Journal of Clinical and Aesthetic Dermatology • Hot Topics in Alopecia November 2025 • JOURNAL WATCH

In the digital edition, click the PMID after each summary to access the article/abstract.

Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata

Gay-Mimbrera J, Gómez-Arias PJ, Álvarez-Heredia P, et al. Front Immunol. 2025;16:1565241.

Summary. This original research integrated single-cell RNA sequencing and single-cell chromatin accessibility profiling of peripheral blood mononuclear cells from patients with alopecia areata (AA) and healthy controls to define systemic immune dysregulation by disease severity. Across 32,453 cells, patients, especially those with severe disease, showed increased transcriptional heterogeneity with enrichment of antigen presentation, interferon, and T-helper type 1 (TH1), T-helper type 2 (TH2), and T-helper type 17 (TH17) pathways, along with chemokine signaling. The most pronounced alterations occurred in CD14+ monocytes, natural killer cells, and CD8+ T cells, which exhibited pronounced epigenetic remodeling with 42,248 significant accessibility peaks linked to differentially expressed genes. Mild disease demonstrated early regulatory failure, including exhaustion signatures in double-negative T cells and increased apoptosis in myeloid populations, whereas severe disease showed amplified effector activation and antigen-presentation machinery. Pseudotime and transcription factor analyses showed altered differentation trajectories. Inferred cell-cell communication analyses indicated revealed monocytes, natural killer cells, and memory T cells as signaling hubs. This study's use of single-cell chromatin profiling revealed peripheral immune dysregulation in AA and systemic alterations that are associated with AA severity, and highlighted candidate pathways for immune modulation and biomarker development.

Evaluation of SALT score severity in correlation with trichoscopic findings in alopecia areata: a study of 303 patients

Summary. This single-center, cross-sectional study assessed the correlation between trichoscopic features and disease severity, measured by the Severity of Alopecia Tool (SALT) score, in 303 patients with AA. Prevalent trichoscopic findings included exclamation mark hair, small vellus hairs, and coudability hair. Markers such as cumulus-like white dots and v-sign correlated with more severe AA based on higher SALT scores. Indicators of hair regrowth, including small vellus hairs and upright regrowing hairs, were most common in patients with milder disease or positive treatment responses. Ordinal regression analysis showed that longer disease duration (odds ratio [OR]: 1.034, 95% confidence interval [CI]: 1.021–1.048, p<0.001), nail involvement (OR: 2.31, 95% CI: 1.57–3.40, p=0.001), and neuropsychiatric comorbidities (OR: 9.165, 95% CI: 1.751–47.985, p=0.009) significantly predicted greater disease severity. The study concluded that trichoscopy is a valuable tool for evaluating AA severity and monitoring treatment response.

Summary. This review explored evidence of cutaneous and gut microbiome dysbiosis in patients with AA and its potential role in immune dysregulation. Scalp microbiome studies showed altered bacterial abundance, including increased Cutibacterium acnes and decreased Staphylococcus epidermidis or Staphylococcus caprae, depending on disease severity. Biopsies from affected hair follicles revealed increased anaerobic bacteria and inflammatory markers, suggesting possible bacterial penetration and local immune activation. Gut microbiome analyses consistently found reduced levels of shortchain fatty acid-producing bacteria, including Bacteroidetes and Lachnospiraceae, implicating impaired intestinal immune regulation in AA. Preliminary therapeutic observations, such as hair regrowth following fecal microbiota transplantation and topical postbiotic use, highlight the potential of microbiome-directed interventions. However, the review concluded that while dysbiosis is evident, a causal link between microbial imbalance and AA pathogenesis remains unproven.

Belpaire A, Demeyer A, Van Caelenberg E, et al. J Transl Autoimmun. 2025;10:100282.

Summary. This observational study evaluated aryl hydrocarbon receptor (AhR) expression in T cell subsets from patients with AA and examined associations with disease activity and immune checkpoint markers. Compared with healthy controls, patients showed significantly reduced AhR expression in CD4, CD8, Th1, and Th17 lymphocytes (p<0.005), with inverse correlations between AhR levels and Severity of Alopecia Tool II (SALT II) scores (p<0.05). Receiver operating characteristic analysis indicated that AhR in CD8 cells differentiated limited disease from controls with 82.35 percent sensitivity and 86.84 percent specificity, supporting potential diagnostic utility. Lower AhR expression was associated with more interferon-gamma–producing lymphocytes and fewer interleukin-17–producing cells, consistent with heightened cytotoxic activity. Immune profiles varied by atopic status and extent of disease. Higher AhR correlated with increased soluble programmed death-1 in extensive disease, whereas AhR failed to upregulate investigated immune checkpoints in limited disease. The findings suggest AhR pathway downregulation contributes to AA pathobiology and may represent a biomarker and therapeutic target.

Summary. This systematic review and meta-analysis of 67 studies including 24,226 individuals assessed familial prevalence and comorbidities in patients with AA. The pooled prevalence of a family history of AA in affected individuals was 17.6 percent (95% CI: 14.9–20.6%), and among relatives the prevalence was 0.90 percent (95% CI: 0.55–1.47%), rising to 3.22 percent (95% CI: 2.31–4.48%) for first-degree relatives. Comorbid autoimmune and related conditions among family members occurred in 9.61 percent (95% CI: 6.98–13.1%) of cases, including atopic dermatitis (18.9%), other autoimmune diseases (12.1%), diabetes (10.1%), vitiligo (5.5%), and thyroid disease (4.7%). The authors concluded that the significant familial clustering and associated autoimmunity underline the hereditary and systemic nature of AA, and highlighted the need for family-based monitoring and genetic counselling.

Psychosocial impact of alopecia areata in pediatric and adolescent populations: a systematic review

Summary. This systematic review evaluated 10 studies on the psychosocial effects of alopecia areata in children and adolescents, with patient ages ranging from 2 to 19 years. Across study designs, alopecia areata was consistently associated with impaired self-esteem, elevated anxiety and depression, and reduced health-related quality of life. Psychiatric comorbidities, including generalized anxiety, social phobia, and major depressive disorder, were more common in this patient population compared with controls. Disease severity was positively correlated with poorer quality of life metrics, such as scores from the Children's Dermatology Life Quality Index. Qualitative studies also highlighted issues of loss of identity, social stigma, and maladaptive coping strategies. These findings underscore the need for integrated dermatologic and psychosocial care models to support affected young patients with AA.

This review outlines the immune-mediated mechanisms underlying alopecia areata (AA) in children, emphasizing the immune privilege collapse of hair follicle bulb and cytotoxic T cell-driven inflammation. The disease is characterized by upregulation of interferon-γ and interleukin-15 signaling, which activate Janus kinase (JAK)–STAT pathways and promote follicular destruction. Genetic susceptibility plays a key role, with pediatric cases often demonstrating strong associations with HLA alleles and family history, particularly among younger children with early onset. Environmental triggers, including viral infections and emotional or physical stress, can further modulate immune responses and precipitate disease flares. Emerging therapies, such as JAK inhibitors, target these pathogenic pathways and have shown promising results in pediatric patients in early clinical trials. Understanding these mechanisms may help refine personalized treatment approaches for children with AA.

Source: Fitzhugh MH, Hansen JG, Jabbari A, Berrebi KG. Pathophysiology of alopecia areata in the pediatric patient. Pediatr Dermatol. 2025;42 Suppl 1(Suppl 1):24–30.

RESEARCH BITE—The role of reactive oxygen species in the pathogenesis of alopecia areata: a systematic review and metaanalysis

This systematic review and meta-analysis evaluated the role of reactive oxygen species in the pathogenesis of alopecia areata (AA) by synthesizing data from 21 studies involving 743 patients. Compared with healthy controls, patients with AA demonstrated significantly elevated oxidative stress index and malondialdehyde levels, with effect sizes of 1.58 and 1.60, respectively. Antioxidant enzyme activity, including superoxide dismutase and glutathione peroxidase, was significantly reduced in patients with AA, with effect sizes of −0.97 and −1.41, respectively (p<0.001). Paraoxonase-1 levels trended lower but did not reach statistical significance. These findings suggest a marked imbalance between oxidants and antioxidants in patients with AA. The study concluded that oxidative stress may contribute to AA pathogenesis and could represent a therapeutic target.

Source: Perlmutter J, Akouris PP, Fremont S, et al. The role of reactive oxygen species in the pathogenesis of alopecia areata: a systematic review and meta-analysis. Skin Pharmacol Physiol. 2025;38(1–2):59–67.