研究者詳細 - 平井　陽至

論文 - 平井　陽至

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Monokine induced by gamma interferon levels in plasma might be a diagnostic marker of Hydroa vaccniforme lymphoproliferative disorder systemic form. 国際誌

Tomoko Miyake, Takenobu Yamamoto, Yoji Hirai, Takahide Takahashi, Takuya Furuhashi, Hisashi Nomura, Yoshio Kawakami, Shin Morizane

Journal of the American Academy of Dermatology 2024年11月

A case of anaphylaxis to kumquat (Citrus japonica). 国際誌

Shogo Ikezawa, Emi Yokoyama, Hitoshi Urakami, Mikiko Takigawa, Tomoko Miyake, Yoji Hirai, Yoshio Kawakami, Shin Morizane

European journal of dermatology : EJD 34 ( 5 ) 539 - 541 2024年10月

The treatment effect of endovascular therapy for chronic limb-threatening ischemia with systemic sclerosis. 国際誌

Yoshihiro Matsuda, Tomoko Miyake, Hironobu Toda, Kota Tachibana, Hayato Nomura, Yoji Hirai, Yoshio Kawakami, Naoya Sakoda, Shin Morizane

The Journal of dermatology 51 ( 8 ) 1108 - 1112 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Systemic sclerosis (SSc) is a collagen disease with immune abnormalities, vasculopathy, and fibrosis. Ca blockers and prostaglandins are used to treat peripheral circulatory disturbances. Chronic limb-threatening ischemia (CLTI) is a disease characterized by extremity ulcers, necrosis, and pain due to limb ischemia. Since only a few patients present with coexistence of CLTI and SSc, the treatment outcomes of revascularization in these cases are unknown. In this study, we evaluated the clinical characteristics and treatment outcomes of seven patients with CLTI and SSc, and 35 patients with uncomplicated CLTI who were hospitalized from 2012 to 2022. A higher proportion of patients with uncomplicated CLTI had diabetes and male. There were no significant differences in the age at which ischemic ulceration occurred, other comorbidities, or in treatments, including antimicrobial agents, revascularization and amputation, improvement of pain, and the survival time from ulcer onset between the two subgroups. EVT or amputation was performed in six or two of the seven patients with CLTI and SSc, respectively. Among those who underwent EVT, 33% (2/6) achieved epithelialization and 67% (4/6) experienced pain relief. These results suggest that the revascularization in cases with CLTI and SSc should consider factors such as infection and general condition, since revascularization improve the pain of these patients.

DOI： 10.1111/1346-8138.17334

Acquired generalized anhidrosis following durvalumab treatment in a patient with advanced non-small cell lung cancer. 国際誌

Yuko Fujimoto, Yoshio Kawakami, Tomoko Miyake, Yoji Hirai, Masahiro Tabata, Shin Morizane

The Journal of dermatology 2024年7月

Phase I/II clinical trial of brentuximab vedotin for pretreated Japanese patients with CD30-positive cutaneous T-cell lymphoma. 国際誌

Yoji Hirai, Jun Sakurai, Shiho Yoshida, Takashi Kikuchi, Toshiharu Mitsuhashi, Tomoko Miyake, Taku Fujimura, Riichiro Abe, Hiroki Fujikawa, Hikari Boki, Hiraku Suga, Sayaka Shibata, Tomomitsu Miyagaki, Takatoshi Shimauchi, Eiji Kiyohara, Yoshio Kawakami, Shin Morizane

The Journal of dermatology 51 ( 8 ) 1037 - 1049 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Brentuximab vedotin (BV), a conjugate of anti-CD30 antibody and monomethyl auristatin E, has emerged as a promising treatment option for refractory CD30+ mycosis fungoides (MF) and primary cutaneous anaplastic large-cell lymphoma (pcALCL). BV has been shown to be safe and effective in treating Hodgkin's lymphoma and peripheral T-cell lymphoma. This multicenter, prospective, single-arm phase I/II study evaluated the efficacy of BV in Japanese patients with CD30+ cutaneous lymphomas, namely CD30+ cutaneous T-cell lymphoma. Participants were divided into two groups: those with CD30+ MF or pcALCL (cohort 1, n = 13) and those with CD30+ lymphoproliferative disorders other than those in cohort 1 (cohort 2, n = 3). The studied population included the full analysis set (FAS), modified FAS (mFAS), and safety analysis set (SAF). These sets were identified in cohorts 1 and 1 + 2 and labeled FAS1 and FAS2, mFAS1 and mFAS2, and SAF1 and SAF2, respectively. Each treatment cycle lasted 3 weeks, and BV was continued for up to 16 cycles after the third cycle based on treatment response. The primary endpoint was the 4-month objective response rate (ORR4) determined by the Independent Review Forum (IRF). ORR4 was 69.2% for FAS1 and 62.5% for FAS2 (P < 0.0001). Secondary endpoints of ORR, assessed using the global response score (53.8% in FAS1) and modified severity-weighted assessment tool (62.5% in FAS1), using the IRF, provided results comparable to the primary findings. The incidence of ≥grade 3 adverse events (≥15%) in SAF1 was peripheral neuropathy in three patients (23%) and fever and eosinophilia in two patients (15%). In conclusion, BV showed favorable efficacy, tolerability, and safety profile in Japanese patients with relapsed or refractory CD30+ primary cutaneous T-cell lymphoma. The trial was registered with University Hospital Medical Information Network Clinical Trials Registry, Japan (protocol ID: UMIN000034205).

DOI： 10.1111/1346-8138.17324

Disseminated Lomentospora prolificans infection presenting with multiple cutaneous lesions in an immunocompromised host: A case report and literature review. 国際誌

Masaya Kawamoto, Yoshio Kawakami, Yoji Hirai, Saya Kubota, Hideaki Fujiwara, Yayoi Ueda, Kazushi Anzawa, Yoshinobu Maeda, Shin Morizane

The Journal of dermatology 51 ( 11 ) e402-e403 2024年6月

Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study.

Katsunori Manaka, Junichiro Sato, Yusuke Hikima, Hirofumi Horikoshi, Maho Taguchi, Akimichi Morita, Hiraku Suga, Hikari Boki, Taku Fujimura, Yoji Hirai, Takatoshi Shimauchi, Chiharu Tateishi, Eiji Kiyohara, Ikko Muto, Hideki Nakajima, Riichiro Abe, Kazuyasu Fujii, Chikako Nishigori, Eiji Nakano, Kentaro Yonekura, Takeru Funakoshi, Masahiro Amano, Tomomitsu Miyagaki, Reiko Yamashita, Makoto Sugaya, Toshihisa Hamada, Masaomi Nangaku, Taroh Iiri, Noriko Makita

Endocrine journal 71 ( 8 ) 777 - 787 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Central hypothyroidism and dyslipidemia are well-known adverse events (AEs) of bexarotene therapy. Although hypothyroidism is known to cause dyslipidemia, no study has examined the association between hypothyroidism and dyslipidemia in patients undergoing bexarotene therapy. The aim of this study is to examine this association. A retrospective observational study was performed among 294 patients who initiated bexarotene therapy in Japan (nation-wide postmarketing complete surveillance). Jonckheere-Terpstra (one sided) test was performed to evaluate the effect of the bexarotene dose on lipid metabolisms, and regression analyses were performed to evaluate associations of bexarotene dose, free thyroxine (FT4), body mass index (BMI), and lipid metabolisms. Most patients developed hypothyroidism. Two-third of patients showed FT4 values below the lower limit at 1 week. Triglycerides (TG) increased in a bexarotene dose-dependent manner, and grade ≥3 AEs on hypertriglyceridemia was observed in 39% of the patients. Additionally, one-third of grade ≥3 AEs on hypertriglyceridemia occurred within 1 week. The delta_FT4 (difference in FT4 from baseline) negatively correlated with TG increase at 1 week (p = 0.012) but not with low density lipoprotein cholesterol (LDL-C) increase at any week. Bexarotene-induced hypothyroidism is almost inevitable and occurred quickly. Bexarotene-induced hypertriglyceridemia showed positive bexarotene dose dependency and negative delta_FT4 dependency. Prophylactic and appropriate thyroid hormone compensation therapy and starting bexarotene at low doses with subsequent titration while managing dyslipidemia may have a beneficial effect for the successful continuation of bexarotene therapy without severe endocrine and metabolic AEs.

DOI： 10.1507/endocrj.EJ23-0699

Pruritic folliculitis of pregnancy with granular deposition of immunoglobulin G along the basement membrane zone. 国際誌

Mana Usui-Taniguchi, Yoshio Kawakami, Yoichiro Toi, Tatsuya Kaji, Yoshiko Matsuura, Emi Yokoyama, Tomoko Miyake, Yoji Hirai, Shin Morizane

The Journal of dermatology 51 ( 4 ) e125-e126 2023年11月

Successful treatment with secukinumab in a patient with generalized pustular psoriasis preceded by palmoplantar lesions. 国際誌

Nozomi Sawai, Yoshio Kawakami, Kota Tachibana, Hayato Nomura, Tomoko Miyake, Emi Yokoyama, Yoji Hirai, Shin Morizane

The Journal of dermatology 50 ( 12 ) e413-e414 2023年8月

Prognostic factors for primary cutaneous anaplastic large cell lymphoma: a multicenter retrospective study from Japan. 国際誌

Tomomitsu Miyagaki, Norihito Inoue, Hiroaki Kamijo, Hikari Boki, Naomi Takahashi-Shishido, Hiraku Suga, Takatoshi Shimauchi, Eiji Kiyohara, Yoji Hirai, Kentaro Yonekura, Kengo Takeuchi, Makoto Sugaya

The British journal of dermatology 189 ( 5 ) 612 - 620 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Clinical implications of DUSP22 rearrangement and the association between DUSP22 rearrangement and lymphoid enhancer-binding factor 1 (LEF1) expression pattern in CD30-positive cutaneous T-cell lymphomas (CTCLs) are unknown. OBJECTIVES: This study assessed the incidence of DUSP22 rearrangement and its clinical and immunohistochemical implications in primary cutaneous anaplastic large cell lymphoma (pcALCL), lymphomatoid papulosis (LyP), and CD30-positive mycosis fungoides (MF) with large cell transformation (MF-LCT), especially focusing on the association with the prognosis and LEF1 expression pattern. Prognostic factors of pcALCL were also examined. METHODS: Multicenter retrospective study including patients with pcALCL, LyP, and MF-LCT diagnosed between January 1, 2000 and December 31, 2018 in Japan. Baseline data at diagnosis, treatment course, overall survival (OS), and disease-specific survival (DSS) were collected. Immunohistochemical analysis and fluorescence in situ hybridization to detect DUSP22 and TP63 rearrangement were performed using skin samples at diagnosis. We investigated the association between staining pattern and these gene rearrangements. We also assessed the prognostic implications of clinical status, immunohistochemical results and the presence of gene rearrangements. RESULTS: DUSP22 rearrangement was detected in 50% of pcALCL cases (11/22), but not in any cases with LyP (0/14) or MF-LCT (0/11). TP63 rearrangement was not detected in any case. Clinically, pcALCL patients with DUSP22 rearrangement did not tend to form ulcers (p = 0.081). There was no significant association between DUSP22 rearrangement status and immunohistochemical results including LEF1 expression pattern. T3 stage and the presence of lower limb lesions were significantly associated with shorter OS (p = 0.012 and 0.021, respectively by log-rank test). Similarly, they were significantly correlated with shorter DSS (p = 0.016 and 0.0001, respectively). CONCLUSION: DUSP22 rearrangement is relatively specific to pcALCL among CD30-positive CTCLs in Japan. Although LEF1 expression pattern was not related with DUSP22 rearrangement in pcALCL, there was no rearrangement if LEF1 was not expressed. We confirmed that T3 stage and the lower limb involvement were significantly associated with the decreased OS and DSS. Presence or absence of lower limb lesions should better be included in T stage subcategory in the future.

DOI： 10.1093/bjd/ljad266

Angioedema‐like eyelid edema following the second NVX‐CoV2373 <scp>COVID</scp>‐19 vaccination

Mari Matsumoto, Yoshio Kawakami, Tomoko Miyake, Yoji Hirai, Hitomi Kataoka, Fumio Otsuka, Shin Morizane

Journal of Cutaneous Immunology and Allergy 6 ( 5 ) 194 - 195 2023年7月

Coexpression of natural killer cell antigens by T-cell large granular lymphocytes in hydroa vacciniforme lymphoproliferative disorder and the involvement of Vδ1 + epithelial-type γδT cells.

Yoji Hirai, Keiji Iwatsuki, Takahide Takahashi, Tomoko Miyake, Yuki Nakagawa, Shogo Tanimoto, Yoshio Kawakami, Shin Morizane

International journal of hematology 118 ( 1 ) 54 - 64 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) is a cutaneous variant of chronic active Epstein-Barr virus disease. We examined the coexpression of T- and natural killer (NK)-cell antigens in five patients with classic HV (cHV) and five with systemic HV (sHV). T-cell receptor (TCR) repertoire analysis was performed with high‑throughput sequencing. All five cHV patients had increased γδT cells (> 5%), whereas five sHV patients showed γδT- and αβT-cell dominance in two patients each, and a mixture of abnormal γδT and αβT cells in one. Circulating CD3 + T cells expressed CD16/CD56 at 7.8-42.3% and 1.1-9.7% in sHV and cHV, respectively. The percentage of CD16/CD56 + T cells was higher in the large granular lymphocyte or atypical T-cell fractions in sHV, but no TCR Vα24 invariant chain characteristic of NKT cells was detected. Considerable numbers of CD3 + cells expressing CD56 were observed in sHV skin infiltrates. Of the circulating γδT cells tested, TCR Vδ1 + cells characteristic of the epithelial type of γδT cells were dominant in two sHV cases. Thus, atypical αβT and γδT cells in HV-LPD can express NK-cell antigens, such as CD16 and CD56, and Vδ1 + epithelial-type γδT cells are a major cell type in some HV-LPD cases.

DOI： 10.1007/s12185-023-03599-7

BNT162b2 mRNA COVID-19ワクチン接種後に発症したacute diffuse and total alopecia of the female scalpの1例

川本雅也, 川上佳夫, 松田吉弘, 平井陽至, 森実真, 多田讓治

日本皮膚科学会雑誌 133 ( 8 ) 1891 - 1891 2023年7月

ダブラフェニブ・トラメチニブ内服中にサルコイド様皮疹を呈した悪性黒色腫の1例

別木祐介, 神野泰輔, 立花宏太, 三宅智子, 平井陽至, 川上佳夫, 森実真

日本皮膚科学会雑誌 133 ( 8 ) 1894 - 1894 2023年7月

Diagnostic and disease severity determination criteria for hydroa vacciniforme lymphoproliferative disorders and severe mosquito bite allergy 国際誌

Yoji Hirai, Hideo Asada, Toshihisa Hamada, Jun‐ichi Kawada, Hiroshi Kimura, Ayako Arai, Koichi Ohshima, Shouichi Ohga, Keiji Iwatsuki

The Journal of Dermatology 50 ( 7 ) e198-e205 2023年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) and severe mosquito bite allergy (SMBA) are both cutaneous forms of Epstein-Barr virus (EBV)-associated T/natural killer (NK) cell LPDs and are closely related to chronic active EBV disease (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). HV-LPD is further divided into classic HV, a benign subtype mediated by EBV-positive γδT cells, and systemic HV, another life-threatening subtype mainly associated with EBV-positive αβT or γδT cells. The vast majority of patients with SMBA have increased numbers of EBV-infected NK cells in the blood. Clinical symptoms of HV-LPD and SMBA often overlap in the same patient and may progress to more serious disease conditions equivalent to the systemic form of CAEBV. To define the disease spectrum of HV-LPD and SMBA, we propose the diagnostic criteria and the determination criteria for disease severity. The proposed diagnostic criteria are consistent with those for CAEBV and EBV-HLH in the guidelines for the management for CAEBV and related disorders 2023.

DOI： 10.1111/1346-8138.16842

ラズベリーによるアナフィラキシーの1例

赤松由規, 川上佳夫, 藤田周作, 川本友子, 三宅智子, 平井陽至, 森実真

日本臨床皮膚科医会雑誌 40 ( 3 ) 465 - 465 2023年5月

当院における強皮症合併重症下肢虚血7例の臨床学的検討

松田吉弘, 三宅智子, 戸田洋伸, 立花宏太, 野村隼人, 平井陽至, 川上佳夫, 迫田直也, 廣田真規, 森実真

日本皮膚科学会雑誌 133 ( 5 ) 1361 - 1361 2023年5月

初診時,手足口病様皮疹を呈した新生児水疱性類天疱瘡の1例

別木祐介, 徳田真優, 前琴絵, 妹尾春佳, 立花宏太, 三宅智子, 平井陽至, 川上佳夫, 森実真, 宇田和宏, 斎藤友希恵, 茂原研司, 津下充, 八代将登

日本皮膚科学会雑誌 133 ( 4 ) 715 - 715 2023年4月

セクキヌマブが奏功した掌蹠膿疱症を背景とする膿疱性乾癬の1例

澤井希望, 川上佳夫, 徳田真優, 廣瀬梓, 別木祐介, 高須賀琴巳, 篠倉美里, 立花宏太, 横山恵美, 三宅智子, 平井陽至, 森実真, 多田譲治

日本皮膚科学会雑誌 133 ( 3 ) 524 - 524 2023年3月

CD8+αβT細胞優位型種痘様水疱症リンパ増殖異常症の1例

大林三裕佳, 中村賢人, 古橋卓也, 岩月啓氏, 三宅智子, 平井陽至, 谷田けい, 金兼弘和, 西田徹也, 木村宏, 森田明理

皮膚科の臨床 65 ( 2 ) 273 - 278 2023年2月

記述言語：日本語出版者・発行元：金原出版(株)

＜文献概要＞26歳,女性。21歳夏頃より頭部,顔面,頸部,上背部に痂皮を伴う丘疹と水疱が出現した。ざ瘡,毛包炎の治療は無効であり,ステロイド外用中も再燃を繰り返した。経過中に発熱も伴うようになり,口唇や顔面が一時的に腫脹することもあった。病変部および末梢血中のEpstein-Barr virus感染細胞の存在を証明し,種痘様水疱症リンパ増殖異常症と診断した。フローサイトメトリーでは,CD8+αβT細胞に優位にEpstein-Barr virus感染があり,成人発症で全身症状を伴う点からも予後不良である可能性が懸念される。現状他臓器障害はなく,Epstein-Barr virus感染細胞数も比較的少数であるが,今後も注意深い観察を行い,造血幹細胞移植の必要性とタイミングについて検討を要する。

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01266&link_issn=&doc_id=20230217120032&doc_link_id=10.18888%2Fhi.0000003782&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000003782&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Cutaneous Pseudolymphoma Caused by an Injury with a Metallic Piece of a Mowing Machine Containing Tungsten. 国際誌

Mayu Tokuda, Yoshio Kawakami, Yoji Hirai, Kota Tachibana, Yuki Nakagawa, Satoru Sugihara, Tomoko Miyake, Osamu Yamasaki, Keiko Manabe, Shin Morizane

Indian journal of dermatology 68 ( 4 ) 468 - 470 2023年

A case of generalized allergic contact dermatitis due to sodium lauroyl methylaminopropionate in a shampoo. 国際誌

Azusa Hirose, Yoshio Kawakami, Tomoko Miyake, Yoji Hirai, Shin Morizane

Contact dermatitis 87 ( 6 ) 546 - 548 2022年12月

シャンプーに含まれるN-ラウロイル-N-メチル-β-アラニンNaによる接触皮膚炎症候群の1例

廣瀬梓, 川上佳夫, 三宅智子, 平井陽至, 森実真

日本皮膚免疫アレルギー学会総会学術大会プログラム・抄録集 52回 201 - 201 2022年12月

Cutaneous toxicity with suprabasal blisters and dyskeratosis following administration of enfortumab vedotin. 国際誌

Ken-Ichi Hasui, Yoshio Kawakami, Tomoko Miyake, Yoji Hirai, Hayato Nomura, Kohei Edamura, Motoo Araki, Shin Morizane

The Journal of dermatology 50 ( 4 ) e115-e116 2022年11月

Novel homozygous missense mutation c.1654G>T in the ALOX12B gene causing congenital ichthyosiform erythroderma. 国際誌

Kotoe Mae, Yoshio Kawakami, Ai Kajita, Takuya Takeichi, Tatsuhiro Noda, Yoji Hirai, Masashi Akiyama, Shin Morizane

The Journal of dermatology 50 ( 1 ) e37-e38 2022年10月

Rituximab therapy for intractable pemphigus: A multicenter, open-label, single-arm, prospective study of 20 Japanese patients. 国際誌

Jun Yamagami, Yuichi Kurihara, Takeru Funakoshi, Yasuko Saito, Ryo Tanaka, Hayato Takahashi, Hideyuki Ujiie, Hiroaki Iwata, Yoji Hirai, Keiji Iwatsuki, Norito Ishii, Jun Sakurai, Takayuki Abe, Ryo Takemura, Naomi Mashino, Masahiro Abe, Masayuki Amagai

The Journal of dermatology 50 ( 2 ) 175 - 182 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

This was a multicenter clinical trial of rituximab, a chimeric monoclonal IgG antibody directed against CD20, for the treatment of refractory pemphigus vulgaris and pemphigus foliaceus. In total, 20 patients were treated with two doses of rituximab (1000 mg; 2 weeks apart) on days 0 and 14. The primary end point was the proportion of patients who achieved complete or partial remission on day 168 following the first rituximab dose. Of the 20 enrolled patients, 11 (55%) and four (20%) achieved complete and partial remission, respectively; therefore, remission was achieved in a total of 15 patients (75.0% [95% confidence interval, 50.9%-91.3%]). It was demonstrated that the remission rate was greater than the prespecified threshold (5%). In addition, a significant improvement in clinical score (Pemphigus Disease Area Index) and decrease in serum anti-desmoglein antibody level were observed over time. Four serious adverse events (heart failure, pneumonia, radial fracture, and osteonecrosis) were recorded in two patients, of which only pneumonia was considered causally related with rituximab. The level of peripheral blood CD19-positive B lymphocytes was decreased on day 28 after rituximab treatment and remained low throughout the study period until day 168. Our results confirm the efficacy and safety of rituximab therapy for refractory pemphigus in Japanese patients.

DOI： 10.1111/1346-8138.16597

【(新規)抗腫瘍薬～光と影～】二次感染を契機に皮膚症状が増悪しモガムリズマブが奏効したSezary症候群

赤松由規, 平井陽至, 三宅智子, 森実真

皮膚病診療 44 ( 5 ) 410 - 413 2022年5月

水疱性類天疱瘡に合併した偽性低アルドステロン症の乳児例

宮原宏幸, 村上美智子, 二川奈都子, 長谷川高誠, 茂原研司, 宇田和宏, 津下充, 八代将登, 平井陽至, 森実真, 塚原宏一

日本小児科学会雑誌 126 ( 4 ) 728 - 728 2022年4月

特異疹が緊満性水疱を呈したATLLの1例

山口春佳, 橋本倫子, 神野泰輔, 川上佳夫, 平井陽至, 谷口恒平, 松岡賢市, 山崎修, 森実真

西日本皮膚科 84 ( 2 ) 134 - 139 2022年4月

記述言語：日本語出版者・発行元：日本皮膚科学会-西部支部

69歳,女性。右前腕部の緊満性水疱を伴う紅斑の精査加療目的に当科を紹介され受診した。1ヵ月前より右前腕部に自覚症状のない紅斑が出現し,次第に緊満性水疱が多発し,右上肢全体の発赤や腫脹,灼熱感および疼痛を伴うようになった。臨床像より水疱性類天疱瘡や蜂窩織炎が鑑別に挙がり血液検査をしたところ,大型な異型リンパ球の増加,好酸球増加,sIL-2R上昇,抗HTLV-1抗体陽性を認めた。水疱部からの病理組織像では,表皮直下に水疱が形成され,真皮から脂肪織に異型リンパ球と好酸球が密に浸潤し,免疫組織化学染色ではCD3,CD4,CD25,CD30陽性,CD20陰性であり,蛍光抗体直接法は全て陰性であった。皮疹部よりサザンブロット法でHTLV-IプロウイルスDNAのモノクローナルな取り込みを認め,Adult T-cell leukemia/lymphoma(ATLL)の特異疹と診断した。皮疹はステロイド全身投与と化学療法開始後に速やかに消退した。臨床経過と検査所見から好酸球性脂肪織炎を併発していると考えた。水疱を呈するATLLの特異疹は稀であり,また,好酸球性脂肪織炎を併発したATLLの報告例はこれまでになく,自験例が初めてである。自験例は血液検査および皮膚生検により診断が明らかとなった。難治性の水疱を呈する皮疹を認めた際はATLLの特異疹の可能性も考え,精査することが重要である。(著者抄録)

その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01003&link_issn=&doc_id=20220517220013&doc_link_id=10.2336%2Fnishinihonhifu.84.134&url=https%3A%2F%2Fdoi.org%2F10.2336%2Fnishinihonhifu.84.134&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

金属異物によって生じた前頸部pseudolymphoma

徳田真優, 平井陽至, 川上佳夫, 立花宏太, 中川裕貴, 杉原悟, 三宅智子, 山崎修, 森実真, 眞部恵子, 浅越健治

日本皮膚科学会雑誌 132 ( 3 ) 506 - 506 2022年3月

特異疹が緊満性水疱を呈したATLLの1例

妹尾春佳, 橋本倫子, 神野泰輔, 川上佳夫, 平井陽至, 山崎修, 森実真, 谷口恒平, 松岡賢市

日本皮膚科学会雑誌 132 ( 1 ) 99 - 99 2022年1月

日本人菌状息肉症患者におけるベキサロテン内服の効果と安全性岡山大学での投薬症例による解析

中川裕貴, 濱田利久, 平井陽至, 三宅智子, 山崎修, 岩月啓氏, 森実真

西日本皮膚科 83 ( 6 ) 549 - 553 2021年12月

記述言語：日本語出版者・発行元：日本皮膚科学会-西部支部

ベキサロテンは本邦で2016年に皮膚T細胞リンパ腫(CTCL)に対し承認され,現在ではCTCL治療に広く用いられている。欧米ではベキサロテン長期投与症例が報告されているが,日本ではまだ承認から日が浅いため長期投与症例の報告は少ない。当院でベキサロテンにて加療された11例の菌状息肉症(MF)患者について解析した。その中で長期に渡りベキサロテンを投与され良好な経過を示した3例を報告する。甲状腺機能低下症と脂質異常症はベキサロテン関連の副作用として頻発し,当院でも11例全例にみられたが,重篤な副作用はみられなかった。長期投与症例ではベキサロテンの減量や一時中止,副作用に対する内服投与にてベキサロテンを長期継続することができた。3例とも治療反応性はよく,2例がCR,1例がPRを得た。ベキサロテンは日本人MF患者においても副作用をコントロールすることで長期に投与でき,有効な治療選択肢となりうる。(著者抄録)

DOI： 10.2336/nishinihonhifu.83.549

咽頭浮腫や腸管浮腫を来した正補体性蕁麻疹様血管炎の1例

川上大輔, 岡優美, 竹内杏奈, 藤井翔太郎, 織田好子, 福永淳, 錦織千佳子, 森田安里, 黒田桂子, 平井陽至

皮膚の科学 20 ( 4 ) 373 - 373 2021年12月

Safety and efficacy of bexarotene for Japanese patients with cutaneous T-cell lymphoma: Real-world experience from post-marketing surveillance. 国際誌

Toshihisa Hamada, Akimichi Morita, Hiraku Suga, Hikari Boki, Taku Fujimura, Yoji Hirai, Takatoshi Shimauchi, Chiharu Tateishi, Eiji Kiyohara, Ikko Muto, Hideki Nakajima, Riichiro Abe, Kazuyasu Fujii, Chikako Nishigori, Eiji Nakano, Kentaro Yonekura, Takeru Funakoshi, Masahiro Amano, Tomomitsu Miyagaki, Noriko Makita, Katsunori Manaka, Yoshihito Shimoyama, Makoto Sugaya

The Journal of dermatology 49 ( 2 ) 253 - 262 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

To establish real-world evidence about the safety and efficacy of bexarotene for Japanese patients with cutaneous T-cell lymphoma, we conducted a nationwide cohort study using data from post-marketing surveillance for bexarotene treatment. In total, 294 patients with cutaneous T-cell lymphoma were identified between June 2016 and June 2018. Of these, 267 patients were included as the safety analysis set. Of the 267 patients, 175 were included in the efficacy analysis set. Of these, 139 patients had mycosis fungoides, including 46 with early stage disease and 93 with advanced stage disease. Among the 139 patients with mycosis fungoides, the objective response rate was 46.8%. A significant difference in objective response rate was detected between patients who started with bexarotene at 300 mg/m2 (61.6%) and patients who started with bexarotene at less than 300 mg/m2 (22.6%, p < 0.001). Of the 139 patients with mycosis fungoides, 92 were treated with a combination of bexarotene plus photo(chemo)therapy. A significant difference in objective response rate was seen between bexarotene with a combination of photo(chemo)therapy (57.6%) and bexarotene without a combination of photo(chemo)therapy (25.5%, p < 0.001). Starting bexarotene at 300 mg/m2 and combination with photo(chemo)therapy were detected as independent factors influencing response. Common treatment-related adverse events included hypothyroidism (85.8%), hypertriglyceridemia (68.5%), hypercholesterolemia (43.8%), and neutropenia (21.3%). Hypertriglyceridemia, hypercholesterolemia, and neutropenia occurred more frequently in patients who started with bexarotene at 300 mg/m2 than patients who started with bexarotene at less than 300 mg/m2 (hypertriglyceridemia, 76.4% vs. 57.0%, p = 0.001; hypercholesterolemia, 49.0% vs. 36.4%, p = 0.045; neutropenia, 28.0% vs. 12.1%, p = 0.002; respectively). The present study indicates that starting bexarotene at 300 mg/m2 and combination of photo(chemo)therapy offer a promising efficacy for the treatment of patients with mycosis fungoides. Efficacy of low-dose bexarotene plus photo(chemo)therapy should be evaluated in future.

DOI： 10.1111/1346-8138.16201

皮膚T細胞性リンパ腫における皮膚FCMの有用性の検討

中川裕貴, 三宅智子, 平井陽至, 山崎修, 岩月啓氏, 森実真, 高橋孝英, 濱田利久

日本皮膚科学会雑誌 131 ( 11 ) 2446 - 2446 2021年10月

Analysis of clonality in cutaneous B-cell lymphoma and B-cell pseudolymphoma using skin flow cytometry: Comparison of immunophenotyping and gene rearrangement studies. 国際誌

Yuki Nakagawa, Toshihisa Hamada, Takahide Takahashi, Tomoko Miyake, Yoji Hirai, Keiji Iwatsuki, Shin Morizane

The Journal of dermatology 49 ( 2 ) 246 - 252 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

To identify clonal neoplastic cells in skin affected by B-cell lymphoma using skin flow cytometry (FCM) techniques, we investigated light-chain restriction using skin FCM with clonality assessed by polymerase chain reaction and light-chain restriction by in situ hybridization (ISH). We retrospectively analyzed 16 cases of B-cell lymphoma with cutaneous involvement: primary cutaneous diffuse large B-cell lymphoma, leg type (pcDLBCL-LT) (n = 7), DLBCL-not otherwise specified (DLBCL-NOS) (n = 6), primary cutaneous follicle center lymphoma (pcFCL) (n = 1), and follicular lymphoma (n = 2), as well as cutaneous B-cell pseudolymphoma (n = 9). Results of skin FCM light-chain restriction analyses were compared with immunoglobulin H (IgH) gene rearrangement and κ/λ ISH findings. Skin FCM detected light-chain restriction in 11 of 14 B-cell lymphoma patients but none of the B-cell pseudolymphoma patients. The sensitivity of skin FCM for distinguishing B-cell lymphoma and B-cell pseudolymphoma was 79%, and the specificity was 100%. Eleven of 13 B-cell lymphoma patients exhibited gene rearrangement (sensitivity 85%), whereas six of seven pseudolymphoma patients were negative (specificity 86%). ISH was positive in three of 16 B-cell lymphoma cases (sensitivity 19%) but none of the B-cell pseudolymphoma cases (specificity 100%). ISH sensitivity was 29% for pcDLBCL-LT, 17% for DLBCL-NOS, and 0% for pcFCL and follicular lymphoma. Skin FCM therefore appears to be more sensitive than ISH in detecting light-chain restriction in DLBCL and follicular lymphoma, and as sensitive as IgH gene rearrangement analysis in detecting clonality. Skin FCM is thus a promising diagnostic tool for identifying monoclonal neoplastic B-cell populations.

DOI： 10.1111/1346-8138.16057

Cutaneous adult T-cell leukemia/lymphoma with granulomatous reaction. 国際誌

Yuki Nakagawa, Yoshio Kawakami, Tomoko Kawamoto, Tomoko Miyake, Yoji Hirai, Osamu Yamasaki, Shin Morizane

The Journal of dermatology 48 ( 6 ) e273-e274 2021年6月

Staphylococcal enterotoxin B- and lipopolysaccharide-induced toxic shock syndrome in a burn patient. 国際誌

Osamu Yamasaki, Satoru Sugihara, Ai Kajita, Emi Yokoyama, Tomoko Miyake, Yoji Hirai, Shin Morizane

The Journal of dermatology 48 ( 4 ) 547 - 550 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Toxic shock syndrome (TSS) is caused by toxic shock syndrome toxin 1 or enterotoxins secreted by Staphylococcus aureus. Lipopolysaccharide (LPS) has also been shown to play a major role in the development of sepsis. Staphylococcal superantigens and LPS operate synergistically in conditioning cytokine release and lethal shock in mice. An 80-year-old woman was admitted because of a 20% mixed-depth flame burn. Despite two excisions and grafts, necrotic ulcers with methicillin-resistant Staphylococcus aureus (MRSA) colonization remained. On the 7th day after the operation, she developed shock with an erythematous rash. Blood examination revealed evidence of disseminated intravascular coagulation, and liver and renal dysfunction. A blood culture revealed a staphylococcal enterotoxin B (SEB)-producing strain of MRSA and Klebsiella pneumoniae. The septic symptoms were prolonged, but the condition gradually improved with extensive treatment. T-cell receptor analysis demonstrated a marked accumulation of SEB-mediated Vβ T cells. Stimulation of peripheral blood mononuclear cells in the recovery phase with SEB and LPS induced additive effects on tumor necrosis factor-α, interferon-γ, and interleukin-6 production. Although the present case did not fulfill the clinical criteria for TSS, the additive effects of SEB and LPS might have caused the severe septic shock.

DOI： 10.1111/1346-8138.15729

A case of allergic contact dermatitis due to 3-glyceryl ascorbate in a skin-lightening lotion. 国際誌

Yoshio Kawakami, Takatsune Umayahara, Yoji Hirai, Shin Morizane

Contact dermatitis 2021年2月

Case of tufted angioma treated successfully with tranilast, topical steroids and tacrolimus ointment. 国際誌

Yuki Nakagawa, Yoji Hirai, Masatoshi Jinnin, Shin Morizane

The Journal of dermatology 48 ( 2 ) e84-e85 2021年2月

臭化カリウム減量により症状が軽快した臭素疹の 1 例

安富陽平, 川上佳夫, 篠倉美理, 平井陽至, 山﨑修, 森実真

西日本皮膚科 83 ( 1 ) 18 - 21 2021年

記述言語：日本語出版者・発行元：日本皮膚科学会西部支部

1 歳，女児。乳児早期発症てんかんで治療中であったが，けいれん発作のコントロールが不良で臭化カリウムの内服を開始した。内服開始 2 カ月半後に四肢に紅色丘疹が出現し，膿疱を伴う紅色局面に進展した。病理組織では表皮内に好中球の浸潤，真皮では全層にわたって膠原線維束に分け入るような好中球の浸潤があり，とくに毛包周囲や毛包上皮への好中球の浸潤が顕著であった。血中臭化物濃度は 91.8 mg/dl と高値であり，臭素疹と診断した。臭化カリウムを減量してステロイド軟膏の外用で皮疹は軽快した。内服減量により皮疹が軽快したことから，臭素疹の機序はアレルギー性ではなく，用量依存性に発症する機序が推測される。

DOI： 10.2336/NISHINIHONHIFU.83.18

その他リンク： https://ndlsearch.ndl.go.jp/books/R000000004-I031318460

The aim of the measurement of Epstein-Barr virus DNA in hydroa vacciniforme and hypersensitivity to mosquito bites. 国際誌

Tomoko Miyake, Keiji Iwatsuki, Yoji Hirai, Takenobu Yamamoto, Toshihisa Hamada, Kazuyasu Fujii, Hideaki Imamura, Shin Morizane

Journal of medical virology 92 ( 12 ) 3689 - 3696 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Epstein-Barr virus (EBV) DNA load in the blood increases in posttransplant lymphoproliferative disorders and chronic active EBV infection. In this report, we analyzed the EBV DNA load in the peripheral blood mononuclear cells (PBMCs) and plasma of patients with hydroa vacciniforme (HV) and/or hypersensitivity to mosquito bites (HMB) to understand the clinical significance of EBV DNA load. All 30 patients showed high DNA loads in the PBMCs over the cut-off level. Of 16 plasma samples, extremely high in two samples obtained from patients with hemophagocytic lymphohistiocytosis (HLH). The amount of cell-free DNA in plasma was correlated to the serum levels of lactate dehydrogenase and inversely correlated to platelet counts. These results indicate that the EBV DNA load in PBMCs can provide one of the diagnostic indicators for HV and HMB and marked elevation of cell-free EBV DNA in plasma might be related to cytolysis such as that observed in HLH.

DOI： 10.1002/jmv.25811

Multifaceted Analyses of Epidermal Serine Protease Activity in Patients with Atopic Dermatitis. 国際誌

Hayato Nomura, Mutsumi Suganuma, Takuya Takeichi, Michihiro Kono, Yuki Isokane, Ko Sunagawa, Mina Kobashi, Satoru Sugihara, Ai Kajita, Tomoko Miyake, Yoji Hirai, Osamu Yamasaki, Masashi Akiyama, Shin Morizane

International journal of molecular sciences 21 ( 3 ) 2020年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin- and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC's serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD.

DOI： 10.3390/ijms21030913

Pediatric-onset annular pustular psoriasis in a patient with Down syndrome. 国際誌

Anri Morita, Yoshio Kawakami, Tatsuya Kaji, Yoji Hirai, Tomoko Miyake, Masayuki Takahashi, Osamu Yamasaki, Kazumitsu Sugiura, Shin Morizane

The Journal of dermatology 46 ( 10 ) e367-e368 2019年10月

TNF-α and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes. 国際誌

Satoru Sugihara, Saeko Sugimoto, Kota Tachibana, Mina Kobashi, Hayato Nomura, Tomoko Miyake, Yoji Hirai, Osamu Yamasaki, Shin Morizane

Journal of dermatological science 96 ( 1 ) 26 - 32 2019年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Serine proteases have important roles in skin barrier function and desquamation, and the aberrant expression or the dysfunction of serine proteases is associated with the pathogenesis of skin diseases. Serine protease activities are tightly regulated by serine proteases such as kallikrein-related peptidases (KLKs) and serine protease inhibitors such as lympho-epithelial Kazal-type related inhibitor (LEKTI). For a better understating of diseases' pathogenesis, the regulation mechanism of serine proteases and the inhibitors' expression in epidermal keratinocytes must be clarified. OBJECTIVES: To investigate the effects of the cytokines on the expression of LEKTI in epidermal keratinocytes. METHODS: Normal human epidermal keratinocytes (NHEKs) were stimulated with panels of inflammatory cytokines. The expression of serine protease inhibitors was analyzed using quantitative real-time PCR and ELISA. LEKTI expression in normal human skin and lesions from psoriasis or atopic dermatitis (AD) were analyzed by immunohistochemically and tape-stripping. Trypsin- and chymotrypsin-like serine protease activities in culture supernatants were measured by using specific substrates. RESULTS: TNF-α and IL-17A significantly induced the expression of LEKTI in NHEKs. The immunohistochemical and tape-stripping analysis revealed that psoriatic skin lesions had higher LEKTI expression compared to normal skin and AD lesions. Trypsin- and chymotrypsin-like protease activities in the culture media were upregulated 3-5 days later but attenuated 6-7 days later period by these cytokines. CONCLUSIONS: In epidermal keratinocytes, the Th1&Th17 cytokines TNF-α and IL-17A induce the expression of serine protease inhibitor LEKTI, and it might occur to suppress the increase in the serine protease activities under inflammation.

DOI： 10.1016/j.jdermsci.2019.08.007

Clinical manifestations of skin, lung and muscle diseases in dermatomyositis positive for anti-aminoacyl tRNA synthetase antibodies. 国際誌

Hiroko Fukamatsu, Yoji Hirai, Tomoko Miyake, Tatsuya Kaji, Shin Morizane, Emi Yokoyama, Toshihisa Hamada, Takashi Oono, Yoshinobu Koyama, Seiichiro Norikane, Keiji Iwatsuki

The Journal of dermatology 46 ( 10 ) 886 - 897 2019年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Patients with dermatomyositis positive for anti-aminoacyl tRNA synthetase (ARS) antibodies, also known as antisynthetase syndrome (ASS), frequently present with mechanic's hand and interstitial lung disease (ILD). We first screened the antibody profiles of 59 patients with dermatomyositis, and then examined the cutaneous, muscular and pulmonary manifestations characteristic for patients with ASS. The anti-ARS antibodies Jo-1, PL-7, PL-12, EJ and KS, along with antibodies to TIF1-γ, MDA5 and Mi-2, were examined. Among the 59 patients, 20, 21, 15 and three patients were classified into the ASS, non-ASS, myositis-specific antibody-negative and unknown groups, respectively. Five of 16 patients (31%) with ASS had six relatives with a history of collagen diseases, within the second degree of relationship, including two cases of dermatomyositis (vs the non-ASS group, P = 0.018). Patients with ASS more frequently presented with fever and arthralgia, and had elevated levels of C-reactive protein. Nine of the 11 finger lesions (82%) clinically diagnosed as mechanic's hands showed a psoriasiform tissue reaction. ILD was observed in 19 of 20 patients (95%) with ASS, and eight of 21 patients (38%) in the non-ASS group, in which six patients possessed anti-MDA5 antibody. Patients with ASS showed higher serum levels of muscle enzymes, and four of 12 patients (33%) had fasciitis-dominant myopathy, while only one of 11 patients (9%) in the non-ASS group had fasciitis-dominant myopathy. Patients with ASS often present with a psoriasiform tissue reaction in the hand lesions and fasciitis-dominant myopathy, and the relatives of those with ASS are at high risk for collagen diseases.

DOI： 10.1111/1346-8138.15049

Successful Treatment of Genital Warts with Ingenol Mebutate Monitored with Optical Coherence Tomography and Reflectance Confocal Microscopy. 国際誌

Markus Reinholz, Benjamin M Clanner-Engelshofen, Markus V Heppt, Yoji Hirai, Thomas Ruzicka, Carola Berking, Tanja von Braunmühl

Annals of dermatology 31 ( 4 ) 434 - 437 2019年8月

記述言語：英語

Ingenol mebutate (IM) is approved for the treatment of actinic keratosis and induces cell death in precancerous lesions. The efficacy of IM in the treatment of genital warts was investigated in a therapy-refractory patient. The 74-year-old male was treated with IM gel for three consecutive days. Treatment course and efficacy were evaluated by clinical inspection and non-invasive diagnostics namely optical coherence tomography (OCT) and reflectance confocal microscopy (RCM). Within 24 to 48 hours IM induced a strong local inflammatory reaction. One week later a complete response was observed. OCT and RCM showed a strong reaction after treatment with erosions, swelling of cells, and a subepidermal dark band in representative lesions. IM has the advantage of a short treatment period in contrast to other topical treatments and shows a promising clinical outcome. Larger studies are needed to validate the data.

DOI： 10.5021/ad.2019.31.4.434

An effective and promising treatment with adalimumab for impetigo herpetiformis with postpartum flare-up. 国際誌

Tamayo Yamashita, Toshihisa Hamada, Yuka Maruta, Ai Kajita, Yoji Hirai, Shin Morizane, Soichiro Watanabe, Kazumitsu Sugiura, Keiji Iwatsuki

International journal of dermatology 58 ( 3 ) 350 - 353 2019年3月

Hydroa vacciniforme: a distinctive form of Epstein-Barr virus-associated T-cell lymphoproliferative disorders. 国際誌

Keiji Iwatsuki, Tomoko Miyake, Yoji Hirai, Takenobu Yamamoto

European journal of dermatology : EJD 29 ( 1 ) 21 - 28 2019年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Hydroa vacciniforme (HV) is a cutaneous subset of Epstein-Barr virus (EBV)-associated T/NK lymphoproliferative disorders (LPDs). Our previous case series study clearly showed a clinical spectrum of EBV-associated T/NK LPDs including HV, hypersensitivity to mosquito bites (HMB), chronic active EBV infection (CAEBV), and hemophagocytic lymphohistiocytosis (HLH). Patients with HV are divided into two groups: a benign subtype designated "classic HV" (cHV) and more serious systemic HV (sHV), also called "HV-like LPD" in the 2017 World Health Organization (WHO) classification. Patients with cHV usually have an increased number of EBV-infected γδT cells and patients with sHV without HMB are further classified into two groups: γδT-cell- and αβT-cell-dominant types. Patients with HMB, with or without HV-like eruptions, have an increased number of EBV-infected NK cells in the blood. Patients with cHV and γδT-cell-dominant sHV show a favourable prognosis, but the other subtypes such as αβT-cell-dominant sHV and HMB have a poor prognosis with mortality rates of 11.5 and 3.51 per 100 person-years, respectively. In addition to the clinical subtypes and the dominant lymphocyte subsets, the poor prognostic indicators include onset age over nine years and expression of the reactivation marker, BZLF1 mRNA. No prognostic correlation has been reported for anti-EBV antibody titres or EBV DNA load. The clinical subtypes and their prognostic factors should be considered for therapeutic interventions.

DOI： 10.1684/ejd.2018.3490

Autophagy in malnutrition-associated dermatoses. 国際誌

Yoji Hirai, Tomoko Miyake, Toshihisa Hamada, Osamu Yamasaki, Shin Morizane, Tatsuhiko Mori, Keiji Iwatsuki

The Journal of dermatology 46 ( 1 ) 43 - 47 2019年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Malnutrition-associated dermatoses including necrolytic migratory erythema (NME) and pellagra share common clinicopathological features; in particular, necrolytic changes in the upper epidermis. Here, we report the involvement of autophagy in the development of necrolysis in three patients with malnutrition-associated dermatoses. First, we examined an autophagy-specific molecule, microtubule-associated protein light chain 3 (LC3), using a monoclonal antibody. LC3 was strongly expressed in the granular layers of the active border, and less intensely observed in the perilesional areas. Little LC3 staining or only background levels were observed in control skin diseases including atopic dermatitis (n = 4), psoriasis vulgaris (n = 3), basal cell carcinoma with amyloid deposits (n = 3) and squamous cell carcinoma (n = 3). Electron microscopic observations revealed the presence of autophagosome-like structures in the necrolytic areas. No apoptotic signals were observed in the necrolytic lesion using the terminal deoxynucleotidyl transferase dUTP nick end labeling method. Epidermal Langerhans cells determined by anti-CD1a antibody were markedly decreased in number. Our observations suggest the possibility that malnutrition-associated necrolysis, as exemplified by NME and pellagra, may be induced by autophagy.

DOI： 10.1111/1346-8138.14694

Clinical and Laboratory Markers Associated With Relapse in Cutaneous Polyarteritis Nodosa. 国際誌

Azusa Kato, Toshihisa Hamada, Tomoko Miyake, Shin Morizane, Yoji Hirai, Osamu Yamasaki, Keiji Iwatsuki

JAMA dermatology 154 ( 8 ) 922 - 926 2018年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Importance: In cutaneous polyarteritis nodosa (CPAN), less aggressive treatments can be selected, because CPAN is not associated with life-threatening or progressive outcomes. Although patients with a recurrent clinical course may require additional immunosuppressive therapies, no pretreatment factors associated with a worse prognosis in CPAN have been reported. Objective: To identify clinical or laboratory markers associated with relapse of CPAN. Design, Setting, and Participants: This retrospective case series was performed at a dermatology clinic of a tertiary referral center in Okayama, Japan, from October 1, 2001, through April 30, 2017. Of 30 patients identified with CPAN, the 21 with histopathologic evidence of disease were eligible and enrolled in the study. Main Outcomes and Measures: The medical database was examined for sex, age at diagnosis, affected anatomical sites, type and extent of skin lesion, laboratory data, initial therapies, duration of follow-up, and current status. Relapse was defined as the first reoccurrence or new onset of cutaneous disease that required further escalation of treatment with prednisolone at a dosage of greater than 20 mg/d and/or add-on use of immunosuppressant therapy, more than 6 months after initial treatment. The pretreatment factors were statistically evaluated between the groups without and with relapse. Results: The 21 patients included 5 males and 16 females with a median age of 49 years (range, 11-74 years) at diagnosis. The median follow-up was 42 months (range, 8-374 months). Pretreatment cutaneous ulcer was significantly associated with relapse between the 2 groups (0 of 11 in the nonrelapse group vs 4 of 10 in the relapse group; χ21 = 4.67; P < .05). In the laboratory test results, significantly higher mean (SD) values were observed in the relapse group for C-reactive protein level (0.23 [2.00] vs 6.03 [3.10] mg/dL; standard error of the mean [SEM], 3.40 mg/dL; 95% CI, 0.01-10.8 mg/dL; P = .01), absolute neutrophil count (ANC) (3.4 × 103/μL [1.1 × 103/μL] vs 6.0 × 103/μL [3.2 × 103/μL]; SEM, 2.9 × 103/μL; 95% CI, 1.9 × 103/μL to 14.6 × 103/μL; P = .001), neutrophil-to-lymphocyte ratio (1.4 [0.8] vs 2.8 [0.9]; SEM, 1.2; 95% CI, 1.1-4.9; P = .002), and systemic immune-inflammation index (5.1 × 105 [3.9 × 105] vs 11.7 × 105 [7.7 × 105]; SEM, 7.3 × 105; 95% CI, 3.3 × 105 to 31.1 × 105; P = .007). The estimated 2-year cumulative relapse rate was significantly high in the patients with blood ANC of greater than 4.9 × 103/μL compared with 4.9 × 103/μL or less (9 of 10 [90%] vs 2 of 11 [18%]; 95% CI, 6%-72%). Conclusions and Relevance: Pretreatment status of cutaneous ulcer, the serum C-reactive protein level, the blood ANC, the neutrophil-to-lymphocyte ratio, and the systemic immune-inflammation index are associated with a worse prognosis in CPAN.

DOI： 10.1001/jamadermatol.2018.1601

Type D (CD8+) lymphomatoid papulosis in a patient with classic (CD4+) mycosis fungoides. 国際誌

Junko Hori-Kosogabe, Toshihisa Hamada, Shin Morizane, Yoji Hirai, Tomoko Miyake, Tadashi Yoshino, Keiji Iwatsuki

European journal of dermatology : EJD 28 ( 2 ) 267 - 268 2018年4月

Epstein-Barr virus-positive mucocutaneous ulcer in a patient with polycythemia vera treated with oral hydroxyurea. 国際誌

Toshihisa Hamada, Mariko Kawata, Yoshinobu Maeda, Tadashi Yoshino, Tomoko Miyake, Shin Morizane, Yoji Hirai, Keiji Iwatsuki

The Journal of dermatology 45 ( 4 ) e82-e83 2018年4月

Clinical outcomes of primary cutaneous anaplastic large cell lymphoma: data from a single Japanese centre. 国際誌

Yuka Maruta, Toshihisa Hamada, Hiroko Fukamatsu, Tatsuya Kaji, Shin Morizane, Yoji Hirai, Tomoko Miyake, Osamu Yamasaki, Tadashi Yoshino, Keiji Iwatsuki

European journal of dermatology : EJD 27 ( 6 ) 669 - 671 2017年12月

皮膚リンパ腫患者の治療抵抗性皮膚病変に対する低線量放射線療法の有用性

浜重純平, 平井陽至, 濱田利久, 岩月啓氏, 勝井邦彰, 金沢右

日本皮膚科学会雑誌 127 ( 2 ) 219 - 219 2017年2月

Comparative study on driver mutations in primary and metastatic melanomas at a single Japanese institute: A clue for intra- and inter-tumor heterogeneity. 国際誌

Tatsuya Kaji, Osamu Yamasaki, Minoru Takata, Masaki Otsuka, Toshihisa Hamada, Shin Morizane, Kenji Asagoe, Hiroyuki Yanai, Yoji Hirai, Hiroshi Umemura, Keiji Iwatsuki

Journal of dermatological science 85 ( 1 ) 51 - 57 2017年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Searching for driver mutations in melanoma is critical to understanding melanoma genesis, progression and response to therapy. OBJECTIVES: We aimed to investigate the frequency and pattern of driver mutations in Japanese primary and metastatic melanomas including cases of unknown primary origin, in relation to their clinicopathologic manifestations. METHODS: Seventy-seven samples from 60 patients with melanoma were screened for 70 driver mutations of 20 oncogenes by Sequenom MelaCarta MassARRAY, and the results for primary and metastatic melanomas were compared. RESULTS: Of 77 tissue samples, BRAF V600E was detected in 21 samples (27%), CDK4 R24C in 7, EPHB6 G404S in 6, BRAF V600K in 2, NEK10 E379K in 2, and CDK4 R24H, NRAS Q61K, NRAS Q61R, KRAS G12A, KIT L576P, KIT V559A, ERBB4 E452K, and PDGFRA E996K in one sample each. No driver mutations related to the MAPK cascade including RAS and BRAF were detected in the chronically sun-damaged (CSD) group of melanoma. Dual or triple driver mutations were found in four of 40 (10%) samples from the primary melanomas, and three of 37 (8%) of the metastatic melanomas. Fourteen of 26 (54%) samples of non-CSD melanoma, and 3 of 6 (50%) melanomas of unknown primary origin had the BRAF V600E mutation. Mutations in membrane-bound receptors including KIT, ERBB4 and EPHB6 were detected in 8 of 77 (10%) samples. Of 17 pairs of primary and metastatic melanomas from the same patient, the primary mutation pattern was changed to a novel one in three cases, and only one of the plural mutations in the primary melanoma was found in the metastatic lesions in two cases. CONCLUSIONS: BRAF V600E is a predominant mutation in non-CSD melanoma and melanomas of unknown primary origin. Mutational heterogeneity may exist in the primary melanoma (intra-tumor heterogeneity), and between the primary and metastatic lesions (inter-tumor heterogeneity).

DOI： 10.1016/j.jdermsci.2016.10.006

Differential diagnosis of herpetiform vesicles by a non-invasive, molecular method using crusts or blister roofs: Sensitivity, specificity and likelihood ratio. 国際誌

Tomoko Miyake, Takenobu Yamamoto, Yoji Hirai, Keiji Iwatsuki

Journal of dermatological science 84 ( 3 ) 358 - 359 2016年12月

IVIGにより血小板減少をきたした難治性尋常性天疱瘡の1例

浜重純平, 野村隼人, 禅正和真, 河野淳子, 難波裕子, 梶田藍, 平井陽至, 岩月啓氏, 松三友子

日本皮膚科学会雑誌 126 ( 11 ) 2135 - 2136 2016年10月

手術室映像システムを活用した皮膚科の手術教育

山崎修, 加持達弥, 平井陽至, 梅村啓史, 濱田利久, 岩月啓氏

日本皮膚科学会雑誌 126 ( 11 ) 2137 - 2137 2016年10月

病院現況および患者視点からみた進行期悪性黒色腫に対する新規治療

山崎修, 加持達弥, 梅村啓史, 平井陽至, 森実真, 濱田利久, 高田実, 岩月啓氏, 勝井邦彰, 合地明

日本皮膚科学会雑誌 126 ( 9 ) 1709 - 1716 2016年8月

記述言語：日本語出版者・発行元：(公社)日本皮膚科学会

進行期悪性黒色腫の新規治療は非常に高額で医療費の増大を招く可能性がある。悪性黒色腫患者に医療費に関するアンケート調査をして治療別に比較した。2015年度上半期の診療実績を前年度と比較し、新規治療施行例の薬剤費を概算した。新規治療群は医療費が生活費の20%以上で負担感が強かった。外来の診療用請求額、診療単価、医療費率が増加し、新規治療が要因の一つと考えた。新規治療症例の薬剤費は高額であった。新規治療による患者の経済的負担、病院の経営的側面、国民医療費の問題を理解し、医療経済面に配慮する必要がある。(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01174&link_issn=&doc_id=20160906460005&doc_link_id=10.14924%2Fdermatol.126.1709&url=https%3A%2F%2Fdoi.org%2F10.14924%2Fdermatol.126.1709&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

色素性乾皮症に生じた頭頂部悪性黒色腫

梶田藍, 河野淳子, 難波裕子, 平井陽至, 加持達弥, 山崎修, 岩月啓氏

日本皮膚科学会雑誌 126 ( 8 ) 1482 - 1482 2016年7月

Epstein-Barr virus reactivation is induced, but abortive, in cutaneous lesions of systemic hydroa vacciniforme and hypersensitivity to mosquito bites. 国際誌

Takenobu Yamamoto, Yoji Hirai, Tomoko Miyake, Toshihisa Hamada, Osamu Yamasaki, Shin Morizane, Wataru Fujimoto, Keiji Iwatsuki

Journal of dermatological science 82 ( 3 ) 153 - 9 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Epstein-Barr virus (EBV)-associated T/natural killer (NK)-lymphoproliferative disorders (LPDs) include hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). The pathomechanisms of these diseases are still unclear. OBJECTIVE: To understand the inflammatory process, we examined EBV reactivation markers, BZLF1 and BDRF1 mRNA in the tissue and blood from patients with EBV-associated T/NK-LPDs. METHODS: Sixty-four patients with EBV-associated LPDs and epithelial neoplasms, and EBV+ cell line cells were studied. DNase-treated and resistant EBV DNA load in blood and cell culture supernatants were calculated. An EBV reactivation signal was analyzed in the tissue, blood and cell line cells. RESULTS: In the tissue, BZLF1 mRNA was detected in 5 of 6 (83%) samples of EBV+ epithelial neoplasms, 16 of 21 (76%) of EBV+ lymphomas, and 5 of 15 (33%) of systemic HV and/or HMB, but negative in all 15 patients with classical HV. In the blood, BZLF1 mRNA was detected in only one of 19 (5.3%) samples of EBV-associated T/NK-LPDs. A down-stream reactivation signal, BDRF1 mRNA was expressed in all 6 samples of EBV+ epithelial neoplasms, but it was positive in only one of 15 (6.7%) samples from systemic HV and HMB in the tissue. EBV+ T/NK-cell line cells treated with phorbol 12-myristate 13-acetate produced BZLF1 and BDRF1 mRNA, and encapsidated EBV DNA was detected in the culture supernatants of cell line cells. CONCLUSION: Stimulation-induced EBV reactivation occurred both in vivo and in vitro, but it was almost abortive in vivo. Reactivation-related EBV antigens might be responsible for induction of systemic HV and HMB.

DOI： 10.1016/j.jdermsci.2016.03.001

種痘様水疱症と蚊刺過敏症における血球・血漿EBV DNA定量の臨床的意義の検討

三宅智子, 平井陽至, 濱田利久, 岩月啓氏, 山本剛伸

日本皮膚科学会雑誌 126 ( 7 ) 1305 - 1305 2016年6月

非バイアス次世代TCRレパトア解析によるEBV関連リンパ増殖性疾患への応用

平井陽至, 三宅智子, 森実真, 濱田利久, 北浦一孝, 松谷隆治, 岩月啓氏

日本皮膚悪性腫瘍学会学術大会プログラム・抄録集 32回 144 - 144 2016年5月

病院現況および患者視点からみた進行期悪性黒色腫に対する新規治療

山崎修, 加持達弥, 平井陽至, 梅村啓史, 森実真, 濱田利久, 岩月啓氏, 勝井邦彰, 合地明

日本皮膚科学会雑誌 126 ( 5 ) 935 - 935 2016年5月

帯状疱疹ウイルス・単純疱疹ウイルスの重複再活性化例の臨床及び遺伝子産物解析

三宅智子, 平井陽至, 山本剛伸, 片山治子, 森実真, 岩月啓氏

日本皮膚科学会雑誌 126 ( 5 ) 994 - 994 2016年5月

抗セントロメア抗体陽性全身性強皮症患者に生じたサルコイドーシス HLA-DR解析と全身性ステロイド療法について

岩月啓氏, 平井陽至, 山崎修, 濱田利久, 森実真, 三宅智子, 加持達弥, 梅村啓史, 武藤正彦

日本皮膚科学会雑誌 126 ( 6 ) 1152 - 1152 2016年5月

【最近のトピックス2016 Clinical Dermatology 2016】新しい検査法と診断法痂皮を用いたウイルス感染症の診断

三宅智子, 山本剛伸, 平井陽至, 岩月啓氏

臨床皮膚科 70 ( 5 ) 75 - 78 2016年4月

記述言語：日本語出版者・発行元：(株)医学書院

ヘルペス様水疱を認める疾患には単純疱疹,帯状疱疹,日常診療では稀であるが種痘様水疱症が挙げられる.これらの疾患を診断するためには,TzanckテストやEBER(Epstein-Barr virus encoded RNA)in situ法が一般的に用いられる.われわれは痂皮や水疱蓋よりRT-PCR(reverse transcriptase polymerase chain reaction)法にてEBER-1を検出する方法を2007年に報告した.本法は,非侵襲的に検体を採取でき,痂皮の場合は数ヵ月保存することができるため,全国各地からの検体を検査することが可能である.さらに抽出したRNAをcDNAとして使用することで遊離しているウイルスDNAを除外できる.本法を用いて単純ヘルペスウイルス,帯状疱疹ウイルス,Epstein-Barrウイルスを検出した結果,いずれのウイルスでも本法は高い鋭敏度と特異度を示した.本法を用いて,ヘルペスウイルス感染症を診断することは有用な検査であると考えた.(著者抄録)

DOI： 10.11477/mf.1412204741

大腿に発生したintraepithelial sebaceous carcinoma

梶田藍, 河野淳子, 難波裕子, 平井陽至, 加持達弥, 山崎修, 岩月啓氏, 谷口恒平, 柳井広之

日本皮膚科学会雑誌 126 ( 3 ) 322 - 323 2016年3月

痂皮と水疱蓋を用いた種痘様水疱症と蚊刺過敏症の低侵襲診断的検査の鋭敏度と特異度に関する研究

三宅智子, 平井陽至, 山本剛伸, 岩月啓氏

日本皮膚科学会雑誌 125 ( 4 ) 947 - 947 2015年4月

種痘様水疱症分子生物学的に検証した記載皮膚科学の確かさ

岩月啓氏, 平井陽至, 三宅智子, 濱田利久, 大熊登, 山本剛伸

皮膚の科学 14 ( 1 ) 37 - 37 2015年2月

Survival rates and prognostic factors of Epstein-Barr virus-associated hydroa vacciniforme and hypersensitivity to mosquito bites. 国際誌

T Miyake, T Yamamoto, Y Hirai, M Otsuka, T Hamada, K Tsuji, S Morizane, D Suzuki, Y Aoyama, K Iwatsuki

The British journal of dermatology 172 ( 1 ) 56 - 63 2015年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Epstein-Barr virus (EBV)-associated T/natural-killer lymphoproliferative disorders form a group of diseases that includes classical and systemic hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). Patients with systemic HV (sHV) and HMB often have a poor prognosis, although little is known about the prognostic factors. OBJECTIVES: To elucidate the prognostic factors of HV and HMB. METHODS: We studied clinicopathological manifestations, routine laboratory findings, anti-EBV titres, EBV DNA load and EBV-encoded gene expression, including expression of BZLF1, in 50 patients with classical HV (cHV), sHV, HMB only and HMB with HV (HMB + HV), and further analysed 30 patients who were available for follow-up. RESULTS: The median age of disease onset was 5 years (range 1-74). A follow-up study indicated that fatal outcomes were observed in three of eight patients with sHV, two of six patients with HMB only, and two of five patients with HMB + HV. The main causes of death were complications from haematopoietic stem-cell transplantation and multiorgan failure. There were no fatalities among the 11 patients with cHV. Univariate analysis revealed two poor prognostic indicators: (i) onset age > 9 years and (ii) the expression of an EBV-encoded immediate-early gene transcript, BZLF1 mRNA, in the skin lesions (P < 0·001 and P = 0·003, respectively). CONCLUSIONS: No prognostic correlation was observed in EBV-infected lymphocyte subsets, anti-EBV antibody titres or EBV DNA load. Late onset and EBV reactivation are both related to more severe phenotypes of the disease, and thus may predict a poor prognosis.

DOI： 10.1111/bjd.13411

Immune escape phenomenon in molluscum contagiosum and the induction of apoptosis. 国際誌

Akiko Yamauchi-Yamada, Takenobu Yamamoto, Yumi Nakayama, Kazuko Ikeda, Tomoko Miyake, Mari Yamaguchi, Yoji Hirai, Yoshinori Shirafuji, Shin Morizane, Yumi Aoyama, Keiji Iwatsuki

The Journal of dermatology 41 ( 12 ) 1058 - 64 2014年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Molluscum contagiosum (MC) may persist for many weeks, evading host immunity. We studied the mechanism of immune escape phenomenon in MC, and the possible inducer of apoptosis. Using tissue samples of MC, we examined the numbers of epidermal Langerhans cells (LC), the expression levels of macrophage inflammatory protein-3α (MIP-3α) and thymic stromal lymphopoietin (TSLP), and the apoptotic signals. After molluscum contagiosum virus (MCV) genotyping, we studied the expression of MCV-encoded MC148 mRNA and MC159 mRNA which correspond to viral antagonist for CCR8 and viral Fas-linked interleukin (IL)-1β converting enzyme (FLICE)-like inhibitor protein (vFLIP), respectively. The nutlin-3-induced apoptosis in MC was observed ex vivo. The numbers of CD1a(+) or Langerin(+) epidermal LC and the expression levels of MIP-3α were markedly decreased in MC. The expression of TSLP was enhanced in the lesional epidermis of atopic dermatitis and human papillomavirus-induced warts, whereas the expression was observed locally in MC. All 14 MC samples examined harbored MCV type 1. The MC148 mRNA was detected in all 14 samples and the MC159 mRNA was detected in 13 samples. Apoptotic cells were absent or at a background level in the living layers of MC, but their numbers were increased in the molluscum bodies by overnight incubation with 5 μmol/L nutlin-3 in culture medium. In conclusion, molluscum bodies are protected from host immune responses and apoptotic signals by being surrounded by LC-depleted epidermal walls and viral immunosuppressive molecules, but could be eradicated by reagents inducing p53-dependent apoptosis.

DOI： 10.1111/1346-8138.12695

Cathelicidin peptide LL-37 increases UVB-triggered inflammasome activation: possible implications for rosacea. 国際誌

Suzanna Salzer, Sonja Kresse, Yoji Hirai, Sarah Koglin, Markus Reinholz, Thomas Ruzicka, Jürgen Schauber

Journal of dermatological science 76 ( 3 ) 173 - 9 2014年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: In patients with rosacea, environmental stressors, especially UVB radiation, trigger disease flares that are characterized by inflammation and vascular hyperactivity. An altered innate immune detection and response system, modulated to a large extent by the aberrant production and processing of human cathelicidin LL-37, is thought to play a central role in disease pathogenesis. OBJECTIVE: To investigate whether the proinflammatory and proangiogenic effects of UV radiation are enhanced in the presence of cathelicidin LL-37. METHODS: Human skin ex vivo and epidermal keratinocytes in vitro were exposed to UVB irradiation. The proinflammatory effects of UVB exposure in the presence and absence of LL-37 were characterized using immunoblot, transfection, qPCR, and a cell-based second messenger assay. ELISA was used to assess cytokine release and the angiogenic potential of endothelial cells was evaluated using an in vitro angiogenesis assay. RESULTS: UVB irradiation triggered the inflammasome-mediated processing and release of IL-1β. LL-37 augmented this UV-induced IL-1β secretion by acting on the P2X7 receptor on keratinocytes. P2X7 receptor activation by UVB and LL-37 resulted in an increase in intracellular calcium concentrations, which enhances inflammasome activation and subsequent IL-1β release. Furthermore, IL-1β and LL-37 worked synergistically to increase the angiogenic potential of endothelial cells. CONCLUSION: Cathelicidin LL-37 modulates the proinflammatory and proangiogenic effects of UV radiation and thereby contributes to enhanced sensitivity to sun exposure in rosacea.

DOI： 10.1016/j.jdermsci.2014.09.002

種痘様水疱症様皮疹を生じるadult-onset例 early-onsetおよびelderly-onset例との比較

平井陽至, 三宅智子, 岩月啓氏, 山本剛伸

Skin Cancer 28 ( 2 ) 234 - 234 2013年11月

【EBウイルス感染症-その多様な病態】EBウイルスと皮膚疾患

平井陽至, 山本剛伸, 三宅智子, 岩月啓氏

成人病と生活習慣病 43 ( 9 ) 1086 - 1093 2013年9月

記述言語：日本語出版者・発行元：(株)東京医学社

EBウイルスが関与している皮膚疾患として、(A)皮膚病変部にEBウイルス感染細胞が検出されるもの(EBウイルス特異疹)と、(B)反応性変化により皮疹形成するもの(非特異疹)とに大別される。EBウイルスリンパ球増殖症におけるEBウイルス特異疹として、T細胞性のものとNK細胞性のものに大別される。T細胞性リンパ球増殖症(多くはγδT細胞)として小児のまれな光線過敏症にHVがあげられるが、予後良好で多くは自然寛解の経過をとる古典型HVと予後不良で発熱・肝機能障害などの全身症状を伴う全身型HVの2タイプに分けられる。NK細胞性リンパ球増殖症としてHMBがあり全身型HV同様にCAEBVを合併していることが多い。(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J03723&link_issn=&doc_id=20131003110010&doc_link_id=%2Faq9seijd%2F2013%2F004309%2F010%2F1086-1095%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9seijd%2F2013%2F004309%2F010%2F1086-1095%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

種痘様水疱症様皮疹を生じるadult-onset例 early-onsetおよびelderly-onset例との比較

平井陽至, 山本剛伸, 三宅智子, 岩月啓氏

日本皮膚悪性腫瘍学会学術大会プログラム・抄録集 29回 134 - 134 2013年8月

ヘルペスウイルス感染に伴うウイルス側・宿主側からみた免疫回避・誘導のメカニズム

山本剛伸, Cohen Jeffrey I., 三宅智子, 平井陽至, 藤本亘, 岩月啓氏

山口医学 62 ( 3 ) 181 - 181 2013年8月

Chronic active Epstein-Barr virus infection with progression to large granular lymphocytic leukemia. 国際誌

Satoshi Komori, Jun Asai, Hideya Takenaka, Junya Kuroda, Yoji Hirai, Keiji Iwatsuki, Norito Katoh

The Journal of dermatology 40 ( 6 ) 487 - 8 2013年6月

最近、当院で経験した術後深部静脈血栓症/肺塞栓症の4例

加持達弥, 杉生真帆, 瀧口徹也, 梅村啓史, 牧野麻貴, 鈴木規弘, 大塚正樹, 濱田利久, 山崎修, 岩月啓氏, 野田和代, 平井陽至

日本皮膚科学会雑誌 123 ( 7 ) 1261 - 1261 2013年6月

EBV関連皮膚リンパ球増殖症

平井陽至, 山本剛伸, 三宅智子, 山内晶子, 鈴木大介, 藤井一恭, 岩月啓氏

血液内科 66 ( 2 ) 219 - 225 2013年2月

【こどもとおとなの皮膚病シリーズ(1)ウイルス感染症】(Part1.)ウイルス感染症 (case04)伝染性単核球症おとなとこどもの症状は同じ? Gianotti症候群もEBV?

三宅智子, 平井陽至, 岩月啓氏, 山本剛伸

Visual Dermatology 11 ( 12 ) 1264 - 1266 2012年11月

Superficial granulomatous pyodermaの臨床・組織病態に着目した長期観察例

三宅智子, 青山裕美, 杉生真帆, 平井陽至, 鈴木大介, 岩月啓氏

西日本皮膚科 74 ( 3 ) 348 - 349 2012年6月

Hydroa vacciniforme is associated with increased numbers of Epstein-Barr virus-infected γδT cells. 国際誌

Yoji Hirai, Takenobu Yamamoto, Hiroshi Kimura, Yoshinori Ito, Kazuhide Tsuji, Tomoko Miyake, Shin Morizane, Daisuke Suzuki, Kazuyasu Fujii, Keiji Iwatsuki

The Journal of investigative dermatology 132 ( 5 ) 1401 - 8 2012年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Hydroa vacciniforme (HV) is a rare photosensitivity disorder of childhood associated with Epstein-Barr virus (EBV)(+) T-cell infiltration. We have summarized clinical manifestations of HV, and analyzed EBV(+) T-cell subsets as well as EBV DNA load in lymphocyte fractions, in comparison with hypersensitivity to mosquito bites (HMB), an EBV-associated T/natural killer (NK) lymphoproliferative disorder. We found that 31 of 33 (93.9%) HV lesions were composed of EBV(+) T cells and reactive EBV(-) cytotoxic T cells, without significant CD56(+) cell infiltration, whereas many CD56(+) cells were present in 8 of 9 (88.9%) HMB lesions. Of 13 (20.6%) HMB patients with or without HV, 12 (92.3%) showed increased percentages (>32%) of NK cells in the peripheral blood, whereas in the 16 patients with HV alone, 14 (87.5%) showed no increase. Of the 11 HV patients, 10 (90.9%) had increased percentages (>5%) of circulating γδT cells, with a mean value of 15.7 ± 2.9%, and the γδT-cell fractions contained larger amounts of EBV DNA than non-γδT-cell fractions. A triple-labeling method revealed that all three HV patients examined had increased percentages of EBER(+), T-cell receptor (TCR)γδ(+), and TCRαβ(-) cells. Our observations indicate that HV is associated with increased numbers of EBV(+) γδT cells, whereas HMB is associated with EBV(+) NK cells.

DOI： 10.1038/jid.2011.461

Oculomucosal and gastrointestinal involvement in Epstein-Barr virus-associated hydroa vacciniforme 査読

Takenobu Yamamoto, Yoji Hirai, Tomoko Miyake, Osamu Yamasaki, Shin Morizane, Keiji Iwatsuki

EUROPEAN JOURNAL OF DERMATOLOGY 22 ( 3 ) 380 - 383 2012年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JOHN LIBBEY EUROTEXT LTD

In a series of patients with Epstein-Barr virus (EBV)-associated hydroa vacciniforme (HV) and related disorders, we reviewed the incidence of oculomucosal and gastrointestinal involvement. Of 63 patients with EBV-related HV and/or hypersensitivity to mosquito bites (HMB), 11 patients (17.5%) presented with mucosal lesions such as aphthous stomatitis and ulcerative gingivitis, 3 patients (4.8%) had ocular symptoms including iritis, conjunctival hyperemia and corneal erosions, and 2 patients (3.2%) presented with severe HV complicated gastrointestinal involvement. Oculomucosal lesions are sometimes complicated in patients with EBV-related HV and HMB, and gastrointestinal involvement may occur in the severe form.

DOI： 10.1684/ejd.2012.1665

【多様化する光線過敏症】Epstein-Barrウイルス感染症と種痘様水疱症

平井陽至, 山本剛伸, 三宅智子, 山内晶子, 藤井一恭, 森実真, 岩月啓氏

Derma. ( 191 ) 48 - 53 2012年4月

記述言語：日本語出版者・発行元：(株)全日本病院出版会

種痘様水疱症(hydroa vacciniforme;HV)は日光露光部に水疱性または痂皮性小丘疹を繰り返す光線過敏症である。皮疹部組織ではEBウイルス(EBV)が潜伏感染したT細胞が浸潤細胞の数%〜20%を占め、またそれ以上の数の細胞障害性T細胞(CTL)の反応性浸潤を認める。検査上では末梢血EBVゲノム数の増加とγδT細胞増多が認められるが、全身症状やEBV抗体価、血液学的な異常は通常認められない。大多数の例は思春期までに自然治癒する予後良好な疾患であるが、重篤な皮膚症状や発熱、リンパ節腫脹などの全身症状、末梢血EBVゲノム数が著明に増加するような重症型HVは、慢性活動性EBV感染症(CAEBV)や蚊刺過敏症(HMB)に伴って発症することがある。そのような例では自然軽快せず悪性リンパ腫、EBV関連血球貪食症候群などへ進展することが多い。(著者抄録)

EBウイルス関連疾患の予後に関する追跡調査

三宅智子, 山本剛伸, 平井陽至, 藤井一恭, 岩月啓氏

日本皮膚科学会雑誌 122 ( 4 ) 1242 - 1242 2012年4月

Occasional traumatic localization of lesion(Boyd) インスリン注射部位、採皮部にケブネル反応として転移性脈管肉腫を生じた2症例

青山裕美, 山崎修, 三宅智子, 杉生真帆, 鈴木大介, 池田佳寿子, 竹島千夏, 平井陽至, 橋本倫子, 浮田彩, 岩月啓氏

西日本皮膚科 74 ( 2 ) 211 - 211 2012年4月

Epstein-Barrウイルス関連T/NKリンパ球増殖症と診断した63症例の検討

平井陽至, 山本剛伸, 三宅智子, 山内晶子, 藤井一恭, 岩月啓氏

皮膚病診療 33 ( 11 ) 1174 - 1178 2011年11月

MTX内服により生じたimmunodeficiency-associated lymphoproliferative disordersの1例

平井陽至, 藤井一恭, 濱田利久, 岩月啓氏, 西田圭一郎, 山本剛伸

日本皮膚科学会雑誌 121 ( 11 ) 2282 - 2282 2011年10月

多彩な皮疹を呈したfolliculotropic mycosis fungoidesの1例

杉生真帆, 三宅智子, 平井陽至, 鈴木大介, 濱田利久, 岩月啓氏

日本皮膚科学会雑誌 121 ( 11 ) 2282 - 2282 2011年10月

母斑性基底細胞癌症候群(nevoid basal cell carcinoma syndrome:NBCCS)の2例

平井陽至, 大野貴司, 濱田利久, 岩月啓氏

日本皮膚科学会雑誌 121 ( 10 ) 2074 - 2074 2011年9月

菌状息肉症/セザリー症候群における、末梢血CD4/8比上昇例の臨床的特徴とTNMB分類およびtumor burdenとの関連について

池田佳寿子, 濱田利久, 鈴木大介, 藤井一恭, 平井陽至, 岩月啓氏

西日本皮膚科 73 ( 3 ) 319 - 320 2011年6月

伝染性軟属腫における宿主免疫回避メカニズムの解析

山本剛伸, 山内晶子, 三宅智子, 平井陽至, 岩月啓氏

日本皮膚科学会雑誌 121 ( 3 ) 620 - 620 2011年3月

種痘様水疱症とその鑑別を要した56症例についての検討

平井陽至, 山本剛伸, 三宅智子, 藤井一恭, 岩月啓氏

日本皮膚科学会雑誌 121 ( 3 ) 620 - 620 2011年3月

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