The Journal of dermatology最新文献

Autoantibodies are key pathogenic factors involved in the development of pemphigus vulgaris (PV). Recent advances in research have shed light on PV pathogenesis and may ultimately facilitate its tailored treatment. This review synthesizes evidence on the pathogenesis of PV, mainly from the past 5 years. The key mechanisms involved in PV development can be categorized into three major aspects. First, components that facilitate B cell differentiation and autoantibody production play a critical role. Second, the pathogenic effects of autoantibodies are mediated through direct damage or activation of signaling pathways, including Ca²⁺ influx, the JAK/STAT pathway, the p38MAPK pathway, the EGFR pathway, and apoptosis-related pathways. Notably, targeted treatments towards these mechanisms such as dupilumab also demonstrate promising efficacy. Third, additional contributing factors, including genetic factors, epigenetic factors, changes in protein expression, and microbial dysbiosis, further elucidate the complexity of PV pathogenesis.

Atherosclerosis is now considered to reflect systemic inflammation involving the elevation of multiple proinflammatory cytokines, sharing common underlying pathophysiological mechanisms with psoriasis. There has been increasing interest in whether anti-inflammatory treatment of psoriasis can prevent or halt the progression of atherosclerosis. Here, we conducted a cross-sectional observational clinical study in psoriasis patients with at least one traditional cardiovascular risk factor, such as diabetes, hypertension, or dyslipidemia, and who were being treated with systemic anti-inflammatory drugs. To assess CAD risk, we performed coronary computed tomography angiography (CCTA). We assessed 27 psoriasis patients (14 males/13 females), whose median PASI score was 0 [range, 0-2.3] at the time of CCTA. They had sustained well-controlled psoriasis for a median of 44 months [range, 1-144]. Coronary plaques of varying degrees were detected in 20 patients (74%) by CCTA. Four patients were diagnosed with silent myocardial ischemia (SMI) by invasive coronary angiography (CAG), revealing severe coronary stenosis in major arteries. The severity of coronary plaque burden was significantly associated with male sex, hypertension, and carotid ultrasound abnormalities. Furthermore, notably, we detected a significant positive correlation between the duration of biologic treatment and calcified plaque burden among patients treated with biologic agents for over 6 months. Our study highlights the importance of tight disease control and screening for CAD even in well-controlled psoriasis patients. Further accumulation of studies may lead to better management of CAD risks in this population.

Systemic sclerosis is an autoimmune disease characterized by vasculopathy, fibrosis, and immune dysregulation. Anti-SS-A antibodies (anti-SSA) have been reported to confer severe clinical manifestations in some Western and Japanese cohorts. We aimed to determine whether anti-SSA seropositivity affects clinical outcomes in Japanese patients. We retrospectively analyzed 307 Japanese patients with systemic sclerosis who underwent initial evaluation between January 2011 and March 2020 in our clinic. "Isolated" anti-SSA seropositivity was defined as positivity for anti-SSA in the absence of anti-topoisomerase I, anti-centromere, anti-RNA polymerase III, and anti-U1 ribonucleoprotein antibodies. Overall survival was defined as time to all-cause mortality, and progression-free survival was defined as time to disease progression necessitating intensified therapy. Cox proportional hazards models were employed to estimate hazard ratios and 95% confidence intervals. For patients with "isolated" anti-SSA seropositivity, further investigation for SSc-related autoantibodies was conducted utilizing Autoantibody Array Assay (A-Cube). Anti-SSA were detected in 31.3% of patients. Although anti-SSA seropositivity overall correlated with interstitial lung disease, it was not independently associated with overall survival or progression-free survival. In contrast, "isolated" anti-SSA seropositivity emerged as an independent risk factor for both shorter overall survival (hazard ratio 21.7, 95% confidence interval 5.57-84.8) and progression-free survival (hazard ratio 4.18, 95% confidence interval 1.05-16.7). Expanded serologic testing revealed additional autoantibodies implicated in severe SSc phenotypes. These findings underscore the importance of routinely assessing anti-SSA and highlight the need for autoantibody screening in depth in this subpopulation.

Diseases associated with skin pigmentation include hyperpigmentation and hypopigmentation. Macrophages are involved in melanogenesis and the development of skin pigmentary disorders, and they affect the production and distribution of melanin mainly through phagocytosis and secretion. They can either phagocytose melanin and deposit it in the dermis or secrete a variety of cytokines like interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and some interleukins (ILs) such as IL-1, IL-6, IL-8, and IL-18. The interaction between macrophages and other cells is responsible for the secretion of these cytokines. Macrophages can also promote pigmentation in hyperpigmentation disorders, such as post-inflammatory hyperpigmentation (PIH), drug-induced pigmentation (DIP), senile lentigo (SL), and melasma, as well as hypopigmentation disorders such as vitiligo and halo nevus (HN). In this review, we summarize the role of macrophages in the development of pigmentary diseases and provide new insights for the identification of potential targets for pigmentary diseases.