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DOI： 10.1111/j.1365-2249.2005.02709.x

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DOI： 10.1093/intimm/dxh171

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Journal of Allergy and Clinical Immunology: Global  

Background: Atopic dermatitis (AD) is a common chronic eczematous skin disease with severe pruritus. Several new therapeutic agents for AD such as dupilumab, an anti–IL-4Rα antibody, have been developed in recent years. We need to predict which agent is the best choice for each patient, but this remains difficult. Objective: Our aim was to examine clinical background factors and baseline biomarkers that could predict the achievement of improved clinical outcomes in patients with AD treated with dupilumab. Methods: A multicenter, prospective observational study was conducted on 110 patients with AD. The Eczema Area and Severity Index was used as an objective assessment, and the Patient-Oriented Eczema Measure and Numerical Rating Scale for Pruritus were used as patient-reported outcomes. In addition, some clinical background factors were evaluated. Results: The achievement of an absolute Eczema Area and Severity Index of 7 or less was negatively associated with current comorbidity of food allergy and baseline serum lactate dehydrogenase (LDH) levels. There were negative associations between achievement of a Patient-Oriented Eczema Measure score of 7 or less and duration of severe AD and between achievement of an itching Numerical Rating Scale for Pruritus score of 1 or less and current comorbidity of allergic conjunctivitis or baseline serum periostin level. Furthermore, signal detection analysis showed that a baseline serum LDH level less than 328 U/L could potentially be used as a cutoff value for predicting the efficacy of dupilumab. Conclusion: Baseline biomarkers such as LDH and periostin and clinical background factors such as current comorbidity of food allergy and a long period of severe disease may be useful indicators when choosing dupilumab for systemic treatment for AD, as they can predict the efficacy of dupilumab.

DOI： 10.1016/j.jacig.2024.100317

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Language：English  

DOI： 10.1016/j.alit.2024.08.010

PubMed

Language：Japanese   Publisher：日本皮膚科学会西部支部  

<p><b>患者</b>：42 歳，女性 </p><p><b>主訴</b>：頭部に多発する皮下結節 </p><p><b>現病歴</b>：高校生の頃に頭部の皮下結節を 2 カ所自覚した。半年前より増大，増数傾向であったため，精査目的に当科を受診した。 </p><p><b>家族歴</b>：父に外毛根鞘囊腫の切除歴があるが，単発か多発かは不明 </p><p><b>既往歴</b>：子宮内膜症，虫垂炎 </p><p><b>臨床像</b>：頭部に 1～2 cm の下床と可能性良好で弾性硬な皮下結節を計 9 カ所認めた（<b>図 1</b>）。爪病変はなかった。 </p><p><b>造影 MRI</b>：頭部に多発する皮下結節を認めた。大きさは最小 7 mm，最大 2.1 cm で，病変は T2W1 で低信号を示した（<b>図 2</b>）。 </p><p><b>治療および経過</b>：局所麻酔下に本人が希望した 4 カ所の皮下結節を摘出した。摘出した皮下結節は肉眼的には白色の壁の厚い囊腫であった（<b>図 3</b>）。いずれの病変も病理組織学的所見より外毛根鞘囊腫と診断した。5 カ所の残存病変も切除する方針となった。 </p><p><b>病理組織学的所見</b>：囊腫状病変で内部には好酸性の角化物を含んでいた。重層扁平上皮からなる囊腫壁と顆粒層を経ずに角化する外毛根鞘性角化を認めた（<b>図 4 a，b</b>）。多房性の囊腫状腫瘍は認めず，増殖性外毛根鞘囊腫の所見は認めなかった。</p>

DOI： 10.2336/nishinihonhifu.86.359

CiNii Research

Language：English   Publisher：JAMA Dermatology  

Importance: Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important. Objective: To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD. Design, Setting, and Participants: The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023. Exposures: At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals. Main Outcomes and Measures: The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline. Results: A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study. Conclusions and Relevance: In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.

DOI： 10.1001/jamadermatol.2024.1536

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Language：English   Publisher：Journal of Dermatology  

Clinical trials of biologics have frequently excluded elderly patients, resulting in inadequate data on their safety and efficacy. Additionally, evidence of their safety and efficacy remains limited, despite some real-world studies. To assess the safety and efficacy of biologics in elderly patients with psoriasis, we compared these outcomes in younger patients using data from the West Japan Psoriasis Registry (WJPR). The WJPR consists of approximately 30 facilities in Western Japan, including various healthcare settings. This study enrolled 1395 patients who participated in the 2022 follow-up survey of the WJPR and were either using or had used biologics during the survey. These included 456 patients in the elderly group (≥65 years) and 939 patients in the younger group (<65 years). Treatment-ending adverse events (TEAEs) occurred in 15.8% and 11.3% of elderly and younger patients, respectively. The incidence rate per 1000 patient-years (PY) for TEAEs was significantly higher in elderly patients than in younger patients (32.9 vs 23.2, p = 0.0234). Infectious diseases were more prevalent in the elderly group than the younger group; however, no significant difference in the frequency of infectious diseases was found between the two groups (p = 0.0807). Malignant neoplasms occurred significantly more frequently in the elderly group than in the younger group (p = 0.0169). Our results indicate a few concerns about infection when prescribing biologics to elderly patients. Biologics were effective for both elderly and younger patients. We found no significant differences in the proportion of patients with a body surface area score ≤3%, Physician's Global Assessment score 0/1, or Patient's Global Assessment score 0/1, as well as in the mean Dermatology Life Quality Index and the Itch Numerical Rating Scale between the younger and the elderly groups. Overall, our results confirm the appropriateness of using biologics in elderly patients with regard to safety and efficacy.

DOI： 10.1111/1346-8138.17385

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Language：Japanese   Publisher：日本小児皮膚科学会  

発達障害とアトピー性皮膚炎との関連は多く報告されている。発達障害のあるアトピー性皮膚炎患者は掻破行動の異常や感覚過敏の合併などにより,治療に難渋し,難治となることがある。突発的な感情で強く掻破し,傷をつける行動がみられることも多い。また,新規治療薬の導入に対して,抵抗が大きいこともある。今回,発達障害・感覚過敏を伴う重症のアトピー性皮膚炎患者2例に対して,注射の本数,用量,頻度,検査の必要性を考慮したうえで,最もストレスが少ないと考えられたネモリズマブを選択し,治療導入した。2例ともに投与翌日に痒みが軽減し,患者自身が治療効果を実感した。掻破行動は軽減し,1回の投与後に炎症に対しても予想以上の効果が示された。IL-31シグナルをブロックすることで感覚過敏の状態が明らかに軽減していると考えられ,ネモリズマブは感覚過敏を有する,掻破行動が著しいアトピー性皮膚炎患者の治療選択肢となりうると考えられた。(著者抄録)

Language：English   Publisher：Journal of Dermatology  

DOI： 10.1111/1346-8138.17318

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Language：English   Publisher：International Journal of Molecular Sciences  

Difamilast, a phosphodiesterase 4 (PDE4) inhibitor, has been shown to be effective in the treatment of atopic dermatitis (AD), although the mechanism involved remains unclear. Since IL-33 plays an important role in the pathogenesis of AD, we investigated the effect of difamilast on IL-33 activity. Since an in vitro model of cultured normal human epidermal keratinocytes (NHEKs) has been utilized to evaluate the pharmacological potential of adjunctive treatment of AD, we treated NHEKs with difamilast and analyzed the expression of the suppression of tumorigenicity 2 protein (ST2), an IL-33 receptor with transmembrane (ST2L) and soluble (sST2) isoforms. Difamilast treatment increased mRNA and protein levels of sST2, a decoy receptor suppressing IL-33 signal transduction, without affecting ST2L expression. Furthermore, supernatants from difamilast-treated NHEKs inhibited IL-33-induced upregulation of TNF-α, IL-5, and IL-13 in KU812 cells, a basophil cell line sensitive to IL-33. We also found that difamilast activated the aryl hydrocarbon receptor (AHR)–nuclear factor erythroid 2-related factor 2 (NRF2) axis. Additionally, the knockdown of AHR or NRF2 abolished the difamilast-induced sST2 production. These results indicate that difamilast treatment produces sST2 via the AHR–NRF2 axis, contributing to improving AD symptoms by inhibiting IL-33 activity.

DOI： 10.3390/ijms25147910

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Language：Japanese   Publisher：日本皮膚科学会西部支部  

<p><b>患者</b>：38 歳，女性</p><p><b>主訴</b>：右足底の黒色小結節</p><p><b>既往歴</b>：盲腸で手術，誤嚥性肺炎後に右下肢麻痺，右大転子部の褥瘡手術</p><p><b>現病歴</b>：初診の約 1 年前に右足底の土踏まずに血豆のような黒いものが出現し，次第に表面がガサガサしてきて大きく硬く盛り上がってきたため当科を受診した。</p><p><b>初診時現症</b>：右足底の土踏まずに径 6 mm の角化を伴う黒色小結節がみられ（<b>図 1 a</b>），拡大すると黒色の小塊が一部角層を破って露出しているようにみえた（<b>図 1 b</b>）。ダーモスコープでは white scales や dark red scabs と呼ばれる過角化と blue-whitish veil，および maroon to blue-black lacunae と呼ばれる，大小の黒色，黒褐色，黒青色の結節構造がみられた（<b>図 1 c</b>）。</p><p><b>病理組織学的所見</b>（HE 染色）：著明な過角化を伴う表皮肥厚がみられ，真皮乳頭層で拡張した壁の薄い血管が増生，集簇し，血管腔内には赤血球が充満して血栓を形成していた。増生した血管群を取り囲むように表皮突起の延長がみられ（<b>図 2 a</b>），表皮直下に位置する拡張血管の一部では実際に表皮突起が閉環している像もみられた（<b>図 2 b</b>）。また，角層内には取り込まれた血栓が幾重にも重層している像もみられた（<b>図 2 c</b>）。</p><p><b>診断</b>：Thrombosed solitary angiokeratoma</p><p><b>治療および経過</b>：2 mm マージンでの切除により病変は消失した。</p>

DOI： 10.2336/nishinihonhifu.86.211

CiNii Research

Language：English   Publisher：Antioxidants  

Semaphorin 3A (SEMA3A), a nerve-repellent factor produced by keratinocytes, has an inhibitory effect on nerve extension to the epidermis. Epidermal innervation is involved in pruritus in inflammatory skin diseases such as atopic dermatitis (AD) and dry skin. We previously reported that tapinarof, a stilbene molecule, upregulates SEMA3A in human keratinocytes. We also showed that this mechanism is mediated via the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, and the nuclear factor erythroid 2-related factor 2 (NRF2) axis. Since some stilbenes activate AHR and NRF2, we attempted to identify other stilbenes that upregulate SEMA3A. We analyzed normal human epidermal keratinocytes (NHEKs) treated with 11 types of stilbenes and examined SEMA3A expression. We found that resveratrol and pinostilbene, antioxidant polyphenols, upregulated SEMA3A and increased nuclear AHR and NRF2 expression. In addition, AHR knockdown by small interfering RNA (siRNA) transfection abolished the NRF2 nuclear expression. Furthermore, AHR and NRF2 knockdown by siRNA transfection abrogated resveratrol- and pinostilbene-induced SEMA3A upregulation. Finally, we confirmed that resveratrol and pinostilbene increased SEMA3A promoter activity through NRF2 binding using ChIP-qPCR analysis. These results suggest that resveratrol and pinostilbene upregulate SEMA3A via the AHR–NRF2 axis in human keratinocytes.

DOI： 10.3390/antiox13060732

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1346-8138.15156.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.alit.2019.10.003.

Publisher：Journal of Cutaneous Immunology and Allergy  

Background: The nature of itch sensation varies depending upon the patient and the disease. However, few studies have focused on verbal expressions describing itch of atopic dermatitis (AD) in quality. Objectives: To investigate itch quality in patients with AD compared with that of urticaria. Methods: We conducted an online questionnaire survey describing itch experiences in June 2021. Participants were Japanese patients who had visited hospitals for their consultations and treatments of AD or urticaria in the last 6 months, and 295 and 290 responses, respectively, to questions using 12 terms describing itch quality were analyzed. Results: The most suitable expression describing intense itch that patients could not help scratching differed between the diseases, where most AD patients selected “muzumuzu” (a mimetic word for creepy–crawly itch) (27%) or “painful itch” (20%), and most urticaria patients selected “muzumuzu” (24%) or “itch like mosquito bites” (22%). The most suitable expressions describing itch that would make patients happiest if improved was “painful itch” (27%) in AD patients, significantly higher than urticaria patients (19%). More AD patients (55%) responded that they sometimes felt itch even after the skin symptoms had subsided than urticaria patients (41%). The most suitable expression of remnant itch selected was “muzumuzu” for AD (58/161 patients, 36%) and urticaria (29/120 patients, 24%). Conclusion: The quality of itch sensations can be classified not only between diseases but also during the clinical course of each disease. Significant expressions that patients with AD use to describe itch sensations could promote more appropriate treatment for itch.

DOI： 10.3389/jcia.2024.12578

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/ijms23073467

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DOI： 10.1111/ijd.16181

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Publisher：Traditional and Kampo Medicine  

Background: Yusho is a 1968 mass food poisoning that was caused by the ingestion of rice oil contaminated with dioxins and related organochlorines. We previously reported that keishibukuryogan (KBG) administration was effective for improvement of the symptoms of Yusho patients. This study used responder analysis to more deeply elucidate the effectiveness of KBG. Method: The data analyzed in the study were collected from our previous clinical study done to predict response to KBG treatment. The patients were divided into responders and non-responders based on whether their symptoms improved after taking KBG. We assessed baseline patient characteristics and the intensity of general fatigue and dermatological, neurological, and respiratory symptoms. Further, we used SF-36 to evaluate Quality of Life (QOL). Results: Of the 42 patients who completed the previous study, 27 were responders and 15 non-responders, with no significant differences in the patient characteristics. The general fatigue, dermatological symptoms, and respiratory symptoms of responders were significantly improved at month 3 of treatment. Analysis of the eight QOL domain profiles of SF-36 showed that the general health of responders was significantly improved from baseline to month 3 compared with non-responders, as was vitality from baseline to month 1. Moreover, the mental health of responders significantly improved from baseline to months 1 and 3. Conclusions: Keishibukuryogan was not only effective for symptoms such as general fatigue, dermatological symptoms, and respiratory symptoms, but also for the mental health of Yusho patients, which indicates that it would be a good first-choice Kampo medicine for the treatment of these patients.

DOI： 10.1002/tkm2.1400

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Publisher：Journal of Cutaneous Immunology and Allergy  

Data on the problems physicians face when providing care for atopic dermatitis (AD) is limited. To understand the current status of AD management in Japan and identify the difficulties physicians are having and their support requirements, a cross-sectional online survey was conducted using the AD task force of the Japanese Society for Cutaneous Immunology and Allergy. Society members were sent an online questionnaire on demographic information, daily clinical practice, and perceptions of AD management. Using responses to 17 items listed as barriers to the treatment of atopic dermatitis (Question 12) and questions about the treatment difficulty of those items, 284 respondents were divided into three groups using unstratified cluster analysis. These three groups were classified as high-difficulty, medium-difficulty, and low-difficulty groups, and the relationship between physicians’ cognition and daily practice was examined for each group. There were no significant differences in affiliations or specializations among the three clusters. The low-difficulty group had a significantly higher proportion of participants believing that it was possible to achieve long-term remission, satisfaction, and motivation in AD management while carrying out precise assessments of skin lesions as part of their daily practice. Some physicians experience problems in their practice. This results indicate that AD management can be improved if satisfaction and motivation can be increased by providing appropriate support.

DOI： 10.3389/jcia.2024.12567

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DOI： 10.1016/j.jid.2023.10.002

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DOI： 10.1111/jocd.16034.

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DOI： 10.1111/exd.15049

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：English   Publisher：Journal of Cosmetic Dermatology  

Background: Daily skin care is important for treatment of skin diseases, but few studies have reported on appropriate washing methods. Aim: This study aimed to provide guidance on washing techniques and examine changes in skin condition after using the recommended washing technique and foaming-type skin cleanser in patients with atopic or asteatotic dermatitis. Methods: An internet-based questionnaire survey on skin symptoms and cleaning methods was conducted. Further, a left–right comparative, nonrandomized trial was performed in 19 patients with asteatotic or atopic dermatitis and xerosis. Participants were instructed to wash with a cotton towel and their normal cleanser during Weeks 1–4 and with bare hands or a cotton towel and the recommended foaming-type cleanser during Weeks 5–8. Results: The survey revealed that the degree of lathering differed depending on the cleaning tool. In the trial, scores for erythema, desquamation, and xerosis in the lower legs were significantly reduced after 4 weeks compared with scores at the start. Between Weeks 4 and 8, scores for erythema, xerosis, and pruritus in the inner forearm on the side washed with bare hands and scores for xerosis, pruritus, and excoriation on the side washed with a cotton towel were significantly reduced. A significant increase was noted in stratum corneum ceramide content on both left and right inner forearms, whereas a significant decrease was noted in stratum corneum thymus and activation-regulated chemokine level ratios in the lower legs on both sides. Conclusions: Xerotic skin disease symptoms can be improved using appropriate body washing methods.

DOI： 10.1111/jocd.16034

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

【背景・目的】アトピー性皮膚炎患者が最も困っている症状である痒みに着目した治療には適切な痒み評価が必要である.痒み治療や研究に精通した医師および研究者で構成されるアトピー性皮膚炎痒みコンセンサス会議において,痒み評価の課題および最適な痒み評価法を協議した.【方法】2歳未満,2～6歳,7～14歳,15歳以上の年齢区分について,最適な痒み評価法のコンセンサス案を作成した.会議参加者の80%以上の同意をもってコンセンサスが得られたと定義した.【結果】参加者20名(皮膚科医8名,小児科医7名,研究者5名)の投票の結果,同意率95%で現状の最適な痒み評価法のコンセンサスが得られた.また,乳幼児は主観評価が困難であるため,養育者が代わりに行う痒み評価のチェックリストを作成した.【結語】患者本人による評価尺度を用いた痒みの主観評価あるいは乳幼児では養育者によるチェックリストを用いた評価と,医師による皮膚病変などの客観評価を組み合わせた評価が推奨される.今後,より客観的な痒み評価指標の確立が期待される.(著者抄録)

Language：English   Publisher：Scientific Reports  

Extramammary Paget disease (EMPD) is a rare skin cancer that primarily affects older individuals predominantly in areas with apocrine sweat glands. Although most early EMPD lesions are indolent, patients with metastatic EMPD have a poor prognosis due to the lack of effective systemic treatment. In this study, we investigated the role of forkhead box M1 (FOXM1), a potent transcription factor, in EMPD and assessed the potential of FOXM1 as a therapeutic target. Immunohistochemistry of 112 primary and 17 metastatic EMPD samples revealed that FOXM1 expression increased with tumor progression. Patients in whom FOXM1 was expressed in more than 10% of tumor cells had significantly shorter disease-specific survival than the other patients (p = 0.0397). In in vitro studies using our newly established EMPD cell line, KS-EMPD-1, we found high expression of FOXM1. Knockdown of FOXM1 impaired tumor cell viability, migration, and invasion. Inhibition of FOXM1 using thiostrepton also reduced tumor cell viability in a dose-dependent manner. These findings suggest that FOXM1 is a promising therapeutic target for patients with EMPD.

DOI： 10.1038/s41598-024-54773-8

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DOI： 10.3389/jcia.2024.12476

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.86.55

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-024-54773-8.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/jog.15832.

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

症例は25歳女性で、PRKAR1A変異を伴うカーニー複合を有していた。10年前に両側卵巣の成熟性嚢胞性奇形腫と診断され、その後、両側嚢胞が増大したためそれらを切除した。切除嚢胞の臨床的観察において異常メラノサイトを含む黒色結節を認め、悪性黒色腫の発生が疑われた。病理組織検査では、黒色病変は円形のheavily pigmented cellから構成され、それらの細胞はvesicular nucleiおよび単一の明瞭な核小体を有していた。さらに核形不整を示す大型細胞を認めた。免疫組織化学染色では、不整形な大型細胞はMelan A、HMB45、S-100タンパク質、SOX10、CD10(限局性)、BRAFV600Eに陽性を示し、PRAMEは陰性であった。これらの病理組織所見から、奇形腫から発生したpigmented epithelioid melanocytomaと診断された。

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

症例1は67歳,男性。当科初診5年前に骨髄異形成症候群に対し同種造血幹細胞移植をし,ボリコナゾール(VRCZ)を内服していた。4ヵ月前から頭頂部に生じた有棘細胞癌(SCC)に腫瘍切除と分層植皮,術後放射線照射を行ったが,右頸部リンパ節転移及び局所再発した。5ヵ月後に頭蓋骨外板含めた拡大切除,右側頸部リンパ節郭清と耳下腺を摘出し,皮弁形成と全層植皮で再建した。再手術25日後にSCCの肝転移が判明し,1年5ヵ月後にSCCで死亡した。症例2は77歳,男性。当科初診13年前に急性リンパ性白血病で臍帯血移植後,8年前より肺アスペルギルス症でVRCZを内服していた。1年前より頭頂部に生じた疣贅状皮疹から転じたSCCで,腫瘍切除と人工真皮植皮を行った。術後は創部感染を繰り返し,6～7ヵ月後に頭蓋骨外板を含めた拡大切除と分層植皮を行ったが,術後は次第に体力が低下し,10ヵ月後に急性腎不全,基礎疾患により死亡した。VRCZによる光線過敏症とSCC発症の本邦報告は未だ少ないが,SCCの侵襲度が高く予後不良例も多い傾向である。VRCZ長期内服患者は基礎疾患も多彩で,高齢,免疫抑制状態など発癌リスク・予後不良因子を併せ持つ患者が多く,遮光指導,定期的な皮膚観察に加え,SCCの病期進行前の早期発見が重要と思われる。今回VRCZの長期内服中に生じ,予後不良であったSCCの2症例を本邦既報例と併せ報告する。(著者抄録)

Language：Japanese   Publisher：(株)協和企画  

＜文献概要＞症例のポイント　・体幹に発生し巨大化した皮下腫瘍であり,類表皮嚢腫や粘液癌,脂肪肉腫との鑑別を要した.・全切除標本の病理組織学的診断で診断確定に至った.

Language：English   Publisher：Journal of Allergy and Clinical Immunology: Global  

Background: To develop precision medicine for atopic dermatitis (AD), it is critical to establish relevant biomarkers. However, the characteristics of various biomarkers have not been fully understood. We previously carried out the Biomarkers to Predict Clinical Improvement of AD in Patients Treated with Dupilumab (B-PAD) study, a comprehensive nationwide study in Japan, to explore biomarkers for AD. Objective: The aim of this study is to find biomarkers associated with objective and subjective clinical findings in patients with moderate-to-severe AD based on the B-PAD study and to identify biomarkers sensitive enough to assess the severity of AD. Methods: We performed the B-PAD study as a consortium composed of 19 medical facilities in Japan, enrolling 110 patients with moderate-to-severe AD. We evaluated the Eczema Area and Severity Index (EASI) for objective assessment as well as the Patient-Oriented Eczema Measure (POEM) and a numeric rating scale for pruritus (pruritis-NRS) for subjective assessment, measuring 19 biomarkers at baseline. Results: We found that 12, 6, and 7 biomarkers showed significant and positive associations with the EASI, POEM, and pruritis-NRS, respectively. Most of the biomarkers associated with either the POEM or the pruritis-NRS were included among the biomarkers associated with EASI. Of the biomarkers examined, CCL26/eotaxin-3 and SCCA2 were the most capable of assessing severity for EASI, as shown by the 2 kinds of receiver operating characteristic analyses, respectively, whereas lactate dehydrogenase was the best for both the POEM and pruritis-NRS, again using the 2 analyses. Conclusion: We found biomarkers associated with the EASI, POEM, and pruritis-NRS, respectively, based on the B-PAD study. Moreover, we identified CCL26/eotaxin-3 and/or SCCA2 as the biomarkers having the greatest ability to assess severity in the EASI; lactate dehydrogenase did the same for the POEM and pruritis-NRS. These findings will be useful in treating patients with moderate-to-severe AD.

DOI： 10.1016/j.jacig.2023.100175

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Language：English   Publisher：Journal of Obstetrics and Gynaecology Research  

A 25-year-old female Carney complex patient with a PRKAR1A mutation who had undergone surgery to remove teratomas visited our dermatology department. She was suspected of having a malignant melanoma in a teratoma. On clinical examination, a black nodule was found within the cyst. On histopathological examination, the black lesion was composed of heavily pigmented round cells with vesicular nuclei and single prominent nucleoli. Additionally, there were large cells with irregularly shaped nuclei. Upon immunohistochemical examination, the large, irregularly shaped cells were positively stained with Melan A, HMB45, S-100 protein, SOX10, CD10 (focally), and BRAFV600E, but negatively stained with PRAME. Based on the histopathological features, we diagnosed the patient with pigmented epithelioid melanocytoma (PEM) in a teratoma of a Carney complex patient. This is the first case of PEM developing from a teratoma. Since PEM lesions may spread to regional lymph nodes, careful follow-up is necessary.

DOI： 10.1111/jog.15832

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Language：English   Publisher：Japan Society of Plastic and Reconstructive Surgery  

<p>Burn, a common injury in daily life, is a potential risk factor for severe sequelae in people, particularly children. Preventing unexpected burn injuries is of the utmost importance. This study examined the current status of pediatric burns in our institute. One hundred children who received intensive therapy in Kyushu University Hospital were analyzed regarding the causes, sites, severity, treatments, and outcomes of burns between 2004 and 2021. The mean patient age was 2.4 years (range: 0-15), and 90% of patients were 6 years old or younger. The mean percent total body surface area was 12.7%. All patients had second- or third-degree burns. The most common cause was scalding (93%), and among them, hot water burns, and kettle burns were predominant in 49.5% and 24.7% of children, respectively. The seasonal fluctuations of occurrence were not remarkable. Basic fibroblast growth factor spray with wet dressing was used, but hypertrophic scars arose in 39 patients. The mean duration of hospitalization was 18.9 ± 18.2 days. This study revealed that more than 90% of pediatric burns were caused by hot liquids, thereby highlighting the importance of educational activities for parents to prevent and reduce pediatric burns because most scalding burns can be avoided with caution.</p>

DOI： 10.53045/jprs.2023-0005

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DOI： 10.1200/JCO.2024.42.3_suppl.493

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Language：English   Publisher：(一社)日本形成外科学会  

Language：English   Publisher：Japanese Society of Allergology  

DOI： 10.1016/j.alit.2023.12.001

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Language：English   Publisher：Frontiers in Medicine  

Background: Anti-programmed death-1 (PD-1) antibodies are the mainstay for the treatment of unresectable or high-risk melanoma. However, real-world data on the safety profile of their extended-interval doses (EDs) are limited, particularly in Asian patients with melanoma. Materials and methods: In this single-center retrospective study, we analyzed the risks of immune-related adverse events (irAEs) among 71 Japanese patients (36 males; mean age, 65.0 years) who received anti-PD-1 monotherapy for melanoma at our institute. Patients who were administered ipilimumab prior to anti-PD-1 monotherapy were excluded. Patients were divided into three groups: canonical-interval dose (CD) group (n = 50, body weight-based dosing or 240 mg Q2W for nivolumab and body weight-based dosing or 200 mg Q3W for pembrolizumab), ED group (n = 14, 480 mg Q4W for nivolumab and 400 mg Q6W for pembrolizumab), and dose-switch (DS) group (n = 7, upfront CD followed by ED). Results: The CD group received nivolumab more frequently in the metastatic setting. There were no significant differences in baseline characteristics among the three groups, including in sex, age, primary tumor site, tumor subtype, and follow-up period. irAEs occurred in 36.6% (26 patients) of all patients (32.0% of the CD group, 35.7% of the ED group, and 71.4% of the DS group), while severe (grade ≥ 3) irAEs occurred in only two patients, both of whom were in the CD group. Most of the irAEs occurred during the first 6 months of anti-PD-1 therapy and, interestingly, all of the irAEs in the DS group occurred before the switch (during the CD). There was no significant difference among the three groups in the probability of irAE estimated by the Kaplan–Meier method. Conclusion: These findings may highlight the safety of ED of anti-PD-1 monotherapy in the treatment of Asian patients with melanoma.

DOI： 10.3389/fmed.2023.1293397

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/bjd/ljad344

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3389/fmed.2023.1293397.

Publisher：Iranian Journal of Dermatology  

Dermoscopy helps detect melanoma on the acral volar skin. A parallel ridge pattern is one of the characteristic dermoscopic findings of melanoma but is also seen in benign lesions, including drug-induced hyperpigmentation. Histological examination is therefore necessary for definitive diagnosis. A 74-year-old Japanese man was referred to our department with irregular-shaped brown macules on his palms and soles. The pigmented lesions had a parallel ridge pattern on dermoscopic examination. The largest lesion was resected at the patient’s insistence and considering the possibility of melanoma. Histopathological examination revealed increased melanin granules in basal keratinocytes and many melanophages in the superficial dermis, especially underlying the crista profunda intermedia, agreeing with the dermoscopic findings. The patient had been receiving tegafur-gimeracil-oteracil (TS-1) for advanced gastric cancer. The pigmented lesions gradually regressed after cessation of TS-1, consistent with TS-1-induced hyperpigmentation. Further studies are needed to elucidate the pathogenesis, including analyses of the relationship between acrosyringeal endothelin-1 expression and the presence of volar melanocytes in relation to potential drug metabolism.

DOI： 10.22034/ijd.2022.283963.1364

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

【背景・目的】アトピー性皮膚炎の長期コントロール指標であるRecap of atopic eczema(RECAP)の日本語版の作成と言語検証を行った.【方法】翻訳過程は2つの独立した順行性翻訳,英語のネイティブスピーカーを交えた調整,第三者による逆行性翻訳,認知デブリーフィング,専門家によるレビューと修正,原著者による調和が含まれた.認知デブリーフィングでは設問項目のわかりやすさ,包括性,関連性について患者を対象に面接を行った.【結果】順行性及び逆行性翻訳において言語上の問題は生じなかった.認知デブリーフィングは成人患者10名と小児患者の保護者10名に実施された.国内の専門家を含む研究チームと原著者による協議によって,必要に応じた修正が行われた.日本語版RECAPは多くの患者とその家族にとって理解しやすく,包括的で関連性があった.【結語】原版との翻訳妥当性が検証された日本語版RECAPが完成した.今後は測定特性についてのさらなる評価が必要である.(著者抄録)

Language：Japanese   Publisher：Japanese Dermatological Association  

<p>For right breast cancer, 42-year-old female underwent total right mastectomy and breast reconstruction with abdominal flaps in May 20XX, and two revisions in October 20XX+1 and November 20XX+2. In January 20XX+1, erythema appeared in part of the surgical scar of the right breast and showed a gradual tendency to expand, but no treatment intervention was provided. The edematous erythema invading the entire suture line of the right breast and hyperpigmentation with scaling around the erythema were diagnosed as nummular eczema, and topical steroid treatment was started. It is important for dermatologists to recognize that nummular eczema may occur after breast reconstruction surgery and to encourage moisturizing and early therapeutic intervention.</p>

DOI： 10.14924/dermatol.133.2849

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.85.366

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2340/actadv.v103.12345

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jdermsci.2023.07.008.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1684/ejd.2023.4568.

Language：English   Publisher：Journal of Dermatological Science  

Background: Bullous pemphigoid (BP) is an autoimmune bullous disease in which abundant eosinophils accumulate in the blisters. Galectin-10 abounds in the cytoplasm of eosinophils and is released as a result of eosinophil extracellular trap cell death (EETosis). Objective: To identify EETosis and the pathological roles of galectin-10 in BP. Methods: EETosis and galectin-10 in BP blisters were confirmed by immunofluorescence and transmission electron microscopy. The concentrations of galectin-10 in serum and blister fluid from BP patients were studied by ELISA. The matrix metalloproteinase (MMP) expression in BP blisters was immunohistochemically compared to that in healthy controls. As an in vitro assay, normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) were stimulated with galectin-10, followed by MMP expression measurement by real-time PCR and ELISA. The signaling pathways activated by galectin-10 were studied using Western blotting and confirmed by inhibition assays. Results: Galectin-10-containing eosinophil infiltration and the extracellular deposition of major basic protein were observed in BP blisters. The ultrastructural characteristics of tissue eosinophils indicated piecemeal degranulation and EETosis. In the BP patients, the concentration of galectin-10 was higher in the blister fluid than in the serum. Several types of MMPs were upregulated in BP blisters. Galectin-10 upregulated the production of MMPs through the pathways of p38 MAPK, ERK and JNK in NHEKs and NHDFs. Conclusion: In the BP blisters, the eosinophils underwent EETosis and released galectin-10. Galectin-10 might contribute to BP blister formation through the production of MMPs by keratinocytes and fibroblasts.

DOI： 10.1016/j.jdermsci.2023.07.008

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Language：Japanese   Publisher：日本皮膚科学会-西部支部  

46歳,男性。幼少時からアトピー性皮膚炎があり難治性のため当科受診3年前よりデュピルマブを投与されていた。1年前より左下腿前面に紅色丘疹が出現し前医の切除生検で皮膚原発性CD30陽性T細胞リンパ増殖症と診断され,精査加療目的に紹介された。当科初診時採血で好酸球増多があり,可溶性IL-2Rは若干高値で血液内科と併診し,全身CTやPETの画像検査で明らかな転移巣は認めなかった。近年,デュピルマブ(デュピクセント)の長期投与における皮膚T細胞性リンパ腫の発症の報告が増えているが関連性については不明な点も多く,更なる研究に加えて経過観察と症例蓄積が必要と考えられる。(著者抄録)

Language：English   Publisher：International Journal of Molecular Sciences  

Interleukin (IL)-33 and IL-37 have been identified as novel cytokines involved in various inflammatory diseases. However, their specific roles remain largely unknown. Recent studies have shown that IL-33, which triggers inflammation, and IL-37, which suppresses it, cooperatively regulate the balance between inflammation and anti-inflammation. IL-33 and IL-37 are also deeply involved in the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. Furthermore, a signaling pathway by which aryl hydrocarbon receptor (AHR), a receptor for dioxins, regulates the expression of IL-33 and IL-37 has been revealed. Here, we outline recent findings on the mechanisms regulating IL-33 and IL-37 expression in AD and psoriasis. IL-33 expression is partially dependent on mitogen-activated protein kinase (MAPK) activation, and IL-37 has a role in suppressing MAPK in human keratinocytes. Furthermore, IL-33 downregulates skin barrier function proteins including filaggrin and loricrin, thereby downregulating the expression of IL-37, which colocalizes with these proteins. This leads to an imbalance of the IL-33–IL-37 axis, involving increased IL-33 and decreased IL-37, which may be associated with the pathogenesis of AD and psoriasis. Therefore, AHR-mediated regulation of the IL-33–IL-37 axis may lead to new therapeutic strategies for the treatment of AD and psoriasis.

DOI： 10.3390/ijms241914633

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Language：English   Publisher：エルゼビア・ジャパン(株)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13577-023-00951-1

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Language：English   Publisher：European Journal of Dermatology  

DOI： 10.1684/ejd.2023.4568

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Language：English   Publisher：日本ヒト細胞学会  

新たに樹立された原発性乳房外Paget病(EMPD)細胞株KS-EMPD-1について述べた。当院で原発性EMPDと診断された86歳の日本人男性の左鼠径部腫瘍を外科切除し、腫瘍組織を細切後培養してKS-EMPD-1細胞を樹立した。KS-EMPD-1細胞は1年以上維持することが可能で、倍加時間は31.2±0.471時間であった。KS-EMPD-1細胞は持続的な増殖、スフェロイド形成及び浸潤性を示し、ショートタンデムリピート解析、全エクソームシーケンシング及び免疫組織染色により元の腫瘍と同じであった。ウェスタンブロッティングにて、KS-EMPD-1細胞はHER2、NECTIN4及びTROP2を発現していた。また、抗癌剤感受性試験においてKS-EMPD-1細胞はドセタキセルとパクリタキセルに対して高い感受性を示した。

Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.85.261

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Virchows Archiv  

Angiosarcoma is a malignant vascular endothelial neoplasm with various histological patterns. Despite its highly malignant potential, histological prognostic prediction has not been adopted for angiosarcoma. This study aimed to establish a method of predicting the prognosis of primary angiosarcoma. Formalin-fixed, paraffin-embedded samples from 104 primary angiosarcomas were prepared. All the cases were reviewed based on histological examinations with H&E staining. Because the French Fédération Nationale des Centres de Lutte Contre Le Cancer system (FNCLCC) is not adopted for angiosarcoma, we experimentally established a modified version of FNCLCC. Immunohistochemical staining for ERG, CD31, CD34, D2-40, HHV-8, p16, C-MYC, and p53 was performed. Fluorescence in situ hybridization (FISH) was performed for 31 cases to assay c-MYC gene amplification. Multivariate analysis revealed that age (> 70 years old) (p = 0.0011), non-cutaneous angiosarcoma (p = 0.0265), metastasis on diagnosis (p < 0.0001), size ≥ 5 cm (p = 0.0388), no taxane chemotherapy (p = 0.0388), strong nuclear atypia (p = 0.0087), and the presence of luminal structure in ≥ 50% of the tumor volume (p = 0.0009) were independent poor prognostic factors. Among angiosarcomas with luminal formation, mFNCLCC scores were significantly correlated with a poorer prognosis. The overexpression of p16 was associated with less luminal formation (p = 0.0192). Immunohistochemical analysis of C-MYC showed a moderate level of concordance with FISH (Kappa value = 0.45). This study suggested that luminal formation and nuclear atypia may be poor histological prognostic factors of angiosarcoma and that mFNCLCC would be useful for predicting the prognosis of angiosarcoma with luminal formation.

DOI： 10.1007/s00428-023-03572-z

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DOI： 10.1093/bjd/ljad162.037

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.85.164

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jdermsci.2023.05.003.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1346-8138.16733.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1346-8138.16737.

Language：English   Publisher：Journal of Dermatology  

Previous studies on family history of psoriasis showed that patients with a family history have an earlier onset of the disease, but such studies in Japan are still limited. To elucidate the characteristics of patients with familial psoriasis, we studied the family history of patients with psoriasis using the West Japan Psoriasis Registry, a multi-institutional registry operated by 26 facilities in the western part of Japan, including university hospitals, community hospitals, and clinics. This study enrolled 1847 patients registered between September 2019 and December 2021, with 199 (10.8%) having a family history of psoriasis. Patients with a family history of psoriasis had significantly earlier onset of the disease than those without a family history. Furthermore, patients with a family history of psoriasis had significantly longer disease duration. Psoriatic arthritis (PsA) was significantly more common in patients with a family history (69/199, 34.7%) than in those without a family history (439/1648, 26.6%) (adjusted P = 0.023). A subanalysis of patients with PsA revealed a significant difference in the patient global assessment (PaGA) score in Fisher's exact test and adjusted test. The numbers of patients with PaGA 0/1 were 29 (43.3%) and 172 (39.9%) in patients with PsA with and without family history of psoriasis, respectively, whereas the numbers of patients with PaGA 3/4 were 13 (19.4%) and 145 (33.6%) in patients with PsA with and without family history of psoriasis, respectively. Other disease severity variables did not show a difference between the two groups. Our findings suggest that genetics play a larger role in the development of PsA than in the development of psoriasis vulgaris. Most cases of PsA occur in patients who already have psoriasis, therefore dermatologists should pay attention to joint symptoms, especially in patients with psoriasis who have a family history of psoriasis.

DOI： 10.1111/1346-8138.16733

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

乾癬患者の家族歴を調査し、家族性乾癬患者の特徴を多施設共同観察研究で検討した。西日本の大学病院、地域病院、診療所等26機関による乾癬レジストリに登録された乾癬患者1847例のうち、家族歴(FH)を有する199例(FH群:男性142例、女性57例)について、当該患者の患者特性、疾患重症度、治療選択肢等のデータを収集し検討した。FH群患者の発症年齢は33.4±16.6歳で、家族歴のない患者(NFH群)の40.7±18.0歳より有意に早く罹患歴も長かった。さらに感染性関節炎(PsA)の罹患率はFH群34.7%とNFH群の26.6%よりも有意に多かった。PsA患者でのサブ解析では、Fisher正確確率検定と調整検定における患者全般評価(PaGA)スコアに有意な差がみられたが、乾癬発症時年齢、罹病期間等では有意差はみられなかった。PaGA 0/1の患者の比率は、FH群PsA患者とNFH群PsA患者でそれぞれ43.3%と39.9%であったのに対し、PaGA 3/4患者ではそれぞれ19.4%と33.6%であった。FH患者は、NFH患者に比べて発症が有意に若く罹患期間が長かったが、これらの有意差はPsAに限定した場合には認められなかった。またPsAは、NFH群よりもFH群で有意に多かった。

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

症例1:35歳,女性。初診4日前より上肢に自覚症状のない紅斑,同2日前には四肢の有痛性紅斑と40度の発熱を生じ,翌日近医皮膚科を受診し,当科に紹介され受診した。皮膚生検で結節性紅斑の診断で,ベッド上安静とロキソプロフェン300mg/日の内服治療で症状は軽快していたが,経過中に妊娠4週が判明した。ロキソプロフェン内服は3週間で終了し,アセトアミノフェン内服に変更してさらに2週間で治療した。その後妊娠37週の正期産,正常産で出産し,皮膚症状の再燃もなかった。症例2:25歳,女性,妊娠24週。初診3週間前より前医で腎盂腎炎のためアモキシシリン内服治療中であった。同10日前に左頬部の擦過創周囲に有痛性紅斑が出現し,その後左右の膝,右肘部,左踵部にも同様の紅斑が出現してきた。皮膚生検で結節性紅斑の診断で,入院してベッド上安静のうえ,遷延する腎盂腎炎にセファゾリン点滴も併用しつつ,妊娠中を考慮しアセトアミノフェン1200mg/日の内服を開始した。同2400mg/日まで増量したが症状制御が不十分で,プレドニゾロン10mg/日内服追加により症状は軽快した。退院後,外来にて両薬の漸減終了後も結節性紅斑は再燃なく,妊娠40週の正期産,正常産で出産した。本症は妊娠も発症因子のひとつであり,妊婦での発症は妊娠時期や合併症など考慮した慎重な治療選択,他科連携,十分な患者説明,経過フォローが重要である。文献的考察も加え報告する。(著者抄録)

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

乾癬に対して全身介入を行った患者における、生物学的製剤と経口治療薬の薬剤継続率を多施設共同後ろ向き研究で調査した。Western Japan Psoriasis Registry(WJPR)に登録され全身介入を施行された乾癬患者1003例(男性729例、女性274例、年齢中央値57.5歳)について、アダリムマブ(ADA)等の8種類の生物学的製剤とシクロスポリン等の2種類の経口薬の薬剤継続率を調査した。インターロイキン23阻害剤であるグセルクマブ、リサンキズマブの継続率が最も高く、次いでIL17阻害剤イキセキズマブ、ブロダルマブの順であった。薬剤中止理由は、一部の生物学的製剤やシクロスポリンでは、皮膚症状や関節症状に対する効果喪失が多かった。生物学的製剤での治療経験、肥満の有無、乾癬性関節炎(PsA)の有無に基づいて薬剤継続率を層別化した結果、生物学的製剤初回群と2回目以降の投与群では全薬剤で初回群の継続率が高く、特にADAでは両群で統計的有意差がみられた。また肥満群、PsA罹患群では大半の薬剤の継続率が低かった。顕著な安全性の懸念は確認されなかった。生物学的製剤の有効性喪失傾向には差があり、継続率に悪影響を与える因子は生物学的製剤の既使用、肥満、PsA罹患であった。

Language：English   Publisher：Journal of Dermatology  

Psoriasis affects approximately 0.3% of the Japanese population. Recently, various effective systemic drugs have become available, and the continuation of a given treatment has become critical because of the chronic nature of psoriasis. Factors affecting drug survival (the time until treatment discontinuation) in psoriasis treatment include efficacy, safety, ease of use, and patient preference. In the present study, the authors retrospectively surveyed a multifacility patient registry to determine the real-world evidence of the survival rate of systemic interventions for psoriasis treatment. Patients with psoriasis who visited 20 facilities in the Western Japan area between January 2019 and May 2020 and gave written consent were registered as study participants, and their medical history of systemic interventions for psoriasis (starting from 2010) was retrospectively collected and analyzed. The drugs investigated were adalimumab, infliximab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, cyclosporine, and apremilast. When drugs were discontinued, the reasons were also recorded. A total of 1003 patients with psoriasis including 268 with psoriatic arthritis (PsA) were enrolled. In biologics, more recently released drugs such as interleukin 17 inhibitors showed a numerically higher survival rate in the overall (post-2010) analysis. However, in the subset of patients who began treatment after 2017, the difference in the survival rate among the drugs was smaller. The reasons for discontinuing drugs varied, but a loss of efficacy against dermatological or joint symptoms were relatively frequently seen with some biologics and cyclosporine. The stratification of drug survival rates based on patient characteristics such as bio-naive or experienced, normal weight or obese, and with or without PsA, revealed that bio-experienced, obese, and PsA groups had poorer survival rates for most drugs. No notable safety issues were identified in this study. Overall, the present study revealed that the biologics show differences in their tendency to develop a loss of efficacy, and the factors that negatively impact the survival rate of biologics include the previous use of biologics, obesity, and PsA.

DOI： 10.1111/1346-8138.16737

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Language：English   Publisher：Journal of Dermatological Science  

DOI： 10.1016/j.jdermsci.2023.05.003

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：(株)協和企画  

＜文献概要＞症例のポイント　・炎症性腸疾患(inflammatory bowel disease:IBD)の腸管外合併症に関節障害がある.・関節炎は関節に一致した蜂窩織炎との鑑別がむずかしい.・関節に一致した蜂窩織炎様症状を診療する際は,関節炎の評価や詳細な問診をとるべきである.

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Language：English   Publisher：エルゼビア・ジャパン(株)  

Language：English   Publisher：Journal of Dermatological Science  

Background: Difamilast, a topical phosphodiesterase 4 (PDE4) inhibitor, has been shown to be effective for treating atopic dermatitis (AD), but the molecular mechanism involved is unclear. Since skin barrier dysfunction including reduced expression of filaggrin (FLG) and loricrin (LOR) contributes to AD development, difamilast treatment may be able to improve this dysfunction. PDE4 inhibition increases transcriptional activity of cAMP-responsive element binding protein (CREB). Therefore, we hypothesized that difamilast may affect FLG and LOR expression via CREB in human keratinocytes. Objective: To elucidate the mechanism by which difamilast regulates FLG and LOR expression via CREB in human keratinocytes. Methods: We analyzed normal human epidermal keratinocytes (NHEKs) treated with difamilast. Results: We observed increases of intracellular cAMP levels and CREB phosphorylation in difamilast (5 μM)-treated NHEKs. Next, we found that difamilast treatment increased mRNA and protein levels of FLG and LOR in NHEKs. Since reduced expression of keratinocyte proline-rich protein (KPRP) is reported to be involved in skin barrier dysfunction in AD, we examined KPRP expression in difamilast-treated NHEKs. We found that difamilast treatment increased mRNA and protein levels of KPRP in NHEKs. Furthermore, KPRP knockdown using siRNA transfection abolished the upregulation of FLG and LOR in difamilast-treated NHEKs. Finally, CREB knockdown canceled the upregulation of FLG, LOR, and KPRP in difamilast-treated NHEKs, indicating that PDE4 inhibition by difamilast treatment positively regulates FLG and LOR expression via the CREB-KPRP axis in NHEKs. Conclusion: These findings may provide further guidance for therapeutic strategies in the treatment of AD using difamilast.

DOI： 10.1016/j.jdermsci.2023.04.007

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Language：English   Publisher：Biomedicines  

Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts quality of life. The pathogenesis of AD is a complex combination of skin barrier dysfunction, type II immune response, and pruritus. Progress in the understanding of the immunological mechanisms of AD has led to the recognition of multiple novel therapeutic targets. For systemic therapy, new biologic agents that target IL-13, IL-22, IL-33, the IL-23/IL-17 axis, and OX40-OX40L are being developed. Binding of type II cytokines to their receptors activates Janus kinase (JAK) and its downstream signal, namely signal transduction and activator of transcription (STAT). JAK inhibitors block the activation of the JAK-STAT pathway, thereby blocking the signaling pathways mediated by type II cytokines. In addition to oral JAK inhibitors, histamine H4 receptor antagonists are under investigation as small-molecule compounds. For topical therapy, JAK inhibitors, aryl hydrocarbon receptor modulators, and phosphodiesterase-4 inhibitors are being approved. Microbiome modulation is also being examined for the treatment of AD. This review outlines current and future directions for novel therapies of AD that are currently being investigated in clinical trials, focusing on their mechanisms of action and efficacy. This supports the accumulation of data on advanced treatments for AD in the new era of precision medicine.

DOI： 10.3390/biomedicines11051303

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.85.124

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Language：Japanese   Publisher：日本皮膚科学会-西部支部  

61歳,女性。明らかな外傷歴はなかったが,初診の約4年前に右足底に褐色斑が出現した。褐色斑は徐々に増大したため,前医を受診し,生検でBowen病と診断された。切除を勧められたが放置していた。当院を紹介され受診した時,右足底の土踏まず部に7×6mmの褐色結節を認めた。前医での生検標本では,表皮全層に異型ケラチノサイトが増殖しており,個細胞角化やclumping cellを認めた。3mmマージンで全切除し,全層植皮術を行った。パラフィン包埋切片よりDNAを抽出し,ヒト乳頭腫ウイルス(human papillomavirus:HPV)の検索を行ったところ,粘膜/粘膜・皮膚型,ハイリスク型であるHPV31型のDNAが検出された。足底発症のBowen病は極めて稀であるが,しばしば粘膜/粘膜・皮膚型のHPVが検出された症例が報告されている。しかし,HPV31型が検出された足底Bowen病は,調べ得た限り国内外での報告はこれまでになく,自験例が第1例目となる。足底の黒褐色病変を認めたときは,Bowen病も鑑別の一つとして考慮し対応すべきであり,外陰部・手指だけでなく,足底のBowen病もHPVが発症に関与している可能性の高い病変であると考えられる。(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/jcm12062203.

Language：English   Publisher：Journal of Clinical Medicine  

Nail apparatus melanoma (NAM) is a rare type of cutaneous melanoma that belongs to the acral melanoma subtype. NAM is managed principally in accordance with the general treatment for cutaneous melanoma, but there is scarce evidence in support of this in the literature. Acral melanoma is genetically different from non-acral cutaneous melanoma, while recently accumulated data suggest that NAM also has a different genetic background from acral melanoma. In this review, we focus on recent advances in the management of NAM. Localized NAM should be surgically removed; amputation of the digit and digit-preserving surgery have been reported. Sentinel lymph node biopsy can be considered for invasive NAM for the purpose of accurate staging. However, it is yet to be clarified whether patients with metastatic sentinel lymph nodes can be safely spared completion lymph node dissection. Similar to cutaneous melanoma, immune checkpoint inhibitors and BRAF/MEK inhibitors are used as the first-line treatment for metastatic NAM, but data on the efficacy of these therapies remain scarce. The therapeutic effects of immune checkpoint inhibitors could be lower for NAM than for cutaneous melanoma. This review highlights the urgent need to accumulate data to better define the optimal management of this rare melanoma.

DOI： 10.3390/jcm12062203

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Language：English   Publisher：Cell Death Discovery  

Acral melanoma (AM) is a rare, life-threatening skin cancer. Since AM bears unique features, existing therapies for other types of malignant melanomas have limited effects and the establishment of effective treatments for AM is strongly desired. Human epidermal growth factor receptor 3 (HER3) is a receptor tyrosine kinase that is frequently elevated in tumors and contributes to tumor progression, so it is considered a promising therapeutic target for tumors. This study was established to evaluate the potential of HER3-targeted therapy to treat AM by investigating the expression and function of HER3. HER3 expression was immunohistochemically analyzed in AM lesions of 72 patients and in AM cell lines. To investigate function of HER3, effects of HER3 inhibition on cell proliferation, apoptosis/survival, anchorage-independent growth, and underlying signals were assessed. HER3 was expressed in patients’ AM tissues with various intensities and HER3 expression was significantly correlated with patient’s disease-free survival. In vitro analyses revealed that HER3 is more highly expressed in AM cells than in normal epidermal melanocytes. AM cells were also shown to be sensitive to the cytotoxic part of a HER3-targeted antibody-drug conjugate. Inhibition of HER3 did not affect cell proliferation, whereas it decreased the anchorage-independent growth of AM cells likely through affecting the nuclear translocation of Yes-associated protein. It is implied that HER3 may serve as a novel therapeutic target for AM.

DOI： 10.1038/s41420-023-01358-5

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.85.5

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Publisher：金原出版  

DOI： 10.18888/hi.0000003756

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.85.46

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Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

基礎疾患や家族歴のない9歳男児。3歳時に頭頸部の石灰化上皮腫を5ヶ所切除した。数年前から頭頸部,腰部,四肢に皮下結節が出現し,合計8ヶ所の皮下結節を認めた。6ヶ所切除し,病理組織学的検査でいずれも石灰化上皮腫の診断となった。過去の報告では,石灰化上皮腫が6個以上多発した症例の多くで筋緊張性ジストロフィー,家族性腺腫性ポリポーシス,Turner症候群,Rubinstein-Taybi症候群など何らかの症候群を合併している。自験例は遺伝子検査を行っていないが,臨床上これらの症候群を疑う所見はなかった。明らかな症候群や家族歴を伴わない場合でも,β-カテニン遺伝子の変異により多発性石灰化上皮腫を来す可能性がある。β-カテニン遺伝子の変異は悪性腫瘍を生じる可能性がある。自験例は遺伝子変異に関しては明らかではないが,今後の悪性腫瘍の発現に注意して経過をみていく必要がある。(著者抄録)

Language：Japanese   Publisher：Japanese Society of Allergology  

DOI： 10.15036/arerugi.72.437

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Language：Japanese   Publisher：Japanese Society of Allergology  

DOI： 10.15036/arerugi.72.1211

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Language：Japanese   Publisher：Japanese Society of Allergology  

<p><b>Background</b>: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated.</p><p><b>Methods</b>: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology.</p><p><b>Results</b>: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients.</p><p><b>Conclusion</b>: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.</p>

DOI： 10.15036/arerugi.72.1240

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Language：English   Publisher：Acta Dermato-Venereologica  

DOI： 10.2340/actadv.v103.4407

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Publisher：Proceedings of the ACM Symposium on Applied Computing  

When reading news articles on social networking services and news sites, readers can view comments marked by other people on these articles. By reading these comments, a reader can understand the public opinion about the news, and it is often helpful to grasp the overall picture of the news. However, these comments often contain offensive language that readers do not prefer to read. This study aims to predict such offensive comments to improve the quality of the experience of the reader while reading comments. By considering the diversity of the readers' values, the proposed method predicts offensive news comments for each reader based on the feedback from a small number of news comments that the reader rated as "offensive"in the past. In addition, we used a machine learning model that considers the characteristics of the commenters to make predictions, independent of the words and topics in news comments. The experimental results of the proposed method show that prediction can be personalized even when the amount of readers' feedback data used in the prediction is limited. In particular, the proposed method, which considers the commenters' characteristics, has a low probability of false detection of offensive comments.

DOI： 10.1145/3555776.3577670

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Language：Japanese   Publisher：Japanese Society of Allergology  

DOI： 10.15036/arerugi.72.410

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.84.483

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.84.547

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.84.534

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/all.15429

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Language：Japanese   Publisher：日本皮膚科学会-西部支部  

我々は,異なる臨床像を呈した3例のEccrine Angiomatous Hamartoma(EAH)を経験した。症例1:78歳,男性。幼少期から右肘窩部に暗赤色腫瘤を自覚し,緩徐に増大傾向であった。症例2:41歳,男性。10年前から左頬部に淡青灰色局面を自覚していた。局面の大きさは10年でほぼ変わりなかった。症例3:41歳,女性。8年前から上腹部に皮下腫瘤を自覚し,2ヵ月前から疼痛を伴うようになった。症例1と3は全切除生検,症例2は部分生検を行った。3症例とも病理組織学的に腫瘍の境界は不明瞭で,真皮にエクリン汗腺や小血管の増生を認め,EAHと診断した。EAHは比較的まれな腫瘍であり,多彩な臨床像をとる。自験例は初診時に鑑別疾患としてEAHは挙がらず,病理組織学的検査で診断がついた。疾患に特徴的な画像所見もこれまで報告されておらず,診断には発症時期や局所多汗などの特徴的な所見を問診することと,皮膚生検が有用と考える。(著者抄録)

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

71歳,男性。2回目のCOVID-19ワクチン接種2週間後より,四肢・体幹にそう痒を伴う皮疹が出現した。初診時,四肢・体幹に扁平隆起した紫紅色丘疹が散在し,そう痒を伴っていた。一部は過去の外傷部に一致して皮疹を認め,肥厚性瘢痕や扁平苔癬などを鑑別に皮膚生検を施行した。病理組織学的に顆粒層の肥厚,表皮直下の帯状のリンパ球浸潤,変性した角化細胞を認め,扁平苔癬と診断した。経過中に口腔内の血疱や下肢の紫斑が出現し,血液検査で血小板の著明な低下がみられ,特発性血小板減少性紫斑病の診断で当院血液内科入院となった。PSL 60mg/日より投与開始され,皮疹の著明な改善を認めた。(著者抄録)

Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.84.422

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.84.391

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/cts.13363.

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

53歳,女性。当科初診の20年前に右拇指球部に自覚症状の伴わない陥凹性紅色局面が出現し,その後拡大した。皮疹部に外傷歴や刺激行為はなかった。ダーモスコピーでは紅色無構造であった。皮膚生検では健常部から病変部にかけて角層が階段状に菲薄化し,それに伴い顆粒層も菲薄化していた。Circumscribed palmar hypokeratosisの診断となった。活性型ビタミンD3製剤を外用し,治療開始後2ヵ月の時点で辺縁の陥凹がわずかに平坦化した。本疾患は表皮の角化異常,ヒトパピローマウイルス感染,外傷などが原因として考えられているが,確立した見解はない。治療法は活性型ビタミンD3製剤の外用,液体窒素凍結療法,外科的切除などの報告があるが,保存的治療では奏効しないことも多く確立した見解はない。本疾患は認知度が低く,誤診されることも多いため,中高年女性の掌蹠に生じた陥凹性紅斑を認めた場合,本疾患に留意する必要がある。本疾患の病態の解明や治療の確立のために,今後さらなる症例の蓄積が望まれる。(著者抄録)

Language：English   Publisher：Journal of Clinical Medicine  

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, and the condition is typified by barrier dysfunction and immune dysregulation. Recent studies have characterized various phenotypes and endotypes of AD and elucidated the mechanism. Numerous topical and systemic narrow targeting therapies for AD have been developed according to these findings. Topical medications, including Janus kinase (JAK) inhibitors, phosphodiesterase 4 inhibitors, and the aryl hydrocarbon receptor agonist tapinarof, are effective and safe for AD compared to topical corticosteroids. Oral JAK inhibitors and monoclonal antibodies targeting interleukin (IL)-4, IL-13, IL-31, IL-33, OX40, thymic stromal lymphopoietin, and sphingosine 1-phosphate signaling have displayed outstanding efficacy against moderate-to-severe AD. We are currently in a new era of AD treatment.

DOI： 10.3390/jcm11206145

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Language：English   Publisher：Clinical and Translational Science  

The pharmacokinetics (PKs) and exposure–efficacy of dupilumab have not been fully described for adults with atopic dermatitis (AD). Our objectives were to analyze the PKs and exposure–efficacy of dupilumab in adults with AD and compare the results of Japanese and overall populations. Adults with moderate-to-severe AD were randomly assigned to dupilumab (300 mg weekly [qw] or every 2 weeks [q2w], 200 mg q2w, 300 mg every 4 weeks [q4w], or 100 mg q4w) or placebo for 16 weeks in a randomized, double-blind, placebo-controlled, dose-ranging phase IIb trial (NCT01859988). This analysis included 379 patients (58 Japanese). Functional dupilumab concentrations increased in a dose-dependent manner; at lower concentrations, increases were greater than dose-proportional because of nonlinear, target-mediated clearance. Dupilumab pharmacokinetics were comparable in Japanese and non-Japanese patients with similar body weights. Week 16 efficacy parameters, including Investigator’s Global Assessment score 0/1, greater than or equal to 75% reduction from baseline in the Eczema Area and Severity Index (EASI), and percentage change from baseline in EASI and pruritus Numerical Rating Scale, generally increased with week 16 trough concentration; the plateau of these exposure–efficacy relationships occurred for most patients at exposures associated with the 300 mg q2w and 300 mg qw regimens. Japanese ethnicity did not remain in the population PK model as covariate with or without accounting for body weight differences. In Japanese and non-Japanese patients, efficacy responses increased with week 16 dupilumab trough concentrations in a similar manner. Dupilumab 300 mg qw and q2w regimens were recommended for further evaluation in larger phase III studies.

DOI： 10.1111/cts.13363

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Language：English   Publisher：Journal of Dermatology  

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, 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.

DOI： 10.1111/1346-8138.16527

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Language：Japanese   Publisher：Fukuoka Medical Association  

Atopic dermatitis is a common, chronic inflammatory skin disease that is characterized by skin barrier dysfunction, inflammation and intense itch. Although the exact mechanisms behind its pathogenesis remain unclear, it is evident that the complex interplay among barrier dysfunction, inflammation and itch are critical in its development, progression and chronicity. Barrier-disrupted skin produces thymic stromal lymphopoietin and interleukin (IL)-33 ; these in turn promote skin inflammation characterized by type 2 immune deviation. This inflammation then downregulates the expression of filaggrin in keratinocytes and exacerbates epidermal barrier dysfunction. Furthermore, various itch mediators/pruritogens produced during this inflammatory process can act directly on sensory nerves and cause itch. Based on this understanding of the pathophysiology, many new drugs are being developed, and a new era of treatment is underway. Specifically, anti-IL-4 receptor antibody, anti-IL-31 receptor antibody, and JAK inhibitors are already available for use in clinical practice. Still, however, how to select the optimal drug remains a major challenge. In this review, we summarize the basics and recent advances in our understanding of the pathophysiology of atopic dermatitis, including our recent research findings. In addition, the status of development of new drugs is also outlined.

DOI： 10.15017/6770310

CiNii Research

Language：Japanese   Publisher：(株)協和企画  

＜文献概要＞ポイント　●高齢者中心の病院で8年間に74例の入院患者の疥癬を診断,加療した.●本検討で48例にイベルメクチン内服とフェノトリン外用の併用を行ったが,有害事象は認めなかった.●集団感染の感染経路として,間接的接触である血圧計のマンシェットやトイレの便座を介するものが考えられた.●高齢者をみるときは常に疥癬を鑑別にあげ,疥癬が否定できない場合は頻回に検鏡することが重要である.

Language：English   Publisher：European Journal of Dermatology  

DOI： 10.1684/ejd.2022.4337

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Language：Japanese   Publisher：(株)協和企画  

＜文献概要＞症例のポイント　・ステロイド外用薬や光線療法に抵抗性で,デュピルマブ投与後も痒みが改善しなかったアトピー性皮膚炎が,デルゴシチニブ外用により痒みが速やかに改善した例を経験した.・デルゴシチニブはJAKファミリーのキナーゼすべてを阻害することで,デュピルマブが直接は抑えられないIL-31やTSLP由来の痒みも抑えることができる.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13555-022-00738-6

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Publisher：Journal of Cutaneous Immunology and Allergy  

DOI： 10.1002/cia2.12220

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3389/fimmu.2022.745997

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s40257-022-00685-0.

Language：English   Publisher：American Journal of Clinical Dermatology  

Background: Moderate‐to‐severe atopic dermatitis (AD) often requires long-term management with systemic therapies. Objective: Our objective was to report the safety and efficacy of dupilumab treatment up to 4 years in adults with moderate-to-severe AD and efficacy in a subgroup of patients who transitioned from dupilumab once-weekly (qw) to administration every other week (q2w). Methods: This interim analysis of the open-label extension study (NCT01949311) evaluated dupilumab 300 mg qw or q2w in adults previously enrolled in dupilumab trials for moderate-to-severe AD. Patients switched from qw to q2w following protocol amendment. The primary outcome was safety; efficacy was also assessed. Results: Of 2677 patients enrolled and treated, 352 (13.1%) completed week 204 (end of efficacy assessments) and 202 (7.5%) completed safety follow-up through week 244. Self-reported compliance was 98.1%. Dupilumab’s safety profile was consistent with previous reports. Common treatment-emergent adverse events (≥5%) included nasopharyngitis, AD, upper respiratory tract infection, oral herpes, conjunctivitis, injection-site reaction, and headache. At week 204, mean ± standard deviation (SD) Eczema Area and Severity Index was 2.46 ± 3.98, and mean percent change from parent study baseline (PSBL) was −91.07%; mean ± SD Pruritus Numerical Rating Scale score was 2.10 ± 1.83, and mean percent change from PSBL was −68.74%. Efficacy was maintained in patients (n = 226) who transitioned from qw to q2w dosing. Limitations of this study included its open-label design, the lack of control arm, and smaller subsets of patients at later timepoints and receiving the approved q2w regimen. Conclusion: These results support dupilumab as continuous long-term treatment for adults with moderate-to-severe AD; efficacy was sustained following transition from qw to q2w dosing. Trial Registration ClinicalTrials.gov: NCT01949311.

DOI： 10.1007/s40257-022-00685-0

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Publisher：European Journal of Inflammation  

Morphea is a rare fibrosing disorder of the skin and underlying tissues. To date, the size of morphea has not been adequately discussed. Here, we report two cases of small-sized superficial circumscribed morphea. Both cases clinically revealed single circumscribed, round to oval area of shiny sclerotic plaque at distal extremities. There are several options for the treatment of superficial circumscribed morphea, such as topical corticosteroid and phototherapy. The early recognition of small-sized morphea enables appropriate diagnosis and follow-up, leading to improve disease prognosis.

DOI： 10.1177/1721727X221105130

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Language：Japanese   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/nishinihonhifu.84.115

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CiNii Research

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

79歳男性。喘息で加療中だった。初診4ヵ月前に喘息に対しベンラリズマブが導入されコントロールは良好であった。当科初診の8日前から,発熱と倦怠感が出現した。肺炎として加療されたが,その後も発熱が持続し全身に皮疹が出現した。当科初診時,体幹四肢にそう痒を伴う紫斑と血疱が散在し,周囲に淡い紅斑を伴っていた。採血では,CRPや血沈などの炎症所見の上昇とIgE高値を認めた。病理組織検査で真皮浅層の血管と神経周囲に好酸球と好中球を中心とした炎症細胞の浸潤とフィブリノイド変性が認められた。好酸球比は初診時は基準範囲内であったが,初診7日後には37.4%と著増した。以上より好酸球性多発血管炎性肉芽腫症(Eosinophilic Granulomatosis with Polyangiitis:以下EGPA)と診断した。高用量ステロイド内服薬(1mg/kg/day)で治療を開始し,翌日には解熱し皮疹の拡大は停止した。その後,ステロイドを漸減した。経過中に神経障害の出現があり,免疫グロブリン静注療法とアザチオプリン内服を追加した。紫斑は黒色壊死組織を伴う潰瘍となり,壊死組織のデブリードマンを要した。EGPAの皮膚症状は多彩であるが,下腿に紫斑を伴った症例が多く報告されている。自験例のように,ほぼ全身に広範囲に皮疹を呈し潰瘍化することは稀である。ベンラリズマブの投与とEGPA発症の関連性については更なる研究が必要と考える。(著者抄録)

Language：English   Publisher：Journal of Dermatology  

This is the English version of guidelines for the management of asteatosis 2021 in Japan. Asteatosis is a synonym of xerosis found in a wide range of diseases that induce dry skin through impaired functions of either water retention of the stratum corneum or skin covering with acid mantle. Patients with asteatosis may be accompanied by pruritus. Moisturizers are the first-line treatment for asteatosis and their adequate use must be recommended. The main purpose of the present guidelines is to define skin symptoms requiring treatment with moisturizers for medical use in patients with asteatosis. If the deterioration of marked scaling or scratch marks is predicted, therapeutic intervention with moisturizers for medical use should be considered even in the absence of pruritus. Regarding six important points requiring decision-making in clinical practice (clinical questions), we evaluated the balance between the benefits and harm of medical interventions in reference to previous reports of clinical research, and presented the recommendation grades and evidence levels to optimize the patient outcome by medical interventions.

DOI： 10.1111/1346-8138.16293

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Publisher：Journal of Cutaneous Immunology and Allergy  

Objectives: The satisfaction level of adult patients receiving drugs for atopic dermatitis and chronic urticaria is unclear. The objective of this multicenter study was to assess the satisfaction level of adult patients receiving treatment for allergic skin diseases, primarily atopic dermatitis and chronic urticaria. Methods: We developed a self-administered questionnaire with multiple-choice questions on patient characteristics, quality of life (QOL), and Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9). We surveyed 302 patients receiving dermatological treatment. Results: The global satisfaction of patients (TSQM-9) was lower for atopic dermatitis treatment compared with that for chronic urticaria. For atopic dermatitis, dupilumab had higher scores for effectiveness and global satisfaction, whereas topical tacrolimus and moisturizers had higher scores for convenience. For chronic urticaria, omalizumab had higher scores for effectiveness and global satisfaction, while antihistamines had a higher score for convenience. The Dermatology Life Quality Index was significantly associated with treatment effectiveness and global satisfaction, and patient satisfaction improved with the corresponding improvement in the QOL. For atopic dermatitis, satisfaction with dupilumab was higher than that with conventional standard therapy, after the confounding factors were eliminated. However, the same trend was not observed for chronic spontaneous urticaria. Conclusions: The satisfaction of the effectiveness for the biologic agents was higher, compared to that with conventional standard therapy. Treatment with biologics is worth exploring for patients who are not satisfied with their existing treatments.

DOI： 10.1002/cia2.12200

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

アレルギー性皮膚疾患に対して薬物療法が施行されている成人患者の満足度を調べた。皮膚科を受診する成人患者302例を対象に、患者特性、QOL(DLQIスコア)、治療満足度質問票(TSQM-9)スコアなどを評価した。患者の内訳は、アトピー性皮膚炎(AD)患者が201例(男性111例、女性89例、不明1例、平均37.7±12.9歳)、慢性特発性蕁麻疹患者が90例(男性32例、女性56例、不明2例、平均52.0±15.4歳)、慢性刺激誘発性蕁麻疹患者が11例(男性2例、女性9例、平均34.5±11.2歳)であった。疾患重症度が中等症であったのはADのうち45%、慢性特発性蕁麻疹のうち34%、慢性刺激誘発性蕁麻疹が55%となっていた。治療薬としてADには局所ステロイド、蕁麻疹には抗ヒスタミンが最も多く用いられていた。DLQIスコアはAD患者の方が慢性特発性蕁麻疹患者より有意に高く、TSQM-9便益ドメインはAD患者の方が慢性特発性蕁麻疹患者より有意に低値を示していた。また、包括的重症度評価(IGA)スコアはDLQI、TSQM-9有効性ドメイン、TSQM-9全般満足度ドメインと負の相関を示し、DLQIとTSQM-9有効性ドメイン、TSQM-9全般満足度ドメインとの間に中等度の相関が認められた。薬剤別にみると生物学的製剤の使用は従来の標準治療と比較して満足度が高まる傾向にあった。

Language：Japanese   Publisher：Japanese Pharmacological Society  

<p>Atopic dermatitis (AD) is a common, chronic inflammatory skin disease that is characterized by skin barrier dysfunction, inflammation and intense itch. Although the exact mechanisms behind its pathogenesis remain unclear, it is evident that the complex interplay among barrier dysfunction, inflammation and itch are critical in its development, progression and chronicity. Therefore, the treatment described in the current guideline are based on the pathogenesis of the disease: 1) topical anti-inflammatory therapy for inflammation, 2) moisturizer skin care for physiological abnormalities of the skin, and 3) search for and countermeasures against aggravating factors. However, in AD, itch is the most common problem for patients and its control is often very difficult. This may be due to the fact that the mechanism of itch in AD is very complex and probably differs from patient to patient.</p><p>With the discovery of key pathways responsible for the atopic skin inflammation and atopic itch, a new era in the treatment of AD began. Various substances involved in the pathogenesis of AD have been identified and many novel therapeutic agents targeting them are under development. New drugs currently employ two strategies of inhibiting specific key mechanisms in the pathogenesis of AD. The first strategy is based on inhibition of the type2 cytokines such as IL-13/IL-4 and IL-31. This group is represented by dupilumab and nemolizumab. The second strategy is based on reducing nonspecific inflammation using JAK-STAT inhibition. The already available baricitinib and upadacitinib, and upcoming abrocitinib are representative.</p><p>In this symposium I would like to discuss the clinical trial results of many new drugs, the action points of new drugs based on the pathogenesis of AD, their expected effects, and the experience of their use in clinical practice. In addition, I would like to discuss the future issues in the new era of treatment with many new drugs.</p>

DOI： 10.1254/jpssuppl.95.0_2-s25-4

CiNii Research

Language：English   Publisher：Japanese Society of Allergology  

<p>This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has 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.</p>

DOI： 10.1016/j.alit.2022.06.009

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Language：English   Publisher：Case Reports in Dermatology  

Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma. VC is histologically a benign tumor, but it grows significantly and eventually forms a huge mass. Many different treatments are known, but the first-line treatment is surgical resection. VC has strong local infiltration and frequently recurs, making its local control very difficult in unresectable cases. We present a rare case of VC that could be treated with combined radiotherapy and Mohs' chemosurgery, as a new option for unresectable VC.

DOI： 10.1159/000525751

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DOI： 10.1111/bjd.19751.

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DOI： 10.3390/ijms21249412.

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DOI： 10.1002/npr2.12144.

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DOI： 10.1097/MD.0000000000022043.

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DOI： 10.1016/j.jdermsci.2020.07.002.

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DOI： 10.1111/ajd.13143.

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DOI： 10.3390/ijms21020434.

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DOI： 10.1016/j.alit.2019.08.006.

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DOI： 10.3390/ijms20133324.

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DOI： 10.1111/all.13712.

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DOI： 10.1111/1346-8138.14745.

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DOI： 10.1016/j.jaci.2018.10.053.

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DOI： 10.1684/ejd.2011.1621

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DOI： 10.1111/j.1346-8138.2011.01267.x

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DOI： 10.1097/CMR.0b013e32834dcfdf

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Venue：広島   Country：Japan  

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2022.5

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Venue：名古屋   Country：Japan  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

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Language：Japanese   Publisher：日本皮膚科学会-西部支部  

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Language：English   Publisher：European Journal of Dermatology  

DOI： 10.1684/ejd.2024.4660

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PubMed

Language：Japanese   Publisher：(株)南山堂  

Language：English   Publisher：Indian Journal of Dermatology  

DOI： 10.4103/ijd.ijd_120_23

Scopus

PubMed

Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞・蕁麻疹では,短時間で消退するかゆみを伴う膨疹(一過性の浮腫を伴う紅斑)が病的に出没する.・自発的に膨疹が出現する特発性の蕁麻疹と,特定の刺激で誘発される刺激誘発型の蕁麻疹に大きく分類される.・病型のなかでは特発性の蕁麻疹が占める割合が多く,6週間以内のものを急性蕁麻疹,6週間を超えたものを慢性蕁麻疹とよぶ.・治療は非鎮静性第二世代抗ヒスタミン薬の内服が第一選択である.・抗IgE抗体omalizumabが新規薬剤として登場し,抗ヒスタミン薬治療抵抗性の慢性蕁麻疹に効果的である.

Language：Japanese   Publisher：(株)日本医事新報社  

Language：Japanese   Publisher：(一社)日本アレルギー学会  

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

Language：Japanese   Publisher：(有)科学評論社  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

42歳女性.右乳がんに対し,20XX年5月右乳房全切除術,遊離腹部皮弁再建術を行い,20XX+1年10月,20XX+2年11月に2回の修正術を行った.右乳房の手術痕の一部に20XX+1年1月紅斑が出現し徐々に拡大傾向を認めたが,治療介入されず,20XX+3年5月当科初診.右乳房の縫合線全体に浸潤を触れる紅斑,その周囲に鱗屑を付す色素沈着を認め,貨幣状湿疹と診断した.保湿励行とステロイド外用治療を開始したが,改善までに時間を要した.乳房再建術後に貨幣状湿疹を生じる場合があることを皮膚科医も認識し,保湿励行,早期治療介入に努めることが重要であると考える.(著者抄録)

Language：Japanese   Publisher：(株)北隆館  

長期に及ぶアトピー性皮膚炎診療においては,治療開始時や治療中に適宜評価を行い,治療方法を選択する必要がある。近年,医師による客観的な評価に加えて,患者自身による評価であるPRO(Patient Reported Outcome,患者報告アウトカム)が重要になってきており,PROを評価するための様々な評価スケールが使用されるようになってきている。このような評価スケールは治療選択目的のみならず,患者とのコミュニケーションツールとしても有用であり,今後さらに広く使用されることが考えられる。(著者抄録)

Language：Japanese   Publisher：(株)全日本病院出版会  

アトピー性皮膚炎は,皮膚バリア機能障害,免疫応答異常・炎症,痒みによって病態が形成される.以前はアトピー性皮膚炎の痒みのメカニズムは不明な部分が多かったが,近年特に末梢性の痒みのメカニズムが徐々に明らかになり,痒みと炎症の密接な相互作用も明らかになってきている.そして病態解明と同時に新規薬剤の開発も進み,それらの痒みへの優れた効果が明らかになってきた.そこで本稿では,アトピー性皮膚炎の全身療法について,その作用メカニズムや効果を痒みの側面から考え,どのように使い分けるべきかについて解説したい.(著者抄録)

Language：Japanese   Publisher：(一社)日本アレルギー学会  

Language：English   Publisher：エルゼビア・ジャパン(株)  

Language：Japanese   Publisher：(有)科学評論社  

Language：Japanese   Publisher：金原出版(株)  

Language：Japanese   Publisher：大道学館出版部  

Language：Japanese   Publisher：(株)北隆館  

近年,アトピー性皮膚炎の新規治療薬の開発は目覚ましい。全身療法に関しては,抗IL-4受容体抗体デュピルマブが2018年に登場し,すでに4年が経過している。2020年以降経口JAK阻害薬が計3剤使用可能になっている。さらに最近,抗IL-31受容体抗体ネモリズマブも使用可能となった。診療ガイドラインも2021年末に改訂され,その中で診断・治療アルゴリズムが大幅にアップデートされて,新規薬剤についても追記されている。そこで本稿では,アトピー性皮膚炎の病態とJAK-STAT経路について解説し,経口JAK阻害薬3剤についてその特徴や使用の実際について解説したい。(著者抄録)

Language：Japanese   Publisher：(株)Gakken  

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

アトピー性皮膚炎(atopic dermatitis:AD)は臨床現場においてよくみられる慢性皮膚疾患である。その発症や病態形成には,遺伝的,免疫学的,環境的な要因が複雑に絡み合うとされ,近年のさまざまな基礎・臨床研究により,数多くの知見が報告されている。ここでは特に,ADの病態に深く関与する2型サイトカインのIL-4およびIL-13について,その機能や役割,これらを標的にした治療薬の最新知見を概説するとともに,今後望まれるAD治療戦略について考察した。(著者抄録)

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

Language：Japanese   Publisher：(同)クリニコ出版  

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

DOI： 10.3390/jcm11206145

Language：Japanese   Publisher：大道学館出版部  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

Language：English   Publisher：(一社)日本アレルギー学会  

Language：Japanese   Publisher：福岡医学会  

アトピー性皮膚炎の病態は複雑であり、経過や年齢、人種や患者間で様々な多様性がある。アトピー性皮膚炎の病態の基本とかゆみの特徴、アトピー皮膚炎におけるTh1、Th17、Th22細胞浸潤ならびにバリア機能の恒常性の維持について概説した。病態解明に基づいて開発された新規治療薬(経口剤の抗IL-4受容体抗体デュピルマブ、抗IL-31受容体抗体ネモリズマブ、経口JAK阻害薬、外用薬のJAK阻害薬とPDE4阻害薬)の特徴を述べた。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：Japanese   Publisher：金原出版(株)  

Language：Japanese   Publisher：大道学館出版部  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：Japanese   Publisher：(株)北隆館  

長期に及ぶアトピー性皮膚炎診療においては、治療開始時や治療中に適宜評価を行い、治療方法を選択する必要がある。近年国際的にアトピー性皮膚炎の評価項目や評価方法を統一する動きも出てきており、その一つHOMEにおいては(特に臨床試験において)、最低限評価すべき項目を、(1)Clinical Signs、(2)Patient-Reported Symptoms、(3)Quality of Life、(4)Long-Term Controlの4項目とし、それぞれに最適な評価ツールとして、(1)にEASI、(2)にPOEMとかゆみNRS、(3)にDLQI、(4)にADCTまたはRECAPが推奨されている。今後は、これらの評価ツールが日常診療においても幅広く使用される可能性がある。(著者抄録)

Language：Japanese   Publisher：日本臨床皮膚科医会  

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc.