Background: Alopecia areata (AA) is a common autoimmune alopecia disease. Evidence suggests that autophagy-related genes (ARGs) may contribute to its pathophysiology. This study aims to explore and identify potential autophagy-related biomarkers and molecular subtypes in AA. Methods: In this study, autophagy-related differential expression genes (ARDEGs) in AA were identified by comparing the differentially expressed genes (DEGs) in the GSE68801 dataset with the ARGs. Then, we applied three different machine learning methods to identify key hub genes and further verified them on independent datasets. We used the receiver operating characteristic (ROC) curve to evaluate the diagnostic potential of these hub genes and constructed a predictive nomogram. In addition, this study also used the consensus clustering method to define two AA subtypes and explored their immune characteristics and functional pathways through ssGSEA, MCPcounter and enrichment analysis. Experimental validation included qRT-PCR for four hub genes and Western blotting for critical autophagy markers. Results: Our analysis detected 10 ARDEGs in AA. Applying three machine learning algorithms, we identified four candidate hub genes, ATG9B, EIF4EBP1, WIPI1 and CCR2, and verified their expression patterns in independent cohorts. The combined four-gene model and nomogram showed potential diagnostic performance. Consensus cluster analysis divided AA cases into two subtypes, each associated with different immune infiltration and functional pathways. Downregulation of ATG9B and EIF4EBP1 and upregulation of CCR2 were verified by qRT-PCR. Western blotting further suggested altered autophagy-related protein expression in AA lesions, characterized by a reduced LC3B-II/I ratio and Beclin-1 expression and increased SQSTM1 expression. Conclusions: This study identified four candidate autophagy-related genes and two exploratory molecular subtypes in AA and may provide clues for understanding autophagy-related immune dysregulation and support further validation of candidate diagnostic markers.

BACKGROUND:Although alopecia areata (AA) typically presents as focal patches, it may manifest as hairline alopecia. We previously described an unusual AA presentation characterized by frontotemporal hairline recession with isolated single hairs. METHODS:Fifty-six patients with frontotemporal hairline recession and isolated single hairs were prospectively enrolled. Clinical, trichoscopic, and histopathologic features were characterized. Treatment outcomes were described by Severity of Alopecia Tool (SALT) score changes at months 3 and 6 and categorical status at last follow-up; 3 month corticosteroid response was compared with matched patchy AA controls. RESULTS:Patients (62.5% female; mean age 30.4 years) had a mean disease duration of 6.5 years and a mean baseline SALT score of 29.0. More than half had prior patchy AA. Trichoscopy consistently showed a predominance of 1-hair follicular units at the hairline. In biopsied cases, histopathology showed preserved pilosebaceous units, markedly increased telogen follicles, and residual solitary terminal hairs, without perifollicular fibrosis or lichenoid inflammation. Among 30 patients with evaluable outcomes, the median percent change in SALT score was 0% at Month 3 and 18.4% at Month 6. At the last evaluable follow-up, 6 patients (20.0%) achieved significant improvement. In the matched analysis, this phenotype showed a lower 3 month SALT50 response to systemic corticosteroids than patchy AA (5.9% vs. 76.5%; p < 0.001). CONCLUSIONS:This expanded cohort characterizes a frontal fibrosing alopecia (FFA)-like phenotype within the AA spectrum, supported by a non-scarring histopathologic profile in biopsied cases. Follow-up data suggest an insidious, chronic course and limited scalp hair regrowth among treated patients.

BackgroundCutaneous squamous cell carcinoma (cSCC) carries a risk of postoperative local recurrence, with nearly 90% of events occurring within 3 years; however, prognostic tools tailored to Asian populations remain limited. This study aimed to identify independent risk factors for postoperative local recurrence and develop a nomogram to predict individualized 1-, 2-, and 3-year recurrence probabilities in patients with cSCC.MethodsClinicopathological data from 603 patients with cSCC who underwent surgical treatment alone at four Chinese centers were retrospectively analyzed. Patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Univariable and multivariable Cox proportional hazards regression analyses were performed in the training cohort to identify independent predictors of postoperative local recurrence. A nomogram was then constructed based on these independent risk factors. The prognostic performance of the model was evaluated using time-dependent receiver operating characteristic curves, calibration curves, and decision curve analysis. Finally, the total nomogram score was calculated for each patient, and all patients were categorized into low-, intermediate-, and high-risk groups based on the optimal cutoff values. Kaplan–Meier analysis was then performed to compare recurrence-free survival among the different risk groups.ResultsA total of 603 patients were included, with 422 in the training cohort and 181 in the validation cohort. During follow-up, 77 recurrence events were observed. Multivariable Cox regression identified age, tumor size, tumor thickness, histologic differentiation, regional stage, and AJCC stage as independent predictors of recurrence. These predictors were incorporated into a nomogram for individualized recurrence risk estimation. The model demonstrated good discrimination, with area under the curve values ranging from 0.759 to 0.869, along with strong calibration and favorable clinical utility in decision curve analysis. Based on the total nomogram score, patients were stratified into low-risk (<99.0), intermediate-risk (99.0–143.9), and high-risk (≥144.0) groups, with significant differences in recurrence-free survival among the three groups (log-rank p < 0.0001).ConclusionsThis nomogram provides a practical tool for individualized prognostic assessment and may support individualized clinical decision-making for 1-, 2-, and 3-year outcomes 1.

Objective: Alopecia areata (AA) is a immune-mediated condition that affects patients’ quality of life, particularly among children and adolescents, and treatment options remain limited. This study aimed to explore the clinical effectiveness and safety of abrocitinib in seven adolescents with moderate-to-severe AA. Methods: This prospective observational study enrolled AA patients aged 12–17 years with a Severity of Alopecia Tool (SALT) score ≥ 25 who received abrocitinib treatment for at least 10 months between August 2023 and December 2024 at the Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College. The primary endpoint was measured by the proportional reduction in SALT score between baseline and the most recent evaluation. Secondary endpoints included the proportion of patients achieving a SALT score ≤20 (SALT 20), SALT50, SALT75, and SALT90 at weeks 12, 24, 36, and the final visit, and safety assessments. Results: Seven patients (one boy and six girls), aged 12 to 17 years, completed a minimum of 10 months of therapy. The median baseline SALT score was 95 (IQR, 50–100), and the mean disease duration was 35.1 months. At week 12, 57.1% achieved SALT ≤20, increasing to 85.7% by week 24 and 100% by week 36; at the final visit, 85.7% maintained this response. SALT50/75/90 response rates improved from 71.4%/42.9%/28.6% at week 12 to 100%/85.7%/85.7% at week 24, reaching 100% each by week 36. The median percentage reduction in SALT score was 100% (mean, 90.6%; IQR, 47.4%–100%). Initial hair regrowth occurred after a mean duration of 7.7 weeks. No serious safety concerns were identified; one patient experienced mild transient bilirubin elevation. Conclusion: Abrocitinib demonstrated favorable efficacy and tolerability in adolescents with AA. The long-term clinical outcomes and safety considerations of abrocitinib and other JAK inhibitors in this age group remain to be established through adequately powered prospective trials.

Under physiological conditions, hair follicle immune privilege protects hair follicles through spatial isolation, immune regulators (e.g., transforming growth factor beta, programmed death-ligand 1), and regulatory T cells. In addition, immune cells actively facilitate hair follicle regeneration by regulating the hair cycle via pathways such as Jag1-Notch, Janus Kinase–Signal Transducer and Activator of Transcription, and Wnt pathways. They also promote wound-induced hair neogenesis through macrophage- and regulatory T cell-mediated mechanisms. In alopecia areata, stress-induced collapse of hair follicle immune privilege initiates autoantigen presentation, thereby triggering an autoreactive inflammatory loop. This review, based on literature retrieved from PubMed, Web of Science, and Embase databases (January 2018–June 2025; approximately 120 studies included), summarizes recent advances in understanding immune regulation of hair follicle immune privilege maintenance, its breakdown in alopecia areata, and its implications for immune-guided hair follicle regeneration. Current therapies, including corticosteroids and Janus Kinase inhibitors, provide symptomatic relief but fail to prevent relapse. Emerging targeted immunotherapies, such as inhibitors of inflammatory pathways and modulation of regulatory T cells, offer promising prospects for the treatment of alopecia areata.

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 Severity of Alopecia Tool (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 3 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 pain score than group A (4.000 ± 1.174 vs 5.281 ± 2.098, P = .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.

BackgroundLupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE.ObjectivesWe aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes.MethodsThis is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study.ResultsIn the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% +/- 6.94% to 81.25% +/- 4.23% (p = 0.0004).ConclusionsThese results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

BackgroundNuclear pleomorphism and tumor microenvironment (TME) play a critical role in cancer development and progression. Identifying most predictive nuclei and TME features of basal cell carcinoma (BCC) may provide insights into which characteristics pathologists can use to distinguish and stratify this entity.ObjectivesTo develop an automated workflow based on nuclei and TME features from basaloid cell tumor regions to differentiate BCC from trichoepithelioma (TE) and stratify BCC into high-risk (HR) and low-risk (LR) subtypes, and to identify the nuclear and TME characteristics profile of different basaloid cell tumors.MethodsThe deep learning systems were trained on 161 H&E -stained sections which contained 51 sections of HR-BCC, 50 sections of LR-BCC and 60 sections of TE from one institution (D1), and externally and independently validated on D2 (46 sections) and D3 (76 sections), from 2015 to 2022. 60%, 20% and 20% of D1 data were randomly splitted for training, validation and testing, respectively. The framework comprised four stages: tumor regions identification by multi-head self-attention (MSA) U-Net, nuclei segmentation by HoVer-Net, quantitative feature by handcrafted extraction, and differentiation and risk stratification classifier construction. Pixel accuracy, precision, recall, dice score, intersection over union (IoU) and area under the curve (AUC) were used to evaluate the performance of tumor segmentation model and classifiers.ResultsMSA-U-Net model detected tumor regions with 0.910 precision, 0.869 recall, 0.889 dice score and 0.800 IoU. The differentiation classifier achieved 0.977 +/- 0.0159, 0.955 +/- 0.0181, 0.885 +/- 0.0237 AUC in D1, D2 and D3, respectively. The most discriminative features between BCC and TE contained Homogeneity, Elongation, T-T_meanEdgeLength, T-T_Nsubgraph, S-T_HarmonicCentrality, S-S_Degrees. The risk stratification model can well predict HR-BCC and LR-BCC with 0.920 +/- 0.0579, 0.839 +/- 0.0176, 0.825 +/- 0.0153 AUC in D1, D2 and D3, respectively. The most discriminative features between HR-BCC and LR-BCC comprised IntensityMin, Solidity, T-T_minEdgeLength, T-T_Coreness, T-T_Degrees, T-T_Betweenness, S-T_Degrees.ConclusionsThis framework hold potential for future use as a second opinion helping inform diagnosis of BCC, and identify nuclei and TME features related with malignancy and tumor risk stratification.

The pathogenesis of alopecia areata,a common autoimmune non-scarring alopecia,remains unclear.Current studies have shown that the loss of immune privilege of hair follicles due to the up-regulation of MHC molecules and the decrease in immunosuppressive molecules leads to the exposure of self-antigens in the affected area.This triggers the infiltration of immune cells(such as CD8+T cells,NK cells,plasmacytoma dendritic cells,and mast cells)around the hair bulb.Various immune cells and related cytokines participate in the pathogenesis and development of this disease through diverse signaling pathways.Due to its complex pathogenesis and diverse clinical manifestations,there are challenges in the diagnosis and treatment in clinic.This paper aims to provide a comprehensive review on recent advances in understanding the immunological pathogenesis of alopecia areata by focusing on mechanisms underlying immune privilege loss a-round hair follicles and the interaction between various immune cells in the microenvironment for a deeper understanding of its pathogenesis.It also seeks to explore new research directions and po-tential treatment strategies.

Alopecia areata is a common autoimmune disorder characterized by non-scarring hair loss on the scalp or other hair-bearing surface. In recent years, Janus kinase (JAK) inhibitors have shown promise in the treatment of alopecia areata by disrupting the signaling pathways involved in immune-mediated hair follicle damage. However, some patients with alopecia areata exhibit insufficient responses to JAK inhibitors. This review aims to explore the predictive factors for poor responses to JAK inhibitors in patients with alopecia areata and to discuss alternative treatment strategies in such cases. Patients with a longer duration of the current episode and higher baseline severity are at an increased risk of inadequate JAK inhibitor responses. Oral administration rather than topical application, and extended treatment durations, correlate with a favorable response. Notably, the poor response to JAK inhibitors in alopecia areata may be related to the amount and functional depletion of regulatory T cells resulting from an augmented T helper-2-type immune response. For patients with poor responses to JAK inhibitors, treatment adjustments may include increasing the dosage, extending the treatment duration, combination therapies, or switching to alternative JAK inhibitors. For patients with atopic comorbidities or psychological problems, it is important to select corresponding treatment options to optimize patient outcomes. Further research is needed to establish more reliable predictors and improve overall patient care.

Journal of the European Academy of Dermatology and VenereologyEarly View LETTER TO THE EDITOR Novel variant in WNT10A caused short anagen hair syndrome in a Chinese pedigree Ran Mo, Ran Mo orcid.org/0000-0002-2394-1896 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorZhiming Chen, Zhiming Chen orcid.org/0000-0002-3097-0126 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorYong Yang, Yong Yang orcid.org/0000-0002-7668-3309 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorYiqun Jiang, Corresponding Author Yiqun Jiang [email protected] orcid.org/0000-0003-4965-0242 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Correspondence Yiqun Jiang, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 12 Jiangwangmiao Street, Nanjing 210042, China. Email: [email protected]Search for more papers by this author Ran Mo, Ran Mo orcid.org/0000-0002-2394-1896 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorZhiming Chen, Zhiming Chen orcid.org/0000-0002-3097-0126 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorYong Yang, Yong Yang orcid.org/0000-0002-7668-3309 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorYiqun Jiang, Corresponding Author Yiqun Jiang [email protected] orcid.org/0000-0003-4965-0242 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Correspondence Yiqun Jiang, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 12 Jiangwangmiao Street, Nanjing 210042, China. Email: [email protected]Search for more papers by this author First published: 23 April 2024 https://doi.org/10.1111/jdv.20035Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Open Research DATA AVAILABILITY STATEMENT The data underlying this article is available upon reasonable request from the corresponding author. ETHICS STATEMENT The study was performed in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the ethics committee of the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College. The patient's parents/guardians in this manuscript have given written informed consent to the publication of their case details. REFERENCES 1Segawa Y, Yamasaki K, Otake E, Kikuchi K, Aiba S. Short anagen syndrome: a unique short hair syndrome without any characteristic hair morphological abnormality. J Dermatol. 2020; 47(10): e349–e351. 10.1111/1346-8138.15494 PubMedWeb of Science®Google Scholar 2Starace M, Gurioli C, Carpanese MA, Bruni F, Piraccini BM, Patrizi A, et al. Short anagen syndrome: a case series and algorithm for diagnosis. Pediatr Dermatol. 2021; 38(5): 1157–1161. 10.1111/pde.14750 PubMedWeb of Science®Google Scholar 3Cesarato N, Schwieger-Briel A, Gossmann Y, Henne SK, Hillmann K, Frommherz LH, et al. Short anagen hair syndrome: association with mono- and biallelic variants in WNT10A and a genetic overlap with male pattern hair loss. Br J Dermatol. 2023; 189: 741–749. 10.1093/bjd/ljad314 PubMedGoogle Scholar 4Doolan BJ, Onoufriadis A, Kantaputra P, McGrath JA. WNT10A, dermatology and dentistry. Br J Dermatol. 2021; 185(6): 1105–1111. 10.1111/bjd.20601 CASPubMedWeb of Science®Google Scholar 5Bohring A, Stamm T, Spaich C, Haase C, Spree K, Hehr U, et al. WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. Am J Hum Genet. 2009; 85(1): 97–105. 10.1016/j.ajhg.2009.06.001 CASPubMedWeb of Science®Google Scholar 6Onoufriadis A. WNT10A gene variants at the root of short anagen hair syndrome. Br J Dermatol. 2023; 189(6): 653–654. 10.1093/bjd/ljad377 PubMedGoogle Scholar Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Citation: Lan X, Sun J, Jiang Y, Wang X. Two New Dermoscopic Features of Trichostasis Spinulosa and Its Reflectance Confocal Microscopic Appearance. Dermatol Pract Concept. 2023;13(1):e2023026. DOI: https://doi.org/10.5826/dpc.1301a26

We describe a patient with classical Hailey–Hailey disease who was successfully treated with the Janus kinase (JAK)1 inhibitor abrocitinib. To our knowledge, abrocitinib has not previously been described in the medical literature as a treatment option for HHD.

Dowling-Degos disease (DDD) is an autosomal dominant hereditary skin disease characterized by acquired reticular hyperpigmentation in flexural sites, and one of its causative genes is KRT5 gene. But the effect of KRT5, expressed only in keratinocytes, on melanocytes is unclear. Other pathogenic genes of DDD include POFUT1, POGLUT1 and PSENEN genes, which is involved in posttranslational modification of Notch receptor. In this study, we aim to determine the ablation of keratinocyte KRT5 affect melanogenesis in melanocyte through Notch signalling pathway. Here we found that KRT5 downregulation decreased the expression of the Notch ligand in keratinocytes and Notch1 intracellular domain in melanocytes, by establishing two cell models of ablation of KRT5 in keratinocytes based on CRISPR/Cas9 site-directed mutation and lentivirus-mediated shRNA. Treatment of melanocytes with Notch inhibitors had same effects with ablation of KRT5 on increase of TYR and decrease of Fascin1. Activation of Notch signalling reverses the effect of ablation of KRT5 on melanogenesis. Immunohistochemistry of DDD lesions with KRT5 gene mutation confirmed changes in the expression of relevant molecules in Notch signalling. Our research elucidates molecular mechanism of KRT5-Notch signalling pathway in the regulation of melanocytes by keratinocytes, and preliminary reveal the mechanism of DDD pigment abnormality caused by KRT5 mutation. These findings identify potential therapeutic targets of the Notch signalling pathway for the treatment of skin pigment disorders.