Journal of Dermatology最新文献

“Wound, Pressure Ulcer, and Burn Guidelines-5: Guidelines for the management of lower leg ulcers and varicose veins, second edition” is revised from the first edition, which was published in the Japanese Journal of Dermatology in 2011. The guidelines were drafted by the Wound, Pressure Ulcer, and Burn Guidelines Drafting Committee delegated by the Japanese Dermatological Association and intend to facilitate physicians' clinical decisions in preventing, diagnosing and management of lower leg ulcers and varicose veins. We updated all sections by collecting documents published since the publication of the first edition. In particular, we added clinical question 8 (CQ8), which addresses endovenous laser ablation for varicose veins, a procedure that became covered by the Japanese national health insurance after the writing of the first edition, and endovenous radiofrequency ablation, which became covered by national health insurance in 2014. We also rearranged the subsequent clinical question (CQs) for easier reading. While the addition of these new techniques has increased the number of options available within the treatment algorithm, differences have arisen in the indication for surgery depending on the facility performing the treatment. Therefore, these have been abbreviated.

Phasing, the process of determining which alleles at different loci on homologous chromosomes belong together on the same chromosome, is crucial in the diagnosis and management of autosomal recessive diseases. Advances in long-read sequencing technologies have significantly enhanced our ability to accurately determine haplotypes. This review discusses the application of low-coverage long-read sequencing, nanopore Cas9-guided long-read sequencing, and adaptive sampling in phasing, highlighting their utility in complex clinical scenarios. Through clinical vignettes, we explore the importance of phasing in gene therapy design for recessive dystrophic epidermolysis bullosa and the role of revertant mosaicism in therapeutic epidermal autografts. Despite its promise, phasing with long-read sequencing faces challenges, including low efficiency in enriching target regions and the inherent error rate of nanopore sequencing. Future developments in long-read sequencing technologies will be critical in overcoming these limitations and expanding the applicability of phasing across various clinical settings.

This is the English version of the 2024 clinical practice guidelines for the management of atopic dermatitis (AD). AD is a disease characterized by relapsing eczema with pruritus as a primary lesion. A crucial aspect of AD treatment is the prompt induction of remission via the suppression of existing skin inflammation and pruritus. To achieve this, topical anti-inflammatory drugs, such as topical corticosteroids, tacrolimus ointment, delgocitinib ointment, and difamilast ointment, have been used. However, the following treatments should be considered in addition to topical therapy for patients with refractory moderate-to-severe AD: oral cyclosporine, subcutaneous injections of biologics (dupilumab, nemolizumab, tralokinumab), oral Janus kinase inhibitors (baricitinib, upadacitinib, abrocitinib), and phototherapy. In these revised guidelines, descriptions of five new drugs, namely, difamilast, nemolizumab, tralokinumab, upadacitinib, and abrocitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Previous research has highlighted a significant association between inflammatory proteins and the development and progression of hidradenitis suppurativa (HS). Nevertheless, the potential causative link between these factors remains to be definitively established. To investigate the genetic correlation between inflammatory proteins and HS, linkage disequilibrium score regression (LDSC) was employed. Mendelian randomization (MR) analysis, incorporating inverse variance weighted, MR-Egger, and weighted median methodologies, was utilized to evaluate the possible causal relationship between circulating inflammatory proteins (CIPs) and HS. Additionally, reverse MR analysis was carried out to explore reverse causality. The data set for 91 CIPs was derived from a genome-wide protein quantitative trait loci study, while HS-related data were acquired from the FinnGen study. Moreover, the stability of the causal relationships was assessed via sensitivity analyses, encompassing tests for pleiotropy, heterogeneity, and leave-one-out analysis. The LDSC analysis suggested the existence of genetic correlations between the levels of Fibroblast growth factor 21 (FGF-21), stem cell factor, and HS. The MR analysis identified a suggestive association of T-cell surface glycoprotein CD5 and C-X-C motif chemokine 11 with an elevated risk of HS. Conversely, C-C motif chemokine 4, Protein S100-A12, Interleukin-10 receptor subunit beta, and Programmed cell death 1 ligand 1 were associated with a diminished risk of HS. Moreover, HS was demonstrated to increase the levels of four CIPs: Interleukin-20, Leukemia inhibitory factor (LIF), LIF receptor, and Thymic stromal lymphopoietin. The findings of this investigation offer suggestive evidence for possible genetic correlations and causal links between various genetically predicted inflammatory proteins and HS. There exists a pressing requirement for additional studies to elucidate the fundamental processes driving these associations.

Although genetic, environmental, autoimmune, and psychological factors are believed to play a role in the onset of alopecia areata (AA), the exact cause remains unknown. This study aimed to investigate whether there are differences in traumatic experiences, dissociative symptoms, and alexithymia levels between groups. Fifty eight patients diagnosed with AA, 58 individuals with dermatological diseases thought to have a low psychosomatic component, and 58 individuals not diagnosed with any chronic disease were included in the study. All participants were assessed using the Childhood Trauma Questionnaire (CTQ-28), Dissociative Experiences Scale (DES), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), and Toronto Alexithymia Scale (TAS-20). A Structured Clinical Interview for DSM-5 (SCID-5-CV) form was used to exclude additional psychiatric diagnoses. Mean scores on the CTQ-28 scale revealed differences between groups in terms of physical neglect and emotional neglect scores (p < 0.001; p = 0.022; p < 0.001). There were no differences in DES scores between groups (p = 0.085). When compared in terms of TAS-20 and PCL-5 scores, differences were found (p = 0.016; p = 0.024). As a result of this study, it was concluded that physical neglect and emotional neglect could play a significant role in the onset of AA. Alexithymia and traumatic stress disorder symptoms might be more prevalent in patients with AA.

Generalized pustular psoriasis (GPP) is a severe autoinflammatory keratinization disease (AiKD) characterized by acute flares of widespread sterile pustules and high fever. GPP is potentially life-threatening. Recently clarified genetic predisposing factors for GPP suggest that the excessive activation of innate immune pathways in the skin, including of interleukin (IL)-1 and IL-36 signaling, plays a significant role in the GPP pathogenesis. IL36RN, CARD14, AP1S3, MPO, SERPINA3, BTN3A3, and MEFV have been identified as GPP-related genes. The pathogenesis of GPP provoked by variants in these seven genes is tightly associated with the excessive activation of innate immune pathways and the resulting autoinflammation in the skin. Various biologics, including inhibitors for the tumor necrosis factor, IL-17, and IL-23 pathways, are used as treatments for GPP. The new understanding of the genetic background of GPP, mentioned above, indicates that the genetic predisposing factors are predominantly related to the excessive activation of innate immunity and autoinflammation. In this context, inhibitors of inflammatory signaling, including of the IL-1 and IL-36 pathways, have been used in clinical practice and investigated as potential future therapies.

Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist approved for the treatment of atopic dermatitis (AD) in Japanese patients aged ≥12 years. We evaluated the efficacy and safety of tapinarof in Japanese pediatric patients aged 2 to 11 years with AD in a phase 2, multicenter, randomized, double-blind, vehicle-controlled trial. Eligible patients (N = 121) were randomized 1:1:1 to receive tapinarof cream 0.5%, tapinarof cream 1%, or vehicle cream once daily for 8 weeks. At week 8, the least-squares mean percent change from baseline in Eczema Area and Severity Index (EASI) score (the primary endpoint) was −81.29% in the tapinarof 0.5% group, −77.62% in the tapinarof 1% group, and − 18.56% in the vehicle group. Reductions in EASI score at week 8 were significantly greater in the tapinarof groups than in the vehicle group (p < 0.0001 for both comparisons). The proportion of patients with ≥75% improvement from baseline in EASI score at week 8 was 77.5% in the tapinarof 0.5% group, 70.7% in the tapinarof 1% group, and 15.0% in the vehicle group. The proportion of patients who achieved an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline at week 8 was 32.5% in the tapinarof 0.5% group, 43.9% in the tapinarof 1% group, and 17.5% in the vehicle group. No treatment-related serious adverse events (AEs) were reported; all of the AEs were mild or moderate. Common AEs in tapinarof-treated patients included gastroenteritis, application site irritation, and nasopharyngitis. The incidence of trial discontinuations due to AEs was low in tapinarof-treated patients (one patient for each strength). In summary, both strengths of tapinarof cream demonstrated greater efficacy than vehicle cream and were well tolerated in Japanese pediatric patients with AD.

Mammalian skin appendages, such as hair follicles and sweat glands, are essential for both esthetic and functional purposes. Conditions such as burns and ulcers can lead to dysfunction or loss of skin appendages and result in hair loss and dry skin, posing challenges in their regeneration. Existing animal models are insufficient for studying acquired dysfunction of skin appendages without underlying genetic causes. This study aimed to develop more clinically relevant mouse models by evaluating two approaches: keratinocyte transplantation and grafting of skin at varying thicknesses. green fluorescent protein (GFP)-expressing keratinocytes were transplanted into ulcers on nude mice, leading to re-epithelialization with minimal skin appendages at 4 weeks after transplantation. However, the re-epithelialized area was largely derived from recipient cells, with the grafted cells contributing to only 1.31% of the area. In the skin-grafting model, donor skin from GFP transgenic mice was grafted onto nude mice at three thicknesses: full thickness, 10/1000 inch, and 5/1000 inch. The grafted area of the 5/1000-inch grafts remained stable at 89.5% of its original size 5 weeks after transplantation, ensuring a sufficiently large skin area. The 5/1000-inch grafts resulted in a significant reduction in skin appendages, with a mean of only 3.73 hair follicles per 5 mm, compared with 69.7 in the control group. The 5/1000-inch skin grafting in orthotopic autologous transplantation also showed the achievement of skin surfaces with a minimal number of skin appendages. Therefore, a mouse model with skin grafting demonstrated stability in producing large areas of skin with minimal appendages. In conclusion, these two models with acquired skin appendage dysfunction and no underlying genetic causes provide valuable tools for researching skin appendage regeneration, offering insights into potential therapeutic strategies for conditions involving skin appendage loss.

Comprehensive studies of the genetic profiles of cutaneous squamous cell carcinoma (cSCC) in Japanese patients have been lacking, although an understanding of these profiles is crucial for improving treatment outcomes. Since 2019, comprehensive genomic profiling (CGP) has been covered by Japan's health insurance, and the resulting data have been compiled into a comprehensive database by the country's Center for Cancer Genomics and Advanced Therapeutics (C-CAT). In this retrospective study, we used CGP data from the C-CAT database to analyze genomic characteristics of cSCC in Japanese patients. The patients' clinical and genomic data, including the chemotherapy regimens, tumor mutational burden (TMB), and survival status, were obtained. We analyzed the cases of 152 patients, with only those evaluated by the FoundationOne® CDx included for accuracy. Among the 152 patients, the most common gene oncogenic alterations were observed in TP53 (67%), CDKN2A (54%), TERT (49%), CDKN2B (33%), and NOTCH1 (18%). TMB-high (≥10 mut/Mb) was observed in 27% (n = 41) of the patients, with a median age of 75 years for this group. TMB-low (<10 mut/Mb) was observed in 73% (n = 111) of the patients; their median age was 67 years.

Bullous pemphigoid (BP) is the most prevalent autoimmune blistering disorder, triggered by autoantibodies targeting hemidesmosome components. It is associated with substantial morbidity and increased mortality. No studies comprehensively evaluate all comorbidities before and after diagnosing patients with BP. We aimed to investigate all BP-associated comorbid diseases and their patterns of associations. This nationwide population-based study included 5066 patients with BP and 10 132 controls between 2011 and 2021. We performed an automated mass screening of 546 diagnostic codes to identify BP-associated comorbidities 5 years before and after BP diagnosis, and analyzed associations patterns of comorbidities. Patients with BP had increased odds of having pressure ulcers, intracerebral hemorrhage, scabies, neuropsychiatric disorders, psoriasis, drug eruption, and acute renal failure before BP diagnosis. After BP diagnosis, they had increased odds pneumonia, sepsis, chronic renal disease, and cardiac arrest. Strong interrelationships were observed between five neuropsychiatric conditions before BP diagnosis and a strong bidirectional association between Alzheimer's dementia and pneumonia after BP diagnosis. This large case–control study of patients with BP thoroughly identified all relevant comorbidities before and after BP diagnosis, highlighting their clinical significance as predisposing and prognostic factors in patients with BP.