Basal cell carcinoma is a common locally invasive and destructive skin cancer, if inadequately treated. Although topical noninvasive treatment has been reported, surgical excision is currently the gold standard. Surgical excision is performed with a predetermined surgical margin. There is worldwide debate on the optimal margin. Some guidelines recommend surgical margins > 4 mm; however, Asians reports suggest a narrow surgical margin may be suitable. We previously reported that a 2-mm margin is acceptable for specific tumors. We aimed to clarify whether a 2-mm margin is suitable for all lesions and the differences in local recurrence between surgical procedures (one-step or two-step surgery). We retrospectively reviewed the data of 112 patients who underwent surgical excision with predetermined 2-mm or > 2-mm margins. Pathological reports and surgical procedure databases were collected and statistically analyzed to clarify topical factors for microscopic margin clearance. We compared differences between macroscopic peripheral margins and the distance of microscopic margins and analyzed associations between surgical procedure and local recurrence. Aggressive type was significantly associated with poorly-defined borders (p < 0.01), and microscopic excisional margin positivity was correlated with tumor thickness (p < 0.01). The correlation coefficient between tumor size and tumor thickness was 0.321 and the p-value was 0.0005, indicating a weak correlation between a larger tumor size and a greater tumor thickness. The macroscopic surgical margin was significantly associated with the microscopic peripheral margin (p < 0.001). Tumor size was significantly associated with tumor thickness, and aggressive type tumors were significantly poorly defined. Additionally, tumor size, tumor thickness, and tumor subtype aggressiveness were the strongest risk factors for microscopic margin positivity. For adequate treatment, poorly defined tumors, wider tumors, and aggressive tumor types were carefully treated, and confirmation after excision with a 2-mm margin by two-step surgery or accompanied with frozen section estimation. For well-pigmented and well-defined basal cell carcinomas, a 2-mm margin may be more suitable than for the two types requiring careful treatment.
{"title":"Risk Factors for Microscopic Margin Positivity in Basal Cell Carcinoma Excision With a 2-mm Surgical Margin: A Japanese Retrospective Study.","authors":"Kaori Kyono, Eiki Tsushima, Satoshi Urushidate, Shintaro Goto, Yui Akemoto, Toshiaki Suzuki, Tadashi Yoshizawa, Yoshihiro Sowa, Kotaro Yoshimura, Akira Kurose","doi":"10.1111/1346-8138.70118","DOIUrl":"10.1111/1346-8138.70118","url":null,"abstract":"<p><p>Basal cell carcinoma is a common locally invasive and destructive skin cancer, if inadequately treated. Although topical noninvasive treatment has been reported, surgical excision is currently the gold standard. Surgical excision is performed with a predetermined surgical margin. There is worldwide debate on the optimal margin. Some guidelines recommend surgical margins > 4 mm; however, Asians reports suggest a narrow surgical margin may be suitable. We previously reported that a 2-mm margin is acceptable for specific tumors. We aimed to clarify whether a 2-mm margin is suitable for all lesions and the differences in local recurrence between surgical procedures (one-step or two-step surgery). We retrospectively reviewed the data of 112 patients who underwent surgical excision with predetermined 2-mm or > 2-mm margins. Pathological reports and surgical procedure databases were collected and statistically analyzed to clarify topical factors for microscopic margin clearance. We compared differences between macroscopic peripheral margins and the distance of microscopic margins and analyzed associations between surgical procedure and local recurrence. Aggressive type was significantly associated with poorly-defined borders (p < 0.01), and microscopic excisional margin positivity was correlated with tumor thickness (p < 0.01). The correlation coefficient between tumor size and tumor thickness was 0.321 and the p-value was 0.0005, indicating a weak correlation between a larger tumor size and a greater tumor thickness. The macroscopic surgical margin was significantly associated with the microscopic peripheral margin (p < 0.001). Tumor size was significantly associated with tumor thickness, and aggressive type tumors were significantly poorly defined. Additionally, tumor size, tumor thickness, and tumor subtype aggressiveness were the strongest risk factors for microscopic margin positivity. For adequate treatment, poorly defined tumors, wider tumors, and aggressive tumor types were carefully treated, and confirmation after excision with a 2-mm margin by two-step surgery or accompanied with frozen section estimation. For well-pigmented and well-defined basal cell carcinomas, a 2-mm margin may be more suitable than for the two types requiring careful treatment.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Red blood cell distribution width-to-platelet ratio (RPR), red blood cell distribution width-to-hemoglobin ratio (RHR), red blood cell distribution width-to-albumin ratio (RAR), and prognostic nutritional index (PNI) have been implicated in disease severity and prognosis. However, their role in predicting severity and mortality in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) remains unclear. This study aimed to investigate the association between RPR, RHR, RAR, PNI and both disease severity and mortality in SJS/TEN patients. In this retrospective study, clinical data from 111 SJS/TEN patients were analyzed. RPR and other laboratory parameters were compared between survivors and non-survivors. The associations of RHR, PNI, RAR, and RPR with SJS/TEN severity were evaluated using Spearman or Pearson correlation analyses. Patients were categorized into survivor and non-survivor groups. Univariate and multivariate logistic regression analyses were employed to examine the correlations between these markers and mortality. The predictive performance of these indicators for SJS/TEN mortality was assessed using receiver operating characteristic (ROC) curve analysis. Correlation analysis revealed that RAR and RHR were positively correlated with SCORTEN, Re-SCORTRN, ABCD-10 and CRISTEN scores (p < 0.05), whereas PNI was negatively correlated (p < 0.05). Correlation analysis revealed that RPR was positively correlated with Re-SCORTRN, ABCD-10 and CRISTEN scores (p < 0.05). RAR, RPR, and RHR were identified as risk factors for mortality in SJS/TEN, while elevated PNI was a protective factor. The optimal cutoff values for RHR and RPR in predicting mortality were 0.13 (sensitivity 75%; specificity 73.6%) and 0.07 (sensitivity 90%; specificity 48.4%), respectively. These findings highlight the potential clinical utility of RHR (AUC = 0.841) and RAR (AUC = 0.729) as meaningful biomarkers for assessing SJS/TEN severity and associated mortality.
{"title":"The Predictive Value of Inflammatory Markers in the Severity and Mortality Risk of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.","authors":"Xinjian Fan, Rui Liu, Xianwei Cao, Zhibin Zhang","doi":"10.1111/1346-8138.70116","DOIUrl":"https://doi.org/10.1111/1346-8138.70116","url":null,"abstract":"<p><p>Red blood cell distribution width-to-platelet ratio (RPR), red blood cell distribution width-to-hemoglobin ratio (RHR), red blood cell distribution width-to-albumin ratio (RAR), and prognostic nutritional index (PNI) have been implicated in disease severity and prognosis. However, their role in predicting severity and mortality in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) remains unclear. This study aimed to investigate the association between RPR, RHR, RAR, PNI and both disease severity and mortality in SJS/TEN patients. In this retrospective study, clinical data from 111 SJS/TEN patients were analyzed. RPR and other laboratory parameters were compared between survivors and non-survivors. The associations of RHR, PNI, RAR, and RPR with SJS/TEN severity were evaluated using Spearman or Pearson correlation analyses. Patients were categorized into survivor and non-survivor groups. Univariate and multivariate logistic regression analyses were employed to examine the correlations between these markers and mortality. The predictive performance of these indicators for SJS/TEN mortality was assessed using receiver operating characteristic (ROC) curve analysis. Correlation analysis revealed that RAR and RHR were positively correlated with SCORTEN, Re-SCORTRN, ABCD-10 and CRISTEN scores (p < 0.05), whereas PNI was negatively correlated (p < 0.05). Correlation analysis revealed that RPR was positively correlated with Re-SCORTRN, ABCD-10 and CRISTEN scores (p < 0.05). RAR, RPR, and RHR were identified as risk factors for mortality in SJS/TEN, while elevated PNI was a protective factor. The optimal cutoff values for RHR and RPR in predicting mortality were 0.13 (sensitivity 75%; specificity 73.6%) and 0.07 (sensitivity 90%; specificity 48.4%), respectively. These findings highlight the potential clinical utility of RHR (AUC = 0.841) and RAR (AUC = 0.729) as meaningful biomarkers for assessing SJS/TEN severity and associated mortality.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bruno de Castro E Souza, Denis Miyashiro, Jade Cury-Martins, Neusa Yuriko Sakai Valente, Luiz Fernando Ferraz da Silva, José Antonio Sanches
Transformed mycosis fungoides (TMF) is a rare, aggressive variant of cutaneous T-cell lymphoma characterized by the presence of large neoplastic cells and poor clinical outcomes. A retrospective cohort of 22 TMF patients was analyzed using immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) tissue for GATA3 (n = 20), T-bet (n = 22), and STAT3 (n = 22). Expression was quantified by image analysis integrated optical density per total area (IOD/area), standardized by z-score and correlated with survival. Seventeen patients with complete data underwent unsupervised clustering (k-means) and principal component analysis (PCA) based on marker expression profiles. High GATA3 expression was strongly associated with worse prognosis (median OS: 8.6 months vs. 41.7 months, p = 0.00094). T-bet and STAT3 expressions showed no significant individual association with survival. Clustering analysis revealed three distinct immunoprofiles: (1) low expression of all markers (intermediate survival, 28.1 months), (2) high STAT3 and T-bet expressions with intermediate GATA3 expression (longest survival, 53.1 months), and (3) high GATA3 expression with low STAT3 and T-bet expressions (poorest survival, 9.5 months). GATA3 is a robust prognostic marker in TMF, identifying patients with particularly poor outcomes. Its elevated expression delineates a Th2-skewed, immunosuppressive phenotype that may inhibit Th1/Th17 pathways via transcriptional repression. Integrative profiling reveals immunobiological subgroups with divergent prognoses, supporting GATA3 as a potential tool for risk stratification and a candidate for targeted intervention in TMF.
{"title":"Immunoprofiling Reveals GATA3 as a Prognostic Marker in Transformed Mycosis Fungoides.","authors":"Bruno de Castro E Souza, Denis Miyashiro, Jade Cury-Martins, Neusa Yuriko Sakai Valente, Luiz Fernando Ferraz da Silva, José Antonio Sanches","doi":"10.1111/1346-8138.70070","DOIUrl":"https://doi.org/10.1111/1346-8138.70070","url":null,"abstract":"<p><p>Transformed mycosis fungoides (TMF) is a rare, aggressive variant of cutaneous T-cell lymphoma characterized by the presence of large neoplastic cells and poor clinical outcomes. A retrospective cohort of 22 TMF patients was analyzed using immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) tissue for GATA3 (n = 20), T-bet (n = 22), and STAT3 (n = 22). Expression was quantified by image analysis integrated optical density per total area (IOD/area), standardized by z-score and correlated with survival. Seventeen patients with complete data underwent unsupervised clustering (k-means) and principal component analysis (PCA) based on marker expression profiles. High GATA3 expression was strongly associated with worse prognosis (median OS: 8.6 months vs. 41.7 months, p = 0.00094). T-bet and STAT3 expressions showed no significant individual association with survival. Clustering analysis revealed three distinct immunoprofiles: (1) low expression of all markers (intermediate survival, 28.1 months), (2) high STAT3 and T-bet expressions with intermediate GATA3 expression (longest survival, 53.1 months), and (3) high GATA3 expression with low STAT3 and T-bet expressions (poorest survival, 9.5 months). GATA3 is a robust prognostic marker in TMF, identifying patients with particularly poor outcomes. Its elevated expression delineates a Th2-skewed, immunosuppressive phenotype that may inhibit Th1/Th17 pathways via transcriptional repression. Integrative profiling reveals immunobiological subgroups with divergent prognoses, supporting GATA3 as a potential tool for risk stratification and a candidate for targeted intervention in TMF.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atopic dermatitis (AD) involves chronic eczema resulting from barrier dysfunction. Fine bubble (FB) technology generates microbubbles (< 100 μm) and ultrafine bubbles (< 1 μm) for surfactant-sparing cleansing. We assessed the short-term safety of an FB shower in AD. In this double-blind, randomized, crossover study, adults with mild AD completed two 2-week periods separated by a 2-week washout in sequence. Bathing instructions and petrolatum moisturizer use were standardized and enforced. The Eczema Area and Severity Index (EASI) was scored using whole-body photographs by a blinded team. Transepidermal water loss (TEWL) and stratum corneum hydration were measured on Days 0, 14, and 28. Because baselines were unavailable for the second 2-week period, the primary analysis compared Day 0-14 changes between groups using baseline-adjusted analysis of covariance; Day 0-28 changes were also explored. The primary outcomes were EASI changes; TEWL and hydration were the secondary outcomes. Groups used a conventional shower (control) first and then FB shower second or vice versa (once each). Twenty-three participants were analyzed (mean age 40.9 ± 8 years; 83% male). Day 0-14 EASI changes did not differ between FB and control (0.62 ± 2.21 vs. 0.05 ± 0.68; F = 0.93, p = 0.35). EASI changes to Day 28 were nonsignificant (0.02 ± 1.65 vs. -0.03 ± 1.02; p = 0.90). TEWL changes for Days 0-14 (0.31 ± 4.75 vs. 1.09 ± 6.21 g/m2/h) and to Day 28 (5.49 ± 14.43 vs. -0.27 ± 5.28 g/m2/h) showed no between-group differences. Hydration changes were similar for Days 0-14 (5.53 ± 13.23 vs. 6.14 ± 7.96 AU) and to Day 28 (18.41 ± 10.33 vs. 21.09 ± 11.07 AU). No serious adverse events or discontinuations for worsening symptoms occurred. Under standardized, low-irritant conditions, the FB shower was well-tolerated by adults with mild AD and did not worsen severity or barrier indices over 4 weeks. However, the superiority of FB to a conventional shower was not demonstrated.
特应性皮炎(AD)涉及由屏障功能障碍引起的慢性湿疹。细泡(FB)技术产生微泡(2个/h),至第28天(5.49±14.43 vs -0.27±5.28 g/m2/h)组间无差异。第0-14天(5.53±13.23 AU对6.14±7.96 AU)和第28天(18.41±10.33 AU对21.09±11.07 AU)的水合变化相似。未发生严重不良事件或因症状恶化而停药。在标准化、低刺激性条件下,轻度AD患者对FB淋浴具有良好的耐受性,并且在4周内没有恶化严重程度或屏障指数。然而,并没有证明FB相对于传统淋浴器的优越性。
{"title":"Safety Evaluation of Fine Bubble Shower Washing for Patients With Atopic Dermatitis: A Double-Blind, Randomized, Prospective Crossover Clinical Trial.","authors":"Hiroshi Kato, Risa Tamagawa-Mineoka, Eiji Nakatani, Kenichi Yoshimura, Yukiko Yasui, Kasumi Kato, Motoki Nakamura, Ako Kurachi, Soshi Takeda, Akimichi Morita","doi":"10.1111/1346-8138.70117","DOIUrl":"https://doi.org/10.1111/1346-8138.70117","url":null,"abstract":"<p><p>Atopic dermatitis (AD) involves chronic eczema resulting from barrier dysfunction. Fine bubble (FB) technology generates microbubbles (< 100 μm) and ultrafine bubbles (< 1 μm) for surfactant-sparing cleansing. We assessed the short-term safety of an FB shower in AD. In this double-blind, randomized, crossover study, adults with mild AD completed two 2-week periods separated by a 2-week washout in sequence. Bathing instructions and petrolatum moisturizer use were standardized and enforced. The Eczema Area and Severity Index (EASI) was scored using whole-body photographs by a blinded team. Transepidermal water loss (TEWL) and stratum corneum hydration were measured on Days 0, 14, and 28. Because baselines were unavailable for the second 2-week period, the primary analysis compared Day 0-14 changes between groups using baseline-adjusted analysis of covariance; Day 0-28 changes were also explored. The primary outcomes were EASI changes; TEWL and hydration were the secondary outcomes. Groups used a conventional shower (control) first and then FB shower second or vice versa (once each). Twenty-three participants were analyzed (mean age 40.9 ± 8 years; 83% male). Day 0-14 EASI changes did not differ between FB and control (0.62 ± 2.21 vs. 0.05 ± 0.68; F = 0.93, p = 0.35). EASI changes to Day 28 were nonsignificant (0.02 ± 1.65 vs. -0.03 ± 1.02; p = 0.90). TEWL changes for Days 0-14 (0.31 ± 4.75 vs. 1.09 ± 6.21 g/m<sup>2</sup>/h) and to Day 28 (5.49 ± 14.43 vs. -0.27 ± 5.28 g/m<sup>2</sup>/h) showed no between-group differences. Hydration changes were similar for Days 0-14 (5.53 ± 13.23 vs. 6.14 ± 7.96 AU) and to Day 28 (18.41 ± 10.33 vs. 21.09 ± 11.07 AU). No serious adverse events or discontinuations for worsening symptoms occurred. Under standardized, low-irritant conditions, the FB shower was well-tolerated by adults with mild AD and did not worsen severity or barrier indices over 4 weeks. However, the superiority of FB to a conventional shower was not demonstrated.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luca Bettolini, Carlo Alberto Maronese, Stefano Bighetti, Giovanni Genovese, Luisa Sarno, Stefano Buffon, Francesca Laura Boggio, Federica Derlino, Angelo Valerio Marzano
Amicrobial pustulosis of the folds (APF) is a rare, chronic-relapsing neutrophilic dermatosis characterized by sterile pustules affecting major and minor skin folds. It predominantly affects women and is frequently associated with autoimmune diseases such as systemic lupus erythematosus, inflammatory bowel disease, and autoimmune thyroiditis. Due to its rarity, standardized treatment guidelines are lacking, and management remains challenging. Systemic corticosteroids, dapsone, colchicine, methotrexate, and biologics have been employed with variable outcomes, but long-term control is often difficult to achieve. Apremilast, an oral phosphodiesterase-4 inhibitor with anti-inflammatory properties, has demonstrated efficacy in various neutrophilic dermatoses. We report two women with treatment-refractory APF who achieved clinical remission within 2 months of initiating apremilast, with sustained disease control at 6 months and successful corticosteroid tapering. A literature review of 78 APF cases confirmed a strong female predominance (93.6%) and frequent association with autoimmune conditions (91%). Systemic corticosteroids were the most frequently employed treatment but often failed to provide sustained disease control without the addition of other systemic agents. These cases represent the first reports of apremilast use in APF and suggest its potential as a safe and effective steroid-sparing option in patients with refractory disease. Further studies are needed to validate its role in this setting.
{"title":"Amicrobial Pustulosis of the Folds Successfully Treated With Apremilast: Report of Two Cases and Review of the Literature.","authors":"Luca Bettolini, Carlo Alberto Maronese, Stefano Bighetti, Giovanni Genovese, Luisa Sarno, Stefano Buffon, Francesca Laura Boggio, Federica Derlino, Angelo Valerio Marzano","doi":"10.1111/1346-8138.70113","DOIUrl":"https://doi.org/10.1111/1346-8138.70113","url":null,"abstract":"<p><p>Amicrobial pustulosis of the folds (APF) is a rare, chronic-relapsing neutrophilic dermatosis characterized by sterile pustules affecting major and minor skin folds. It predominantly affects women and is frequently associated with autoimmune diseases such as systemic lupus erythematosus, inflammatory bowel disease, and autoimmune thyroiditis. Due to its rarity, standardized treatment guidelines are lacking, and management remains challenging. Systemic corticosteroids, dapsone, colchicine, methotrexate, and biologics have been employed with variable outcomes, but long-term control is often difficult to achieve. Apremilast, an oral phosphodiesterase-4 inhibitor with anti-inflammatory properties, has demonstrated efficacy in various neutrophilic dermatoses. We report two women with treatment-refractory APF who achieved clinical remission within 2 months of initiating apremilast, with sustained disease control at 6 months and successful corticosteroid tapering. A literature review of 78 APF cases confirmed a strong female predominance (93.6%) and frequent association with autoimmune conditions (91%). Systemic corticosteroids were the most frequently employed treatment but often failed to provide sustained disease control without the addition of other systemic agents. These cases represent the first reports of apremilast use in APF and suggest its potential as a safe and effective steroid-sparing option in patients with refractory disease. Further studies are needed to validate its role in this setting.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The stratum corneum, as the outermost layer of the skin, functions as a critical barrier that maintains cutaneous hydration and systemic homeostasis. Among its structural lipids, ceramides constitute the most abundant and diverse component. These molecules are essential for the formation of lamellar structures that secure barrier integrity. Increasing evidence has established that abnormalities in stratum corneum ceramides are not merely epiphenomena but fundamental contributors to the pathophysiology of atopic dermatitis (AD). In this review, we provide an overview of the structure, biosynthesis, and diversity of ceramides within the stratum corneum, followed by a discussion of their pivotal role in skin barrier function. We highlight recent insights into how ceramide abnormalities manifest in AD, including reduced total content, altered class distribution, and a shift toward shorter-chain fatty acids. Such alterations are associated with increased transepidermal water loss and impaired hydration. Mechanistic studies further reveal that type 2 cytokines, particularly IL-4 and IL-13, directly disrupt lipid metabolism by inhibiting enzymes, thereby establishing a vicious cycle of inflammation and barrier dysfunction. Beyond pathophysiology, advances in lipidomics and tape-stripping techniques now enable noninvasive assessment of stratum corneum ceramides. These analyses have revealed their utility as biomarkers of disease activity, therapeutic response, and relapse risk. Collectively, ceramides of the stratum corneum provide a unique window into the biology of AD. Their accessibility, mechanistic relevance, and prognostic potential underscore their importance not only for understanding disease pathogenesis but also for advancing personalized management and the concept of disease modification in AD.
{"title":"Stratum Corneum Ceramide Abnormalities in Atopic Dermatitis: Pathophysiology and Implications for Disease Management.","authors":"Takashi Sakai","doi":"10.1111/1346-8138.70098","DOIUrl":"https://doi.org/10.1111/1346-8138.70098","url":null,"abstract":"<p><p>The stratum corneum, as the outermost layer of the skin, functions as a critical barrier that maintains cutaneous hydration and systemic homeostasis. Among its structural lipids, ceramides constitute the most abundant and diverse component. These molecules are essential for the formation of lamellar structures that secure barrier integrity. Increasing evidence has established that abnormalities in stratum corneum ceramides are not merely epiphenomena but fundamental contributors to the pathophysiology of atopic dermatitis (AD). In this review, we provide an overview of the structure, biosynthesis, and diversity of ceramides within the stratum corneum, followed by a discussion of their pivotal role in skin barrier function. We highlight recent insights into how ceramide abnormalities manifest in AD, including reduced total content, altered class distribution, and a shift toward shorter-chain fatty acids. Such alterations are associated with increased transepidermal water loss and impaired hydration. Mechanistic studies further reveal that type 2 cytokines, particularly IL-4 and IL-13, directly disrupt lipid metabolism by inhibiting enzymes, thereby establishing a vicious cycle of inflammation and barrier dysfunction. Beyond pathophysiology, advances in lipidomics and tape-stripping techniques now enable noninvasive assessment of stratum corneum ceramides. These analyses have revealed their utility as biomarkers of disease activity, therapeutic response, and relapse risk. Collectively, ceramides of the stratum corneum provide a unique window into the biology of AD. Their accessibility, mechanistic relevance, and prognostic potential underscore their importance not only for understanding disease pathogenesis but also for advancing personalized management and the concept of disease modification in AD.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Case of Anti-SRP Antibody-Positive Necrotizing Myopathy That Initially Presented With Raynaud's Phenomenon and a Digital Ulcer.","authors":"Tomomichi Shimizu, Fumikazu Yamazaki, Akio Kondoh, Eimi Kato, Atsushi Mizuma, Eiichiro Nagata, Tomotaka Mabuchi","doi":"10.1111/1346-8138.70114","DOIUrl":"https://doi.org/10.1111/1346-8138.70114","url":null,"abstract":"","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}