The Journal of dermatology最新文献

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.

Accurate diagnosis is essential for timely intervention in atopic dermatitis (AD), yet delays in diagnosis remain common. To better understand current clinical practices regarding infantile AD, a questionnaire survey was conducted among Japanese pediatricians working at medical institutions with 19 or fewer beds. Respondents who provided informed consent completed an online questionnaire that included items on screening practices, physician background, understanding of diagnostic and treatment practices, and recognition of key clinical issues. In total, 238 valid responses were analyzed. Most respondents indicated that they were non-allergists (85.7% of responses), aged 50 years or older (68.9% of responses) and reported high clinical experience in treating infantile eczema. Only 44.1% of respondents correctly recognized that AD is a condition within the collective term of infantile eczema. Almost all (92.0%) respondents correctly agreed that early intervention was effective for infantile AD and most recognized that AD treatment is prolonged, that AD induces other allergic diseases, and that AD is unlikely to resolve spontaneously in most cases. Understanding of the primary nature of AD was poor with 62.6% of respondents either incorrectly stating that AD is caused by other allergic diseases or that they did not know. The mean (SD) minimum age of AD diagnosis was 7.4 (4.81) months (median, 6.0 months) and 23.9% of physicians diagnosed AD after 1 year of age. Only 16.4% of respondents correctly identified a case of infantile AD and only 19.3% of respondents correctly selected the most appropriate treatment for a known case of infantile AD. Reluctance to inform parents/caregivers of an AD diagnosis was high and mostly due to anticipation of parental shock. Certain pediatricians in Japan have misunderstandings about infantile AD. Further awareness of infantile AD is necessary to ensure early diagnosis and intervention as well as management aligned with guideline recommendations.

Systemic Janus kinase inhibitors (JAKIs) have markedly advanced the therapeutic landscape for alopecia areata (AA). Although baricitinib and ritlecitinib are approved in the United States (US) and Europe, and deuruxolitinib in the US for severe AA, the lack of head-to-head randomized controlled trials (RCTs) limits evidence-based prescribing decisions. Moreover, prior meta-analyses excluded data on certain oral JAKIs or incorporated findings from agents and dosing regimens that were abandoned, investigational, clinically ineffective, or associated with unacceptable safety profiles. To compare the efficacy of oral JAKIs, limited to FDA, EMA, or MHRA approved drugs and doses-baricitinib (2 and 4 mg QD), ritlecitinib (50 mg QD), and deuruxolitinib (8 mg BID)-for severe AA, using advanced indirect comparison methodologies. A systematic review was performed following PRISMA 2020 guidelines (CRD420251116775). Bayesian network meta-analysis (NMA) synthesized data from RCTs reporting Week 24 outcomes on Severity of Alopecia Tool (SALT) ≤ 10 and SALT ≤ 20 thresholds. Multilevel network meta-regression (ML-NMR) evaluated heterogeneity and adjusted for baseline imbalances. Additionally, unanchored matching-adjusted indirect comparisons (MAIC) were conducted using individual patient-level data from THRIVE trials. Surface under the cumulative ranking (SUCRA) values were calculated to rank treatments. Seven RCTs (n = 4560 participants) were included. Deuruxolitinib 8 mg significantly outperformed baricitinib 2 and 4 mg on both SALT endpoints. Differences with ritlecitinib 50 mg were directionally favorable for deuruxolitinib but not statistically significant in NMA and ML-NMR models. MAICs confirmed superior odds for deuruxolitinib versus baricitinib 2 mg (OR = 71.55) and ritlecitinib (OR = 18.27) for SALT ≤ 20. SUCRA rankings also consistently favored deuruxolitinib. Among approved oral JAKIs, deuruxolitinib 8 mg shows the highest short-term efficacy for severe AA. These findings provide preliminary evidence to guide treatment decisions but should be interpreted as exploratory pending confirmation.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by barrier dysfunction, immune dysregulation, and microbial dysbiosis. Recent studies have highlighted the multifaceted roles of antimicrobial peptides (AMPs) both as innate defenders against microbial invasion and as regulators of immune responses and skin barrier homeostasis. This review synthesizes the current knowledge on the dysregulation of AMP expression in AD, the impact of Th2-dominant inflammation on AMP-mediated defense, and the complex relationship between AMP activity and the cutaneous microbiota (particularly in the context of Staphylococcus aureus colonization). We also explore the immunomodulatory and barrier-stabilizing functions of AMPs, emphasizing their dual roles as both protective and potentially pathogenic agents depending on their expression levels and processing. Furthermore, emerging therapeutic strategies that aim to restore AMP function (such as vitamin D signaling, aryl hydrocarbon receptor activation, and synthetic AMPs) are discussed. A deeper understanding of AMP-related mechanisms in AD may offer novel insights for precision-targeted interventions that simultaneously address inflammation, barrier repair, and microbial imbalance.

Dupilumab, a fully human IgG4 monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling by blocking the shared IL-4α subunit, is the first targeted systemic therapy for moderate-to-severe atopic dermatitis (AD). The drug was introduced in Japan in April 2018, along with other countries around the same time, leading to a dramatic improvement in patients' quality of life. This study aims to provide practical insights into the real-world use of dupilumab to support decision-making in drug selection and patient education. We retrospectively analyzed the clinical course of 314 AD patients who commenced the treatment in a university hospital and two clinics in Tokyo and Yokohama, both in the greater Tokyo metropolitan area, from the launch of the drug until December 2022. Of the 314 patients, 180 (57.3%) remained on the treatment until June 2023, whereas 134 (42.7%) discontinued. Discontinuation reasons included: (i) negative outcomes, such as lack of efficacy or adverse effects, in 46 patients (14.6%) with a median treatment duration of 224 days; (ii) disease remission in 53 patients (16.9%); and (iii) non-disease-related or unknown reasons in 35 patients (11.1%). The drug survival rates at 1, 2, 3, and 4 years after initiation were 72.2%, 56.9%, 49.8%, and 42.3%, respectively. However, when considering only discontinuations due to negative outcomes, these increased to 89.3%, 82.7%, 78.8%, and 75.6%, respectively. To summarize, the drug survival rate in this group was significantly lower than those reported in Western countries. However, when discontinuations due to negative outcomes were considered separately, the rates were comparable. These findings highlight the excellent efficacy of dupilumab, while also suggesting that the doctors and patients in this region may be more inclined to discontinue the treatment despite its success compared with their Western counterparts.

Atopic dermatitis (AD) is a chronic inflammatory disease characterized by recurrent remissions and relapses. Topical anti-inflammatory steroids are commonly used for treatment, but their long-term use poses concerns because of potential side effects. Delgocitinib ointment, a Janus kinase inhibitor, has demonstrated efficacy in several clinical studies and is expected to be a viable alternative to topical corticosteroids (TCS). To evaluate the real-world safety and efficacy of delgocitinib in Japanese patients, we assessed the benefits of switching from TCS to delgocitinib ointment in AD patients with rashes on the trunk and extremities. Overall, data from 93 patients (mean age: 35 years) were analyzed. Patients switched from TCS to delgocitinib ointment and were followed for up to 12 weeks. Treatment outcomes were assessed using the treatment Satisfaction questionnaire for medication-9 (TSQM-9), Eczema Area and Severity Index (EASI), modified EASI (mEASI), Numerical Rating Scale (NRS) for itching, Atopic Dermatitis Control Tool (ADCT), and Patient Preference Questionnaire (PPQ). During the observation period, TSQM-9 scores were significantly improved (effectiveness 68.3 to 72.9, p < 0.05; global satisfaction 61.7 to 67.9, p < 0.01). Additionally, mEASI (8.82 to 6.92, p < 0.05), EASI (9.60 to 7.43, p < 0.001), NRS (5.6 to 4.5, p < 0.001), and ADCT (8.8 to 5.5, p < 0.001) scores were decreased during treatment. Moreover, local side effects were improved, with a > 20% reduction in the severity of skin atrophy and telangiectasia. Approximately 72% of patients reported that "the study drug is more effective" using the PPQ. Taken together, our study demonstrates that delgocitinib ointment is an effective treatment option for AD patients with rashes of the trunk and extremities, as well as for those concerned about the potential side effects of TCS. Trial Registration: The study was registered at the Japan Registry of Clinical Trials (jRCTs031230102).

Nemolizumab, an anti-interleukin-31 receptor A monoclonal antibody, has been approved in Japan for treating atopic dermatitis (AD)-associated pruritus. While it is effective for itch control, nemolizumab-associated cutaneous adverse events have been increasingly recognized, yet their clinical features remain poorly characterized. In this study, we aimed to investigate the incidence, clinical characteristics, and timing of cutaneous manifestations associated with nemolizumab treatment in patients with AD, and to explore potential associations with baseline disease severity and immunological parameters. We conducted a multicenter retrospective study involving 219 patients aged ≥ 13 years with AD who received nemolizumab at 13 institutions in Japan between August 2022 and February 2024. Cutaneous eruptions were classified into six categories based on clinical consensus. Patients who received fewer than three doses without developing skin reactions were excluded. Clinical and laboratory parameters were compared between patients with and without cutaneous manifestations. Cutaneous manifestations occurred in 88 patients (40.2%), most commonly within the first three doses. Erythema was the most frequent presentation (69.3%), and 62.5% of eruptions were non-pruritic. No significant associations were observed between the occurrence of skin reactions and baseline eczema area and severity index scores, eosinophil counts, serum immunoglobulin E, or thymus and activation-regulated chemokine levels. Two cases of bullous pemphigoid were identified. Despite topical corticosteroid treatment, nemolizumab therapy was discontinued in 42% of the patients affected. In conclusion, nemolizumab frequently induces early-onset, morphologically distinct cutaneous eruptions that appear to be independent of baseline disease severity or biomarkers.