LncRNA NEAT1 and miRNA 101 as potential diagnostic biomarkers in patients with alopecia areata.

Background: Alopecia areata (AA) commonly displays as non-scarring, irregular hair loss. Experimental and clinical research have specifically implicated autoimmunity and genetics in the disruption of anagen hair follicles. AA patients' scalp lesions and peripheral blood mononuclear cells (PBMCs) exhibited an immune state imbalance. Numerous studies attempt to establish a connection between the occurrence and prognosis of AA and the epigenetic modulation of gene expression by long noncoding RNA (lncRNA) and microRNA (miRNA). The current study aimed to examine the serum levels of nuclear enriched abundant transcript 1 (NEAT1) and its target miRNA101 (miR-101) in AA and investigate the ability to use them as diagnostic biomarkers in the disease. Methods: Seventy-two AA patients were included in this prospective cohort study. Demographics, patient history, laboratory characteristics, and treatments were recorded. The miR-101 and NEAT1 levels were evaluated. Results: Serum NEAT1 levels were lower in AA patients, but there was no significant difference. However, there was no substantial disparity in NEAT1 level regarding other disease characteristics. There was a substantial positive association between NEAT1 and miR-101 levels among cases. On the other hand, the results showed a markedly low mean of miR-101 levels among patients, but the miR-101 marker shows no significant difference regarding different disease characteristics. The specificity and sensitivity test for the miR-101 marker shows a significant specificity of 60 % and sensitivity of 75 % with a p-value of 0.001 and a cut-off value of 0.897. Conclusions: The current research determined that miR-101 works as a diagnostic biomarker for AA.

Uveodermatological syndrome associated with alopecia areata in a one-year-old female spayed Cavalier King Charles Spaniel dog.

Uveodermatological syndrome and alopecia areata are autoimmune disorders causing ocular and dermatological inflammation and alopecia, respectively, in dogs. This is the first report to document concurrent development of the two diseases in a dog, as has been reported in human patients. Clinical presentation and histopathological diagnosis, treatment and clinical follow-up are described.

Association Between Scalp Microbiota Imbalance, Disease Severity, and Systemic Inflammatory Markers in Alopecia Areata.

INTRODUCTION: Alopecia areata (AA) is an autoimmune disease causing non-scarring hair loss, with both genetic and environmental factors implicated. Recent research highlights a possible role for scalp microbiota in influencing both local and systemic inflammatory responses, potentially impacting AA progression. This study examines the link among scalp microbiota imbalances, AA severity, and systemic inflammation. METHODS: We conducted a cross-sectional study with 24 participants, including patients with AA of varying severities and healthy controls. Scalp microbial communities were analyzed using swab samples and ion torrent sequencing of the 16S rRNA gene across multiple hypervariable regions. We explored correlations among bacterial abundance, microbiome metabolic pathways, and circulating inflammatory markers. RESULTS: Our findings reveal significant dysbiosis in the scalp microbiota of patients with AA compared to healthy controls. Severe AA cases had an increased presence of pro-inflammatory microbial taxa like Proteobacteria, whereas milder cases had higher levels of anti-inflammatory Actinobacteria. Notable species differences included abundant gram-negative bacteria such as Alistipes inops and Bacteroides pleibeius in severe AA, contrasted with Blautia faecis and Pyramydobacter piscolens predominantly in controls. Significantly, microbial imbalance correlated with AA severity (SALT scores) and systemic inflammatory markers, with elevated pro-inflammatory cytokines linked to more severe disease. CONCLUSION: These results suggest that scalp microbiota may play a role in AA-related inflammation, although it is unclear whether the shifts are a cause or consequence of hair loss. Further research is needed to clarify the causal relationship and mechanisms involved.

Psychosocial impact of alopecia areata in paediatric and adolescent populations: A systematic review.

Alopecia areata is an autoimmune disorder characterised by sudden hair loss, and can range from patchy baldness to more severe forms such as alopecia totalis and universalis. Hair loss can have a profound impact on self-esteem and body image, particularly during childhood and adolescence. Understanding the psychosocial impact of alopecia areata in paediatric and adolescent populations is crucial to address the emotional and social challenges faced by these patients. The aim is to review the existing literature for clinical studies and reports investigating the psychosocial impact of alopecia areata in paediatric and adolescent populations. A systematic review of the literature was performed using PubMed, Cochrane and Embase databases from inception to July 2023. Included articles assessed the psychosocial impact of alopecia areata in paediatric and adolescent populations. Of 79 total articles, 10 were identified as meeting the inclusion criteria. Several studies highlighted self-esteem, emotional distress and social challenges as features of psychosocial manifestations. Factors such as stress, psychiatric comorbidities and familial issues are significantly associated with alopecia areata in these populations. The heterogeneity of studies precluded data synthesis and analysis. A majority of the included studies evaluated short-term findings. Alopecia areata has significant psychosocial impacts in paediatric and adolescent populations, with studies emphasising the negative effects on self-esteem, body image and quality of life. Additional research is required to better elucidate this relationship and draw meaningful conclusions to guide clinical support and interventions.

Efficacy and Tolerability of Brevilin-A, a Natural JAK Inhibitor, in Pediatric Alopecia Areata: A Case Series.

Alopecia areata represents an autoimmune disease that specifically damages growing hair follicles on the scalp and/or around the body. Janus kinase inhibitors have been identified as an effective therapy in adult patients and topical formulations, such as Brevilin-A, might represent a well-tolerated treatment for mild-moderate disease in children and adolescents. The mechanism of action of Brevilin-A, a sesquiterpene lactone isolated from Centipeda minima, could consist in blocking STAT3 and STAT1 signaling as well as the JAKs activity by inhibiting the JAKs tyrosine kinase domain JH1. We report our cases of successful application of Brevilin-A in pediatric patients, suggesting this treatment as a safe and effective therapeutic option also for recalcitrant alopecia areata in pediatric population.

Innovative strategies for the discovery of new drugs against alopecia areata: taking aim at the immune system.

INTRODUCTION: The autoimmune hair loss condition alopecia areata (AA) exacts a substantial psychological and socioeconomic toll on patients. Biotechnology companies, dermatology clinics, and research institutions are dedicated to understanding AA pathogenesis and developing new therapeutic approaches. Despite recent efforts, many knowledge gaps persist, and multiple treatment development avenues remain unexplored. AREAS COVERED: This review summarizes key AA disease mechanisms, current therapeutic methods, and emerging treatments, including Janus Kinase (JAK) inhibitors. The authors determine that innovative drug discovery strategies for AA are still needed due to continued unmet medical needs and the limited efficacy of current and emerging therapeutics. For prospective AA treatment developers, the authors identify the pre-clinical disease models available, their advantages, and limitations. Further, they outline treatment development opportunities that remain largely unmapped. EXPERT OPINION: While recent advancements in AA therapeutics are promising, challenges remain, including the lack of consistent treatment efficacy, long-term use and safety issues, drug costs, and patient compliance. Future drug development research should focus on patient stratification utilizing robust biomarkers of AA disease activity and improved quantification of treatment response. Investigating superior modes of drug application and developing combination therapies may further improve outcomes. Spirited innovation will be needed to advance more effective treatments for AA.

Alopecia areata (AA) is an autoimmune condition that causes hair loss. It significantly affects a patient's emotional well-being and quality of life. Companies, clinics, and researchers are working hard to understand AA and create better treatments. Despite these efforts, there are still many unanswered questions, and new treatment methods still need to be explored.This review summarizes how AA develops, current treatment options, and new therapies like Janus Kinase (JAK) inhibitor drugs. JAK inhibitors show promise, but they are not fully effective for everyone. We emphasize that there is still a need for new and innovative drug discovery strategies to meet the medical needs of AA patients, as current treatments often fall short.For researchers and developers of AA treatments, we discuss the available pre-clinical models used to test new drugs, highlighting their strengths and weaknesses. We also point out new areas for treatment development that have not been thoroughly investigated.Although recent advancements in AA treatments are encouraging, several challenges remain. These include inconsistent effectiveness of treatments, safety concerns with long-term use, high drug costs, and issues with patient adherence to treatment programs. We believe future research should focus on identifying biomarkers that can help tailor treatments to individual patients and improving measurements of treatment success. Additionally, exploring better ways to apply drugs and combining different therapies together may enhance treatment outcomes.Ultimately, innovative approaches and spirited efforts will be required to develop more effective treatments for AA to improve the lives of those affected by this challenging condition.

Increased CRHR1 expression on monocytes from patients with AA enables a pro-inflammatory response to corticotrophin-releasing hormone.

Stress may play a key role in alopecia areata (AA), though the exact interactions of stress with AA remain undefined. Corticotropin-releasing hormone (CRH), the proximal regulator of the stress axis, has been recognized as an immunomodulatory factor in tissues and peripheral blood mononuclear cells (PBMCs). We used multicolour flow cytometry to identify receptor CRHR1 expression on PBMC subsets in AA patients (n = 54) and controls (n = 66). We found that CRHR1 was primarily expressed by circulating monocytes. CRHR1 expression on monocytes was enhanced in AA compared with controls (3.17% vs. 1.44%, p = 0.002, chi-squared test). AA incidence was correlated to elevated CD14+ monocyte numbers (R = 0.092, p = 0.036) and markedly independently correlated with increased CRHR1 expression (R = 0.215, p = 0.027). High CRHR1 expression was significantly related to chronic AA (disease duration >1 year; p = 0.003, chi-squared test), and large lesion area (AA area >25%; p = 0.049, chi-squared test). We also observed enhanced percentages of active monocytes and reduced CD16+ CD3- NK cell numbers in AA patients' PBMCs (p = 0.010; 0.025, respectively). In vitro CRH treatment of PBMCs and human monocyte cell line THP-1 promoted CD86 upregulation. The findings imply that stress-related factors CRH and CRHR1 contribute to AA development and progression where higher CRHR1 expression is associated with chronic AA and larger lesions.

Alopecia Areata and malignancies: uncertainties clarified by a large-scale population-based study.

The association of AA with malignancies has been a scope of controversy as the current literature is highly inconsistent in this regard. To evaluate the association between AA and hematological malignancies (HMs) and solid malignancies (SMs) using a large-scale, real-life computerized database. A cross-sectional study was conducted to compare the prevalence of HMs and SMs among patients with AA relative to age-, sex-, and ethnicity-matched control subjects. Chi-square and t-tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study included 51,561 patients with AA and 51,410 controls. AA was significantly associated with HMs (adjusted OR, 1.27; 95% CI, 1.07-1.51; P = 0.006). This association was more robust among patients with late-onset AA (≥ 50 years; OR, 1.33; 95% CI, 1.04-1.71; P = 0.025). On the other hand, AA was not found to be significantly associated with SM (adjusted OR, 0.97; 95% CI, 0.88-1.06; P = 0.487), excluding among patients with alopecia totalis and universalis (OR, 2.10; 95% CI, 1.03-4.27; P = 0.036). In a granular analysis including 5 HMs and 18 SMs, non-Hodgkin lymphoma was the only malignancy that proved positively associated with AA (adjusted OR, 1.32; 95% CI, 1.03-1.69; P = 0.028). AA is associated with HMs but not SMs. Further research is warranted to validate our observations in other study cohorts.

Identification of Potential Hub Genes in Alopecia Areata.

Alopecia areata (AA) is an immune-mediated chronic alopecia disease, but its specific pathogenesis is unclear. Gene expression data for AA patients (AAs) and healthy controls (HCs) were retrieved from the GEO database, and the differentially expressed genes (DEGs) between AAs and HCs were identified. Then, GO, KEGG and GSEA analysis were performed. A PPI network for the DEGs was then constructed to screen for hub genes, which were validated by three additional datasets. Subsequently, the potential miRNAs interacting with the hub genes were obtained through TarBase and miRNet. The differentially expressed lncRNAs (DElncRs) were obtained for subcellular localisation analysis, and the DElncRs located in the cytoplasm were further screened to identify miRNAs that interact with them. The shared miRNAs interacting with the hub genes and lncRNAs were used to construct a network of mRNA-miRNA-lncRNA interactions. Lastly, ROC analysis was performed to evaluate the potential diagnostic value of the hub genes and DElncRs identified. A total of 173 DEGs were obtained, mainly enriched in cytokines, chemokines, hair follicle development and hair cycle related signalling pathways. Through PPI screening and validation based on 3 additional datasets, 24 hub genes were finally yielded. Of them, five hub genes were upregulated and the potential miRNAs that interact with these five hub genes were identified. Additionally, 26 DElncRs were obtained, including 9 upregulated lncRNAs located in the cytoplasm that were predicted to interact with the miRNAs. Finally, an mRNA-miRNA-lncRNA regulatory network was constructed using five hub genes, four lncRNAs and their shared five miRNAs. The regulatory relationship between CD8A, mir-185-5p and FOXD2-AS1 might be crucial in AA pathogenesis, with CD8A and FOXD2-AS1 exhibiting diagnostic potential. CD8A and FOXD2-AS1 may serve as potential therapeutic targets in AA.

Alopecia Areata Treatment Patterns and Satisfaction: Results of a Real-World Cross-Sectional Survey in Europe.

INTRODUCTION: Alopecia areata (AA) is an autoimmune disease that causes scalp, face, and/or body hair loss. Recently, oral treatments with kinases inhibition became the first approved therapies for severe AA. An understanding of the use and effectiveness of traditional therapies in real-world treatment settings is needed to guide integration of novel therapies into the treatment paradigm. This study aimed to describe traditional treatment patterns, dermatologists' reasons for therapy choice, and dermatologists' satisfaction with disease control among patients with AA. METHODS: Data were drawn from the 2021-2022 Adelphi Real World AA Disease Specific Programme™, a cross-sectional survey of dermatologists and adult patients with AA, conducted in France, Germany, Italy, Spain, and the UK. For each patient, using data from patient consultation and medical records, dermatologists reported % scalp hair loss (SHL), characteristics of current and prior AA therapies, and satisfaction with disease control. RESULTS: Overall, 239 dermatologists provided data for 1720 patients with AA. Mean (SD) patient age was 35.8 (11.6) years, and 51% were male. Based on dermatologist perception, among patients with ≤ 10% SHL, 74% were experiencing mild AA, while ≥ 95% of patients with ≥ 50% SHL were experiencing severe/very severe AA. In patients with ≥ 50% SHL, the most common therapies received included systemic immunosuppressants (31%), topical corticosteroids (24%), and oral corticosteroids (24%). Among all patients who had switched therapies, 49%, 26%, and 24% switched because of worsening AA, lack of initial efficacy with prior treatment, and loss of response over time, respectively. Among those with SHL ≥ 50%, dermatologists reported satisfaction with current therapy in < 30% of patients. CONCLUSION: Dermatologists reported low satisfaction with traditional AA therapies used in patients with extensive SHL, with some patients discontinuing treatment because of worsening disease. This suggests more effective treatments are needed for patients with severe AA.

Long-term outcomes of intravenous corticosteroid pulse therapy for rapidly progressive alopecia areata: A single-center retrospective analysis of 106 cases and usefulness evaluation of a scoring system originally designed for half-year efficacy prediction for extended periods.

Intravenous corticosteroid pulse therapy (IVPT) has been preferentially conducted for rapidly progressive alopecia areata (RP-AA); however, the evaluation of long-term outcomes has been insufficient. In this study, 106 IVPT-treated RP-AA patients (36 males and 70 females) who were followed up for more than 1 year and up to 6.8 years were retrospectively analyzed. The mean observation period was 1137.8 ± 587.9 days (range 380-2490). The mean severity of alopecia tool (SALT) score before IVPT was 21.3 ± 23.4 but whole-scalp hair loss was observed in all cases after the intervention, suggesting that IVPT was performed soon after the onset. With additional interventions represented by intralesional triamcinolone acetonide injection with or without topical potent corticosteroid for those who insufficiently responded at 6 months after IVPT, 64.2%, 14.2%, and 21.7% of the patients respectively achieved good response (GR; SALT score ≤25), moderate response (MR; 25 < SALT score <75), and poor response (PR; 75 ≤ SALT score) 1 year after IVPT. On the final evaluation, the proportions of patients with GR, MR, and PR were 79 (74.5%), 7 (6.6%), and 20 (18.9%). Sixteen patients achieved and maintained full hair regrowth with IVPT alone until the end of observation. A previously reported scoring system for the short-term outcome prediction was shown to be useful for distinguishing the final-point GR responders from PR responders (P = 0.003). Of note, 21 patients were found to have some symptoms suggestive of the existence of preceding infectious diseases and tended to relapse. The revised scoring system adding the absence of preceding infectious diseases as one factor successfully predicted the occurrence of the relapse in our cohort (P = 0.002). Taken together, previously unreported real-world efficacy of IVPT to RP-AA was elucidated with the invention of a tool putatively enabling optimal long-term management.

Microneedle Transdermal Delivery of Compound Betamethasone in Alopecia Areata - A Randomized Controlled Trial.

BACKGROUND: Alopecia areata (AA) places a considerable burden on patients. While intralesional glucocorticoid injection is an important therapy, it can cause severe pain. OBJECTIVE: To compare the efficacy and pain levels of microneedle transdermal delivery of compound betamethasone versus traditional intralesional injection in mild-to-moderate AA. METHODS: We conducted a randomized controlled trial in AA patients with a SALT score < 50. Both groups received monthly compound betamethasone injections: Group A via intralesional injections, and Group B via transdermal microneedle delivery. The primary outcome was the reduction in SALT score after three months. RESULTS: With 80 patients enrolled, baseline SALT scores were similar between group A (9.250±5.300) and group B (10.65±9.445). After 3 months, the mean SALT reduction was 7.000±4.5017 in group A and 8.075±8.014 in group B, with no statistical difference. Remission rates for SALT30/50/75/90 were 92.50/90.00/57.50/42.50% in group A and 95.00/87.50/72.50/40% in group B, with no significant difference. Group B had a significantly lower Visual Analog Scale (VAS) pain score than group A (4.000±1.174 vs. 5.281±2.098, p=0.0047). LIMITATIONS: The study focused on mild-to-moderate patchy AA, limiting insights into severe cases. CONCLUSION: Microneedle transdermal delivery of compound betamethasone in mild-to-moderate patchy AA demonstrates efficacy comparable to traditional intralesional injection, with reduced pain.

Corticosteroid Atrophy Plaque on the Scalp Treated with 5-Fluourouracil and Bleomycin Infusion in the MMP Technique.

Alopecia areata (AA) is a disease with a great impact on quality of life of patients. Among several treatment modalities, intralesional injectable corticosteroid therapy is the first option, with corticosteroid-induced cutaneous atrophy as a common adverse event. We describe a case of plaque AA in the frontal region of the scalp that evolved with cutaneous atrophy induced by the application of intralesional corticosteroids but presented complete and sustained repilation after being treated with 5-Fluorouracil and Bleomycin using the technique of MMP (Microinfusion of Medicines into the Skin).

Comparative study on sexual dysfunction in alopecia areata: prevalence and associated factors.

BACKGROUND AND OBJECTIVES: Alopecia areata (AA) impairs quality of life. However, there is no evidence on the impact of this disease in terms of sexual dysfunction (SD). The aim of the present study was to assess the prevalence of SD and possible associated factors in a cohort of patients with AA. PATIENTS AND METHODS: A cross-sectional study was conducted in a cohort of AA patients matched with healthy controls. Sexual function was assessed using a numerical scale and gender-specific questionnaires. RESULTS: A total of 60 patients with AA and 60 healthy controls were included. The prevalence of SD was higher in women with AA than in healthy controls and in men with AA (p < 0.05). Female SD was associated with younger age, shorter duration of illness and higher rates of anxiety and depression (p < 0.05). Male SD was associated with older age and greater severity of AA (p < 0.05). CONCLUSIONS: Women with AA appear to have higher rates of SD than healthy controls and men with AA. Similarly, the factors associated with SD differ between men and women, with mood disturbance being of greater relevance in women, whereas disease severity seems to play a key role in men.

Refractory Myasthenia Gravis and Concurrent Alopecia Areata Postthymectomy With Improvements After Cortisone Taper: A Case Report.

This case report presents a unique clinical scenario of a 58-year-old male suffering from severe refractory myasthenia gravis and concurrent alopecia areata postthymectomy. Myasthenia gravis, a common autoimmune disorder, is characterized by muscle weakness due to autoantibodies targeting neuromuscular junction proteins. Alopecia areata, another autoimmune disease, is often seen in individuals with myasthenia gravis, suggesting a shared immunological basis. The patient's condition was resistant to conventional treatment, and he developed alopecia areata following thymectomy. Despite the challenges in managing refractory myasthenia gravis and the associated alopecia areata, significant improvements were observed following a cortisone taper. This case highlights the potential therapeutic role of cortisone tapering in managing refractory myasthenia gravis and associated alopecia areata. This case also prompts further exploration into the immunological shifts following thymectomy, particularly its potential role in triggering alopecia areata.

Thyroid Dysfunction and Alopecia Areata: A Genetic Prediction Causality Analysis Study.

BACKGROUND: Observational studies have suggested a correlation between alopecia areata (AA) and thyroid dysfunction (TD). However, the causal relationship between AA and TD remains uncertain. The purpose of this study is to investigate the causal relationship between these two conditions. Understanding the potential causal relationship between AA and TD is valuable for elucidating the pathogenesis of AA and for designing innovative methods to prevent and treat AA and its related complications. METHODS: All data for this two-sample Mendelian randomization (MR) study were sourced from public databases. This study selected hypothyroidism, Hashimoto's thyroiditis, hyperthyroidism, subacute thyroiditis, and Graves' disease as exposure factors, with AA as the outcome variable. Data for hypothyroidism, Hashimoto's thyroiditis, hyperthyroidism, subacute thyroiditis, Graves' disease, and AA were obtained from related genome-wide association studies (GWAS). Various MR analysis methods such as inverse variance weighted (IVW), MR-Egger, and weighted median were utilized. Additionally, Cochrane's Q test was used to detect heterogeneity in MR results, and the MR-Egger intercept test and MR pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy. A leave-one-out analysis was conducted to investigate the sensitivity of this association. RESULTS: We found statistically significant genetic predictions of AA with hypothyroidism, Hashimoto's thyroiditis, and subacute thyroiditis (IVW OR = 1.4009815, 95% confidence interval [CI]: 1.1210399-1.750829; p = 0.003030698, OR = 1.396101, 95% CI: 1.030134-1.89208; p = 0.03144273, OR = 0.732702, 95% CI: 0.604812-0.887634; p = 0.001483368). Furthermore, tests for pleiotropy showed no evidence of pleiotropy, enhancing the credibility of the study results. Finally, the leave-one-out test demonstrated the stability and robustness of this association. CONCLUSION: This study provides new evidence of a potential genetic link between thyroid issues and AA. By employing the two-sample MR method to eliminate confounding factors and reverse causation, unbiased results were obtained, confirming a causal relationship between hypothyroidism, Hashimoto's thyroiditis, subacute thyroiditis, and AA. This lays the foundation for further mechanistic studies and potential clinical applications. Future research should further explore the specific biological mechanisms between TD and the onset of AA.

Fractionated CO2 Laser in Combination with Topical Tacrolimus for Chronic Alopecia Areata: A Case Series Study.

Alopecia areata (AA) is a non-scarring autoimmune disease requiring long-term treatments. Topical, intralesional or systemic corticosteroids are the first option. However, considering the risk of skin atrophy and the possible lack of clinical response, new treatment options are urgently needed. A fractional carbon dioxide laser (FCL) has been proven to be effective alone or in combination with other drugs. However, no study has ever evaluated the association between FCL and topical tacrolimus. We report three cases of AA resistant to corticosteroids for at least 12 months, treated with topical tacrolimus 0.1% ointment and FCL on some patches. After 16 weeks from the beginning of treatment, all patients showed improvement in clinical and trichoscopic parameters in the areas treated in combination. FCL and tacrolimus may represent a new therapeutic option, but further studies are needed for confirmation.