Recent advances in generative artificial intelligence (AI) have expanded its applications in diagnostic support within dermatology, but its clinical accuracy requires ongoing evaluation. This study compared the diagnostic performance of three advanced AI models, ChatGPT-4o, Claude 3.5 Sonnet, and Gemini 1.5 Pro, with that of board-certified dermatologists, using a dataset of 30 cases encompassing a variety of dermatological conditions. The AI models demonstrated diagnostic accuracy comparable to, and sometimes exceeding, that of the specialists, particularly in rare and complex cases. Statistical analysis revealed no significant difference in accuracy rates between the AI models and dermatologists, indicating that AI may serve as a valuable supplementary diagnostic tool in dermatological practice. Limitations include a small sample size and potential selection bias. However, these findings underscore the progress in AI's diagnostic capabilities, supporting further validation with larger datasets and diverse clinical scenarios to confirm its practical utility.

The COVID-19 pandemic has increased mRNA vaccine usage and revealed various cutaneous adverse events, such as injection site reactions, urticaria, and morbilliform eruptions. Multiple centers have reported erythema multiforme (EM) as a COVID-19 vaccine-associated adverse event. Our center observed two cases of EM in patients receiving immune checkpoint inhibitors (ICI) after COVID-19 vaccination. Notably, ICI administration is known to cause cutaneous adverse events, including EM. A previous report indicated that administering COVID-19 vaccination to patients receiving ICI treatment could promote severe systemic symptoms. This raise concerns that COVID-19 vaccination might rapidly worsen skin rashes in these patients. Our report demonstrates that skin rash related to COVID-19 vaccine-induced EM in ICI-treated patients does not significantly differ from that of COVID-19 vaccine-related EM. Additionally, in both cases, the skin rash resolved without exacerbation. Further research is necessary to determine optimal management strategies. However, our findings provide reassurance that COVID-19 vaccination is safe in ICI-treated patients and should not be avoided.

Abstract In December 2019, a new infectious pathogen named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified in Wuhan, China. Transmitted through respiratory droplets, SARS‐CoV‐2 is the causative pathogen of coronavirus disease 2019 (COVID‐19). Although this new COVID‐19 infection is known to cause primarily interstitial pneumonia and respiratory failure, it is often associated with cutaneous manifestations as well. These manifestations with COVID‐19 can be classified into seven categories: (i) chilblain‐like skin eruption (e.g., COVID toes), (ii) urticaria‐like skin eruption, (iii) maculopapular lesions, (iv) vesicular eruptions, (v) purpura, (vi) livedo reticularis and necrotic lesions, (vii) urticarial vasculitis, and others such as alopecia and herpes zoster. The pathogenesis of skin eruptions can be broadly divided into vasculitic and inflammatory skin eruptions. Various cutaneous adverse reactions have also been observed after COVID‐19 mRNA vaccination. The major cutaneous adverse reactions are type I hypersensitivity (urticaria and anaphylaxis) and type IV hypersensitivity (COVID arm and erythema multiform). Autoimmune‐mediated reactions including bullous pemphigus, vasculitis, vitiligo, and alopecia areata have also been reported. Several cases with chilblain‐like lesions and herpes zoster after COVID‐19 mRNA vaccination have been published. Various skin diseases associated with COVID‐19 and COVID‐19 vaccination have been reported, and the mechanism has been partly elucidated. In the process, for example, some papers have reported that it is not related to COVID‐19 infection, although it was initially called COVID‐toe and considered a COVID‐19‐associated cutaneous eruption. In fact, some COVID‐19‐associated skin reactions are indistinguishable from drug eruptions. In the future, the mechanisms of COVID‐19‐ or COVID‐19 vaccine‐associated skin reactions need to be elucidated and verification of causal relationships is required.

A decrease in the number of basophils in the peripheral blood, or basopenia, has been noted, reflecting the activity of chronic spontaneous urticaria (CSU). Infiltration of basophils into the skin has also been reported, but the mechanism of basopenia in CSU has not been clarified. The phenomenon of basopenia during the active phase of urticaria was confirmed, and basophil numbers increased following symptom improvement in 15 out of 17 patients treated with omalizumab and in 13 of 15 patients treated with antihistamines. Our examination by immunostaining also revealed basophil infiltration of the CSU lesions, as in previous reports, but since most of our patients were already taking oral steroids, it was not considered appropriate to examine the relationship between basophil numbers in tissue and peripheral blood. Then, we used mouse model of contact hypersensitivity with a single application of oxazolone, which is known to stimulate basophil infiltration, and investigated basophil counts in the skin, peripheral blood, and bone marrow. In this model, a decrease in peripheral blood basophil numbers was observed one day after challenge, but not after 2 days, reflecting supplementation from the bone marrow. Indeed, when cultured basophils expressing GFP were transplanted into the peripheral blood, GFP-positive basophil numbers in the peripheral blood remained low even after 2 days of challenge. Despite differences among species and models, these results suggest that one reason for the decrease of basophils in the peripheral blood in CSU may involve migration of circulating basophils into the skin.

Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions. The knowledge on the pathogenesis of AD is driving the development of new drugs. From the research results, it has been revealed that Th2 cell-mediated immunity, skin barrier dysfunction, and pruritus cause a vicious cycle of AD. On the other hand, the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway are one of the essential signaling pathways in various inflammatory diseases including AD. In particular, TSLP, IL-4, IL-13 and IL-22 occupy an important position for Th2 cell-mediated immune reaction. Moreover, experimentally pan-JAK inhibitor suppress the STAT3 activation and improved the skin barrier function. Furthermore TSLP, IL-4, IL-13 and IL-31 contribute a lot to chronic pruritus of AD, and transmitted via JAK-STAT pathway. Therefore, JAK inhibitors are promising candidates for the treatment of severe AD. Here we review clinical trials of topical dergocitinib; a pan-JAK inhibitor, ruxolitinib; a JAK1 and JAK2 inhibitor, and tofacitinib; a JAK1, JAK2, and JAK3 inhibitor and oral baricitinib; a JAK1 and JAK2 inhibitor, abrocitinib and upadacitinib; JAK1 inhibitor. Significant improvements in the symptoms were obtained by each drug with low frequency of adverse events. In particular, oral JAK inhibitors have the ability to improve the pruritus and skin symptoms quickly. Therefore, the emergence of these topical and oral JAK inhibitors would be regarded as an innovation in the treatment of atopic dermatitis.

BACKGROUND: Sensory nerves regulate cutaneous local inflammation indirectly through induction of pruritus and directly by acting on local immune cells. The underlying mechanisms for how sensory nerves influence cutaneous acquired immune responses remain to be clarified. OBJECTIVE: This study aimed to explore the effect of peripheral nerves on cutaneous immune cells in cutaneous acquired immune responses. METHODS: We analyzed contact hypersensitivity (CHS) responses as a murine model of delayed-type hypersensitivity in absence or presence of resiniferatoxin-induced sensory nerve denervation. We conducted ear thickness measurements, flow cytometric analyses, and mRNA expression analyses in CHS. RESULTS: CHS responses were attenuated in mice that were denervated during the sensitization phase of CHS. By screening neuropeptides, we found that pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA expression was decreased in the dorsal root ganglia after denervation. Administration of PACAP restored attenuated CHS response in resiniferatoxin-treated mice, and pharmacological inhibition of PACAP suppressed CHS. Flow cytometric analysis of skin-draining lymph nodes showed that cutaneous dendritic cell migration and maturation were reduced in both denervated mice and PACAP antagonist-treated mice. The expression of chemokine receptors CCR7 and CXCR4 of dendritic cell s was enhanced by addition of PACAP in vitro. CONCLUSION: These findings indicate that a neuropeptide PACAP promotes the development of CHS responses by inducing cutaneous dendritic cell functions during the sensitization phase.

Mast cells, eosinophils and basophils are central effector immune cells in allergic skin inflammation including atopic dermatitis (AD). Recent studies revealed that the bidirectional interaction between these three immune cell types (mast cells, eosinophils and basophils) and the nervous system is involved in the pathogenesis of neurogenic inflammation, pain and pruritus. Emerging evidence shows that these cells are the main source of pruritogens such as histamine, neuropeptides and cytokines, which are potential new therapeutic targets for drug development in chronic pruritus. For instance, many Th2 cytokines including interleukin (IL)-4, 13 and 31 have been recognized as some of the most promising targets for the treatment of chronic pruritus in AD. In this review, we highlight the link between these three immune cell subsets and peripheral nerves, with emphasis on the development of chronic pruritus such as AD. We present cytokines and receptors of these three immune cells and peripheral nerves, and discuss the therapeutic potential of targeting these neuro-immunological processes.

Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti-programmed death ligand-1 (PD-L1) is a well-studied biomarker for response to anti-programmed death-1 PD-1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3-dioxygenase (IDO) is correlated to a response to anti-CTLA-4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti-PD-1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD-L1 expression with response to anti-PD-1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti-PD-1 antibody from the perspective of IDO and PD-L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression-free survival (HR = 0.33, 95% CI = 0.13-0.81, P = 0.016), whereas PD-L1 expression on tumors was not associated with progression-free survival. Significantly lower expression of IDO in tumors was found in non-responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti-PD-1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings.

Cancer immunotherapy has highlighted the clinical relevance of enhancing anti-tumor response of CD8+ T cells in several cancer types. Little is known, however, about the involvement of the immune system in extramammary Paget's disease (EMPD). We examined the cytotoxicity and the effector functions of CD8+ T cells using paired samples of peripheral blood and tumors by flow cytometry. Expression levels of perforin, granzyme B, IFN-g, TNF-a, and IL-2 in CD8+ tumor-infiltrating lymphocytes (TILs) were significantly lower than those in CD8+ T cells of peripheral blood. Significantly higher expression of PD-1 was found in CD8+TILs than in CD8+ T cells of peripheral blood. A high number of CD8+ cells was significantly associated with poor overall survival (OS) adjusted with age, sex, and clinical stage (hazard ratio [HR] = 5.03, P = 0.045, 95% confidence interval [CI] 1.03-24.4). On the other hand, the number of PD-1+ cells was not associated with OS or disease-free survival (DFS). Moreover, we found that tumor cells produced immunosuppressive molecule indoleamine 2,3-dyoxygenae (IDO). In conclusion, CD8+ TILs displayed an exhausted phenotype in EMPD. IDO expression seemed more relevant in inducing CD8 exhaustion than PD-1 upregulation or PD-L1 expression by immune cells. Restoring the effector functions of CD8+ TILs could be an effective treatment strategy for advanced EMPD.

Immune checkpoint blockade (ICB) induces a remarkable response in patients with certain cancers. However, the response rate is not yet satisfactory. Biomarkers that help physicians identify patients who would benefit from ICB need to be developed. Killer immunoglobulin-like receptors (KIRs) are a class of receptors that are mainly expressed by natural killer cells. KIR genotypes have been shown to influence the outcomes of patients with neuroblastoma and hematopoietic malignancies. KIRs may thus influence the clinical outcomes of melanoma patients receiving nivolumab. We aimed to identify the KIR genotype, or KIR/KIR-ligand combinations, which influence the outcomes of melanoma patients receiving nivolumab. We genotyped 112 melanoma patients who were treated with nivolumab for KIR and human leukocyte antigen. The clinical records of the patients were analyzed to determine if they showed a response to nivolumab, and whether or not they experienced adverse events. Our analysis showed that no KIR gene was associated with a response to nivolumab. The KIR/KIR-ligand combination did not correlate with a response to nivolumab. KIR genes were not predictive of experiencing adverse events of grade 2 or greater. We conclude that the KIR genotype or KIR/KIR-ligand genotype do not show predictive value in melanoma patients receiving nivolumab.

BACKGROUND: Repetitive frictional trauma can be induced in daily and occupational activities, such as daily ablutions with washcloths. The influence of frictional trauma on the skin barrier function, especially in the perspective of the components of stratum corneum (SC), has not yet been studied in detail. Raman spectroscopy is a noninvasive optical technique based on inelastic light scattering that is capable of measuring several components in the skin. In this study, we used Raman spectroscopy to investigate the change in natural moisturizing factor (NMF) components in the SC following repetitive physical friction. METHODS: Six healthy volunteers, who were included in the study after obtaining an informed consent, performed repetitive washing with soap using nylon towels on the forearm twice a day for 2 weeks and used Raman spectroscopy to investigate the change in NMF components in the SC. RESULTS: Compared with the control, which was washed with soap at the same frequency on the opposite forearm, a significant increase in the transepidermal water loss (TEWL) and a decrease in NMF, serine, and total lactate, responsible for maintenance the SC hydration and structuring and maintaining the epidermal barrier function, in the SC were found. CONCLUSIONS: Increased TEWL and decreased NMF are considered as an etiology of atopic dermatitis (AD); therefore, our findings provide evidence that daily activities with repetitive frictional trauma may be related to the predisposition of AD.

78歳，男性。5年前に発熱，呼吸困難を伴う肺炎，痒みを伴う皮疹を生じ，ステロイド内服を開始した。以後ステロイド減量により紅斑を再燃する経過を繰り返し，そのために5年来ステロイドを服用していた。悪性腫瘍の合併は認めなかった。前医でも薬疹が疑われたが患者の申告では内服薬はないとのことであり，皮疹の精査を目的に当科に紹介された。当院受診後，フルバスタチンがかかりつけ医で処方されていた事が判明した。処方した医師に問い合せ，7年前からの処方が判明した。フルバスタチン中止後，皮疹は2週間以内に消失し，以後9ヶ月間再燃はない。しかし，CT 上間質性肺炎の所見は残存している。フルバスタチンにより誘発された薬疹と肺炎と考えた。薬剤内服後2年後の発症であった点，再燃時にもステロイド内服中止から再発までしばらくの期間を要する点からアレルギー性の薬疹にしては非典型的である。(皮膚の科学，9: 526-531, 2010)

皮膚アレルギー疾患、例えばアトピー性皮膚炎患者の多くはかゆみを有しているが、そのメカニズムの詳細についてはまだ不明な部分が多い。また近年の報告で、アトピー性皮膚炎患者では、症状の増悪時に皮膚常在細菌叢の菌の種類が著しく減少し、黄色ブドウ球菌が過半数を占めると報告されている。そこで、我々は黄色ブドウ球菌の死菌をマウス耳介に塗布し慢性皮膚炎を誘発し、皮膚末梢神経と免疫細胞の役割について検証した。その中で、皮膚末梢神経と好塩基球が協調して黄色ブドウ球菌誘発皮膚炎の形成に寄与していることが分かった。

掻痒は生活の質を低下させる身体症状の一つである。特に既存の治療では効果が不十分な事から新規治療法の開発は緊要の課題である。 これまでにアトピー性皮膚炎（AD）患者や乾皮症患者では多数の知覚神経線維が表皮内に侵入し、増生する。そこで我々は、皮膚透明化（CUBIC）の手法を用い、様々なマウスアレルギー性皮膚炎モデルにおける皮膚内の末梢神経の動態を観察した。イミキモド誘発乾癬様皮膚炎モデルにおいても、病変部の表皮内に神経線維の増生を認めた。また、VEGF-Aが表皮内神経線維の増生を促し、乾癬モデルマウスにおける掻痒の病態形成に関与している可能性が示唆された。