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.

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.

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.

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.

Validation of alopecia coding in US claims data among women of childbearing age.

BACKGROUND: Accurately identifying alopecia in claims data is important to study this rare medication side effect. OBJECTIVES: To develop and validate a claims-based algorithm to identify alopecia in women of childbearing age. METHODS: We linked electronic health records from a large healthcare system in Massachusetts (Mass General Brigham) with Medicaid claims data from 2016 through 2018 to identify all women aged 18 to 50 years with an ICD-10 code for alopecia, including alopecia areata, androgenic alopecia, non-scarring alopecia, or cicatricial alopecia, from a visit to the MGB system. Using eight predefined algorithms to identify alopecia in Medicaid claims data, we randomly selected 300 women for whom we reviewed their charts to validate the alopecia diagnosis. Positive predictive values (PPVs) were computed for the primary algorithm and seven algorithm variations, stratified by race. RESULTS: Out of 300 patients with at least 1 ICD-10 code for alopecia in the Medicaid claims, 286 had chart-confirmed alopecia (PPV = 95.3%). The algorithm requiring two diagnosis codes plus one prescription claim for alopecia treatment identified 55 patients (PPV = 100%). The algorithm requiring 1 diagnosis code for alopecia plus 1 procedure claim for intralesional triamcinolone injection identified 35 patients (PPV = 100%). Across all 8 algorithms tested, the PPV varied between 95.3% and 100%. The PPV for alopecia ranged from 94% to 100% in White and 96%-100% in 48 non-White women. The exact date of alopecia onset was difficult to determine in charts. CONCLUSION: At least one recorded ICD-10 code for alopecia in claims data identified alopecia in women of childbearing age with high accuracy.

Role of neurogenic inflammation in the pathogenesis of alopecia areata.

Alopecia areata refers to an autoimmune illness indicated by persistent inflammation. The key requirement for alopecia areata occurrence is the disruption of immune-privileged regions within the hair follicles. Recent research has indicated that neuropeptides play a role in the damage to hair follicles by triggering neurogenic inflammation, stimulating mast cells ambient the follicles, and promoting apoptotic processes in keratinocytes. However, the exact pathogenesis of alopecia areata requires further investigation. Recently, there has been an increasing focus on understanding the mechanisms of immune diseases resulting from the interplay between the nervous and the immune system. Neurogenic inflammation due to neuroimmune disorders of the skin system may disrupt the inflammatory microenvironment of the hair follicle, which plays a crucial part in the progression of alopecia areata.

Lasers in the management of alopecia: a review of established therapies and advances in treatment.

Alopecia, also known as hair loss, is a highly prevalent condition affecting millions of men and women in the United States and worldwide, making it one of the most common complaints by patients presenting to a dermatologist. The symptomology on the presentation of alopecia can be highly variable, ranging from diffuse thinning of hair, discrete and localized patches completely absent of hair, or noticing significant shedding when brushing and showering. Although alopecia does not have a direct negative health impact on patients, it is nonetheless a debilitating disease as it can profoundly impact an individual's self-image and psychosocial well-being. There are multiple treatment options available to patients with alopecia, and they are typically tailored to the patient's needs and preferences. The most common of these is the Food and Drug Administration-approved drugs for alopecia, minoxidil, and finasteride. However, both of these are known to be partially efficacious for all patients, so clinicians often use different modalities in conjunction with them, in particular laser-based therapies. This review article will provide a comprehensive assessment of lasers and other light therapies that may be used to manage the two most common types of alopecia: androgenetic alopecia and alopecia areata.

Effect of minoxidil combined with triamcinolone acetonide on alopecia areata by microneedle injection.

OBJECTIVE: Alopecia areata (AA) is often characterized by sudden onset of patchy hair loss. Topical corticosteroid injection is the most common treatment. This study retrospectively observed the clinical efficacy of microneedle minoxidil combined with triamcinolone acetonide in the treatment of AA. METHODS: A total of 230 patients with AA were selected. The experimental group (n = 120) received physician training and home microneedle treatment with minoxidil combined with triamcinolone acetonide once a week. Topical minoxidil and triamcinolone acetonide were used twice daily at other times. The control group (n = 110) was treated with minoxidil combined with triamcinolone acetonide, twice a day. Cure rate, response rate, SALT, dermatological Quality of Life Index (DLQI), visual analogue (VAS), and cost were assessed at weeks 4 and 12. RESULTS: Treated group SALT score(Severity of Alopecia Tool) remarkable lower than control group after treated 4 and 12 weeks. After 12 weeks treatment, DLQI score of the treated group (1.8 ± 1.67) were significantly lower than those of the control group (2.45 ± 1.88) (p < 0.05). VAS score and adverse reaction between two group showed no significant different (p = 0.823, p = 0.484 respectively). The total cost was 53.93 ± 15.85 in the treatment group and 53.26 ± 11.51 in the control group. There was no significant difference between the two groups (p = 0.72). In the treated group, the complete response rate (CR: 78.33%) and total effective rate (CR+PR: 95%) were significantly higher than those in the control group (CR: 40.91% and CR+PR: 51.82%), with statistically significant differences (p < 0.001). CONCLUSION: Microneedle introduction of minoxidil and triamcinolone acetonide in the treatment of AA is a safe, effective, economical, and convenient method, with few adverse reactions, and has a good application prospect.

Real world evidence: patients with alopecia areata in Italy.

BACKGROUND: This real-world analysis aimed at characterizing patients hospitalized for alopecia areata (AA) in Italy, focusing on comorbidities, treatment patterns and the economic burden for disease management. METHODS: Administrative databases of healthcare entities covering 8.9 million residents were retrospectively browsed to include patients of all ages with hospitalization discharge diagnosis for AA from 2010 to 2020. The population was characterized during the year before the first AA-related hospitalization (index-date) and followed-up for all the available successive period. AA drug prescriptions and treatment discontinuation were analyzed during follow-up. Healthcare costs were also examined. RESULTS: Among 252 patients with AA (mean age 32.1 years, 40.9% males), the most common comorbidities were thyroid disease (22.2%) and hypertension (21.8%), consistent with literature; only 44.4% (112/252) received therapy for AA, more frequently with prednisone, triamcinolone and clobetasol. Treatment discontinuation (no prescriptions during the last trimester) was observed in 86% and 88% of patients, respectively at 12 and 24-month after therapy initiation. Overall healthcare costs were 1715€ per patient (rising to 2143€ in the presence of comorbidities), mostly driven by hospitalization and drugs expenses. CONCLUSIONS: This first real-world description of hospitalized AA patients in Italy confirmed the youth and female predominance of this population, in line with international data. The large use of corticosteroids over other systemic therapies followed the Italian guidelines, but the high discontinuation rates suggest an unmet need for further treatment options. Lastly, the analysis of healthcare expenses indicated that hospitalizations and drugs were the most impactive cost items.

Exploring the Role of Gut Microbiota in Patients with Alopecia Areata.

Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA) and gut microbial dysbiosis remains unclear. This cross-sectional study was conducted to identify and compare the composition of the gut microbiome in patients affected by AA and those in a healthy control (HC) group, and to investigate possible bacterial biomarkers for the disease. Fecal samples were collected from 19 AA patients and 20 HCs to analyze the relationship with fecal bacteria. The three major genera constituting the gut microbiome of AA patients were Bacteroides, Blautia, and Faecalibacterium. The alpha diversity of the AA group was not statistically significant different from that of the HC group. However, bacterial community composition in the AA group was significantly different from that of HC group according to Jensen-Shannon dissimilarities. In patients with AA, we found an enriched presence of the genera Blautia and Eubacterium_g5 compared to the HC group (p < 0.05), whereas Bacteroides were less prevalent (p < 0.05). The gut microbiota of AA patients was distinct from those of the HC group. Our findings suggest a possible involvement of gut microbiota in in the as-yet-undefined pathogenesis of AA.

The role of thymic stromal lymphopoietin in cutaneous disorders.

Thymic Stromal Lymphopoietin (TSLP) is an important cytokine that invokes early immune responses. TSLP, an IL-7-like cytokine encoded by the TSLP gene, activates JAK1 and JAK2 signaling pathways, stimulating dendritic cells to induce inflammatory Th2 cells. This cytokine is associated with pruritus in various cutaneous disorders, particularly atopic dermatitis. Varying levels of the cytokine TSLP have been demonstrated in studies of different cutaneous disorders. Pharmacological treatment targeting TSLP has been explored recently, particularly in the realm of atopic dermatitis.This review explores the relation of TSLP to cutaneous diseases, highlighting its potential as a biomarker for monitoring disease progression in discoid lupus erythematosus (DLE). The pharmacological therapy involving TSLP is discussed, along with the potential role of TSLP promotion in the treatment of alopecia areata. This overview examines the background, structure, and functions of TSLP, with a focus on its association with cutaneous disorders and a special focus on the impact of the atopic march.

Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences.

Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-ß (TGF-ß), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/ß-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.

Interleukin-15 is a hair follicle immune privilege guardian.

The autoimmunity-promoting cytokine, Interleukin-15 (IL-15), is often claimed to be a key pathogenic cytokine in alopecia areata (AA). Yet, rhIL-15 promotes human hair follicle (HF) growth ex vivo. We have asked whether the expression of IL-15 and its receptor (IL-15R) isoforms is altered in human AA and how IL-15 impacts on human HF immune privilege (HF-IP) in the presence/absence of interferon-γ (IFNγ), the well-documented key AA-pathogenic cytokine, as well as on hair regrowth after experimental AA induction in vivo. Quantitative immunohistomorphometry showed the number of perifollicular IL-15+ T cells in AA skin biopsies to be significantly increased compared to healthy control skin, while IL-15, IL-15Rα, and IL-15Rγ protein expression within the hair bulb were significantly down-regulated in AA HFs. In organ-cultured human scalp HFs, rhIL-15 significantly reduced hair bulb expression of MICA, the key "danger" signal in AA pathogenesis, and increased production of the HF-IP guardian, α-MSH. Crucially, ex vivo, rhIL-15 prevented IFNγ-induced HF-IP collapse, restored a collapsed HF-IP by IL-15Rα-dependent signaling (as documented by IL-15Rα-silencing), and protected AA-preventive immunoinhibitory iNKT10 cells from IFNγ-induced apoptosis. rhIL-15 even promoted hair regrowth after experimental AA induction in human scalp skin xenotransplants on SCID/beige mice in vivo. Our data introduce IL-15 as a novel, functionally important HF-IP guardian whose signaling is constitutively defective in scalp HFs of AA patients. Our data suggest that selective stimulation of intrafollicular IL-15Rα signaling could become a novel therapeutic approach in AA management, while blocking it pharmacologically may hinder both HF-IP restoration and hair re-growth and may thus make HFs more vulnerable to AA relapse.

Exploring the Gut Microbiome and Metabolome in Individuals with Alopecia Areata Disease.

In recent years, heightened attention has been devoted to unravelling the intricate interplay between genetic and environmental factors shaping the gut microbiota and its significance for human health. This study delves into exploring the plausible connection between Alopecia Areata (AA), an autoimmune disease, and the dynamics of the gut microbiome. Examining a cohort of healthy adults and individuals with AA, both the gut microbiota composition and volatile organic compound (VOC) metabolites from faeces and urine were analysed. While overall microbiota composition showed no significant differences, intra-individual variability revealed distinctions related to age, gender, and pathology status, with AA individuals exhibiting reduced species richness and evenness. Differential abundance analysis identified microbial biomarkers for AA, notably Firmicutes, Lachnospirales, and Blautia, while Coprococcus stood out for healthy individuals. The Data Integration Analysis for Biomarker discovery using Latent Components (DIABLO) method further supported these findings including metabolite biomarkers, such as esters of branched chain fatty acids and branched chain amino acids as predictors for AA, suggesting potential links to oxidative stress. Despite certain limitations, the study highlights the complexity of the gut microbiome and its metabolites in the context of AA, while the biomarkers identified could be useful starting points for upcoming studies.

Treatment Options for Alopecia Areata in Children and Adolescents.

Alopecia areata (AA) lifetime incidence is around 2%, with many patients first experiencing symptoms during childhood. However, ritlecitinib is the only FDA-approved treatment for pediatric patients 12 years and older. This review outlines reported topical, injectable, and oral treatment options for pediatric patients with AA. Clinical studies were obtained via a PubMed search using the following search terms: alopecia areata, areata, universalis, or totalis and medication, therapy, treatment, drug, or management. Only studies with pediatric patients were included in this review. Commonly used therapies, including corticosteroids, methotrexate, and minoxidil, newer promising medications, such as Janus kinase inhibitors, and less frequently used topical and systemic treatments are included. A summary of the drug development pipeline and ongoing interventional clinical trials with pediatric patients is provided. Treatments demonstrate variable efficacy, and many patients require combination therapy for maximal response. More robust clinical data is needed for many of the medications reviewed in order to provide better care for these patients.