The Journal of dermatology最新文献

Extramammary Paget disease (EMPD) is a rare skin cancer with an estimated incidence rate of 0.13 per 100 000 population/year in Caucasians and 0.28 in Asians. Although distant metastases have been reported in 10%-20% of EMPD cases, standardized systemic chemotherapy has not been established. Prospective clinical trials are essential to establish standard treatments for advanced EMPD. Therefore, this retrospective study examined a substantial number of patients with EMPD to assess the efficacy of systemic chemotherapy. This study included 164 patients with advanced EMPD who underwent treatment at 16 Japanese institutions. Treatment efficacy was evaluated in a cohort of 138 patients, after excluding 26 patients without lesions outside the radical irradiation field from the 164 patients. The efficacy of each treatment was evaluated by determining the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) using Kaplan-Meier analysis. Multivariate analysis was performed to account for potential confounding factors, such as age, sex, and performance status. The patients received the following treatments: docetaxel hydrate (DOC) (65.9%); tegafur/gimeracil/oteracil potassium, DOC (S-1/DOC) (9.8%); fluorouracil and cisplatin (FP) (15.9%); and other drugs (8.5%). DOC is the most commonly used in Japan. The ORRs in the DOC, S-1/DOC, and FP groups were 51.6%, 78.6%, and 27.8%, respectively. Logistic regression analysis revealed that, compared with the DOC group, the odds ratio for the ORR of the S-1/DOC group was 3.29 (95% CI: 1.49-7.25, p = 0.003). However, no significant differences in OS or PFS were observed between the treatment groups (p = 0.122 and p = 0.422, respectively). This study provides valuable information on EMPD and may serve as a useful historical control for the future evaluation of new treatments for EMPD.

Chronic itch represents a social burden due to its high prevalence, negative impact on quality of life, and limited treatment options. Spatial (simultaneously applied stimuli at multiple skin sites) and temporal (repeated stimuli over time) summation are key mechanisms in itch processing but have not been investigated in detail in humans. This study assessed experimentally induced histaminergic and non-histaminergic itch provocations in healthy volunteers. In the spatial summation experiment, histamine or cowhage was applied in randomized order to one area, two areas on the same arm, or two areas on different arms. Itch and pain intensities were recorded for 9 min, followed by assessment of alloknesis and hyperknesis. In the temporal summation experiment, each pruritogen was applied either once or repeatedly at intervals of 90 or 180 s apart to the forearm. Itch and pain intensities were recorded for 15 min, after which superficial blood perfusion (SBP), alloknesis, and hyperknesis were assessed. Itch intensity and calculated area under the curve (AUC) were significantly facilitated by special summation after both ipsilateral and contralateral applications of both pruritogens. Temporal summation significantly increased AUC after reapplication of either of the pruritogens after 180 s. Reapplication after 90 s significantly increased cowhage-induced SBP, while reapplication after 180 s increased histamine-induced SBP. In conclusion, spatial summation augmented itch intensity and AUC, whereas temporal summation increased AUC and enhanced SBP. Both effects were observed for histaminergic and non-histaminergic itch, highlighting differences in fundamental mechanisms.

Psoriasis is frequently associated with comorbidities such as metabolic syndrome and acute coronary syndrome (ACS). Coronary artery calcification (CAC), an independent predictor of coronary events, has been reported to be more prevalent in psoriasis patients than in healthy controls. However, its clinical significance and relationship with ACS risk in psoriasis remain incompletely understood. We conducted a single-center retrospective cross-sectional study involving 89 Japanese patients with psoriasis who underwent chest computed tomography (CT) to assess the presence of CAC. In selected patients with CAC, coronary CT angiography (CCTA) was performed, and the fractional flow reserve derived from CT (FFR_CT) was calculated. Thirty-one patients with CAC were more likely to have psoriasis vulgaris, were older, had lower estimated glomerular filtration rates (eGFR), and exhibited higher hemoglobin A1c (HbA1c) levels compared with those without CAC. Among the 22 patients who underwent CCTA, coronary artery calcium scores (CACS) were positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum C-reactive protein (CRP), and HbA1c levels. FFR_CT was measured in 10 patients with ≥ 40% coronary stenosis; six had FFR_CT value ≤ 0.80, indicating a high risk of ACS. Multivariable logistic regression analysis using a stepwise selection method identified age as the only significant predictor of ACS risk. In conclusion, elderly psoriasis patients with concomitant diabetes mellitus (DM) may have an elevated risk of ACS and could benefit from cardiology referral for cardiovascular risk assessment.

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.

Tralokinumab, an anti-IL-13 antibody, is effective for atopic dermatitis (AD); however, its long-term (> 1 year) effectiveness specific to each anatomical site is unknown in real-world settings. To evaluate 72-week effectiveness of tralokinumab on different anatomical sites in AD, we studied 208 patients with moderate-to-severe AD treated with tralokinumab for 72 weeks. Eczema area and severity index (EASI) scores were analyzed on four anatomical sites (head/neck, trunk, upper limbs, and lower limbs). Tralokinumab consistently reduced EASI on all anatomical sites. The achievement rates of EASI 75 and 100 on each site gradually increased from Week 4 to Week 72, and those on lower limbs appeared higher compared to the other sites. The percent reductions of EASI throughout 72 weeks appeared slightly lower on head and neck compared to the other sites. Week 72 achievement rate of EASI 75 on head/neck, trunk, upper limbs, or lower limbs was 80.4%, 80%, 80.3%, or 86.7%, while that of EASI 100 was 37.3%, 25.0%, 27.4%, and 40.0%, respectively. Tralokinumab reduced EASI scores through 72 weeks across different anatomical sites in AD patients. The achievement rates of EASI 75 and 100 appeared slightly higher on lower limbs compared to the other sites.