基本情報
- 所属
- 自治医科大学 医学部 皮膚科学講座 /医師・研究者キャリア支援センター 教授東京大学医学部 非常勤講師
- 学位
- 医学博士(東京大学)
- J-GLOBAL ID
- 201401086537031824
- researchmap会員ID
- B000238728
- 外部リンク
研究キーワード
30経歴
2-
2018年8月 - 現在
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2007年6月 - 2018年7月
論文
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The Journal of dermatology 2023年11月30日Plaque psoriasis (PsO) is a chronic immune-mediated inflammatory disease with skin lesions accompanied by an inflammation-related comorbidity risk. The development of various oral drugs and biologics for PsO has provided increasing systemic treatment options for patients with PsO, and the guidance regarding the use of biologics and PsO treatment schemes are widespread in Japan. However, no comprehensive guidelines regarding systemic drug use are available, and the current treatment patterns of systemic drugs for PsO in Japan remain unclear. We conducted a retrospective chart review to clarify the current treatment patterns of systemic drugs for PsO. We enrolled 114 patients who started systemic drugs for PsO between January 2017 and December 2020 at four institutes, with a mean follow-up of 37.2 months. The mean disease duration was 7.8 (standard deviation 9.5) years at the systemic drug initiation. Of all the patients, 78.1% started with oral drugs (phosphodiesterase [PDE] 4 inhibitors 56.1%. calcineurin inhibitors 14.0%. vitamin A derivatives 7.9%), whereas 21.9% started with biologics (interleukin [IL]-17 inhibitors 9.6%. tumor necrosis factor inhibitors 7.0%. IL-23 inhibitors 3.5%. IL-12/23 inhibitors 1.8%). Oral drugs had shorter drug persistence than biologics: the 12-month persistence of the oral drugs vitamin A derivative, calcineurin inhibitor, and PDE4 inhibitor, was 35.5%, 25.8%, and 60.1%, respectively, compared with that of the biologics IL-23 and IL-17 inhibitors, which was 85.6% and 84.7%, respectively. During the study period, the incidence of treatment changes was 59.1/100 patient-years. Lack of efficacy was the most common reason for treatment changes from monotherapy (34.1%). This retrospective medical chart review allowed us to understand the real-world, long-term treatment patterns of systemic drugs for PsO and the relationships between the reasons for treatment changes and subsequent treatment selection, indicating that there is still room for improvement in the appropriate use of systemic drugs for PsO in Japan.
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The Journal of dermatology 50(5) e138-e150 2023年5月This is the English version of Japanese guidance for the use of oral Janus kinase (JAK) inhibitors (JAK1 and tyrosine kinase 2 [TYK2] inhibitors) in the treatments of psoriasis. Several cytokines, such as interleukin (IL)-6, IL-7, IL-12, IL-21, IL-22, IL-23, interferon (IFN)-α, and IFN-γ, are involved in the pathogenesis of psoriasis (including psoriatic arthritis). As oral JAK inhibitors hinder the JAK-signal transducers and activators of transcription signal transduction routes involved in the signal transduction of these cytokines, they may be effective for the treatment of psoriasis. JAK has four types: JAK1, JAK2, JAK3, and TYK2. Regarding the use of oral JAK inhibitors for the treatment of psoriasis in Japan, indications of the JAK1 inhibitor upadacitinib were extended also to psoriatic arthritis in 2021, and the use of the TYK2 inhibitor deucravacitinib for plaque-type psoriasis, pustular psoriasis, and erythrodermic psoriasis became covered by health insurance in 2022. This guidance was developed for board-certified dermatologists who specialize in the treatment of psoriasis and to promote the proper use of oral JAK inhibitors. In the package inserts and guides for appropriate use, upadacitinib and deucravacitinib are classified as a "JAK inhibitor" and a "TYK2 inhibitor", respectively, and it is possible that there may be differences in safety between the two drugs. The safety of these drugs will be evaluated for the future by the postmarketing surveillance for molecularly targeted drugs for psoriasis of the Japanese Dermatological Association.
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The Journal of dermatology 2023年3月20日This real-world study at a single academic center retrospectively examined the drug survival of apremilast for patients with psoriasis. Retrospective information was extracted from the medical records of patients with psoriasis treated with apremilast at the Department of Dermatology, Jichi Medical University Hospital, between March 1, 2017, and June 31, 2021. In total, 281 patients were included in this study. Of these patients, 22% had psoriatic arthritis and 57% had a history of prior systemic treatment, including biologics, before the initiation of apremilast. The 1-, 2-, 3-, and 4-year drug survival rates were 54%, 41%, 32%, and 30%, respectively. Cox regression analysis revealed that sex, duration of plaque psoriasis (<10 years vs ≥10 years), presence of psoriatic arthritis, involvement of scalp lesions, involvement of palmoplantar lesion, involvement of nail lesions, having cardiometabolic comorbidities, and a history of prior systemic treatment did not have any significant impact on drug survival. The most common reason for apremilast discontinuation was inadequate efficacy (27%), followed by adverse events (12%). Approximately 49% of the patients experienced one or more adverse events. Diarrhea was the most common adverse event (24%), followed by nausea (19%) and headache (11%).
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Scientific reports 13(1) 4384-4384 2023年3月16日Narrow band-ultraviolet B (NB-UVB) is an effective treatment for psoriasis. We aim to generate a potential mechanism of NB-UVB through comparing the transcriptomic profile before and after NB-UVB treatment between the peripheral edge of lesional skin (PE skin) and the center of lesional skin (CE skin) on the basis of molecular mechanisms of these two areas display different downstream functions. More than one-fourth of the NB-UVB-altered genes were found to be plaque-specific. Some of them were psoriasis signature genes that were downregulated by NB-UVB in, both, PE and CE skin (core alteration), such as IL36G, DEFB4A/B, S100A15, KRT16, and KRT6A. After NB-UVB treatment, the activity score of upstream cytokines, such as interferons, interleukin (IL)-6, IL-17, and IL-22 in pathogenesis decreased. In addition, NB-UVB could restore normal keratinization by upregulating LORICRIN and KRT2, particularly in the CE skin. Finally, we illustrated that NB-UVB is capable of suppressing molecules from the initiation to maintenance phase of plaque formation, thereby normalizing psoriatic plaques. This finding supports the usefulness of NB-UVB treatment in clinical practice and may help in the development of new treatment approaches in which NB-UVB treatment is included for patients with psoriasis or other inflammatory skin diseases.
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The Journal of dermatology 2023年2月20日Long-term psoriasis (PsO) management remains challenging. With growing variation in treatment efficacy, cost, and modes of administration, patient preferences for different treatment characteristics are not well understood. A discrete choice experiment (DCE), informed by qualitative patient interviews, was conducted to assess patient preferences for different attributes of PsO treatments; 222 adult patients with moderate-to-severe PsO receiving systemic therapy participated in the DCE web survey. Better long-term efficacy and lower cost were preferred (preference weights p < 0.05). Long-term efficacy had the highest relative importance (RI) and mode of administration was as important as the outcome attributes (efficacy and safety). Patients also preferred oral to injectable administration. In subgroup analyses by disease severity, residence, psoriatic arthritis as a comorbidity, and gender, the trends for each subgroup were the same as the overall population although the extent of RI for administration mode varied. Mode of administration was more important for patients with moderate versus severe disease, or rural versus urban residence. This DCE utilized attributes related to both oral and injectable treatment as well as a broad study population of systemic treatment users. Preferences were further stratified by patient characteristics to explore trends in different subgroups. Understanding the RI of treatment attributes and the attribute trade-offs acceptable to patients helps inform moderate-to-severe PsO systemic treatments decisions.
MISC
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 129 S107-S107 2009年4月
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日本皮膚科学会雑誌 119(1) 39-47 2009年1月20日腎障害を伴った汎発性膿疱性乾癬の3症例を報告し,当科における汎発性膿疱性乾癬症例と腎障害に関するまとめと考察を行った.症例1:56歳男性.1983年(33歳時)発症.1992年7月よりシクロスポリン(CyA)内服開始.時に紅皮症化,膿疱化あり.一時メソトレキセート(MTX),エトレチナート等も併用.2000年11月より血清クレアチニン(Cre)値上昇,2003年3月CyA中止後もクレアチニン値さらに上昇し2005年6月透析導入.症例2:34歳男性.1985年(14歳時)発症,1992年より頻回に膿疱化,紅皮症化.ぶどう膜炎,関節症状を合併.1993年よりCyA内服開始,2003年血清Cre値上昇のため中止.症例3:66歳男性.1974年(34歳時)発症.ぶどう膜炎,関節症状を合併.1993年よりCyA内服開始するも時に膿疱化,2000年血清Cre値上昇のためCyA内服中止.当科において血清Cre値が2.0 mg/dlを超えた症例は,膿疱性乾癬では22例中5例存在したが,CyA内服歴のある尋常性乾癬55例ではそのような症例はみられなかった.腎障害を認めた汎発性膿疱性乾癬5例は難治性であり,全例CyA投与例で関節症状を合併していた.また5例中4例に高血圧を,2例に眼症状を認めた.長期にわたり時に紅皮症化,膿疱化を示す難治性膿疱性乾癬では,CyAやMTX,エトレチナートなどの高用量かつ長期の内服が必要であり,ぶどう膜炎や関節症状を伴う症例では非ステロイド系消炎鎮痛剤(NSAID)の併用が避けられず,腎障害を発症するリスクが高いと考えられる.特にCyAは慢性腎毒性を有するため,長期投与の際は,適宜腎生検の適応を考慮し,不可逆的な腎障害への進行に留意しつつ投与継続を慎重に判断するべきである.
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稀少難治性皮膚疾患に関する調査研究 平成20年度 総括・分担研究報告書 100-102 2009年
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自治医科大学紀要 31 23-29 2008年12月1日1992年から2007年まで, 自治医科大学皮膚科学教室で経験した16例の血管肉腫について検討した。年齢は58歳から96歳で,平均77歳。頭部の血管肉腫は,男7例,女3例で合計10例。慢性浮腫を伴った血管肉腫は,女性5例で,全例下肢の発症であり,子宮癌の治療歴があった。予後は,治癒と判定したのは背部皮下に生じた1例のみで,2例が現在治療中,他の13例は死亡した。死亡例の,初診後からの平均生存期間は13ヶ月だった。皮膚の血管肉腫は未だに治療法が確立されておらず,予後の非常に悪い腫瘍である。今後,より有効な治療方法を求め努力していくとともに,早期発見治療開始のためには,一般の人々,特に高齢者や術後四肢に慢性浮腫を持つ人たちに対して啓蒙していくことが重要である。
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 128 S17-S17 2008年4月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 128 S72-S72 2008年4月
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JOURNAL OF PHARMACOLOGICAL SCIENCES 106 41P-41P 2008年
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BRITISH JOURNAL OF DERMATOLOGY 157(6) 1287-1289 2007年12月
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日本皮膚科学会雑誌 = THE JAPANESE JOURNAL OF DERMATOLOGY 117(12) 1969-1976 2007年11月20日患者自身が乾癬皮疹の面積および重症度を評価するSelf-PASI(Self-administered Psoriasis Area and Severity Index)の妥当性を,日本人乾癬患者 200 例を対象に検討するとともに,医師によるPASIとBSA (Body Surface Area),乾癬特異的QOL尺度であるPDI(Psoriasis Disability Index),包括的健康関連尺度であるSF-36 との関連性を検討した.結果として,Self-PASIとPASIの相関係数は 0.65,Self-BSA(Self-administered BSA)と BSA の相関係数は 0.69 といずれも高くかつ有意であった.Self-BSA と BSA の関連性は,体幹,上肢,下肢では高く,頭部では低かった.また,PDIはPASIよりもSelf-PASI,BSAよりもSelf-BSAとの関連性が高かったが,SF-36とSelf-PASI,Self-BSA との関連性は高くなかった.以上の検討から,Self-PASI は妥当性が高く,乾癬診療において役立つ指標になりうることが示された.
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 127 S113-S113 2007年4月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 127 S42-S42 2007年4月
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CLINICAL AND EXPERIMENTAL DERMATOLOGY 32(1) 107-108 2007年1月
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Clinical and Experimental Dermatology 32(1) 57-59 2007年1月We describe a patient with Sézary syndrome (SS) who was successfully treated with topical steroid and narrowband UVB. Sézary cells in peripheral blood correlated with severity of skin lesions. In addition, serum levels of CCL17 and CCL27 decreased as disease activity improved. These chemokines may be important for the pathogenesis of SS. © 2007 The Author(s).
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BRITISH JOURNAL OF DERMATOLOGY 155(5) 1062-1063 2006年11月
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日本皮膚科学会雑誌 = THE JAPANESE JOURNAL OF DERMATOLOGY 116(11) 1583-1591 2006年10月20日
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 126 37-37 2006年4月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 126 144-144 2006年4月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 126 33-33 2006年4月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 126 109-109 2006年4月
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PROSTAGLANDINS & OTHER LIPID MEDIATORS 79(1-2) 163-164 2006年3月
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日本皮膚科学会雑誌 = THE JAPANESE JOURNAL OF DERMATOLOGY 116(2) 193-200 2006年2月20日爪白癬は 60 歳代以降に高い罹患率を示す.今回,趾爪白癬患者を60 歳未満の群と 65 歳以上の群に分け,イトラコナゾール400mg パルス療法の臨床効果と安全性について比較検討した.併用禁忌薬及びカルシウム拮抗薬内服中の患者および肝酵素が基準値の上限の2.5 倍を超える患者を内服不適応とし,各クール前と 3クール終了1 カ月後に血液検査を行った.60 歳未満群は 37 人,平均 39.0±9.3(18~59)歳,65 歳以上群は32 人,平均 70.9±4.4(65~83)歳であった.安全性については全症例を解析対象としたが,混濁比については第 1 趾爪に病変を認めた症例(各群25 人,20 人)において検討することとした.有害事象は 60 歳未満群で2 例(5.4%)(総ビリルビン上昇,薬疹,各1例),65 歳以上群で 2 例(6.3%)(ALP 上昇,LDH 上昇,各1例)で,頻度に有意差はなく,いずれも軽度でイトラコナゾール中止にて無治療で軽快した.混濁比については,開始前は 60歳未満群8.14±2.38,65歳以上群8.27±2.29 で有意差はなかった.パルス療法開始後4,8,12,24,36 週での混濁比の減少は 60 歳未満群0.40±0.82 ,2.64±2.06 ,3.68±2.93 ,4.40±2.92 ,4.80±3.35,65 歳以上群0.30±0.57,1.45±1.28,2.83±1.76,4.83±2.61,5.03±2.77 で,有意差はなかった.以上よりイトラコナゾールパルス療法は,高齢者においても爪白癬の有用な治療法であり,安全に行えると考えられる.
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炎症・再生 : 日本炎症・再生医学会雑誌 = Inflammation and regeneration 25(3) 186-191 2005年5月25日Mechanical stress has profound influences on human body. Muscle training strengthens the muscles, and high blood pressure thickens the vessel walls. Intense studies have been made by various investigators on how mechanical stress influences the human tissues. Epidermal keratinocytes are continuously exposed to mechanical forces. The human skin surface can be thickened and enlarged by various stress such as tissue expander or abrasive pressure. Keratinocytes were plated on flexible silicone dishes, and they were continuously stretched. Stretching of keratinocytes caused up-regulation of 5-bromo-2'-deoxyuridine (BrdU)-positive cells and activation of extracellular signal-regulated kinases (ERK) 1/2. EGF receptor, calcium channel, and ERK were involved in stretch-induced BrdU incorporation. Stretching also induced keratin K6, which is expressed in activated and proliferating keratinocytes, and suppressed keratin K10, which is expressed in differentiated keratinocytes, and their regulation was inhibited by MEK1/2 inhibitor. EGF receptor as well as adhesion molecules have been reported to be involved in transducing mechanical stresses. Several diseases involving heart and palmoplantar skin are caused by the mutation in desmosomal proteins, indicating that adhesion molecules play an important part in sustaining normal structure of skin under the mechanical stress.
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 124(4) A63-A63 2005年4月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 124(4) A110-A110 2005年4月
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皮膚科の臨床 47(4) 521-524 2005年4月症例1:68歳男.冠動脈造影(CAG)1回,経皮的冠動脈形成術(PTCA)2回施行され,4ヵ月後に右背部の照射部位に一致して境界明瞭な紅斑を認め,中央にびらんを伴った.再度CAGを行ったところ,中央が黒色調を呈する壊疽組織を付着する潰瘍を認め,現在保存治療を行っている.症例2:65歳男.CAG 3回,PTCA 4回施行され,5ヵ月後に右背部に手拳大の暗紅色紅斑が出現し潰瘍化した.保存的治療で出現・消退を繰り返している.症例3:52歳男.CAG 4回,PTCD 3回施行後,2ヵ月後より右側胸部に皮膚萎縮を伴う紅褐色局面と中央に黄白色壊死を付着する拇指頭大の潰瘍を認めた.病理組織像で潰瘍面は壊死組織で覆われ真皮膠原線維は硝子化を伴い著しく膨化・増生していた.デブリードマン,広背筋弁,分層植皮術を行ったが,術後30ヵ月の現在,潰瘍の再発はないが疼痛がある.症例4:39歳男.カテーテルアブレーション施行後,右上腕のマンシェット装着部位の発赤,水疱,潰瘍形成を認めた.現在,皮膚硬化に対し軟膏外用で加療中であるが,改善していない
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 122(3) A150-A150 2004年3月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 122(3) A156-A156 2004年3月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 122(3) A115-A115 2004年3月
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日本研究皮膚科学会年次学術大会・総会プログラム 27回 116-116 2002年8月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 119(1) 304-304 2002年7月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 119(1) 345-345 2002年7月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 119(1) 262-262 2002年7月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 119(1) 274-274 2002年7月
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