores were recorded. Serum samples were collected and analyzed for TGF-ß and IL-35 levels using ELISA kits. The cytokine levels in both groups were statistically compared. Their relation with parameters of demographic and severity of disease was evaluated. The patient and control groups had no statistically significant difference, there was 71.4% males and 28.6% females in patient group, while the control group had 63.2% males and 36.8% females, Severity analysis classified 18 patients with mild AA, 19 with moderate AA, and 5 with alopecia totalis/areata universalis. While TGF-ß levels exhibited no significant difference between groups, IL-35 levels were significantly elevated in AA patients (p = 0.002). Logistic regression identified IL-35 as a significant parameter influencing disease status (OR = 1.055). Correlation analysis revealed a weak positive correlation between patient age and IL-35 levels (r = 0.436; p = 0.004). Notably, IL-35 levels displayed a significant decrease in individuals with antinuclear antibody (ANA) positivity. No correlations were identified between cytokine levels and disease severity, prognosis, or disease activity. Elevated IL-35 levels suggest that IL-35 and specific Treg cell subsets can play a role in AA pathogenesis. The nuanced roles of TGF-ß and IL-35 highlight the need for comprehensive studies to interpret their implications in the complex immunopathogenesis of AA. These findings open avenues for further research, positioning IL-35 as a prospective target for investigating and potentially intervening in AA pathogenesis.

Amygdalin ameliorates alopecia areata on C3H/HeJ mice by inhibiting inflammation through JAK2/STAT3 pathway.

BACKGROUND: Evidence has demonstrated that Chinese medicine formula Xuefu Zhuyu decoction can markedly promote the formation of new hair in patients and mice with alopecia areata (AA). Amygdalin is one of the active components of Xuefu Zhuyu decoction, but its therapeutic effects and the underlying mechanisms on AA remains largely unrevealed. PURPOSE: Therefore, this study aims to investigate the therapeutic effects and to probe its molecular mechanisms of inflammation and immune regulation on AA model of C3H/HeJ mice. STUDY DESIGN: The C3H/HeJ female mice were divided into control, AA, rusolitinib (60 mg/kg), and amygdalin groups (60, 90, and 120 mg/kg, 0.2 ml/10 g, i.g.). METHODS: The optical microscope was used to observe the feature of the local skin, and the number of lanugo and terminal hair. H&E staining was performed to determine the degree of pathological damage to the skin. ELISA was performed to detect levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mice serum. Flow cytometry was carried out to analyze the CD4+CD25+FOXP3+, CD4+ and CD8+ of skin tissue. And the levels of CD4+ and CD8+, p-JAK/JAK2, p-STAT3/STAT, and SOCS3 were detected by immunohistochemistry. Western blot and qRT-PCR were employed to examine the expression levels of IL-6, TNF-α, IFN-γ, JAK2, p-JAK, STAT, p-STAT3 and SOCS3 proteins and genes in skin tissues. RESULTS: Compared with AA group, amygdalin immensely increased the number of vellus hairs and decreased the number of terminal hairs determined by skin microscopy and H&E staining. ELISA, Western blot and qRT-PCR data showed that the levels of IL-6, TNF-α and IFN-γ in serum and skin tissues of AA mice were significantly increased, while amygdalin administration dramatically restrained the contents of the three pro-inflammatory factors. Flow cytometry and immunohistochemistry hinted that amygdalin observably enhanced the number of CD4+CD25+FOXP3+ and CD4+ cells, while inhibited the number of CD8+ positive cells in mice with AA. Moreover, amygdalin signally reduced JAK2/STAT3 pathway-related protein and gene levels in AA mice. CONCLUSION: Amygdalin could inhibit inflammatory response and improve immune function in the treatment of AA. The underlying molecular mechanism may be related to inhibition of JAK2/STAT3 pathway.

Dissecting hair breakage in alopecia areata: the central role of dysregulated cysteine homeostasis.

In the initial stages of Alopecia Areata (AA), the predominance of hair breakage or exclamation mark hairs serves as vital indicators of disease activity. These signs are non-invasive and are commonly employed in dermatoscopic examinations. Despite their clinical salience, the underlying etiology precipitating this hair breakage remains largely uncharted territory. Our exhaustive review of the existing literature points to a pivotal role for cysteine-a key amino acid central to hair growth-in these mechanisms. This review will probe and deliberate upon the implications of aberrant cysteine metabolism in the pathogenesis of AA. It will examine the potential intersections of cysteine metabolism with autophagy, ferroptosis, immunity, and psychiatric manifestations associated with AA. Such exploration could illuminate new facets of the disease's pathophysiology, potentially paving the way for innovative therapeutic strategies.

Risks of alopecia areata in long COVID: Binational population-based cohort studies from South Korea and Japan.

Previous studies have proposed alopecia areata (AA) as a potential outcome of COVID-19 infection among autoimmune diseases, yet the findings might be inconclusive and difficult to generalize due to limited sample sizes and evidence levels. Thus, we aimed to investigate in detail the long-term risk of AA following SARS-CoV-2 infection based on large, binational, general population-based cohort studies. Our study investigated the long-term AA risk after SARS-CoV-2 infection by analyzing bi-national, claim-based cohorts in South Korea and Japan: a Korean nationwide cohort (K-COV-N cohort; discovery cohort; total n = 10 027 506) and a Japanese claims-based cohort (JMDC cohort; validation cohort; total n = 12 218 680). AA was identified based on the international classification of diseases 10th revision code (L63) requiring at least three claims within 1 year. After exposure-driven propensity score matching, SARS-CoV-2 infection was associated with an increased risk of incident AA (aHR, 1.66; 95% CI, 1.38-1.99). This increased risk was observed and persisted for up to 6 months. A similar pattern was observed in the validation cohort. As modifiable factors, severe COVID-19 increased the risk of AA, whereas receiving two or more doses of the COVID-19 vaccine before infection decreased the risk of AA. Through a bi-national cohort study in South Korea and Japan, SARS-CoV-2 infection was associated with an elevated risk for incident AA in the aspect of long COVID.

Parenting styles and psychological effects on children with alopecia areata: exploring family dynamics, anxiety, and depression.

Alopecia areata (AA) is an autoimmune disease that develops due to inflammation and causes sudden hair loss. Ithas been observed that family circumstances may contribute to the development of AA. This study aims to assessthe relationship between the development of alopecia areata in children, family functions, and depression andanxiety levels in their parents.Thirty-nine participants diagnosed with AA and 41 healthy controls (HC), agedbetween 8 and 18 years, and their parents participated in the study. The assessment of the children included thecompletion of a socio-demographic data form, the Parenting Style Scale (PSS), and the Revised Children's Anxietyand Depression Scale (RCADS). The parents provided information on a sociodemographic form, the BeckDepression Inventory (BDI), and the Beck Anxiety Inventory (BAI). The children in the control group scoredsignificantly higher on the PSS acceptance/ involvement subscale than those with AA. In the AA group, the numberof authoritative and indulgent (PSS) families was statistically significantly lower than that of the families in the HC,and the number of neglectful families was statistically significantly higher than those of the control group. Totalanxiety and depression t scores (RCADS) were statistically significantly higher in the AA children than in theHC. Our study demonstrates the importance of considering familial factors and parental mental health tounderstand and address alopecia areata in children. Our findings support the psychosomatic component of AA.Implementing comprehensive treatment strategies that target psychological well-being and family dynamics couldprove crucial.

Research trends in alopecia areata: a cross-sectional bibliometric analysis of the top cited studies.

In the field of alopecia areata research, various focuses including risk factors, epidemiology, molecular pathways, and treatment were constantly improving. However, to date, a bibliometric analysis summarizing the research trend is not available to date. The main objective of this study was to provide researchers with an overview of the research trend on alopecia areata in the past two decades. In Web of Science database, screening and extraction of studies related to alopecia areata has been performed. Within studies related to alopecia areata, the most cited 100 studies were appraised and the information of articles, including the citation amounts, keywords and publication types, was extracted for analyses. On average, each study in the top 100 list was cited 104.72 times. Within the top 100 list, the most focused fields were on the management of alopecia areata (34%), molecular mechanisms (28%) and epidemiological issues (23%). Approximately one third of the management-associated studies focused on Janus kinase (JAK) inhibitors (10 studies) and 5 studies focused on the efficacy of corticosteroids for alopecia areata. According to the results of the keyword analysis, JAK inhibitors had become the most mentioned keywords in the field of alopecia areata research since 2016. The top 100 most referenced papers in the field of alopecia areata mostly focused on essential aspects such as treatment options, pathogenesis, risk factors, and comorbidities. The results of the current study could be considered a potential resource for future research and patient care information.

To evaluate the role of interleukin-6 in alopecia areata.

Objective: TTo investigate the level of interleukin-6 in alopecia areata patients. METHODS: The exploratory study was conducted from September to December 2021 at the Sindh Institute of Skin Disease, Karachi, and comprised alopecia areata patients regardless of age and gender in group A, while healthy controls matched for age and gender formed group B. Alopecia areata classification and severity were done using the Severity of Alopecia Tool. Serum interleukin-6 was measured using enzyme-linked immune sorbent assay. Data was analysed using R statistical software v4.2.1. RESULTS: Of the 100 subjects, 50(50%) with mean age 15.52±10.14 years were cases in group A; 26(52%) females with mean age 16.78±10.77 years, and 24(48%) males with mean age 16.44±10.3 years. The remaining 50(50%) were controls in group B. Interleukin-6 concentration was significantly higher in group A (p<0.05). The concentration was not significantly different between the genders (p>0.05). The concentration was the highest in patients aged 11-20 years, followed by 21-30 years, 31-40 years and 1-10 years. Conclusion: The concentration of circulatory pro-inflammatory interleukin-6 was significantly higher in alopecia areata patients than in the healthy controls.

Association between non-scarring alopecia and hypothyroidism: a bidirectional two-sample Mendelian randomization study.

Background: Non-scarring alopecia is typically represented by two main types: alopecia areata (AA) and androgenetic alopecia (AGA). While previous observational studies have indicated a link between non-scarring alopecia and hypothyroidism, the precise causal relationship remains uncertain. To determine the potential links between non-scarring alopecia and hypothyroidism, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. Methods: We used independent genetic instruments from the FinnGen consortium for AA (682 cases, 361,140 controls) and AGA (195 cases, 201,019 controls) to investigate the association with hypothyroidism in the UK Biobank study (22,687 cases, 440,246 controls). The primary analysis was performed using the inverse variance-weighted method. Complementary approaches were employed to evaluate the pleiotropy and heterogeneity. Results: Genetically predicted AA exhibited a positive causal effect on hypothyroidism (odds ratio [OR], 1.0017; 95% confidence interval [CI], 1.0004-1.0029; P = 0.0101). Additionally, hypothyroidism was found to be strongly correlated with an increase in the risk of AA (OR, 45.6839; 95% CI, 1.8446-1131.4271, P = 0.0196). However, no causal relationship was demonstrated between AGA and hypothyroidism. A sensitivity analysis validated the integrity of these causal relationships. Conclusion: This MR study supports a bidirectional causal link between AA and hypothyroidism. Nevertheless, additional research is needed to gain a more thorough comprehension of the causal relationship between non-scarring alopecia and hypothyroidism.