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Objective: This study aims to fill the knowledge gap regarding the effects of high frequency facial neuromuscular electrical stimulation (fNMES) on facial aging, using a device equipped with CERTEC (Cell Energy Regeneration Technology) operating between 40 and 190 kHz. Methods: This prospective split‐face study was conducted at Tokyo University Hospital between March and May 2023 with 24 healthy adult women aged 30–59. The intervention group used the fNMES device along with basic skin care on one side of the face, and basic skin care alone on the other side for 8 weeks. Evaluations included changes in skin wrinkles, sagging, and blood flow. Results: This study found significant improvements in skin elasticity and degree of wrinkles in the areas intervened with fNMES (p < 0.05, respectively). In addition, the intervention resulted in significant improvements in jawline angle (p < 0.01), submental volume (p < 0.05), cheek volume (p < 0.05), maximum nasolabial fold depth (p = 0.03), and total volume of the nasolabial folds (p = 0.03). The fNMES intervention also showed improvement in blood flow (p < 0.05). These improvements were also subjectively assessed by the participants in subject questionnaires at 8 weeks after the intervention (p < 0.05). Conclusion: This study suggests that high frequency fNMES effectively improves facial skin elasticity, reduces wrinkles and sagging, promotes blood flow, and contributes to overall facial appearance rejuvenation. Although further studies are needed, high frequency fNMES appeared promising as a noninvasive anti‐aging therapy. [ABSTRACT FROM AUTHOR]

As the clinical course of systemic sclerosis (SSc) varies widely, prognostic indicators have been sought to predict the outcomes of individual patients. Racial differences in SSc render it necessary to validate prognostic indicators in different patient cohorts. In this study, we aimed to assess clinical and laboratory parameters in Japanese patients with early‐stage SSc with diffuse cutaneous involvement and/or interstitial lung disease, and identify predictive factors for disease progression. We performed multivariate analyses of baseline clinical information to estimate symptoms 4 years later in Japanese patients with diffuse cutaneous SSc and/or SSc with interstitial lung disease. Patients were enrolled in the study within 5 years of disease onset at 10 Japanese SSc centers. Over 12 years, 115 patients followed up for 4 years were included in this study. The modified Rodnan skin score (mRSS) at 4 years correlated with the baseline mRSS and finger‐to‐palm distance, defined as the average length from the distal tip of the fourth finger to the distal palmar crease. The percentage predicted vital capacity (%VC) in year 4 positively and negatively correlated with initial %VC and the presence of anti‐topoisomerase I antibodies, respectively. The Health Assessment Questionnaire Disability Index (HAQ‐DI) at 4 years was positively and negatively associated with baseline HAQ‐DI and %VC, respectively. The occurrence of digital ulcers within 4 years was associated with the initial presence of digital ulcers, finger‐to‐palm distance, and the presence of digital pitting scars and anti‐topoisomerase I antibodies. This study identified several factors that may predict the progression of early‐stage SSc in Japanese patients. Finger‐to‐palm distance may be a useful tool for predicting the progression of skin thickening and the development of digital ulcers in the early stages of severe SSc, but larger, long‐term prospective studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) and cryopyrin‐associated periodic syndrome (CAPS) are distinct clinical entities belonging to the autoimmune and autoinflammatory diseases, respectively. The coexistence of the two entities has rarely been reported and is poorly characterized. Here, we described a case of a 38‐year‐old Japanese woman diagnosed with anti‐centromere antibody‐positive SSc and CAPS carrying the pathogenic mutation in the NLRP3 gene, with a detailed autoantibody profile by a high‐throughput comprehensive protein array covering approximately 90% of the human transcriptome. The clinical manifestations of the patient were typical of both SSc and CAPS. Comprehensive autoantibody profiling identified 65 autoantibodies in the patient's serum and 78 autoantibodies in the serum of her daughter with CAPS, who carried the same NLRP3 mutation as the patient. SSc‐associated autoantibodies (anti‐DBT, anti‐ CENP‐B, and anti‐CENP‐A) and anti‐CD320 antibody were detected at high levels only in the patient's serum, while autoantibodies to the following four proteins were detected in the sera of both the patient and her daughter: TRIM21, LIMS1, CLIP4, and KAT2A. The TRRUST enrichment analysis identified NF‐κB1 and RelA as overlapping key transcription factors that regulate the genes encoding proteins to which autoantibodies were detected in the patient and her daughter, therefore the autoantibody profile of the patient cannot be solely attributed to SSc, but may also be influenced by CAPS. Although autoimmune and autoinflammatory diseases are considered to be at opposite ends of the immunological spectrum, detailed autoantibody profiling may reveal a unique immunological landscape in an overlapping case of the two entities. [ABSTRACT FROM AUTHOR]

In recent years, rapid advances in research methods have made single cell analysis possible. Systemic sclerosis (SSc), a disease characterized by the triad of immune abnormalities, fibrosis, and vasculopathy, has also been the subject of various analyses. To summarize the results of single cell analysis in SSc accumulated to date and to deepen our understanding of SSc. Four databases were used to perform a database search on 23rd June 2023. Assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed according to PRISMA guidelines. The analysis was completed on July 2023. 17 studies with 358 SSc patients were included. Three studies used PBMCs, six used skin, nine used lung with SSc-interstitial lung diseases (ILDs), and one used lung with SSc-pulmonary arterial hypertension (PAH). The cells studied included immune cells such as T cells, natural killer cells, monocytes, macrophages, and dendritic cells, as well as endothelial cells, fibroblasts, keratinocytes, alveolar type I cells, basal epithelial cells, smooth muscle cells, mesothelial cells, etc. This systematic review revealed the results of single cell analysis, suggesting that PBMCs, skin, SSc-ILD, and SSc-PAH show activation and dysfunction of cells associated with immune-abnormalities, fibrosis, and vasculopathy, respectively. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a rare and refractory systemic disease characterized by fibrosis and vasculopathy in the presence of autoimmune abnormalities. While the exact cause of SSc is incompletely understood, the specific autoantibodies identified in SSc are closely linked to disease severity and prognosis, indicating a significant role of autoimmune abnormalities in the pathogenesis of SSc. Although the direct pathogenic mechanisms of autoantibodies in SSc are not fully elucidated, numerous prior investigations have demonstrated the involvement of B cells in the pathogenesis of SSc through various mechanisms. Additionally, several clinical trials have explored the efficacy of B‐cell depletion therapy for SSc, with many reporting positive outcomes. However, the role of B cells in SSc pathogenesis is multifaceted, as they can both promote inflammation and exert inhibitory functions. This article provides an overview of the involvement of B cells in SSc development, incorporating the latest research findings. [ABSTRACT FROM AUTHOR]

Few studies have made direct comparisons between treatments for palmoplantar pustulosis (PPP); therefore, it is difficult to select the best treatment for each patient. To determine the best therapy and to compare reported measures of efficacy in clinical trials of systemic treatments for PPP in this systematic review and network meta‐analysis. Six databases were used to perform database search on 10 July 2022. Randomized controlled trials (RCTs) were identified through a systematic literature search. The titles and abstracts of articles were initially screened for inclusion by two authors independently using our predetermined criteria. The full texts of selected articles were then independently assessed for inclusion in a blinded fashion. Disagreement between the authors was resolved by consensus. Data were abstracted in duplicate. Random‐effects model was accepted to perform network meta‐analysis. Assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed according to the PRISMA guidelines. The analysis was completed in July 2022. The primary outcome was the change of PPP Area and Severity Index (PPPASI) from baseline and the secondary outcome was the achievement of PPPASI‐50 response. Seven RCTs with 567 patients were included. Guselkumab 100 mg was the one with the highest probability of reaching the proposed outcomes (mean difference [MD], −8.00; 95% confidence interval [CI], 4.88–11.11), while the achievement of PPPASI‐50 response did not show a significant difference (odds ratio [OR], 3.79; 95% CI, 0.51–28.37). Guselkumab 200 mg was next to 100 mg of reaching the proposed outcomes (MD, −4.71; 95% CI, 2.12–7.30), while the achievement of PPPASI‐50 response did not show a significant difference (OR, 2.34; 95% CI, 0.48–11.43). Network meta‐analysis showed guselkumab 100 mg was the treatment with the highest probability of reaching both PPPASI and PPPASI‐50 outcomes. Absolute PPPASI may be more appropriate as an outcome than PPPASI‐50. [ABSTRACT FROM AUTHOR]

Psoriasis is a persistent inflammatory skin disease thought to arise as a result of the infiltration of inflammatory cells and activation of keratinocytes. Recent advances in basic research and clinical experience revealed that the interleukin (IL)‐23/IL‐17 axis has been identified as a major immune pathway in psoriasis. However, it remains unclear how keratinocyte factors contribute to the pathology of psoriasis. Keratinocyte proline‐rich protein (KPRP) is a proline‐rich insoluble protein, which is present in the epidermis and is likely to be involved in the skin barrier function. Here, to investigate the potential roles of KPRP in psoriatic skin inflammation, Kprp‐modified mice were applied in the imiquimod (IMQ)‐induced skin inflammation model, which develops psoriasis‐like epidermal hyperplasia and cutaneous inflammation features. Then, heterozygous knockout (Kprp+/−) but not homozygous knockout (Kprp−/−) mice displayed attenuated skin erythema compared to control wild‐type mice. In addition, RNA sequencing, quantitative PCR and/or histological analysis detected changes in the expression of several molecules related to psoriatic inflammation or keratinocyte differentiation in Kprp+/− mice, but not Kprp−/− mice. Further analysis exhibited reduced IL‐17‐producing γδlow T cells and amplified epidermal hyperplasia in Kprp+/− mice, which were implied to be related to decreased expression of β‐defensins and increased expression of LPAR1 (Lysophosphatidic acid receptor 1), respectively. Thus, our results imply that KPRP has the potential as a therapeutic target in psoriatic skin inflammation. [ABSTRACT FROM AUTHOR]