研究者詳細 - 足立　剛也

論文 - 足立　剛也

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IgA vasculitis presenting with Achilles peritendinitis: A case report

Keita Hirata, Takeya Adachi, Saeko Takamiyagi, Masaki Arai, Yoshio Nakamura, Takeru Funakoshi, Masayuki Amagai, Akiko Tanikawa, Masatoshi Kawai, Ayano Fukushima‐Nomura

The Journal of Dermatology 2025年01月

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Research team diversity impacts scientific output in allergy and immunology programs

Takeya Adachi,, Norika Narimatsu, Yasushi Ogawa,, Masako Toriya,, Tamami Fukushi,, Masashi Shirabe,, Masaki Futamura,, Takenori Inomata,, Keigo Kainuma,, Keiko Kan-o,, Yosuke Kurashima,, Katsunori Masaki,, Saeko Nakajima,, Masafumi Sakashita,, Sakura Sato,, Mayumi Tamari,, Hideaki Morita,, Amane Koizumi,

World Allergy Organization Journal 2025年01月

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Delayed and immediate cutaneous adverse events during pembrolizumab combination chemotherapy against cervical cancer: Case series

Takeya Adachi, Tomoya Matsui, Utako Okata‐Karigane, Chiaki Takahashi, Umi Tahara, Mari Hyodo, Akihiro Miyagawa, Kenta Kobayashi, Yoshio Nakamura, Takeru Funakoshi, Hiroshi Nishio, Wataru Yamagami, Hayato Takahashi

The Journal of Dermatology 2025年01月

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Minimal Clinically Important Differences With the Outcomes of the App-Based Japanese Allergic Conjunctival Diseases Quality of Life Questionnaire: Cross-Sectional Observational Study

Ken Nagino, Jaemyoung Sung, Akie Midorikawa-Inomata, Yasutsugu Akasaki, Takeya Adachi, Nobuyuki Ebihara, Ken Fukuda, Atsuki Fukushima, Kenta Fujio, Yuichi Okumura, Atsuko Eguchi, Keiichi Fujimoto, Hurramhon Shokirova, Alan Yee, Yuki Morooka, Tianxiang Huang, Kunihiko Hirosawa, Shintaro Nakao, Hiroyuki Kobayashi, Takenori Inomata

JMIR Formative Research 2024年11月

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Acidic oral environment’s potential contribution to palladium-induced systemic contact dermatitis: Case report

Takeya Adachi, Katsunori Masaki, Kazuyo Sujino, Utako Okata-Karigane, Taro Murakami, Chiaki Takahashi, Shiori Nakayama, Saki Tomiyasu, Masato Asaoka, Hiroki Kabata, Jun Miyata, Hayato Takahashi, Koichi Fukunaga

Journal of Allergy and Clinical Immunology: Global 2024年11月

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Successful treatment of the dupilumab-induced psoriatic dermatitis/arthritis and atopic dermatitis with a JAK inhibitor: A case report and literature review

Misuzu Tsunoda, Takeya Adachi, Yuuri Nakajima, Yoshihiro Yatomi, Tomoko Shimizu, Katsuki Nakasute

Journal of Allergy and Clinical Immunology: Global 2024年11月

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The impact of COVID-19 on hay fever treatment in Japan: A retrospective cohort study based on the Japanese claims database.

Yasutsugu Akasaki, Takenori Inomata, Masao Iwagami, Jaemyoung Sung, Ken Nagino, Takeya Adachi, Hideaki Morita, Mayumi Tamari, Keigo Kainuma, Keiko Kan-O, Hiroaki Ogata, Masafumi Sakashita, Masaki Futamura, Yosuke Kurashima, Saeko Nakajima, Katsunori Masaki, Yasushi Ogawa, Sakura Sato, Akihiro Miyagawa, Akie Midorikawa-Inomata, Keiichi Fujimoto, Yuichi Okumura, Kenta Fujio, Tianxiang Huang, Kunihiko Hirosawa, Yuki Morooka, Akira Murakami, Shintaro Nakao

Clinical and translational allergy 14 （ 9 ） e12394 2024年09月

BACKGROUND: Hay fever (HF) presents with various symptoms, including allergic conjunctivitis and rhinitis, and requires cross-organ treatment. This study assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on HF treatment trends. METHODS: This retrospective cohort study utilized data from the JMDC database collected between January 2018 and May 2021. Patients with HF were identified based on the relevant International Classification of Diseases 10th Revision diagnosis codes and the prescription of HF-related medications. The treatment approaches were compared during the cedar and cypress pollen allergy season (January to May in Japan) before and during the COVID-19 pandemic (2018 and 2019, and 2020 and 2021, respectively). RESULTS: This study included 2,598,178 patients with HF. The numbers of prescribed HF-related claims in 2018, 2019, 2020, and 2021 were 3,332,854, 3,534,198, 2,774,380, and 2,786,681 times, respectively. Oral second-generation antihistamine prescriptions decreased by >10% from 2019 to 2020, with a <10% change in the subsequent year. Anti-allergic eye drop prescriptions also decreased by >10% from 2019 to 2020 but increased by >10% from 2020 to 2021. Compared with 2018, 2019, and 2020, the number of claims in the rhinitis symptoms dominant group was significantly decreased in 2021 (p < 0.001, all). In contrast, the number of claims in the eye symptoms dominant group and the rhinitis and eye symptoms dominant group increased in 2021 compared with that in 2018, 2019, and 2020 (p < 0.001, all). CONCLUSION: Changes in HF treatment and related outcomes could be attributed to lifestyle modifications resulting from the COVID-19 pandemic. Measures, such as limiting outdoor activities and adopting mask-wearing practices may have influenced HF symptoms, preventive behaviors, and the overall approach to treating HF.

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メトトレキサート過量内服により皮膚粘膜障害,汎血球減少を生じたSAPHO症候群の1例

梶間諒, 足立剛也, 宮川明大, 今井悠気, 花岡洋成, 野村彩乃, 高橋勇人, 天谷雅行, 大内健嗣

臨床皮膚科（(株)医学書院） 78 （ 10 ） 731 - 736 2024年09月

ISSN 0021-4973

＜文献概要＞66歳,女性.SAPHO症候群に対してメトトレキサート(MTX)内服中,関節痛増悪がありMTX 6mg/週から8mg/週に処方量を増量した.最終内服2日後に発熱,口唇・口腔内のびらん,背部の紅斑・びらんが出現した.血液検査ではHb 10.5g/dl,好中球数1,320/μl,血小板数5×104/μlと汎血球減少を認めた.詳細な薬歴聴取により,本人がMTXの内服方法を誤ったことを自覚しながら自己判断で内服を継続しており,MTXを32mg/週内服していたことが判明した.MTX休薬等の加療で最終内服11日後には皮膚・粘膜症状,汎血球減少は改善した.以上よりMTX急性毒性と診断した.MTXは内服法が特殊で認知機能に問題がなくても誤用する可能性がある.MTX過量内服による副作用を予防するためには内服方法,過量内服した際の対応,副作用に関して十分に指導することが必要である.

アレルギー領域における診療科・職種横断的リカレント教育の重要性　「出前授業による教育の機会創出事業」参加者データの分析

正木克宜, 坂下雅文, 小川靖, 猪俣武範, 貝沼圭吾, 神尾敬子, 佐藤さくら, 玉利真由美, 中島沙恵子, 森田英明, 倉島洋介, 二村昌樹, 高橋浩一郎, 春田淳志, 百武美沙, 門川俊明, 石塚全, 意元義政, 尾山徳孝, 神崎晶, 木戸口正典, 福島敦樹, 福永興壱, 藤枝重治, 安冨素子, 足立剛也, 免疫アレルギー疾患研究10か年戦略次世代タスクフォース(ENGAGE-TF)

アレルギー（(一社)日本アレルギー学会） 73 （ 4 ） 329 - 339 2024年06月

ISSN 0021-4884

【背景】多職種・複数診療科が関与するアレルギー診療水準の向上には,専門医以外も対象とした教育の必要性が考えられるが,そのニーズ調査と方法に関する検討は不十分である.【目的・方法】免疫アレルギー疾患研究10か年戦略次世代タスクフォース(ENGAGE-TF)は学会支援下に慶應義塾大学,福井大学と連携した複数回のバーチャル教育企画「出前授業」を企画した.そのニーズと有用性を検証するため,SNSや各大学・医師会等を通じて周知し,メーリングリストを用いてアンケート調査を行った.【結果】のべ1139人・回より回答を得た.半数以上が専門医以外の医師であり,幅広い医療関連職種も参加した.7割が「とても満足」,6割以上が「ちょうどよい」難易度と回答した.自由記載の感想から,職種毎の学びの焦点,経験年数による学びのスタンスの違いが見られた.【考察・結語】9割を占める専門医以外の参加者のプライマリケアにおけるアレルギー疾患対応ニーズの高さと,経験11年以上の医療関連職種の遠隔教育・リカレント教育の有用性が示唆された.(著者抄録)

Minimal Clinically Important Differences With the Outcomes of the App-Based Japanese Allergic Conjunctival Diseases Quality of Life Questionnaire: Cross-Sectional Observational Study (Preprint)

2024年05月

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足立剛也, 早野元詞, 伊藤靖典, 猪俣武範, 小川靖, 貝沼圭吾, 神尾敬子, 倉島洋介, 桑原優, 坂下雅文, 佐藤さくら, 富田康裕, 中島沙恵子, 二村昌樹, 正木克宜, 玉利真由美, 海老澤元宏, 森田英明, 日本アレルギー学会医療戦略検討委員会

アレルギー（(一社)日本アレルギー学会） 73 （ 3 ） 268 - 278 2024年05月

ISSN 0021-4884

【背景】2022年「新しい資本主義のグランドデザイン及び実行計画」が閣議決定され,スタートアップ等の推進・環境整備が始まった中,アレルギー領域の国内外のスタートアップ投資状況の調査は喫緊の課題と言える.【方法】2010-2021年までの日米欧のアレルギー関連スタートアップ156社を対象に,データベースやVCウェブサイトから投資情報等を集計した.【結果】投資額は7.2億USDで,米国:欧州:日本の比率は20:6:1であった.米国は2016-2018年をピークに鈍化する一方,日欧は増加傾向だった.米国はアトピー性皮膚炎・食物アレルギーに対するバイオ医薬品,欧州は喘息アプリ,日本はヘルスケアアプリ・疾患横断型等への投資が多く見られた.【考察・結語】アレルギー領域の国内投資環境整備は今後の発展が望まれるものの,米国や欧州が先行している.日本のスタートアップ増加や資金調達の限界を考慮すると,米国等からの資金調達の可能性が検討される.アレルギー研究開発におけるスタートアップの戦略的活性化に寄与する結果と期待される.(著者抄録)

【水疱をきたす疾患】バンコマイシン誘発性線状IgA水疱性皮膚症

小野寺潤一, 足立剛也, 朱瀛瑤, 中村善雄, 高橋勇人, 天谷雅行, 齋藤昌孝

皮膚病診療（(株)協和企画） 46 （ 3 ） 246 - 250 2024年03月

ISSN 0387-7531

＜文献概要＞症例のポイント　・術後敗血症に対するバンコマイシン塩酸塩(VCM)投与後に四肢・体幹と口腔内に緊満性水疱を認め,病歴と精査の結果から,VCM誘発性線状IgA水疱性皮膚症(linear IgA bullous dermatosis:LABD)と診断した.・過去の報告も含めて,VII型コラーゲン特異的IgA ELISAの結果について,VCM中止後の発症早期とVCM中止1ヵ月以降とで比較したところ,後者ではVCM添加下でもELISAが陰性となる症例が多かった.・この結果を踏まえると,発症早期に通常のELISA検査に加えて,VCM添加下でのELISA検査を実施することが重要と考えられた.

Insights from the trends of omalizumab and mepolizumab utilization in patients with asthma: A population-based cohort study using the National Database in Japan

Keiko Kan-o, Tatsuya Noda, Hiroaki Ogata, Katsunori Masaki, Yuichi Nishioka, Tomoya Myojin, Takeya Adachi, Hideaki Morita, Tomoaki Imamura, Mayumi Tamari, Keigo Kainuma

Respiratory Investigation （Elsevier BV） 62 （ 1 ） 113 - 120 2024年01月

ISSN 2212-5345

BACKGROUND: Biologics are increasingly being used in patients with severe uncontrolled asthma. However, the trends in their use for treating severe asthma in Japan remain unclear. METHODS: The number of patients with asthma prescribed omalizumab or mepolizumab between April 2017 and March 2018 was estimated according to sex, age, and geographical region using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. RESULTS: Overall, 5,014, 3,449 and 7,977 patients were prescribed omalizumab, mepolizumab, or either combination, respectively. The total number of patients prescribed biologics displayed a bimodal distribution with peaks in their early teens and seventies. Biologics were most commonly used by male and female patients in their seventies. Prescription was 1.24 times higher in males than in females up to the teenage years, whereas it was 1.95 times higher in females than in males from their twenties onwards. Omalizumab was prescribed 1.45 times more frequently than mepolizumab, especially in pediatric patients, and was prescribed 1.96 times more often to female patients than to male patients. Regional differences were observed in the proportion of patients prescribed biologics. Correlation analysis suggested a weak relationship (r = 0.3226, p = 0.0270) between the proportion of patients prescribed biologics and board-certified allergists according to the geographic region. CONCLUSIONS: In Japan, biologics are prescribed more often to older patients with severe asthma compared to those in other countries. Thus, eliminating the regional disparities in asthma treatment by specialists is necessary to provide appropriate medical care to patients with severe asthma.

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[STATE-OF-THE-ART OF GLOBAL START-UP INVESTMENT FOR ALLERGY AND IMMUNOLOGY 2022].

Takeya Adachi, Motoshi Hayano, Yasunori Ito, Takenori Inomata, Yasushi Ogawa, Keigo Kainuma, Keiko Kan-O, Yosuke Kurashima, Yu Kuwabara, Masafumi Sakashita, Sakura Sato, Yasuhiro Tomita, Saeko Nakajima, Masaki Futamura, Katsunori Masaki, Mayumi Tamari, Motohiro Ebisawa, Hideaki Morita

Arerugi = [Allergy] 73 （ 3 ） 268 - 278 2024年

BACKGROUND: In 2022, the "New Capitalism Grand Design and Implementation Plan" was adopted in Japan, emphasizing the promotion and environmental development of startups. Given this context, an investigation into the startup and investment landscape in the allergy sector, both domestically and internationally, becomes imperative. METHODS: We analyzed 156 allergy-related startups from Japan, the US, and Europe from 2010 to 2021. Data on corporate information and investment trends were extracted from databases and VC websites. RESULTS: The total investment reached approximately 7.2 billion USD, with a ratio of 20:6:1 for the US, Europe, and Japan, respectively. The US showed a decline post its peak from 2016-2018, while Europe and Japan experienced growth. Notably, the US primarily invested in biopharmaceuticals for atopic dermatitis and food allergies, Europe in asthma-related apps, and Japan in healthcare apps and cross-border startups. DISCUSSION AND CONCLUSION: While Japan's investment environment in the allergy sector remains in its nascent stages and has room for development, the US and Europe are evidently ahead. Considering the rise of startups and funding limitations in Japan, external funding from regions like the US becomes a potential avenue. These findings are anticipated to contribute to the strategic activation of startups in allergy research and development.

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[RECURRENT AND VIRTUAL EDUCATION FOR ALL DISCIPLINES AND OCCUPATIONS IN THE ALLERGY REALM : A SURVEY OF THE PARTICIPANTS FROM THE INITIATIVE 'OUTREACH LECTURES' TO CREATE EDUCATIONAL OPPORTUNITIES].

Katsunori Masaki, Masafumi Sakashita, Yasushi Ogawa, Takenori Inomata, Keigo Kainuma, Keiko Kan-O, Sakura Sato, Mayumi Tamari, Saeko Nakajima, Hideaki Morita, Yosuke Kurashima, Masaki Futamura, Koichiro Takahashi, Junji Haruta, Misa Hyakutake, Toshiaki Monkawa, Tamotsu Ishizuka, Yoshimasa Imoto, Noritaka Oyama, Sho Kanzaki, Masanori Kidoguchi, Atsuki Fukushima, Koichi Fukunaga, Shigeharu Fujieda, Motoko Yasutomi, Takeya Adachi

Arerugi = [Allergy] 73 （ 4 ） 329 - 339 2024年

BACKGROUND: In the enhancement of allergy care involving multidisciplinary and multiple medical departments, there is a perceived need for education that targets not only specialists but also non-specialists. However, research on the need for and methods of such education remains inadequate. OBJECTIVE: To design a remote allergy care education program for all medical practitioners and to validate its necessity and utility. METHODS: The Empowering Next Generation Allergist/immunologist toward Global Excellence Task Force (ENGAGE-TF), supported by the Japanese Society of Allergology, initiated a virtual educational program called 'Outreach Lectures' in collaboration with Keio University and Fukui University. This initiative was widely promoted through social media and various institutions, and a survey was conducted through its mailing list. RESULTS: 1139 responses were obtained. More than half were physicians from non-allergy specialties, representing a diverse range of healthcare professions. Over 70% expressed being 'very satisfied,' and over 60% found the difficulty level 'appropriate.' Free-form feedback revealed differences in learning focus based on profession and learning approach based on years of experience. CONCLUSION: The high participation rate (90%) of non-specialist physicians underscores the demand for addressing allergic conditions in primary care. The effectiveness of virtual / recurrent education, particularly for healthcare professionals with over 11 years of experience, was implied. Further follow-up investigation focusing on quantitative and objective assessment of educational effectiveness is indispensable.

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A case of drug‐induced hypersensitivity syndrome complicated with fulminant type 1 diabetes and type 2 myocardial infarction

Yuki Kobayashi, Takeya Adachi, Hiroki Arakawa, Yugo Minakata, Ken Yajima, Toyoko Inazumi

The Journal of Dermatology 50 （ 12 ） 1603 - 1607 2023年12月

Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a type of drug eruption that causes multiorgan disorders after the administration of certain drugs such as anticonvulsants. Herein, we report the case of a 66-year-old man with DiHS/DRESS complicated by fulminant type 1 diabetes (FT1D), shock, and cardiac involvement who was treated conservatively without systemic corticosteroid administration. He had taken carbamazepine for trigeminal neuralgia for 7 weeks until he noticed eruptions on his trunk. Two days after admission, he developed diabetic ketoacidosis, resulting in hypovolemic shock. The patient was diagnosed with FT1D, and insulin was administered. Additionally, the patient had a fever over 38°C, elevated white blood cells (>20 000/μL), liver dysfunction, atypical lymphocytes, and lymphadenopathy, but no evidence of viral reactivation. The lymphocyte transformation test for carbamazepine was positive, and human leukocyte antigen typing revealed the A31:01 haplotype, a risk factor for carbamazepine-induced cutaneous adverse drug reactions. Collectively, a diagnosis of atypical DiHS and a definitive case of DRESS was made. Moreover, myocardial dysfunction wall motion was observed. A close examination revealed mild coronary artery stenosis, leading to a diagnosis of type 2 myocardial infarction due to relative ischemia. The patient was carefully monitored without systemic corticosteroid administration because both clinical findings and laboratory data peaked on the same day. The patient's eruption and general condition improved, and he was discharged 4 weeks later. While most cases of DiHS/DRESS with cardiac involvement present with myocarditis, the possibility of ischemic heart disease should be considered in patients with cardiac involvement under shock.

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Impact of COVID‐19 on care‐seeking patterns for hay fever in Japan: A retrospective claims database cohort study

Yasutsugu Akasaki, Masao Iwagami, Jaemyoung Sung, Ken Nagino, Takeya Adachi, Hideaki Morita, Mayumi Tamari, Keigo Kainuma, Keiko Kan‐o, Hiroaki Ogata, Masafumi Sakashita, Masaki Futamura, Yosuke Kurashima, Saeko Nakajima, Katsunori Masaki, Yasushi Ogawa, Sakura Sato, Akihiro Miyagawa, Akie Midorikawa‐Inomata, Keiichi Fujimoto, Yuichi Okumura, Kenta Fujio, Tianxiang Huang, Kunihiko Hirosawa, Yuki Morooka, Shintaro Nakao, Akira Murakami, Hiroyuki Kobayashi, Takenori Inomata

Allergy （Wiley） 79 （ 4 ） 1056 - 1060 2023年11月

ISSN 0105-4538

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アレルギー疾患拠点病院ネットワークを活用したアナフィラキシーの全国調査と疾患レジストリーの構築

佐藤さくら, 小太刀豪, 足立剛也, 伊藤靖典, 大嶋勇成, 緒方美佳, 北村勝誠, 鈴木慎太郎, 長尾みづほ, 中野泰至, 福家辰樹, 福冨友馬, 正木克宜, 三浦克志, 森田英明, 矢上晶子, 高橋亨平, 柳田紀之, 海老澤元宏

アレルギー（(一社)日本アレルギー学会） 72 （ 6-7 ） 794 - 794 2023年08月

ISSN 0021-4884

Enhancing Equitable Access to Rare Disease Diagnosis and Treatment around the World: A Review of Evidence, Policies, and Challenges

Takeya Adachi, Ayman W El-Hattab, Ritu Jain, Katya A Nogales Crespo, Camila I Quirland Lazo, Maurizio Scarpa, Marshall Summar, Duangrurdee Wattanasirichaigoon

International Journal of Environmental Research and Public Health 20 （ 6 ） 2023年03月

This document provides a comprehensive summary of evidence on the current situation of rare diseases (RDs) globally and regionally, including conditions, practices, policies, and regulations, as well as the challenges and barriers faced by RD patients, their families, and caregivers. The document builds on a review of academic literature and policies and a process of validation and feedback by a group of seven experts from across the globe. Panelists were selected based on their academic merit, expertise, and knowledge regarding the RD environment. The document is divided into five main sections: (1) methodology and objective; (2) background and context; (3) overview of the current situation and key challenges related to RDs covering six dimensions: burden of disease, patient journey, social impact, disease management, RD-related policies, and research and development; (4) recommendations; and (5) conclusions. The recommendations are derived from the discussion undertaken by the experts on the findings of this review and provide a set of actionable solutions to the challenges and barriers to improving access to RD diagnosis and treatment around the world. The recommendations can support critical decision-making, guiding efforts by a broad range of RDs stakeholders, including governments, international organizations, manufacturers, researchers, and patient advocacy groups.

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A severe case of hidradenitis suppurativa with chronic anemia treated with adalimumab

Hiroki Arakawa, Takeya Adachi, Yuki Kobayashi, Toyoko Inazumi

The Journal of Dermatology 50 （ 1 ） e22-e23 2023年01月

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Erythema multiforme following vaccination for SARS‐CoV‐2: Report of a case and review of the literature − Secondary Publication

Yuki Kobyashi, Takeya Adachi, Hiroki Arakawa, Mie Takeuchi, Toyoko Inazumi

Australasian Journal of Dermatology 63 （ 4 ） e381-e385 2022年11月

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A case of refractory leg ulcers caused by micro‐arteriovenous fistula: Potential utility of ultrasonography in the diagnosis

Akihiro Miyagawa, Takeya Adachi, Hiroki Arakawa, Mariko Hamada, Yoshinobu Akiyama, Toyoko Inazumi

The Journal of Dermatology 49 （ 10 ） e389-e390 2022年10月

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【デジタルヘルスを取り巻く法と倫理】地域開発型イノベーション・エコシステム構築に資する国内外の若手研究者ニーズ実態調査研究

足立剛也, 武内歩, 早野元詞, 黒田垂歩

Journal of Internet of Medical Things （(一社)IoMT学会） 5 （ 1 ） 34 - 40 2022年10月

ISSN 2433-9571

世界に伍するイノベーション・エコシステムの構築には,テクノロジーと研究者を含む人材の集積基盤が必須となる.そこで,海外で活躍する日本人研究者6,000人をつなぐ海外日本人研究者ネットワーク(UJA)等の協力のもと,国内だけでなく海外在住の日本人研究者も対象とし,異動先の研究・居住環境やスタートアップのニーズに関する実態調査を行った.結果,海外在住若手研究者は,立地よりも予算支援が大きいことが明らかとなった.また,研究環境だけでなく,家族・パートナーを含めた居住環境の整備,オープンイノベーション推進に関する人的・財政的支援は,研究者を誘致する上で,さらに考慮すべき項目となってくると推測された.(著者抄録)

Palpation Robot System - Reproduction Method by Deep Neural Network of Skin Palpation Judgment Focusing on Softness Classification-

2022年09月

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Six years' accomplishment of the Initiative on Rare and Undiagnosed Diseases: nationwide project in Japan to discover causes, mechanisms, and cures.

Yuji Takahashi, Hidetoshi Date, Hideki Oi, Takeya Adachi, Noriaki Imanishi, En Kimura, Hotake Takizawa, Shinji Kosugi, Naomichi Matsumoto, Kenjiro Kosaki, Yoichi Matsubara, Hidehiro Mizusawa

Journal of human genetics 67 （ 9 ） 505 - 513 2022年09月

The identification of causative genetic variants for hereditary diseases has revolutionized clinical medicine and an extensive collaborative framework with international cooperation has become a global trend to understand rare disorders. The Initiative on Rare and Undiagnosed Diseases (IRUD) was established in Japan to provide accurate diagnosis, discover causes, and ultimately provide cures for rare and undiagnosed diseases. The fundamental IRUD system consists of three pillars: IRUD diagnostic coordination, analysis centers (IRUD-ACs), and a data center (IRUD-DC). IRUD diagnostic coordination consists of clinical centers (IRUD-CLs) and clinical specialty subgroups (IRUD-CSSs). In addition, the IRUD coordinating center (IRUD-CC) manages the entire IRUD system and temporarily operates the IRUD resource center (IRUD-RC). By the end of March 2021, 6301 pedigrees consisting of 18,136 individuals were registered in the IRUD. The whole-exome sequencing method was completed in 5136 pedigrees, and a final diagnosis was established in 2247 pedigrees (43.8%). The total number of aberrated genes and pathogenic variants was 657 and 1718, among which 1113 (64.8%) were novel. In addition, 39 novel disease entities or phenotypes with 41 aberrated genes were identified. The 6-year endeavor of IRUD has been an overwhelming success, establishing an all-Japan comprehensive diagnostic and research system covering all geographic areas and clinical specialties/subspecialties. IRUD has accurately diagnosed diseases, identified novel aberrated genes or disease entities, discovered many candidate genes, and enriched phenotypic and pathogenic variant databases. Further promotion of the IRUD is essential for determining causes and developing cures for rare and undiagnosed diseases.

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患者教育・チーム医療・医療連携多職種が集うリカレント教育の重要性アレルギー診療ITC教育(出前授業による教育の機会創出事業)活動と展望

正木克宜, 坂下雅文, 小川靖, 猪俣武範, 神尾敬子, 佐藤さくら, 中島沙恵子, 福島敦樹, 森田英明, 神崎晶, 福永興壱, 石塚全, 尾山徳孝, 木戸口正典, 安冨素子, 足立剛也

アレルギー（(一社)日本アレルギー学会） 71 （ 6-7 ） 839 - 839 2022年08月

ISSN 0021-4884

患者教育・チーム医療・医療連携多職種が集うリカレント教育の重要性アレルギー診療ITC教育(出前授業による教育の機会創出事業)活動と展望

アレルギー（(一社)日本アレルギー学会） 71 （ 6-7 ） 839 - 839 2022年08月

ISSN 0021-4884

アレルギー診療教育のための多職種・学際的学習共同体の形成(Formation of an interdisciplinary learning community for multidisciplinary allergology education)

正木克宜, 春田淳志, 百武美沙, 坂下雅文, 小川靖, 猪俣武範, 神尾敬子, 佐藤さくら, 中島沙恵子, 福島敦樹, 森田英明, 神崎晶, 福永興壱, 石塚全, 尾山徳孝, 木戸口正典, 安冨素子, 足立剛也, 免疫アレルギー疾患研究10か年戦略次世代タスクフォース

医学教育（(一社)日本医学教育学会） 53 （ Suppl. ） 137 - 137 2022年07月

ISSN 0386-9644

アレルギー診療教育のための多職種・学際的学習共同体の形成(Formation of an interdisciplinary learning community for multidisciplinary allergology education)

医学教育（(一社)日本医学教育学会） 53 （ Suppl. ） 137 - 137 2022年07月

ISSN 0386-9644

Prevalence of Comorbidity between Dry Eye and Allergic Conjunctivitis: A Systematic Review and Meta-Analysis

Yasutsugu Akasaki, Takenori Inomata, Jaemyoung Sung, Masahiro Nakamura, Koji Kitazawa, Kendrick Co Shih, Takeya Adachi, Yuichi Okumura, Kenta Fujio, Ken Nagino, Akie Midorikawa-Inomata, Mizu Kuwahara, Kunihiko Hirosawa, Tianxiang Huang, Yuki Morooka, Hurramhon Shokirova, Atsuko Eguchi, Akira Murakami

Journal of Clinical Medicine 11 （ 13 ） 2022年06月

This systematic review aimed to determine the comorbid dry eye (DE) and allergic conjunctivitis (AC) prevalence. We searched PubMed and EMBASE for articles published until 22 March 2022, combining the terms "(dry eye OR keratoconjunctivitis sicca) AND allergic conjunctivitis." Study-specific estimates (DE and AC incidence rates among patients with AC and DE, respectively) were combined using the one-group meta-analysis in a random-effects model. The initial search yielded 700 studies. Five articles reporting AC incidence among individuals with DE and six articles reporting DE incidence among individuals with AC were included in the qualitative synthesis. In these nine articles, the total sample size was 7254 patients. The DE incidence among individuals with AC was 0.9-97.5%; the AC incidence among individuals with DE was 6.2-38.0%. One-group meta-analysis using a random-effects model showed that 47.2% (95% confidence interval: 0.165-0.779; 320/1932 cases) of patients with AC had comorbid DE and 17.8% (95% confidence interval: 0.120-0.236; 793/4855 cases) of patients with DE had comorbid AC, as defined by each article. Complimentary screening and treatment for patients with DE and AC may improve long-term outcomes and prevent chronic ocular damage in highly susceptible populations.

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Research impact analysis of international funding agencies in the realm of allergy and immunology

Takeya Adachi, Yasushi Ogawa, Tamami Fukushi, Kei Ito, Amane Koizumi, Masashi Shirabe, Masako Toriya, Jun Hirako, Takenori Inomata, Katsunori Masaki, Ryohei Sasano, Sakura Sato, Keigo Kainuma, Masaki Futamura, Keiko Kan-O, Yosuke Kurashima, Saeko Nakajima, Masafumi Sakashita, Hideaki Morita, Aikichi Iwamoto, Sankei Nishima, Mayumi Tamari, Hajime Iizuka

Allergy 77 （ 5 ） 1602 - 1606 2022年02月

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新型コロナウィルスワクチン接種後に出現した多形紅斑-DLST結果を含めた症例報告

小林由季, 足立剛也, 新川宏樹, 稲積豊子

日本皮膚科学会雑誌（(公社)日本皮膚科学会） 132 （ 1 ） 69 - 73 2022年01月

ISSN 0021-499X

77歳男性。新型コロナウィルスワクチン(コミナティ筋注)2回目接種2日後より紅斑が出現し、全身へ拡大した。接種3週間後の初診時、躯幹四肢に環状で6cm大までの融合傾向のある浮腫状暗紅色斑が散在し、一部標的様を呈した。経過・検査所見より、コミナティ筋注接種後の多形紅斑と診断した。新型コロナウィルスワクチン接種後の多形紅斑の報告はまだ少なく、今後ワクチンのさらなる普及に伴い、同様の皮疹を呈する例の増加も予想される。陰性対照も含め提出したコミナティ筋注のDLST結果及び文献的考察を加え報告する。(著者抄録)

Evaluation of adrenaline auto-injector prescription profiles: A population-based, retrospective cohort study within the National Insurance Claims Database of Japan

Sato S., Kainuma K., Noda T., Ebisawa M., Futamura M., Imamura T., Miyagawa A., Nakajima S., Ogawa Y., Inomata T., Kan-o K., Kurashima Y., Masaki K., Myojin T., Nishioka Y., Sakashita M., Tamari M., Morita H., Adachi T.

Allergology International （Allergology International） 71 （ 3 ） 354 - 361 2022年

ISSN 13238930

Background: Adrenaline is the first-line medication for managing anaphylaxis. A better understanding of prescription trends for adrenaline auto-injectors (AAIs) is important to improving patient care as well as information on health education interventions and medical guidelines. However, it has been difficult to gather comprehensive data in a sustainable manner. Thus, we aimed to investigate trends in AAI prescriptions in Japan. Methods: We searched the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), a unique and comprehensive database of health insurance claims, and investigated prescriptions for AAIs for all ages (April 2017 to March 2018). We assessed the annual number of prescriptions per person as well as prescription rates per 100,000 population per year by age, sex, and geographic region. Results: A total of 88,039 subjects (56,109 males, 31,930 female) and 116,758 devices (1.33 AAIs per patient per year) were prescribed AAIs at least once a year for all ages. The prescription rate for AAIs was 69.5 per 100,000 population-years. Patients aged 0–9 years were prescribed AAIs at the rate of 278.9 per 100,000 population-years. Patients aged 0–19 years were 6.4 times more likely to be prescribed AAIs than those over 20 years of age. Males were more frequently prescribed AAIs than females in all age groups, except for those aged 20–24 years. We also evaluated differences in prescription rates by geographic region. Conclusions: This comprehensive evaluation revealed trends in AAI prescriptions, thus helping develop preventive strategies with respect to anaphylaxis in Japan.

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A case of aggressive and protuberant nodular fasciitis on the finger with repeated contact

Hiroki Arakawa and Takeya Adachi and Akihiro Miyagawa and Keiko Miura and Kentaro Ogata and Toyoko Inazumi

Australasian Journal of Dermatology （Wiley） 63 （ 1 ） e102-e103 2021年12月

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Plasmapheresis as a promising treatment option in apalutamide‐associated toxic epidermal necrolysis

Akihiro Miyagawa and Takeya Adachi and Yuki Kobayashi and Saeko Takamiyagi and Hiroki Arakawa and Koji Futatsugi and Toyoko Inazumi

The Journal of Dermatology （Wiley） 49 （ 3 ） e102-e103 2021年11月

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A case of vancomycin‐induced linear IgA bullous dermatosis with toxic epidermal necrolysis‐like symptoms: Palmoplantar eruptions as a possible risk marker

Motoki Adachi and Takeya Adachi and Masaki Yokota and Chika Ichimura and Kenji Yoshida and Ken Ishii and Akira Ishiko

The Journal of Dermatology （Wiley） 48 （ 12 ） e610-e611 2021年09月

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【好中球が関与する皮膚病】下腿紫斑が先行し,フルニエ壊疽が合併したseptic vasculitis

宮川明大, 足立剛也, 高宮城冴子, 新川宏樹, 小幡祥子, 稲積豊子

皮膚病診療（(株)協和企画） 43 （ 5 ） 444 - 447 2021年05月

ISSN 0387-7531

First case of lenvatinib‐induced pyoderma gangrenosum: Possible management with dose reduction

Akihiro Miyagawa, Takeya Adachi, Saeko Takamiyagi, Hiroki Arakawa, Misako Matsushita, Toyoko Inazumi

The Journal of Dermatology 48 （ 5 ） e221-e222 2021年03月

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Strategic Outlook toward 2030: Japan's research for allergy and immunology – Secondary publication

Adachi T., Kainuma K., Asano K., Amagai M., Arai H., Ishii K.J., Ito K., Uchio E., Ebisawa M., Okano M., Kabashima K., Kondo K., Konno S., Saeki H., Sonobe M., Nagao M., Hizawa N., Fukushima A., Fujieda S., Matsumoto K., Morita H., Yamamoto K., Yoshimoto A., Tamari M.

Allergology International （Allergology International） 69 （ 4 ） 561 - 570 2020年10月

ISSN 13238930

Strategic Outlook toward 2030: Japan's Research for Allergy and Immunology (Strategy 2030) is the national research strategy based on Japan's Basic Law on Measures Against Allergic Diseases, a first of its kind worldwide. This strategy was established by a multi-disciplinary committee consisting of administrators of the Ministry of Health, Labour and Welfare of Japan, young and senior experts from various research societies and associations, and representatives of patient and public groups. Whereas the issues of transition, integration, and international collaboration have yet to be solved in this research realm in Japan, identification of unmet needs, digitization of information and transparent procedures, and strategic planning for complex problems (a process dubbed MIERUKA by the Toyota Way) are crucial to share and tackle the same vision and goals. The committee developed three specific actions focusing on preemptive treatment, interdisciplinarity and internationality, and life stage. The real success of Strategy 2030 is made by the spontaneous contributions of doctors, dentists, veterinarians, and other medical professionals; basic and clinical research scientists, research supporters, and pharmaceutical/medical device companies; manufacturers of food, healthcare, and home appliances; and patients, their families, and the public. The hope is to establish a stable society in which people can live long, healthy lives, as free as possible from allergic and immunological diseases, at each individual life stage. This article is based on a Japanese review first reported in Arerugi, introduces the developmental process and details of Strategy 2030.

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Strategic outlook toward 2030: Japan's research for allergy and immunology

Japanese Journal of Allergology （Japanese Journal of Allergology） 69 （ 1 ） 23 - 33 2020年

ISSN 00214884

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Survey on patients with undiagnosed diseases in Japan: Potential patient numbers benefiting from Japan's initiative on rare and undiagnosed diseases (IRUD)

Adachi T., Imanishi N., Ogawa Y., Furusawa Y., Izumida Y., Izumi Y., Suematsu M.

Orphanet Journal of Rare Diseases （Orphanet Journal of Rare Diseases） 13 （ 1 ） 208 - 208 2018年11月

査読有り

Background: There is now an international partnership to establish global programs for patients with rare and undiagnosed diseases, involving interdisciplinary expert panels and phenotype-driven genetic analyses utilizing next-generation sequencing and analytics. Whereas it is crucial to have data such as the actual number of undiagnosed patients, to help inform the implementation plan with such programs, there have been no systematic studies to quantitate the numbers of patients principally because of the inherent difficulty in most health systems to identify patients whose condition has not yet been diagnosed and coded. Our national experience with a rare disease program, Nan-Byo which was established in 1972, and the more recently expanded Initiative on Rare and Undiagnosed Diseases (IRUD), provided a unique opportunity to design a cross-sectional study to ascertain the undiagnosed patients in Japan based on the IRUD referral criteria. Results: Two rounds of online surveys were performed: one survey targeting physicians affiliated with general hospitals (GH) and family clinics (FC) (the response rate: 30.6% (242/792)) and one nationwide survey targeting university hospitals (UH) in Japan (47.1% (839/1781)). A high percentage of doctors needing IRUD was seen in pediatrics at GH, FC, while there was a clear demand for IRUD in most departments at UH. We calculated the number of undiagnosed patients in Japan, as the "percentage of doctors needing IRUD" × "number of patients who would be referred to IRUD per doctor needing IRUD (cases/person)" × "total number of doctors in the relevant facilities in Japan (persons)", resulting in 3681 cases in pediatrics/pediatric surgery and 33,703 cases in other departments, for a total of 37,384 cases. Conclusions: Our study revealed the extant demand for IRUD in most departments and 37,000+ potential patients with undiagnosed diseases in the Japanese health system. These data inform the establishment of an equitable, sustainable, efficient and effective outpatient-based IRUD. These findings would serve as a valuable reference for undiagnosed diseases programs in different international jurisdictions and for countries and regions who also share vision(s) for societal implementation that help to advance international efforts to support patients with rare diseases who are direly waiting for diagnosis, subsequent treatment and care.

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Case of lamotrigine-induced drug adverse reaction under tocilizumab treatment with clinical and virological features of drug-induced hypersensitivity syndrome

Iriki H., Ouchi T., Ito H., Sawada M., Mukai M., Nomura H., Baba Y., Adachi T., Funakoshi T., Amagai M., Takahashi H.

Journal of Dermatology （Journal of Dermatology） 45 （ 6 ） 738 - 741 2018年06月

査読有り, ISSN 03852407

The pathological mechanisms and immunological kinetics of drug-induced hypersensitivity syndrome (DIHS), including the relevance of interleukin (IL)-6, remain unclear. We report a case of drug adverse reaction that does not fulfill the diagnostic criteria of DIHS but mimics its characteristic features. Because the patient was under anti-IL-6 therapy at the onset, some symptoms typically seen in DIHS were absent, such as fever and leukocyte count abnormalities. However, the characteristic features of DIHS were clearly observed in the subsequent course, including the repeated recurrence of skin rash, prolonged liver dysfunction and reactivation of herpes viruses. This case suggested that IL-6 role at the onset is not a main factor to determine the subsequent pathomechanism of DIHS and attention should be paid to the preceding therapy for achieving accurate diagnosis.

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Langerhans Cells Prevent Autoimmunity via Expansion of Keratinocyte Antigen-Specific Regulatory T Cells

Kitashima D.Y., Kobayashi T., Woodring T., Idouchi K., Doebel T., Voisin B., Adachi T., Ouchi T., Takahashi H., Nishifuji K., Kaplan D.H., Clausen B.E., Amagai M., Nagao K.

EBioMedicine （EBioMedicine） 27 293 - 303 2018年01月

査読有り, ISSN 2352-3964

Langerhans cells (LCs) are antigen-presenting cells in the epidermis whose roles in antigen-specific immune regulation remain incompletely understood. Desmoglein 3 (Dsg3) is a keratinocyte cell-cell adhesion molecule critical for epidermal integrity and an autoantigen in the autoimmune blistering disease pemphigus. Although antibody-mediated disease mechanisms in pemphigus are extensively characterized, the T cell aspect of this autoimmune disease still remains poorly understood. Herein, we utilized a mouse model of CD4+ T cell-mediated autoimmunity against Dsg3 to show that acquisition of Dsg3 and subsequent presentation to T cells by LCs depended on the C-type lectin langerin. The lack of LCs led to enhanced autoimmunity with impaired Dsg3-specific regulatory T cell expansion. LCs expressed the IL-2 receptor complex and the disruption of IL-2 signaling in LCs attenuated LC-mediated regulatory T cell expansion in vitro, demonstrating that direct IL-2 signaling shapes LC function. These data establish that LCs mediate peripheral tolerance against an epidermal autoantigen and point to langerin and IL-2 signaling pathways as attractive targets for achieving tolerogenic responses particularly in autoimmune blistering diseases such as pemphigus.

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Japan’s initiative on rare and undiagnosed diseases (IRUD): towards an end to the diagnostic odyssey

Takeya Adachi, Kazuo Kawamura, Yoshihiko Furusawa, Yuji Nishizaki, Noriaki Imanishi, Senkei Umehara, Kazuo Izumi, Makoto Suematsu

European Journal of Human Genetics （Springer Nature） 25 （ 9 ） 1025 - 1028 2017年09月

査読有り

Japan has been facing challenges relating to specifically defined rare diseases, called Nan-Byo in Japanese (literally 'difficult'+'illness'), and has already taken measures for them since 1972. This governmental support has surely benefited Nan-Byo patients; however, those suffering from medically unidentified conditions do not fall into this scheme and thus still confront difficulty in obtaining an examination, a diagnosis, and a treatment. To identify such rare and often undiagnosed diseases, we must integrate systematic diagnosis by medical experts with phenotypic and genetic data matching. Thus, in collaboration with Nan-Byo researchers and the Japanese universal healthcare system, the Japan Agency for Medical Research and Development launched the Initiative on Rare and Undiagnosed Diseases (IRUD) in 2015. IRUD is an ambitious challenge to construct a comprehensive medical network and an internationally compatible data-sharing framework. Synergizing with existing next-generation sequencing capabilities and other infrastructure, the nationwide medical research consortium has successfully grown to accept more than 2000 undiagnosed registrants by December 2016. We also aim at expanding the concept of microattribution throughout the initiative; that is, proper credit as collaborators shall be given to local primary care physicians, nurses and paramedics, patients, their family members, and those supporting the affected individuals whenever appropriate. As it shares many challenges among similar global efforts, IRUD's future successes and lessons learned will significantly contribute to ongoing international endeavors, involving players in basic research, applied research, and societal implementation.

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A Single-Center Open-Label Single-Arm Study Evaluating Efficacy and Safety of Skin Adhesive Epinexus<sup>TM</sup> in Surgical Patients

Kazuo Kishi, Noriko Aramaki-Hattori, Yoshiaki Sakamoto, Keisuke Okabe, Tetsu Hayashida, Maiko Takahashi, Yuko Kitagawa, Masataka Saito, Takeya Adachi, Aki Honda, Hiromitsu Jinno

Modern Plastic Surgery （Scientific Research Publishing, Inc,） 07 （ 04 ） 31 - 38 2017年

査読有り, ISSN 2164-5213

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Improved Diagnosis and Care for Rare Diseases through Implementation of Precision Public Health Framework.

Gareth Baynam, Faye Bowman, Karla Lister, Caroline E Walker, Nicholas Pachter, Jack Goldblatt, Kym M Boycott, William A Gahl, Kenjiro Kosaki, Takeya Adachi, Ken Ishii, Trinity Mahede, Fiona McKenzie, Sharron Townshend, Jennie Slee, Cathy Kiraly-Borri, Anand Vasudevan, Anne Hawkins, Stephanie Broley, Lyn Schofield, Hedwig Verhoef, Tudor Groza, Andreas Zankl, Peter N Robinson, Melissa Haendel, Michael Brudno, John S Mattick, Marcel E Dinger, Tony Roscioli, Mark J Cowley, Annie Olry, Marc Hanauer, Fowzan S Alkuraya, Domenica Taruscio, Manuel Posada de la Paz, Hanns Lochmüller, Kate Bushby, Rachel Thompson, Victoria Hedley, Paul Lasko, Kym Mina, John Beilby, Cynthia Tifft, Mark Davis, Nigel G Laing, Daria Julkowska, Yann Le Cam, Sharon F Terry, Petra Kaufmann, Iiro Eerola, Irene Norstedt, Ana Rath, Makoto Suematsu, Stephen C Groft, Christopher P Austin, Ruxandra Draghia-Akli, Tarun S Weeramanthri, Caron Molster, Hugh J S Dawkins

Advances in experimental medicine and biology （Springer International Publishing） 1031 55 - 94 2017年

査読有り, ISSN 0065-2598

Public health relies on technologies to produce and analyse data, as well as effectively develop and implement policies and practices. An example is the public health practice of epidemiology, which relies on computational technology to monitor the health status of populations, identify disadvantaged or at risk population groups and thereby inform health policy and priority setting. Critical to achieving health improvements for the underserved population of people living with rare diseases is early diagnosis and best care. In the rare diseases field, the vast majority of diseases are caused by destructive but previously difficult to identify protein-coding gene mutations. The reduction in cost of genetic testing and advances in the clinical use of genome sequencing, data science and imaging are converging to provide more precise understandings of the 'person-time-place' triad. That is: who is affected (people); when the disease is occurring (time); and where the disease is occurring (place). Consequently we are witnessing a paradigm shift in public health policy and practice towards 'precision public health'.Patient and stakeholder engagement has informed the need for a national public health policy framework for rare diseases. The engagement approach in different countries has produced highly comparable outcomes and objectives. Knowledge and experience sharing across the international rare diseases networks and partnerships has informed the development of the Western Australian Rare Diseases Strategic Framework 2015-2018 (RD Framework) and Australian government health briefings on the need for a National plan.The RD Framework is guiding the translation of genomic and other technologies into the Western Australian health system, leading to greater precision in diagnostic pathways and care, and is an example of how a precision public health framework can improve health outcomes for the rare diseases population.Five vignettes are used to illustrate how policy decisions provide the scaffolding for translation of new genomics knowledge, and catalyze transformative change in delivery of clinical services. The vignettes presented here are from an Australian perspective and are not intended to be comprehensive, but rather to provide insights into how a new and emerging 'precision public health' paradigm can improve the experiences of patients living with rare diseases, their caregivers and families.The conclusion is that genomic public health is informed by the individual and family needs, and the population health imperatives of an early and accurate diagnosis; which is the portal to best practice care. Knowledge sharing is critical for public health policy development and improving the lives of people living with rare diseases.

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Skin-infiltrating CD4+ lymphoma cells depend on hair follicle-derived IL-7

Takeya Adachi, Tetsuro Kobayashi, Eiji Sugihara, Keitaro Fukuda, Manabu Ohyama, Hideyuki Saya, Taketo Yamada, Masayuki Amagai, Keisuke Nagao

Journal of Dermatological Science （Elsevier {BV}） 84 （ 1 ） e60 2016年10月

査読有り, ISSN 0923-1811

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Case of isolated epidermolytic acanthoma: Genetic and immunohistochemical analysis

Takeya Adachi, Keiji Tanese, Takeshi Ouchi, Satomi Igawa, Hajime Nakano, Akira Ishiko

The Journal of Dermatology （Wiley-Blackwell） 43 （ 8 ） 974 - 975 2016年03月

査読有り, ISSN 0385-2407

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Hair follicle–derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma

Takeya Adachi, Tetsuro Kobayashi, Eiji Sugihara, Taketo Yamada, Koichi Ikuta, Stefania Pittaluga, Hideyuki Saya, Masayuki Amagai, Keisuke Nagao

Nature Medicine （Springer Nature） 21 （ 11 ） 1272 - 1279 2015年10月

査読有り, ISSN 1078-8956

The skin harbors a variety of resident leukocyte subsets that must be tightly regulated to maintain immune homeostasis. Hair follicles are unique structures in the skin that contribute to skin dendritic cell homeostasis through chemokine production. We demonstrate that CD4(+) and CD8(+) skin-resident memory T cells (TRM cells), which are responsible for long-term skin immunity, reside predominantly within the hair follicle epithelium of the unperturbed epidermis. TRM cell tropism for the epidermis and follicles is herein termed epidermotropism. Hair follicle expression of IL-15 was required for CD8(+) TRM cells, and IL-7 for CD8(+) and CD4(+) TRM cells, to exert epidermotropism. A lack of either cytokine in the skin led to impaired hapten-induced contact hypersensitivity responses. In a model of cutaneous T cell lymphoma, epidermotropic CD4(+) TRM lymphoma cell localization depended on the presence of hair follicle-derived IL-7. These findings implicate hair follicle-derived cytokines as regulators of malignant and non-malignant TRM cell tissue residence, and they suggest that the cytokines may be targeted therapeutically in inflammatory skin diseases and lymphoma.

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Postherpetic Wolf's isotopic response: possible contribution of resident memory T cells to the pathogenesis of lichenoid reaction

M. Ise, K. Tanese, T. Adachi, W. Du, M. Amagai, M. Ohyama

British Journal of Dermatology （Wiley-Blackwell） 173 （ 5 ） 1331 - 1334 2015年10月

査読有り, ISSN 0007-0963

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Toxic epidermal necrolysis in the absence of circulating T cells: A possible role for resident memory T cells

Hisato Iriki, Takeya Adachi, Mariko Mori, Keiji Tanese, Takeru Funakoshi, Daiki Karigane, Takayuki Shimizu, Shinichiro Okamoto, Keisuke Nagao

Journal of the American Academy of Dermatology （Elsevier {BV}） 71 （ 5 ） e214 - e216 2014年11月

査読有り, ISSN 0190-9622

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Hapten-induced lymphadenosis benigna cutis secondary to squaric acid dibutylester sensitization for alopecia areata

Takeya Adachi, Takeshi Ouchi, Tamotsu Ebihara, Manabu Ohyama

The Journal of Dermatology （Wiley-Blackwell） 41 （ 2 ） 182 - 183 2014年01月

査読有り, ISSN 0385-2407

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Comparison of basophil activation test and lymphocyte transformation test as diagnostic assays for drug hypersensitivity

Takeya Adachi, Hayato Takahashi, Takeru Funakoshi, Hiroyuki Hirai, Akihiko Hashiguchi, Masayuki Amagai, Keisuke Nagao

Clinical and Translational Allergy （Springer Nature） 4 （ Suppl 3 ） P30 2014年

査読有り, ISSN 2045-7022

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Rheumatoid neutrophilic dermatosisの1例　関節リウマチの病勢との関連について

足立剛也, 崎山とも, 大内健嗣, 高江雄二郎, 安岡秀剛, 谷川瑛子

臨床皮膚科（(株)医学書院） 67 （ 7 ） 501 - 505 2013年06月

ISSN 0021-4973

55歳,女性.7年前より抗リウマチ薬およびメトトレキサートで関節リウマチ(rheumatoid arthritis:RA)を治療中であった.発熱と関節炎の増悪を認め,同時に四肢伸側に爪甲大までの浸潤性紅斑が出現した.病理組織学的に,真皮全層の好中球を主体とする稠密な炎症細胞浸潤であり,血管炎の所見は認めなかった.Rheumatoid neutrophilic dermatosis(RND)と診断し,エタネルセプト投与でRAの諸症状(発熱,関節炎)の軽快とともに皮疹の消退を認めた.RNDはRAに伴う稀な皮疹である.その発症機序は不明だが,過去の報告例よりコントロール不良のRA患者に多く発症し,その症状軽快に伴って消退する傾向が認められた.RNDはRAの病勢を反映し,その評価に有用である可能性が示唆された.(著者抄録)

Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin

Keisuke Nagao, Tetsuro Kobayashi, Kazuyo Moro, Manabu Ohyama, Takeya Adachi, Daniela Y Kitashima, Satoshi Ueha, Keisuke Horiuchi, Hideaki Tanizaki, Kenji Kabashima, Akiharu Kubo, Young-hun Cho, Björn E Clausen, Kouji Matsushima, Makoto Suematsu, Glaucia C Furtado, Sergio A Lira, Joshua M Farber, Mark C Udey, Masayuki Amagai

Nature Immunology （Springer Nature） 13 （ 8 ） 744 - 752 2012年06月

査読有り, ISSN 1529-2908

Langerhans cells (LCs) are epidermal dendritic cells with incompletely understood origins that associate with hair follicles for unknown reasons. Here we show that in response to external stress, mouse hair follicles recruited Gr-1(hi) monocyte-derived precursors of LCs whose epidermal entry was dependent on the chemokine receptors CCR2 and CCR6, whereas the chemokine receptor CCR8 inhibited the recruitment of LCs. Distinct hair-follicle regions had differences in their expression of ligands for CCR2 and CCR6. The isthmus expressed the chemokine CCL2; the infundibulum expressed the chemokine CCL20; and keratinocytes in the bulge produced the chemokine CCL8, which is the ligand for CCR8. Thus, distinct hair-follicle keratinocyte subpopulations promoted or inhibited repopulation with LCs via differences in chemokine production, a feature also noted in humans. Pre-LCs failed to enter hairless skin in mice or humans, which establishes hair follicles as portals for LCs.

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骨吸収を伴った小児口唇の線状強皮症の1例

足立剛也, 宮本樹里亜, 大内健嗣, 大山学, 海老原全, 角田和之, 天谷雅行

臨床皮膚科（(株)医学書院） 66 （ 4 ） 311 - 315 2012年04月

ISSN 0021-4973

12歳,女児.初診2年前より下口唇に白色調の色調変化を認め,次第に病変が線状に拡大し,白色調も増強してきた.初診時,下口唇正中右側の赤唇部に,軽度に陥凹する線状の白色萎縮性病変を認め,白唇部から下顎の一部にも病変が及んでいた.また,同部位の延長線上の歯肉にも萎縮を伴っており,歯槽骨の一部にも吸収像がみられ,歯の動揺を伴った.病理組織所見では,表皮に著変なく,真皮浅層の浮腫と真皮全層にわたる膠原線維の膨化,均質化を認めた.硬化性萎縮性苔癬との鑑別が問題となったが,小児期の発症で,骨病変を合併したことより,線状強皮症と診断した.小児口唇の線状強皮症はきわめて稀であり,成長障害,機能障害をきたすこともあるため注意が必要である.文献的考察を加えて報告する.(著者抄録)

Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome

Takeshi Ouchi, Akiharu Kubo, Mariko Yokouchi, Takeya Adachi, Tetsuro Kobayashi, Daniela Y. Kitashima, Hideki Fujii, Björn E. Clausen, Shigeo Koyasu, Masayuki Amagai, Keisuke Nagao

The Journal of Experimental Medicine （Rockefeller University Press） 208 （ 13 ） 2607 - 2613 2011年

査読有り, ISSN 0022-1007

Epidermal Langerhans cells (LCs) extend dendrites through tight junctions (TJs) to survey the skin surface, but their immunological contribution in vivo remains elusive. We show that LCs were essential for inducing IgG(1) responses to patch-immunized ovalbumin in mice that lacked skin dendritic cell subsets. The significance of LC-induced humoral responses was demonstrated in a mouse model of staphylococcal scalded skin syndrome (SSSS), a severe blistering disease in which the desmosomal protein Dsg1 (desmoglein1) is cleaved by Staphylococcus aureus-derived exfoliative toxin (ET). Importantly, ET did not penetrate TJs, and patch immunization did not alter epidermal integrity. Nevertheless, neutralizing anti-ET IgG(1) was induced after patch immunization and abolished upon LC depletion, indicating that antigen capture through TJs by LCs induced humoral immunity. Strikingly, the ET-patched mice were protected from developing SSSS after intraperitoneal ET challenge, whereas LC-depleted mice were susceptible to SSSS, demonstrating a vital role for LC-induced IgG(1) in systemic defense against circulating toxin in vivo. Therefore, LCs elicit humoral immunity to antigens that have not yet violated the epidermal barrier, providing preemptive immunity against potentially pathogenic skin microbes. Targeting this immunological process confers protection with minimal invasiveness and should have a marked impact on future strategies for development of percutaneous vaccines.

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