Abstract Bullous pemphigoid (BP) is an inflammatory autoimmune skin disease primarily caused by anti-BP180 autoantibodies. Recent investigations have uncovered the critical involvement of extracellular traps (ETs) in BP pathogenesis. These web-like structures released by leukocytes are mainly composed of DNA, histones, and granular proteins. Both neutrophil ETs (NETs) and eosinophil ETs (EETs) are found at relatively high levels in BP lesions, particularly near the dermal–epidermal junction (DEJ). These ETs significantly influence immune cell differentiation within the BP environment. NETs promote the differentiation of B cells into CD19 + CD138 + plasma cells, leading to increased autoantibody production. Similarly, EETs drive the differentiation of T cells into follicular helper T cells and contribute to DEJ separation. DNase can block these effects by degrading the DNA structure. In addition, granular proteins within ETs, such as neutrophil elastase, eosinophil cationic protein, and eosinophil-derived neurotoxin, have been demonstrated to play critical roles in the pathogenesis of BP. In this review, we focus on the formation mechanism and structural characteristics of ETs and reveal the role of ETs in the BP.
Abstract Background: To explore the mechanism by which Astilbin ameliorates psoriasis-like symptoms through gut microbiota. Objectives: An imiquimod (IMQ)-induced psoriasis-like mouse model was established. Skin lesions were evaluated by Psoriasis Area and Severity Index, Hematoxylin and Eosin staining, and immunohistochemistry. Inflammatory cytokines (interleukin [IL]-17A, IL-22, and IL-23) were measured by Enzyme-Linked Immunosorbent Assay. Methods: The role of intestinal microbiota in Astilbin’s mitigation of psoriasis-like lesions was verified through fecal microbiota transplantation experiments. Flow cytometry was employed to determine the proportion of T helper 17 (Th17) and regulatory T cell (Treg), and quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed to test the expression of Retinoic acid receptor-related orphan receptor gamma t and Forkhead box protein P3. 16S rRNA sequencing was used to analyze fecal microbiota changes. Results: Results showed Astilbin reduced psoriasis-like skin damage, Ki67 expression, and cytokine secretion, suggesting that these effects are potentially dependent on gut microbiota. Astilbin decreased the Th17/Treg ratio, alleviating inflammation. Further 16S rRNA sequencing analysis indicated that Astilbin alleviated psoriasis in mice, possibly by reducing the abundance of Firmicutes and the proportion of Lachnospiraceae within Firmicutes . Thus, our data suggest that Astilbin may modulate Th17/Treg differentiation balance via gut microbiota to mitigate IMQ-induced psoriasis-like dermatitis in mice. Conclusion: Overall, our study supports that Astilbin alleviates inflammatory response, potentially by modulating Th17/Treg differentiation balance through intestinal microbiota, thereby reducing the severity of IMQ-induced psoriasis-like lesions in mice.
Abstract Background: Intravenous methylprednisolone pulse (IVMP) therapy has been widely used for treating severe or recalcitrant alopecia areata (AA), but treatment protocols and efficacy vary. Objectives: This study aims to evaluate the efficacy of IVMP, identify predictive factors for treatment response, and optimize treatment protocols. Methods: A total of 122 AA patients received IVMP (500 mg/day for 3 consecutive days) and were followed for 12 months. Treatment response was classified as remarkable response (RR, ≥75% hair regrowth), partial response (PR, 25%–75% regrowth), and relapse (>10% new-onset hair loss). Results: RR was achieved in 55 patients (45.1%), with a relapse rate of 27.4% (mean interval: 5.3 months). Patients with a disease duration of <6 months had significantly better responses than those with ≥6 months (odds ratio = 0.148, P < 0.0001). RR rates did not significantly differ among IVMP session groups (1–3: 42.5%, 4–6: 60.9%, >6: 20%; P = 0.161). However, among patients with a disease duration ≥6 months, repetitive IVMP (2–11 sessions) was more effective than a single session (RR + PR: 68.6% vs. 20%, P = 0.0497). No severe adverse effects were observed. Conclusion: Monthly IVMP is a safe and effective treatment option for severe AA. Treatment regimens should be individualized based on disease duration and clinical response.
Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disorder, affecting intertriginous areas and characterized by painful nodules, abscesses, fistulae, and scarring. Despite its impact on patients’ quality of life (QoL), HS remains underdiagnosed and mismanaged due to its heterogeneous clinical presentation. A panel of 14 Malaysian dermatologists, HS special interest group, developed a set of consensus-based recommendations on diagnosis, disease assessment, comorbidities, treatment, and follow-up care to improve HS management. A modified Delphi process was utilized to draft and finalize statements based on evidence sourced from literature between 2013 and 2023. The consensus highlights the importance of early recognition of HS clinical signs, differential diagnosis, and the use of validated tools such as Hurley staging, International HS Severity Score System, and Dermatology Life Quality Index to assess disease severity and QoL. Treatment recommendations for HS were stratified by disease severity, including topical, systemic, and biologic therapies, and surgical interventions for advanced cases. Adalimumab and secukinumab are currently the only approved biologics in Malaysia, showing sustained efficacy in moderate-to-severe HS. Adjunctive therapies such as zinc supplementation, lifestyle modifications, and wound care are also recommended. The consensus emphasizes a multidisciplinary approach to address the multifaceted nature of HS and optimize long-term outcomes, and aims to standardize HS care in Malaysia, promote early intervention, and enhance QoL for affected patients.
Background: Vitiligo is an autoimmune-related pigment disorder. Previous studies have demonstrated the therapeutic effects of phototherapy, topical treatments, and systemic immunomodulators in promoting repigmentation in patients with vitiligo. A network meta-analysis can provide the relative efficacy of various topical medications for which head-to-head clinical trials are lacking. Objectives: To identify the optimal topical treatments for repigmentation in vitiligo patients. Methods: A systematic search of electronic databases up to July 2024 identified randomized controlled trials involving vitiligo patients receiving topical treatment. The primary outcome was a 50% improvement in the Vitiligo Area Scoring Index (VASI50), a secondary analysis focused on the VASI75. Subgroup analyses were also conducted. Results: Thirty randomized controlled trials with 2,031 patients were included in the network meta-analysis. Compared with the control groups, the most effective monotherapy for achieving VASI50 was 0.05% clobetasol (risk ratio [RR]: 11.44; 95% confidence interval [CI]: 5.14–25.47), followed by 0.01% bimatoprost, 0.1% tacrolimus, and 0.1% mometasone, respectively. Among combination therapies, 0.05% clobetasol plus 5% fluorouracil (RR: 42.89; 95% CI: 11.71–157.19) was the most effective. Subgroup analyses yielded consistent findings, with 0.05% clobetasol plus 5% fluorouracil and 0.05% clobetasol monotherapy remaining the top treatments, except in facial lesion treatments, where 0.01% bimatoprost ranked highest. Conclusion: Our study provides a comparative efficacy ranking of different topical treatments for vitiligo and supports site-specific treatment strategies. Overall, 0.05% clobetasol plus 5% fluorouracil demonstrated the highest effectiveness for repigmentation, whereas 0.05% clobetasol was the most effective monotherapy, except in facial lesion treatment, for which 0.01% bimatoprost was superior.
Background:Although correlative evidence from observational research points toward an involvement of inflammatory molecules in hypertrophic scar formation, the concrete causal roles and mechanisms linking these elements have not yet been definitively proven.Objectives:This study aimed to explore the potential causal relationship between genetically predicted inflammatory factors and hypertrophic scars using a two-sample Mendelian randomization (MR) approach.Methods:We employed a two-sample MR design using summary statistics from genome-wide association studies for inflammatory factors and hypertrophic scars. The primary MR analysis method was inverse variance weighted (IVW). Additional methods included weighted median, weighted mode, and MR-Egger regression analyses. Robust causal estimates were assessed through sensitivity analyses, incorporating MR-Egger intercept tests, MR-PRESSO, Cochran's Q test, and leave-one-out procedures.Results:IVW analysis revealed significant evidence for a causal association between CCL27 (odds ratio [OR] =1.256, 95% confidence interval [CI]: 1.020-1.545), macrophage inflammatory protein-1 beta (MIP-1 beta) (OR = 0.849, 95% CI: 0.732-0.984), and interleukin-2 (IL-2) (OR = 1.422, 95% CI: 1.012-1.998) with hypertrophic scarring. However, these associations did not remain significant after false discovery rate correction and were not consistently supported by other MR methods (P > 0.05). Furthermore, the weighted median method suggested a potentially protective effect for CXCL9 and interferon-gamma against hypertrophic scars.Conclusion:This study contributes preliminary causal insights into the role of inflammation in hypertrophic scar formation by hinting at possible associations for CCL27, MIP-1 beta, and IL-2, but these signals were attenuated upon further testing and should therefore be interpreted with caution. The results warrant further mechanistic investigation to better understand scar pathogenesis and potentially inform targeted interventions.
Previous studies have shown that porokeratosis (PK) arises from mutations in the enzyme-encoding genes - mevalonate kinase, phosphomevalonate kinase, mevalonate diphosphate decarboxylase (MVD), farnesyl diphosphate synthase, and farnesyl-diphosphate farnesyltransferase 1. This study reports a case of early-onset, generalized linear PK associated with cutaneous squamous cell carcinomas (cSCCs), focusing on the genetic context and molecular mechanisms underlying carcinogenesis. Paired skin specimens were collected from the proband and his father, along with blood samples from all four family members. Germline and somatic mutations were identified through whole-exome sequencing. To investigate the expression of the causative gene, we employed several approaches, including allelic expression imbalance assays, ribonucleic acid-seq, reverse transcription quantitative polymerase chain reaction, and immunohistochemistry. A germline NM_002461.1 (MVD): C.746T>C (p.Phe249Ser) mutation was identified in three family members. In the proband, a novel second-hit postzygotic mutation, NM_002461.1 (MVD): C.252_253dup (p.Glu85Glyfs*32), was detected in PK lesions. The proband's cSCC exhibited both MVD: C.252_253dup (p.Glu85Glyfs*32) and a novel NM_000546.5 (TP53): C.966_967del (p.Leu323Glyfs*13) somatic mutations, accompanied by significantly reduced MVD expression levels. Immunohistochemical analysis revealed a progressive decrease in MVD staining from adjacent normal-appearing skin to cSCC tissue. Transcriptomic analyses further revealed a downregulation of mevalonate pathway genes in cSCCs compared to matched controls. These findings highlight prenatal somatic mosaicism, leading to MVD deficiency in the epidermis, which may contribute to the development and carcinogenesis of linear PK.
Background: Patients with systemic lupus erythematosus (SLE) are at increased risk of developing additional autoimmune disorders. The coexistence of SLE and psoriasis (PSO) is rare but may pose diagnostic and therapeutic challenges. Objectives: This study aimed to compare patients with coexisting SLE and PSO with those having SLE alone in a Taiwanese cohort. Methods: We conducted a retrospective, single-center study from 2007 to 2023, identifying patients diagnosed with both SLE and PSO. Clinical features, laboratory profiles, treatment patterns, and comorbidities were analyzed. Results: A total of 12 patients with coexisting SLE and PSO were identified, yielding a prevalence of 1.5% among patients with SLE. Plaque PSO was the predominant subtype, and the disease was mild in most cases. Compared to the SLE-only group, the coexistence group had a higher proportion of males. No significant differences were observed in typical lupus manifestations or most laboratory parameters, except for a lower frequency of reduced complement levels in the coexistence group. No additional cardiovascular risk was identified. Conclusion: This single-center study highlights the clinical, laboratory, and treatment characteristics of patients with coexisting SLE and PSO in Taiwan and provides insight into this rare overlap condition.
Background:Sensitive skin is a complex syndrome lacking effective assessment and diagnostic methods.Objectives:This study compared the sensitive scale-10 (SS-10) and the lactic acid sting test (LAST) in a preselected cohort of women with self-reported sensitivity, LAST >= 3, and visible erythema.Methods:Eighty-eight eligible Chinese females completed the SS-10 questionnaire and LAST, along with objective measurements including transepidermal water loss (TEWL), erythema index (EI), facial red area, and a* value. The correlation among scales, skin biological indices, and the LAST score was analyzed. The participants were classified into sensitive and slightly sensitive skin groups based on the SS-10 scores for comparison.Results:Eighty-seven participants were included in the overall statistical analysis, with the sensitive and slightly sensitive skin groups accounting for 77.9% (one participant was excluded) and 22.1%, respectively. The EI and a* value were significantly higher, and the facial red area and TEWL were higher in the sensitive skin group than in the slightly sensitive group. The scores for the SS-10 items, except pain and general discomfort, were significantly higher in the sensitive skin group than in the slightly sensitive skin group. The LAST showed a significant but weakly positive correlation with SS-10 scores, pain, stinging, and itching scores. The facial red area showed a significant but weakly positive correlation with the SS-10 score, but not with the LAST score. TEWL showed the opposite.Conclusion:In this preselected cohort, SS-10 correlated more with erythema-related measures, whereas LAST associated more with barrier function, indicating distinct assessment dimensions.
Background: Three immune-mediated skin diseases, alopecia areata, atopic dermatitis, and psoriasis, impose a substantial burden among nonfatal conditions and are associated with marked cross-regional health disparities. Objectives: This study utilized epidemiological data on three immune-mediated skin diseases from 1990 to 2021 with the objective of investigating disease patterns and trends at global, regional, and population levels. Methods: This study conducted a secondary analysis of epidemiological data on three immune-mediated skin diseases, including alopecia areata, psoriasis, and atopic dermatitis, obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database for the years 1990-2021. This study investigates average annual percentage changes in age-standardized incidence rates, age-standardized prevalence rates (ASPRs), and disability-adjusted life years across 204 countries and regions, stratified by the five quintiles of the sociodemographic index (SDI), gender, and 20-year age groups, while also calculating the slope index of inequality and the Concentration Index to quantify the epidemiological trends and health inequities associated with these diseases. Results: In 2021, ASPRs for three immune-mediated skin diseases were 215.011 (95% uncertainty intervals (UI): 208.320-221.475), 1,728.507 (95% UI: 1658.507-1798.596), and 515.951 (95% UI: 500.199-531.618) per 100,000 for alopecia areata, atopic dermatitis, and psoriasis, respectively, with only psoriasis incidence rising. All three diseases exhibited a positive correlation with the SDI and significant health inequities; however, the concentration index demonstrated a downward trend. The burden of these diseases was characterized by demographic patterns, with alopecia areata predominantly affecting young and middle-aged women, atopic dermatitis primarily impacting children, and psoriasis being more prevalent among the elderly. Conclusion: This study highlights significant health inequities in three immune-mediated skin diseases linked to the SDI, regional development, and racial disparities. It urges researchers and global health organizations to investigate these issues to enhance understanding and inform equitable public health policies for better patient outcomes.
Posttranslational modifications, particularly histone acetylation and deacetylation, regulated by histone acetyltransferases and histone deacetylases (HDACs), play a fundamental role in the epigenetic regulation of gene expression by modulating chromatin structure and accessibility. HDACs are involved in diverse cellular processes, including cell cycle regulation, differentiation, apoptosis, immune responses, and metabolism. Dysregulation of HDAC activity has been implicated in the pathogenesis of various diseases, notably several dermatological conditions. Emerging evidence from preclinical and clinical studies highlights the role of HDACs in diseases such as psoriasis, scleroderma, atopic dermatitis, vitiligo, and cutaneous malignancies. In these disorders, HDACs influence critical pathological mechanisms, including keratinocyte proliferation, fibroblast activation, inflammatory signaling, autoimmune responses, and apoptosis of malignant cells. HDAC inhibitors (HDACis) represent a novel class of epigenetic therapeutics that have demonstrated potential in modulating these disease processes. This review aims to comprehensively assess the biological functions of HDACs in dermatological diseases and evaluate the therapeutic prospects of HDACis. Understanding the epigenetic mechanisms mediated by HDACs could pave the way for innovative treatment strategies in dermatology.
Hair follicle epithelial stem cells (HFeSCs) in the bulge region are emerging targets for therapeutic intervention or candidate for hair regeneration due to their self-renewal capacity and ability to drive the hair cycle. However, most of the current understanding of HFeSCs is based on mouse models, which may not fully reflect human biology. Therefore, understanding the characteristics and regulatory mechanisms of human HFeSCs is essential for advancing clinical applications. This review summarizes recent advances in identifying human HFeSC markers and the molecular mechanisms that control their activity, including signaling pathways and endocrine hormones. We also explore current knowledge on how HFeSCs are altered in non-scarring alopecia, scarring alopecia, and age-related hair loss. In addition, the therapeutic potential of human HFeSCs in the treatment of hair disorders, as well as the current challenges in achieving de novo hair regeneration and precise in situ modulation of HFeSCs, is discussed. Future single-cell multi-omic studies could help elucidate the biology of HFeSCs in humans, potentially guiding new therapeutic strategies for alopecia.
Alopecia areata (AA) is a complex autoimmune disorder causing non-scarring hair loss, from localized patches to total scalp or body hair loss. It significantly impacts quality of life, with an unpredictable course that challenges effective management. Traditional treatments like such as corticosteroids, systemic immunosuppressives, and contact immunotherapy are commonly used but are often associated with high relapse rates and inconsistent efficacy. Real-world evidence emphasizes individualized strategies, particularly for severe cases and pediatric populations. Off-label medications such as methotrexate and sulfasalazine, though potentially beneficial, are limited to second-line use due to insufficient high-quality evidence for optimal dosing and intervals. Novel therapies such as Janus kinase inhibitors have emerged, targeting immune pathways with promising results in severe AA. However, these require long-term use to maintain efficacy and prevent relapse. Innovations such as fractional laser-assisted drug delivery and microneedling have shown encouraging outcomes in preliminary studies, though statistically significant results remain limited. Combination therapies, such as systemic corticosteroids with immunomodulators or topical agents, show promise in refractory cases. While advancements have expanded AA treatment options, further research is essential to validate their long-term safety, efficacy, and standardize protocols. A personalized approach that integrates traditional and emerging therapies may achieve more durable outcomes and enhance patient quality of life. This review highlights current and novel strategies, focusing on efficacy, safety, and real-world applicability.
