Takemichi Fukasawa

Background: Skin care is widely regarded as a fundamental component of self‐care. However, few studies have systematically evaluated the effects of structured skin care instruction on both objective parameters and subjective perceptions. This study aims to elucidate these effects through a controlled clinical investigation. Methods: This clinical trial was conducted at the University of Tokyo Hospital between July and September 2023. Twenty‐one healthy women aged 30–60 years applied a microneedle cream to the face for 8 weeks. They were randomly assigned to either the intervention group, which received skin care instructions from the start, or the control group, which received them after 4 weeks. Skin hydration, transepidermal water loss, viscoelasticity, and melanin content were assessed at baseline, week 4, and week 8. Subjective evaluations were obtained via structured questionnaires. Statistical analyses were conducted using Prism (version 10.2.3). Results: At week 4, the intervention group showed significantly greater improvements in skin hydration (intracorneal water content: −0.98% ± 13.49% [control] vs. 14.06% ± 14.61% [intervention], p < 0.05) and elasticity (R7: −3.48% ± 10.36% [control] vs. 7.92% ± 10.29% [intervention], p < 0.05) compared to the control group. At week 8, melanin pigmentation was significantly reduced in the intervention group (Mark‐Vu: 11.44% ± 26.67% [control] vs. −15.01% ± 11.10% [intervention], p < 0.05). Subjective assessments were consistent with these objective results, reflecting improved skin perception. Conclusions: This is the first study to demonstrate that appropriate skin care practices can lead to the moisturizing, firming, and elasticity effects of a microneedle cream. These findings highlight the importance of proper product use in maximizing the efficacy of skin care interventions. Trial Registration: UMIN: UMIN000052080

Objectives: Rituximab is emerging as a promising therapeutic option for systemic sclerosis-associated interstitial lung disease (SSc-ILD). However, little is known about factors that predict the efficacy of rituximab in SSc-ILD. Methods: A post-hoc analysis was performed on prospective data from 48 patients with SSc-ILD in the double-blind, randomized, placebo-controlled DESIRES trial. A total of 28 baseline factors were selected as candidates to predict the efficacy of rituximab on the percentage of predicted forced vital capacity (ppFVC) at 24 weeks. A machine learning causal tree algorithm was used to explore the combination of predictors to identify subpopulations with a good response to rituximab. Results: Serum levels of C-reactive protein (CRP) and Krebs von den Lungen-6 (KL-6) were selected as branches of the decision tree to stratify patients into three subpopulations. In the subpopulation with serum CRP levels ≥0.055 mg/dl, ΔppFVC was significantly higher in the rituximab group than in the placebo group [difference 8.01% (95% CI: 4.40%, 11.62%)]. In the subpopulation with serum CRP levels <0.055 mg/dl and serum KL-6 levels ≥364 U/ml, ΔppFVC was comparable between the two groups [difference 2.47% (95% CI: −1.99%, 6.92%)]. In the subpopulation with serum CRP levels <0.055 mg/dl and serum KL-6 levels <364 U/ml, ΔppFVC was significantly lower in rituximab than in placebo [difference −6.85% (95% CI: −10.80%, −2.91%)]. Conclusion: Even slight elevations in serum CRP levels are associated with the improvement in ppFVC and may serve as predictors of rituximab efficacy in SSc-ILD.

Objective: Epitope spreading (ES), involving autoantibodies, plays a crucial role in the development and persistence of autoimmune reactions in various autoimmune diseases. This study aimed to investigate the relationship between ES of anti–RNA polymerase III (RNAP III) antibodies (ARAs) and the clinical manifestations of systemic sclerosis (SSc).Methods: We investigated whether intermolecular ES occurs in the subunits of the RNAP III complex and whether intramolecular ES targets the major antigen, RNA polymerase III subunit A (RPC1), in patients with SSc. To achieve this, we synthesized 17 full‐length subunit proteins of the RNAP III complex and 5 truncated forms of RPC1 in vitro using a wheat germ cell‐free translation system. Subsequently, we prepared antigen‐binding plates and measured autoantibodies in the serum of patients with SSc.Results: Autoantibodies against different RNAP III complex subunits were found in patients who were ARA‐positive with SSc. The intermolecular ES indicators significantly correlated with the modified Rodnan skin thickness score (mRSS) and surfactant protein‐D, a biomarker of interstitial lung disease. However, the extent of disease on high‐resolution computed tomography or pulmonary function tests did not show any significant correlation. Intramolecular ES indicator against RPC1 were significantly correlated with mRSS and renal crisis. Furthermore, longitudinal assessment of ES in RNAP III complex subunits correlated with mRSS and exhibited potential as a disease activity biomarker.Conclusion: Our findings indicate a correlation between ES levels and the severity of skin sclerosis or the risk of other complications in SSc. This study suggests that measuring ES in SSc serves as a novel biomarker for disease activity. image

Although topical agents have been used to treat cutaneous lupus erythematosus (CLE), there was previously no high-quality evidence of which agents were most effective and which clinical scores were most suitable. On 22 December 2023, a search was conducted across five databases to identify randomized controlled trials (RCTs) for CLE. Two authors independently screened the titles and abstracts of articles based on predetermined criteria. Selected articles were then assessed for inclusion in a blinded manner, with any disagreements resolved through consensus. Data were abstracted in duplicate, and a random-effects model was utilized for network meta-analysis. The certainty of the evidence was evaluated according to the PRISMA guidelines, using the GRADE approach. The analysis was finalized in January 2024, with the primary outcome focused on the change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) from baseline. Seven RCTs involving 231 participants were analysed. The network meta-analysis revealed that nicotinamide 4% demonstrated the highest probability of achieving the intended outcomes, with a mean difference (MD) of 3.10 and a 95% confidence interval (CI) of 1.99–4.21. Additionally, clobetasol 0.05%, nicotinamide 2% and tacrolimus 0.1% also exhibited statistically significant differences, with MDs of 2.30 (95% CI of 0.73–3.88), 2.30 (95% CI 0.97–3.63) and 1.30 (95% CI 0.03–2.57), respectively. This NMA demonstrates with a high level of evidence that nicotinamide 4%, clobetasol 0.05%, nicotinamide 2% and tacrolimus 0.1% are statistically significant topical agents for CLE. CLASI may be an appropriate outcome to evaluate drug efficacy in CLE.

Is missing (Short communication)

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.

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.

Systemic sclerosis (SSc) and dermatomyositis (DM) are autoimmune collagen diseases. Specific autoantibodies are known to be involved in their pathogeneses, each presenting with a different clinical manifestation. Although immunoprecipitation is the gold standard method for detecting autoantibodies, it is difficult to perform in all cases owing to the use of radioisotopes. In this study, we developed a new detection method for SSc and DM autoantibodies (A-cube) using cell-free protein synthesis and examined its validity. Proteins were synthesized using wheat germ cell-free protein synthesis. A total of 100 cases of SSc, 50 cases of DM, and 82 healthy controls were examined. The validity of the method was examined by a comparison with existing test results. Anti-centromere antibody, anti-topoisomerase I antibody, anti-RNA polymerase III antibody, anti-U1RNP anti-body, anti-Jo-1 antibody, anti-TIF1γ antibody, anti-Mi-2 antibody, and anti-ARS antibody were tested for. The results suggested that A-cube is comparable with existing testing methods or has a high sensitivity or specificity. In addition, there was a case in which the diagnosis was reconsidered using the A-cube. The quality of the A-cube was ensured, and its usefulness for a comprehensive analysis was demonstrated. The A-cube can therefore contribute to the clinical assessment and treatment of SSc and DM.