Updated on 2025/11/10

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写真a

 
Yuko Watanabe
 
Organization
Graduate School of Medicine Department of Medicine Dermatology Lecturer
School of Medicine Medical Course
Title
Lecturer
External link

Degree

  • 医学博士

Research Areas

  • Life Science / Dermatology  / psoriasis, derug eruption

Education

  • Yokohama City University

    2012.4 - 2016.3

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Research History

  • Yokohama City University   Environmental Immuno-Dermatology   Lecturer

    2022.4

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  • Yokohama City University

    2020.4 - 2022.3

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  • Yokohama City University Hospital, Department of Dermatology   Assistant Professor

    2016.10 - 2020.3

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  • 横浜市立大学 医学部 博士課程

    2012.4 - 2016.3

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Professional Memberships

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Committee Memberships

  • 日本アレルギー学会   薬物アレルギー委員会 委員  

    2025.5   

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    Committee type：Academic society

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  • 日本脊椎関節炎学会   国際委員  

    2024.6   

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  • 日本皮膚科学会東京支部   代議員  

    2023.12   

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  • 日本研究皮膚科学会   評議員  

    2023.3   

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  • 日本アレルギー学会   代議員  

    2021.6   

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    Committee type：Academic society

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  • 日本皮膚免疫アレルギー学会   薬疹専門部会  

       

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Papers

  • Efficacy and Safety of Etanercept in Japanese Patients With Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Unresponsive to Systemic Steroid Therapy: A Multicenter, Open‐Label, Single‐Arm Study International journal

    Haruna Kimura, Mahoko Oginezawa, Natsumi Hama, Yuko Watanabe, Yukie Yamaguchi, Saeko Nakajima, Hideaki Watanabe, Riichiro Abe

    The Journal of Dermatology   2025.7

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

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, life-threatening cutaneous adverse reactions that have limited treatment options when systemic corticosteroids prove ineffective. To assess the efficacy and safety of etanercept in patients with SJS/TEN who failed to respond adequately to systemic corticosteroid therapy. In this multicenter, open-label, single-arm study conducted in Japan, patients with SJS or TEN unresponsive to ≥ 2 days of systemic corticosteroids (prednisolone-equivalent ≥ 20 mg/day) were enrolled. Etanercept 50 mg was administered subcutaneously on Day 1, with additional doses on Days 8 and 15 if re-epithelialization remained incomplete. The primary outcome was time to complete re-epithelialization. Secondary endpoints included time to cessation of skin progression, hospitalization duration, disease severity scores, ocular complications, and safety outcomes. Eight Japanese patients (mean age: 63.4 years; SJS: 5, TEN: 3) were treated. The median time to complete re-epithelialization was 10 days (95% Confidence interval: 6.0-20.0). All patients achieved re-epithelialization within 29 days. The mean time to cessation of skin progression was 4.0 days, and the mean hospitalization duration was 19.3 days. No deaths occurred. Adverse events were reported in six patients (75%), including two serious infections (cytomegalovirus and cryptococcosis). However, none were judged related to etanercept. No treatment discontinuations occurred. Etanercept could be an effective and safe treatment option for patients with SJS/TEN unresponsive to systemic corticosteroids. These findings warrant validation in larger, controlled studies.

    DOI： 10.1111/1346-8138.17860

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  • Recent advances in the diagnosis and treatment of Stevens–Johnson syndrome/toxic epidermal necrolysis International journal

    Yuko Watanabe, Natsumi Hama

    Allergology International   74 ( 3 )   345 - 355   2025.6

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

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but serious mucocutaneous disorders primarily caused by medications. Despite their low incidence, both conditions remain associated with high mortality and significant long-term complications. Recent studies have advanced the understanding of their pathogenesis, including the roles of neutrophil extracellular traps and several cell death pathways. However, reliable biomarkers for early diagnosis are lacking, and no internationally standardized diagnostic criteria have been established. To address these gaps, new diagnostic frameworks have been proposed that incorporate conventional cutaneous and mucosal findings with mandatory histopathological confirmation. These are expected to enhance diagnostic precision and facilitate global comparability. The increasing incidence of SJS/TEN-like reactions associated with immune checkpoint inhibitors and molecular targeted therapies further highlights the importance of accurate histopathological differentiation. Prognostic tools are essential for therapeutic planning. Although the Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) score remains widely used, newer systems offer improved risk stratification and practical utility in diverse clinical settings. However, the optimal use of immunomodulatory therapies remains uncertain owing to limited consensus and evidence. Corticosteroids continue to serve as first-line treatment, but more selective agents are gaining attention for their potential efficacy and reduced toxicity. This review summarizes recent progress in SJS/TEN diagnosis, severity assessment, and management. It discusses the utility and limitations of novel scoring systems and emerging therapies while highlighting persistent challenges, including high mortality, regional practice variation, and delayed standardization. International collaboration and high-quality evidence generation remain essential for improving patient outcomes.

    DOI： 10.1016/j.alit.2025.05.008

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  • Comparing immunopathogenesis of non-human immunodeficiency virus immune reconstitution inflammatory syndrome and immune-related adverse events: A prospective multicenter cohort study. International journal

    Hirohiko Sueki, Seiko Sugiyama, Yumi Aoyama, Takenobu Yamamoto, Hideaki Watanabe, Naoko Inomata, Yutaro Kubota, Atsushi Horiike, Takuya Tsunoda, Toru Tanaka, Yuko Watanabe, Yukie Yamaguchi, Yoshiko Mizukawa, Yukihiko Kato, Natsumi Hama, Riichiro Abe, Kazuteru Noguchi, Kiyoshi Matsui, Hiroyuki Niihara, Takemi Otsuki, Yurika Shimizu, Tatsuo Ito, Eisuke Inoue, Kaoru Kubota

    The Journal of dermatology   52 ( 6 )   1015 - 1030   2025.3

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    The concept of immune reconstitution inflammatory syndrome (IRIS) has recently been applied to patients with non-HIV infection with immune fluctuations. However, quantitative criteria to diagnose non-HIV IRIS have not been established. Similarly, immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) are also caused by immune fluctuations. No study has directly compared the immunological indicators of non-HIV IRIS and irAEs. Thus, we investigated whether irAEs can be included in non-HIV IRIS. We aimed to search for diagnostic biomarkers for non-HIV IRIS and to compare the immunopathogenesis of non-HIV IRIS and irAEs based on immunological indicators. We selected drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) and dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid (DPP4i-BP) as underlying diseases of non-HIV IRIS. Blood cell counts, cytokines or chemokines, and herpesvirus-derived DNA in saliva were quantified and compared between IRIS/irAE-positive and -negative as well as non-HIV IRIS and irAEs groups. The DPP4i-BP group had a shorter incubation time to IRIS onset than the DIHS/DRESS group; the irAE group had a longer incubation time than the DIHS/DRESS group. A higher neutrophil-to-lymphocyte ratio and serum interferon gamma inducible protein 10 levels could be potential biomarkers of IRIS and irAEs onset; however, no useful cut-off values for diagnosis were indicated. Meanwhile, the transition of  regulatory T cells (Tregs) from the baseline to the onset of IRIS or irAEs differed between IRIS in DIHS/DRESS and irAEs. Only the DIHS/DRESS group showed an increase of Epstein-Bar virus (EBV) (p < 0.0001) and human herpesvirus 6 (p < 0.05) positivity in saliva at the onset of IRIS compared to that at baseline. Although non-HIV IRIS and irAEs have a small number of common immunological indicators, the dynamics of Tregs, cytokines, or chemokines and positivity of herpesvirus-derived DNA in saliva differ, suggesting that non-HIV IRIS and irAEs should remain as separate entities.

    DOI： 10.1111/1346-8138.17706

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  • Painful nodule on the left fifth finger

    Chihiro Hishinuma, Yuko Watanabe, Hideyuki Ishikawa, Atsuhito Nakazawa, Yukie Yamaguchi

    JEADV Clinical Practice   2025.3

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    DOI： 10.1002/jvc2.583

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  • Enhancing clinical reasoning skills in medical students through team-based learning: a mixed-methods study. International journal

    Kosuke Ishizuka, Kiyoshi Shikino, Naoko Takada, Yohei Sakai, Yasushi Ototake, Takashi Kobayashi, Tetsuhiko Inoue, Ryosuke Jikuya, Yuri Iwata, Kenichi Nishimura, Ryusuke Yoshimi, Yasufumi Oi, Yuko Watanabe, Yu Togashi, Fumihiro Ogawa, Daisuke Sano, Takeshi Asami, Yuichi Imai, Ichiro Takeuchi, Kengo Funakoshi, Mitsuyasu Ohta, Masahiko Inamori, Akihiko Kusakabe

    BMC medical education   25 ( 1 )   221 - 221   2025.2

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    BACKGROUND: Clinical reasoning skills are essential competencies for medical students; therefore, effective, evidence-informed teaching methodologies are needed worldwide. This study investigated the benefits of team-based learning (TBL) for developing the skills in medical students. METHOD: A mixed-methods sequential explanatory design was used to investigate the effectiveness of TBL for medical students acquiring clinical reasoning skills. The study participants comprised 92 fourth-year medical students at Yokohama City University School of Medicine, participating in TBL sessions that covered 10 major clinical symptoms identified in the core curriculum. Each session lasted 240 min. Before and after the educational intervention, student performance was measured using the script concordance test (SCT) on a 30-point scale, and self-assessed clinical reasoning competency was measured on a 7-point Likert scale. The SCT included pre-tests and post-tests of 30 questions each, with students randomly assigned to one of two test sets. Following the quantitative evaluation, a qualitative content analysis was conducted to explore the advantages of TBL for learning clinical reasoning skills. The analytic categories were set according to the six levels of Fink's taxonomy of significant learning. RESULT: Student performance improved significantly after the educational intervention (A test: 16.5 ± 4.4 to 18.7 ± 4.5, p = 0.019; B test: 18.1 ± 3.7 to 19.8 ± 4.4, p = 0.028). After the educational intervention, self-assessed clinical reasoning competency was significantly higher in "recalling appropriate physical examination and tests on clinical hypothesis generation," "recalling appropriate differential diagnosis from patient's chief complaint," "verbalizing points that fit/don't fit the recalled differential diagnosis appropriately," "verbalizing and reflecting appropriately on own mistakes," "selecting keywords from the whole aspect of the patient," and "practicing the appropriate clinical reasoning process" (all p < 0.001). The content analysis extracted 23 subcategories and 233 codes of the advantages of TBL for learning clinical reasoning skills, covering all six levels of Fink's taxonomy of significant learning: Foundational knowledge (7 codes); Application (40 codes); Integration (69 codes); Human dimension (89 codes); Caring (8 codes); and Learning how to learn (20 codes). CONCLUSION: This study demonstrates that TBL supports the acquisition of critical clinical reasoning skills among medical students.

    DOI： 10.1186/s12909-025-06784-w

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  • Regarding response to Yamaguchi et al's "Anti-SS-A antibody is a potential predictor of severe Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective cohort study". International journal

    Yuko Watanabe, Yukie Yamaguchi

    Journal of the American Academy of Dermatology   92 ( 3 )   e73-e74   2024.11

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  • Retrospective study of the clinical significance of the neutrophil-to-lymphocyte ratio in 79 patients with palmoplantar pustulosis. International journal

    Tomoya Watanabe, Yuko Watanabe, Chika Asai, Miho Asami, Naoko Takamura, Yukie Yamaguchi

    The Journal of dermatology   51 ( 9 )   1208 - 1215   2024.9

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

    Palmoplantar pustulosis (PPP) is a chronic relapsing inflammatory skin disease characterized by multiple vesicles, pustules, and erythematous plaques on the palms and soles. The exacerbation of PPP is strongly associated with focal infections, such as tonsillitis, dental infections, and sinusitis, in Japan. Recently, the neutrophil-to-lymphocyte ratio (NLR) has been widely used as a convenient and useful marker for clinical conditions and various diseases; however, an association between PPP and NLR has not yet been established. We retrospectively analyzed 79 patients with PPP from our hospital to evaluate the clinical significance of the NLR. The average NLR value in patients with PPP was significantly higher than that in healthy controls (2.30 ± 1.02 vs 1.69 ± 0.45, P < 0.001). A comparative analysis of patients with PPP with and without infectious complications showed that there was a statistical difference in the NLR between patients with PPP with and without focal infections, whereas no significant difference was found for metal allergy, smoking, and pustulotic arthro-osteitis. Multivariate analysis indicated that the NLR was significantly associated with focal infections (odds ratio = 18.38, 95% confidence interval 3.86-87.35, P < 0.001). The NLR was also significantly correlated with C-reactive protein levels (P = 0.013, r = 0.2857). Interestingly, after symptom improvement, the NLR significantly decreased from the baseline levels. Furthermore, statistical analysis using the Youden's index revealed that an NLR of 2.28 or higher was associated with the risk of any focal infections in patients with PPP. These results suggest that the NLR has potential applications as a biomarker of the presence of focal infections in patients with PPP.

    DOI： 10.1111/1346-8138.17272

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  • Improvement of the Ocular Prognosis of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A National Survey in Japan. International journal

    Miho Kojima, Hiroki Mieno, Mayumi Ueta, Mitsuko Nakata, Satoshi Teramukai, Yuma Sunaga, Hirotaka Ochiai, Masafumi Iijima, Akatsuki Kokaze, Hideaki Watanabe, Michiko Kurosawa, Hiroaki Azukizawa, Hideo Asada, Yuko Watanabe, Yukie Yamaguchi, Michiko Aihara, Zenro Ikezawa, Yoshiko Mizukawa, Manabu Ohyama, Tetsuo Shiohara, Natsumi Hama, Riichiro Abe, Hideo Hashizume, Saeko Nakajima, Takashi Nomura, Kenji Kabashima, Mikiko Tohyama, Koji Hashimoto, Hayato Takahashi, Hiroyuki Niihara, Eishin Morita, Hirohiko Sueki, Shigeru Kinoshita, Chie Sotozono

    American journal of ophthalmology   267   50 - 60   2024.5

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    PURPOSE: To investigate the incidence and prognostic factors of ocular sequelae in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) cases arising between 2016 and 2018 in Japan, and compare the findings with those presented in the previous 2005-2007 survey. DESIGN: Retrospective, national trend survey. METHODS: Dermatologic case report forms (CRFs) (d-CRFs) were sent to 257 institutions that treated at least 1 SJS/TEN case, and 508 CRFs were collected from 160 institutions. Ophthalmologic CRFs (o-CRFs) regarding patient demographic data, onset date, ocular findings (first appearance, day of worst severity, and final follow-up), topical treatment (betamethasone), outcome (survival or death), and ocular sequelae (visual disturbance, eye dryness) were sent to the ophthalmologists in those 160 institutions. The results of this survey were then compared with that of the previous 2005-2007 survey. RESULTS: A total of 240 cases (SJS/TEN: 132/108) were included. The incidence of ocular sequelae incidence was 14.0%, a significant decrease from the 39.2% in the previous survey (SJS/TEN: 87/48). In 197 (82.1%) of the cases, systemic treatment was initiated within 3 days after admission, an increase compared to the previous survey (ie, treatment initiated in 82 [60.7%] of 135 cases). Of the 85 cases with an Acute Ocular Severity Score of 2 and 3, 62 (72.9%) received corticosteroid pulse therapy and 73 (85.9%) received 0.1% betamethasone therapy; an increase compared to the 60.0% and 70.8%, respectively, in the previous survey. Ocular-sequelae-associated risk factors included Acute Ocular Severity Score (P < .001) and specific year in the survey (P < .001). CONCLUSIONS: The ophthalmologic prognosis of SJS/TEN has dramatically improved via early diagnosis, rapid assessment of acute ocular severity, and early treatment.

    DOI： 10.1016/j.ajo.2024.05.011

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  • Association of HLA-A∗11:01, HLA-B∗39:01, and HLA-B∗56:03 with salazosulfapyridine-induced cutaneous adverse drug reactions Reviewed International journal

    Koya Fukunaga, Eri Tsukagoshi, Ryosuke Nakamura, Kayoko Matsunaga, Takeshi Ozeki, Hideaki Watanabe, Akito Hasegawa, Natsumi Hama, Maiko Kurata, Yoshiko Mizukawa, Yuko Watanabe, Yukie Yamaguchi, Hiroyuki Niihara, Eishin Morita, Hideo Asada, Riichiro Abe, Yoshiro Saito, Taisei Mushiroda

    The Journal of Allergy and Clinical Immunology: In Practice   12 ( 5 )   1355 - 1358   2024.4

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    DOI： 10.1016/j.jaip.2024.02.041

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  • Differential Effects of HLA-B∗15:11 and HLA-A∗31:01 on Carbamazepine-Induced Cutaneous Adverse Reactions International journal

    Koya Fukunaga, Eri Tsukagoshi, Maiko Kurata, Yoshiko Mizukawa, Hiroyuki Niihara, Eishin Morita, Yuko Watanabe, Yukie Yamaguchi, Hideaki Watanabe, Saeko Nakajima, Takashi Nomura, Kenji Kabashima, Mikiko Tohyama, Hiroaki Azukizawa, Hideo Asada, Akito Hasegawa, Natsumi Hama, Takeshi Ozeki, Yoichi Mashimo, Akihiro Sekine, Kayoko Matsunaga, Yoichi Tanaka, Ryosuke Nakamura, Riichiro Abe, Taisei Mushiroda, Yoshiro Saito

    Journal of Investigative Dermatology   144 ( 4 )   908 - 911.e7   2024.4

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.jid.2023.09.282

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  • Granulomatous reaction as a postherpetic isotopic response after primary varicella infection in a healthy adult

    Tomoki Niimura, Yuko Watanabe, Michiko Aihara, Yukie Yamaguchi

    Journal of Cutaneous Immunology and Allergy   2023.10

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    DOI： 10.1002/cia2.12306

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  • Anti-SS-A antibody is a potential predictor of severe Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective cohort study. International journal

    Yuko Watanabe, Tomoya Watanabe, Yukie Yamaguchi

    Journal of the American Academy of Dermatology   90 ( 2 )   385 - 387   2023.9

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    DOI： 10.1016/j.jaad.2023.09.061

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  • Development and validation of a novel score to predict mortality in Stevens-Johnson syndrome and toxic epidermal necrolysis: CRISTEN. Reviewed International journal

    Natsumi Hama, Yuma Sunaga, Hirotaka Ochiai, Akatsuki Kokaze, Hideaki Watanabe, Michiko Kurosawa, Hiroaki Azukizawa, Hideo Asada, Yuko Watanabe, Yukie Yamaguchi, Michiko Aihara, Yoshiko Mizukawa, Manabu Ohyama, Hideo Hashizume, Saeko Nakajima, Takashi Nomura, Kenji Kabashima, Mikiko Tohyama, Akito Hasegawa, Hayato Takahashi, Hiroki Mieno, Mayumi Ueta, Chie Sotozono, Hiroyuki Niihara, Eishin Morita, Marie-Charlotte Brüggen, Iris Motro Feingold, Marc G Jeschke, Roni P Dodiuk-Gad, Eva Maria Oppel, Lars E French, Wei-Ti Chen, Wen-Hung Chung, Chia-Yu Chu, Hye-Ryun Kang, Saskia Ingen-Housz-Oro, Kazutoshi Nakamura, Hirohiko Sueki, Riichiro Abe

    J. Allergy Clin. Immunol. Pract.   2023.7

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    BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However previous prediction scores have been based on data of blood tests. OBJECTIVE: This study aimed to present a novel score that predicts mortality in patients with SJS/TEN in the early stages, based on only clinical information. METHODS: We retrospectively evaluated 382 patients with SJS/TEN in development study. A clinical risk score for TEN (CRISTEN) was created according to the association of potential risk factors with death. We calculated the sum of these risk factors using CRISTEN, and this was validated in a multinational survey of 416 patients and was compared to previous scoring systems. RESULTS: The significant risk factors for death in SJS/TEN comprised of 10 items, including patients' age of ≥65 years, ≥10% BSA involvement, the use of antibiotics as culprit drugs, the use of systemic corticosteroid therapy prior to the onset, and mucosal damage affecting ocular, buccal, and genital mucosa. Renal impairment, diabetes, cardiovascular disease, malignant neoplasm, and bacterial infection were included as underlying diseases. The CRISTEN model showed good discrimination (AUC=0.884) and calibration. In the validation study, the AUC was 0.827, which was statistically comparable to those of previous systems. CONCLUSION: A scoring system based on only clinical information was developed to predict mortality in SJS/TEN and was validated in an independent multinational study. CRISTEN may predict individual survival probabilities and direct the management and therapy of patients with SJS/TEN.

    DOI： 10.1016/j.jaip.2023.07.001

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  • Post-orgasmic illness syndrome with positive intradermal test for autologous semen. International journal

    Hisho Kawamura, Tomoya Watanabe, Hitomi Yamamura, Saori Sano, Miwa Kanaoka, Yuko Watanabe, Mitsuyasu Ohta, Yukie Yamaguchi

    The Journal of dermatology   50 ( 7 )   951 - 955   2023.7

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    Post-orgasmic illness syndrome (POIS) is a rare disease characterized by flu-like symptoms persisting for 2-7 days after ejaculation. POIS has been chiefly attributed to allergic reactions to autologous seminal plasma. However, the exact pathophysiology remains unclear, and there is no effective treatment. We present the case of a 38-year-old man with a 10-year history of recurrent episodes of flu-like symptoms of 1-week duration after ejaculation. The patient was diagnosed with irritating bowel syndrome because of fatigue, myalgia, and lateral abdominal pain. After starting infertility treatment and increasing the frequency of intercourse with his wife, the patient noticed these symptoms after ejaculation. Based on these episodes and symptoms, POIS was suspected. To diagnose POIS, a skin prick test and an intradermal test were performed using his seminal fluid, with the latter yielding a positive result. The patient was diagnosed with POIS, and treatment with antihistamines was continued. Due to its rarity, POIS is often underdiagnosed and underreported; however, the skin test can be a valid diagnostic tool. In this case, the intradermal test result was positive according to the broadly accepted criteria for POIS. Although quality of life is often severely affected in patients with POIS, a lack of a clear understanding of the pathogenesis of POIS prevents early diagnosis. To make diagnoses earlier, it is undoubtedly important to take a detailed medical history and perform skin allergy tests, although the latter requires further validation.

    DOI： 10.1111/1346-8138.16762

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  • Eyelid and Vaginal Adhesions as Severe Sequelae of Toxic Epidermal Necrolysis. International journal

    Kaori Suzuki, Yuko Watanabe, Yuichi Imai, Yukie Yamaguchi

    Cureus   15 ( 7 )   e41496   2023.7

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    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are mucocutaneous diseases featured by severe sequelae and high mortality rates. In addition to ocular involvement, gynecological involvement is often observed in patients with TEN with possible occurrence of partial or complete adhesions of the labia majora, labia minora, and vaginal walls as severe sequelae. Although the gynecological sequelae of TEN severely affect patients' quality of life, there is a lack of awareness among medical professionals. Moreover, preventive measures and the effectiveness of treatment have not yet been fully verified. Herein, we describe a case of TEN with severe sequelae of eyelid and vaginal adhesions.

    DOI： 10.7759/cureus.41496

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  • Stevens-Johnson症候群と鑑別を要したチオテパによる皮膚障害の1例

    鈴木 毅, 渡邉 裕子, 渡邊 友也, 高村 直子, 山口 由衣, 辻本 信一

    日本皮膚科学会雑誌   133 ( 4 )   703 - 703   2023.4

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

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  • Serum levels of C-C motif chemokine ligand 2 and interleukin-8 as possible biomarkers in patients with toxic epidermal necrolysis accompanied by acute respiratory distress syndrome. International journal

    Tomoya Watanabe, Yuko Watanabe, Noriko Ikeda, Michiko Aihara, Yukie Yamaguchi

    The Journal of dermatology   2022.11

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    Toxic epidermal necrolysis (TEN) is a fatal cutaneous adverse reaction that occasionally affects multiple organs. Acute respiratory distress syndrome (ARDS) is a rare complication that can cause rapid and potentially fatal pulmonary dysfunction. However, the mechanisms underlying TEN-induced ARDS remain unknown. This retrospective single-center study aimed to identify potential biomarkers for predicting ARDS onset in TEN patients. Pre-treatment serum samples were collected from 16 TEN patients and 16 healthy controls (HCs). The serum levels of cytokines/chemokines were determined using the Luminex Assay Human Premixed Multi-analyte kit. The expression levels of cytokines and chemokines in the skin were examined via immunohistochemistry. The serum levels of C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-6, and IL-8 were significantly higher in TEN patients with ARDS than in those without ARDS and in HCs, whereas those of CCL2 and IL-8 were not significantly different between TEN patients without ARDS and HCs. There was no significant difference in CCL2 and IL-8 expression in the skin between TEN patients with and without ARDS. Interestingly, there were no significant differences in the cytokine/chemokine levels between TEN and other organ damage, other than ARDS and TEN without any organ damage. We further analyzed the changes in cytokine/chemokine levels before and after treatment in two TEN patients with ARDS. CCL2, IL-6, and IL-8 levels decreased after systemic treatment compared to their baseline levels before treatment at an early stage. These results suggest that IL-8 and CCL2 may be involved in the pathogenesis of TEN-induced ARDS and have potential application as predictive markers for ARDS onset.

    DOI： 10.1111/1346-8138.16647

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  • Risks of malignancies among patients with psoriasis: A cohort study of 360 patients. International journal

    Tomoya Watanabe, Yuko Watanabe, Chika Asai, Miho Asami, Yukihiko Watanabe, Yusuke Saigusa, Yukie Yamaguchi

    The Journal of dermatology   2022.11

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    Psoriasis is a systemic, chronic, immunologically-mediated disease affecting approximately 2%-4% of the worldwide population. It is well known that psoriasis is associated with several comorbidities such as metabolic syndrome, cardiovascular disease, and malignancy. Although meta-analyses and large prospective cohort studies have shown an increased risk of malignancies in patients with psoriasis worldwide, an association between psoriasis and malignancy onset has not yet been established in Japan. We retrospectively analyzed 360 patients with psoriasis at our hospital to evaluate the incidence and types of malignancies in these patients. The incidence rate of malignancy was 14.4% (52/360). Colorectal cancer was the most commonly associated malignancy (20.9%), followed by skin cancer (16.4%), gastric cancer (10.4%), and lung cancer (10.4%). The calculated age- and sex-standardized incidence ratio of malignancies was 1.235 (95% CI 0.952-1.601) which indicated that the malignancy rate was higher in patients with psoriasis than in the general population, although the difference was not statistically significant. Furthermore, the multivariate analysis revealed increased risk of malignancy in males (HR = 3.15; 95% CI 1.381-7.187; p < 0.001), psoriasis onset at older age (HR = 1.08; 95% CI 1.058-1.111; p < 0.01), and psoriatic erythroderma (HR = 4.44; 95% CI 1.354-14.581; p < 0.05). We also observed that treatment with biological agents tends to reduce the risk of developing malignancy; however, no statistical significance was found. These results suggest that periodic screening for malignancy should be recommended in patients with psoriasis having these risk factors and in those with poorly controlled psoriatic inflammation.

    DOI： 10.1111/1346-8138.16644

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  • Efficacy and safety of apremilast and phototherapy versus phototherapy only in psoriasis vulgaris. International journal

    Akimichi Morita, Yukie Yamaguchi, Chiharu Tateishi, Kyoko Ikumi, Aya Yamamoto, Haruna Nishihara, Daisuke Hayashi, Yukihiko Watanabe, Yuko Watanabe, Ayano Maruyama, Koji Masuda, Daisuke Tsuruta, Norito Katoh

    The Journal of dermatology   49 ( 12 )   1211 - 1220   2022.9

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    Phototherapy and apremilast (oral phosphodiesterase-4 inhibitor) are well-known in the treatment of moderate to severe psoriasis vulgaris. However, current evidence on the efficacy and safety of their combination is not sufficient. This multicenter, randomized controlled study compared the efficacy and safety between phototherapy as monotherapy and phototherapy and apremilast as combination therapy in patients with psoriasis vulgaris. Patients with moderate to severe psoriasis vulgaris were assigned to combination (n = 29) and monotherapy (n = 13) groups. All patients underwent an 8-week phototherapy regimen comprising irradiation with narrowband UV-B. The patients in the combination group were also administered 10 mg to 60 mg of oral apremilast. We evaluated the improvement percentage based on the Psoriasis Area and Severity Index (PASI) score from baseline to week 8. Additionally, we evaluated the percentage of patients who achieved ≥75% improvement; changes in body surface area (BSA) and scores of EuroQol 5-dimensions 5-level, Dermatology Life Quality Index, and visual analog scale for pruritis from baseline to 4 and 8 weeks; and adverse events. Compared with the monotherapy group, the combination group had significantly lower PASI scores at 4 and 8 weeks and more patients who achieved a PASI score improvement of ≥75% at 8 weeks. Both groups exhibited a significant decrease in BSA; at 8 weeks, no significant difference was observed between the two groups, although the combination group tended toward a greater reduction in BSA. The intergroup differences in the changes at the three time points were not significant. Adverse events were more frequent in the combination group than in the monotherapy group. Our findings suggest that an 8-week combined apremilast and phototherapy regimen may not be adequate in patients for improvements in their subjective assessment of psoriasis, and longer treatment periods may be necessary.

    DOI： 10.1111/1346-8138.16566

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  • 皮内テストにより確定診断が得られたオーガズム後症候群の1例

    川村 飛翔, 渡邊 友也, 山村 一美, 佐野 沙織, 金岡 美和, 渡邉 裕子, 山口 由衣, 太田 光泰

    日本皮膚科学会雑誌   132 ( 10 )   2369 - 2369   2022.9

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  • Abnormal inflammatory traits and downregulated caveolin-1 expression in monocytes of psoriasis patients may be associated with psoriatic inflammation and atherosclerosis. International journal

    Miho Asami, Yasushi Ototake, Naoko Takamura, Yuko Watanabe, Michiko Aihara, Yukie Yamaguchi

    Journal of dermatological science   107 ( 2 )   65 - 74   2022.8

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    BACKGROUND: Monocytes and macrophages are implicated in inflammation and atherosclerosis, whereas monocytes are involved in psoriasis lesion formation. We previously reported a psoriatic inflammation-associated significant decrease in the membrane protein caveolin-1 (CAV-1) in psoriasis patient monocytes. However, the phenotype of circulating monocytes and their macrophage differentiation in psoriasis patients remain unclear. OBJECTIVE: We sought to clarify circulating monocyte and monocyte-derived macrophage (MDM) phenotypes in psoriasis patients with and without comorbidities. METHODS: Thirty-one patients with psoriasis vulgaris and 28 control subjects were included. Surface macrophage markers and inflammatory status were examined in circulating monocytes and MDMs from both groups. Expression of CD36, which mediates macrophage uptake of oxidized low-density lipoprotein (oxLDL), was evaluated in these cells. CAV-1-silenced monocytes were differentiated into macrophages to investigate the effects of CAV-1 downregulation on psoriatic inflammation and atherosclerosis. RESULTS: Macrophage surface markers were detectable in circulating monocytes. A significant M1 shift was detected in monocytes and MDMs in psoriasis patients, including those without cardiovascular disease risk factors, as compared to controls. MDMs of psoriasis patients had more CD36-expressing cells, which are associated with atherosclerosis risk. Additionally, CAV-1-silencing in monocytes increased the likelihood of M1-biased macrophage differentiation and increased pro-inflammatory cytokine production. CONCLUSIONS: Monocytes from psoriasis patients were more likely to differentiate into M1-dominant macrophages, correlating with inflammatory status and CAV-1 expression. These aberrant inflammatory monocytes not only contribute to psoriatic inflammation by producing psoriatic cytokines, but also have a phenotype that could increase atherosclerosis risk by uptake of oxLDL and formation of foam cells.

    DOI： 10.1016/j.jdermsci.2022.07.003

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  • Case of hyperpigmentation associated with the use of Morinda citrifolia (noni)

    Yuto Mizuno, Yuko Watanabe, Michiko Aihara, Yukie Yamaguchi

    Journal of Cutaneous Immunology and Allergy   2022.8

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    DOI： 10.1002/cia2.12233

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  • Risk factors for sepsis and effects of pretreatment with systemic steroid therapy for underlying condition in SJS/TEN patients: Results of a nationwide cross-sectional survey in 489 Japanese patients. International journal

    Yuma Sunaga, Natsumi Hama, Hirotaka Ochiai, Akatsuki Kokaze, Eun Seon Lee, Hideaki Watanabe, Michiko Kurosawa, Hiroaki Azukizawa, Hideo Asada, Yuko Watanabe, Yukie Yamaguchi, Michiko Aihara, Yoshiko Mizukawa, Manabu Ohyama, Riichiro Abe, Hideo Hashizume, Saeko Nakajima, Takashi Nomura, Kenji Kabashima, Mikiko Tohyama, Hayato Takahashi, Hiroki Mieno, Mayumi Ueta, Chie Sotozono, Hiroyuki Niihara, Eishin Morita, Hirohiko Sueki

    Journal of dermatological science   107 ( 2 )   75 - 81   2022.7

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    BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). Sepsis has been shown to be the main cause of death in SJS/TEN. The European SCAR study reported that 14.8 % of SJS/TEN patients were receiving systemic steroid therapy for their underlying condition prior to onset. However, it remained unclear whether this factor affected the mortality rate. OBJECTIVE: This study was performed to identify risk factors for sepsis in SJS/TEN patients. In addition, we compared patients who had and had not received systemic steroid therapy for their underlying condition. METHODS: A primary survey regarding the numbers of SJS/TEN patients between 2016 and 2018 was sent to 1205 institutions in Japan. A secondary survey seeking more detailed information was sent to institutions reporting SJS/TEN patients. We analyzed 315 SJS patients and 174 TEN patients using a logistic regression model, Wilcoxon's rank-sum test, χ2 test, and Fisher's exact test. RESULTS: Significant risk factors for sepsis included TEN, diabetes, and intensive care unit (ICU) admission. The mortality rate was significantly higher among patients with sepsis. Patients who had received systemic steroid therapy had a lower incidence of fever, and showed a higher mortality rate. CONCLUSION: Based on a nationwide epidemiological survey of SJS/TEN in Japan, we identified risk factors for sepsis and found that patients who had received steroid therapy for their underlying condition had a lower incidence of fever and a higher mortality rate.

    DOI： 10.1016/j.jdermsci.2022.07.004

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  • Drug allergy and non-HIV immune reconstitution inflammatory syndrome. International journal

    Hirohiko Sueki, Yuko Watanabe, Seiko Sugiyama, Yoshiko Mizukawa

    Allergology international : official journal of the Japanese Society of Allergology   71 ( 2 )   185 - 192   2022.2

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    Non-HIV immune reconstitution inflammatory syndrome (non-HIV IRIS) is associated with the recovery from an immunocompromised condition. It is defined as inflammatory disorders caused by antigens, including drugs or pathogenic microorganisms present prior to immune recovery, or by the exacerbation of an inflammatory disorder that was already present. Drug-induced hypersensitivity syndrome is a prototype of IRIS, and the pathophysiology of non-HIV IRIS can be recognized in several disorders treated with corticosteroids, immunosuppressants, molecular-targeted drugs, TNF-α antibody drugs, immune checkpoint inhibitors, and dipeptidyl peptidase-4 inhibitors. This review focuses on the relationship between the immune mechanism of non-HIV IRIS and drug allergies, especially severe drug eruption. The antigen recognition mechanism in drug allergy varies depending on the clinical type and the causative drug. The p-i concept is the main mechanism in severe drug eruption such as Stevens-Johnson syndrome/toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Lymphocytes activated by an antigen other than a drug, such as a virus, can also develop drug allergy by the loose binding of drugs with immune receptors of T cells or human leukocyte antigen. Therefore, fluctuations in the immune environment affect the onset of severe drug eruption. Novel agents that cause major changes in immunity have been marketed mainly for autoimmune diseases and malignant tumors; therefore, it is necessary to consider their effects when treating severe drug eruptions. Moreover, although a list of diagnostic criteria for this syndrome has been drafted, predictive and diagnostic biomarkers for this syndrome needs to be urgently developed.

    DOI： 10.1016/j.alit.2021.12.002

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  • Drug allergy and autoimmune diseases. International journal

    Yuko Watanabe, Yukie Yamaguchi

    Allergology international : official journal of the Japanese Society of Allergology   71 ( 2 )   179 - 184   2022.2

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    Systemic autoimmune diseases are reportedly associated with a high frequency of drug allergies. In particular, systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and adult-onset Still's disease (AOSD) have recently drawn attention. Based on previous reports, drug allergies have been reported in 17.1-63%, 7-40.1%, and 17.6-54% of patients with SS, SLE, and AOSD patients, respectively. Antimicrobial agents, including sulfa drugs and nonsteroidal anti-inflammatory drugs, are the most common causative agents of drug allergies. However, few studies have examined in detail the relationship between drug eruptions, a major symptom of drug allergy, and systemic autoimmune diseases, and their actual status remains unclear. These autoimmune diseases commonly exhibit a diverse range of skin manifestations in the course of these diseases, rendering it may be difficult to determine whether it is a true drug eruption. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), a fatal, severe drug eruption, has also been associated with autoimmune diseases. The development of SS-like symptoms after SJS/TEN onset and high prevalence of anti-SS-A antibodies in SJS/TEN are intriguing observations. Although the presence of SLE is known to be a risk factor for SJS/TEN, common pathological conditions, such as excessive immune status, abnormal function of regulatory T cells, and neutrophil extracellular traps in autoimmune diseases such as SS and SLE, are potentially involved in the development of drug eruptions.

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  • A pediatric case of Stevens-Johnson syndrome with acute liver failure, resulting in liver transplantation. International journal

    Michiru Totsuka, Tomoya Watanabe, Naoko Takamura, Yuko Watanabe, Takafumi Kumamoto, Yasushi Honda, Masato Yoneda, Satoru Saito, Shoji Yamanaka, Michiko Aihara

    The Journal of dermatology   48 ( 9 )   1423 - 1427   2021.5

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    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are fatal adverse skin reactions characterized by high fever, epidermal detachment, and mucositis. It is well known that SJS/TEN occasionally affects various organs, leading to permanent damage and death in some patients. Although acute liver dysfunction is a relatively common complication of SJS/TEN, severe acute liver dysfunction requiring liver transplantation is rare. We present the case of a 14-year-old girl with SJS complicated by severe and rapidly progressive liver dysfunction, specifically, acute liver failure (ALF) requiring liver transplantation. A lymphocyte transformation test showed positive results for acetaminophen and cefdinir. Furthermore, human leukocyte antigen (HLA) genotyping revealed the presence of the HLA-A*02:06 genotype, which is reported to be strongly associated with acetaminophen-related SJS/TEN with severe ocular complications. These results suggested that our patient may have presented with acetaminophen-induced SJS complicated by ALF, but no ocular complications. This is the first report of a pediatric patient with SJS who required liver transplantation. In rare instances, severe liver dysfunction requiring liver transplantation should be considered as a possible complication of SJS/TEN.

    DOI： 10.1111/1346-8138.15963

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  • Mortality and risk factors on admission in toxic epidermal necrolysis: A cohort study of 59 patients. International journal

    Tomoya Watanabe, Hirofumi Go, Yusuke Saigusa, Naoko Takamura, Yuko Watanabe, Yumiko Yamane, Michiru Totsuka, Hideyuki Ishikawa, Kazuko Nakamura, Setsuko Matsukura, Takeshi Kambara, Shunsuke Takaki, Yukie Yamaguchi, Michiko Aihara

    Allergology international : official journal of the Japanese Society of Allergology   70 ( 2 )   229 - 234   2021.4

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    BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening disorders characterized by widespread epidermal necrosis of the skin and mucosa. The severity-of-illness scoring system for TEN (SCORTEN) was widely used since 2000 as a standard prognostic tool consisting of seven clinical values. METHODS: To evaluate the prognosis using current treatments and risk factors for mortality, we retrospectively analyzed 59 cases of TEN, including SJS/TEN overlap treated in two university hospitals from January 2000 to March 2020. RESULTS: The mortality rate of TEN was 13.6% (8/59). All patients treated with high-dose steroid administration in combination with plasma exchange and/or immunoglobulin therapy recovered. Logistic regression analysis showed nine clinical composite scores, namely: heart rate (≧120 bpm), malignancy present, percentage of body surface area with epidermal detachment (>10%), blood urea nitrogen (>28 mg/dL), serum bicarbonate level (<20 mEq/L), serum glucose level (>252 mg/dL), age (≧71 years), the interval between disease onset and treatment initiation at the specialty hospital (≧8 days), and respiratory disorder within 48 h after admission. The receiver operating characteristic curves confirmed a high potential for predicting the prognosis of TEN. CONCLUSIONS: Recent developments in treatment strategies have contributed to the improved prognosis of TEN patients. A modified severity scoring model composed of nine scores may be helpful in the prediction of TEN prognosis in recent patients. Further large-scale studies are needed to confirm mortality findings to improve prognostication in patients with TEN.

    DOI： 10.1016/j.alit.2020.11.004

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  • Pork-cat syndrome caused by ingestion of beef intestines in an 8-year-old child. International journal

    Nobuko Sagawa, Naoko Inomata, Kaori Suzuki, Saori Sano, Yuko Watanabe, Michiko Aihara

    Allergology international : official journal of the Japanese Society of Allergology   70 ( 3 )   395 - 397   2021.1

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  • The nationwide epidemiological survey of Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan, 2016-2018. International journal

    Yuma Sunaga, Michiko Kurosawa, Hirotaka Ochiai, Hideaki Watanabe, Hirohiko Sueki, Hiroaki Azukizawa, Hideo Asada, Yuko Watanabe, Yukie Yamaguchi, Michiko Aihara, Yoshiko Mizukawa, Manabu Ohyama, Natsumi Hama, Riichiro Abe, Hideo Hashizume, Saeko Nakajima, Takashi Nomura, Kenji Kabashima, Mikiko Tohyama, Hayato Takahashi, Hiroki Mieno, Mayumi Ueta, Chie Sotozono, Hiroyuki Niihara, Eishin Morita, Akatsuki Kokaze

    Journal of dermatological science   100 ( 3 )   175 - 182   2020.12

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    BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). The first national epidemiological survey of SJS/TEN was carried out in 2008. We conducted a new survey to identify changes from the previous survey. OBJECTIVE: The present survey aimed to estimate the number of SJS/TEN patients in Japan between 2016 and 2018 (primary survey) and to clarify clinical epidemiological profiles (secondary survey). METHODS: A primary survey asking for numbers of SJS/TEN patients during the study period was sent to 1205 institutions nationwide. A secondary survey was sent to institutions reporting SJS/TEN patients, seeking detailed information. RESULTS: Yearly prevalence per million was 2.5 for SJS and 1 for TEN. The secondary survey allowed analysis of 315 SJS cases and 174 TEN cases from 160 institutions. Mean age was 53.9 years in SJS, and 61.8 years in TEN. Mortality rate was 4.1 % for SJS and 29.9 % for TEN. In TEN, mean age and mortality rates had increased from the previous survey. The ratio of expected to observed mortality calculated by SCORTEN score was lowest with high-dose steroid therapy (0.40), followed by steroid pulse therapy (0.52). CONCLUSION: The present findings suggest that the mortality rate of TEN has increased because of increases in mean ages of patients and patients with malignant neoplasm as underlying disease. When comparing the ratio of expected mortality to actual mortality, high-dose steroid therapy achieved the greatest reduction in mortality.

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  • A case of toxic epidermal necrolysis associated with apalutamide administration

    Nobuko Sagawa, Yuko Watanabe, Yuto Mizuno, Saki Takahashi, Tomoya Watanabe, Nobuaki Ikeda, Yukie Yamaguchi, Michiko Aihara

    JOURNAL OF CUTANEOUS IMMUNOLOGY AND ALLERGY   3 ( 6 )   134 - 135   2020.12

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    DOI： 10.1002/cia2.12138

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  • HIV-associated psoriasis with fasciitis and arthritis successfully treated using antiretroviral therapy. International journal

    Yukihiko Watanabe, Yukie Yamaguchi, Yuko Watanabe, Miho Asami, Naoko Takamura, Tomoya Watanabe, Hideaki Kato, Michiko Aihara

    The Journal of dermatology   47 ( 11 )   e386-e387   2020.11

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    DOI： 10.1111/1346-8138.15535

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  • Increased level of high mobility group box 1 in the serum and skin in patients with generalized pustular psoriasis. International journal

    Tomoya Watanabe, Yukie Yamaguchi, Yuko Watanabe, Naoko Takamura, Michiko Aihara

    The Journal of dermatology   47 ( 9 )   1033 - 1036   2020.9

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    High-mobility group box 1 (HMGB-1) is a highly abundant pro-inflammatory protein associated with the pathogenesis of inflammatory and autoimmune diseases. HMGB-1 expression level increases in patients with psoriasis vulgaris (PV). However, HMGB-1 expression in patients with generalized pustular psoriasis (GPP) is unknown. In this study, we investigated HMGB-1 expression in GPP. HMGB-1 expression levels were examined in the skin and serum of patients with GPP, PV, atopic dermatitis (AD) and healthy controls (HC) using enzyme-linked immunosorbent assay and immunohistochemistry. The elevation in HMGB-1 expression was significantly higher in GPP patients than in PV, AD and HC patients. In addition, patients with GPP had elevated serum HMGB-1 levels compared with those with AD and HC. Furthermore, serum HMGB-1 levels were significantly decreased after systemic treatment. In the correlation analysis, a significant positive correlation was detected between serum HMGB-1 levels and the Japanese severity score for GPP. HMGB-1 may be involved in the pathogenesis of GPP and can be useful to evaluate disease severity and the effectiveness of GPP treatment.

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  • Toxic epidermal necrolysis accompanied by several immune-related adverse events developed after discontinuation of nivolumab. Reviewed International journal

    Yuko Watanabe, Yukie Yamaguchi, Naoko Takamura, Yukitoshi Takahashi, Michiko Aihara

    European journal of cancer (Oxford, England : 1990)   131   1 - 4   2020.5

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  • Leptin induces interleukin-6 production in keratinocytes via decreased expression of caveolin-1: a possible link between obesity and psoriatic inflammation. Reviewed International journal

    Y Watanabe, Y Yamaguchi, N Takamura, N Komitsu, M Aihara

    The British journal of dermatology   183 ( 4 )   768 - 770   2020.4

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

    It has been reported that obesity may be an aggravating factor for psoriasis. However, its pathological mechanism remains elusive. The adipocyte-derived hormone leptin primarily controls energy homeostasis by regulating appetite and modulates immunity. Strikingly, serum leptin levels are elevated in obese patients and positively correlate with body mass index. Additionally, leptin levels also correlate with severity of psoriasis, and knocking out leptin suppresses imiquimod-induced psoriatic inflammation in mice.

    DOI： 10.1111/bjd.19133

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  • A case of toxic epidermal necrolysis with refractory acute respiratory distress syndrome

    Hideyuki Ishikawa, Yuko Watanabe, Naoko Takamura, Tomoya Watanabe, Yukie Yamaguchi, Michiko Aihara

    JOURNAL OF CUTANEOUS IMMUNOLOGY AND ALLERGY   3 ( 2 )   43 - 44   2020.4

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  • Case of toxic epidermal necrolysis occurring after bone marrow transplantation accompanied by engraftment failure. Reviewed International journal

    Chika Asai, Yuko Watanabe, Junko Mukaijo, Naoko Takamura, Tomoko Okawa, Yukie Yamaguchi, Ayako Matsumura, Kenji Matsumoto, Michiko Aihara

    The Journal of dermatology   46 ( 6 )   540 - 543   2019.6

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    DOI： 10.1111/1346-8138.14913

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  • Case of severe bullous erythema including intertrigo-like eruptions with angioedema induced by pegylated liposomal doxorubicin. Reviewed International journal

    Michiru Totsuka, Yuko Watanabe, Chika Asai, Saki Takahashi, Hideyuki Ishikawa, Naoko Takamura, Mayumi Hagiwara, Michiko Aihara

    The Journal of dermatology   46 ( 6 )   535 - 539   2019.6

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    Pegylated liposomal doxorubicin (PLD) is an anthracycline anticancer agent used in ovarian cancer and a form of doxorubicin enclosed in pegylated liposomes. There are only a few reports on intertrigo-like eruptions caused by PLD. We describe the first case of severe bullous erythema, including intertrigo-like eruptions with angioedema, induced by PLD in Japan. We present the case of a 53-year-old woman who was diagnosed with stage IIIC ovarian cancer. After receiving three cycles of PLD, the patient developed swelling of the upper lip and painful erythema with blisters and erosions on the axilla, upper back, flank and wrists. The patient was diagnosed with angioedema and severe skin lesions, including intertrigo-like eruptions induced by PLD. Although treatment with oral prednisolone and topical steroids was effective against these eruptions, the administration of PLD was discontinued because of its ineffectiveness against the primary disease. Several risk factors, such as obesity, perspiration and racial differences, may contribute toward a severe manifestation such as that seen in our patient. Moreover, our case was the first accompanied by angioedema. The mechanism of coexistence of intertrigo-like eruptions and angioedema is not clear; further studies are required to clarify the pathological mechanism of intertrigo-like eruptions.

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  • Downregulated Caveolin-1 expression in circulating monocytes may contribute to the pathogenesis of psoriasis. Reviewed International journal

    Naoko Takamura, Yukie Yamaguchi, Yuko Watanabe, Miho Asami, Noriko Komitsu, Michiko Aihara

    Scientific reports   9 ( 1 )   125 - 125   2019.1

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    DOI： 10.1038/s41598-018-36767-5

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  • Allergic contact dermatitis caused by 2-hydroxyethyl acrylate in a moisturizing face pack in a handmade acrylic accessory enthusiast. International journal

    Junko Mukaijo, Naoko Inomata, Mai Higashihira, Nao Koh, Yui Togashi, Chika Asai, Yuko Watanabe, Seiichi Kurihara, Michiko Aihara

    Contact dermatitis   79 ( 6 )   383 - 385   2018.12

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    DOI： 10.1111/cod.13088

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  • Elevation of serum squamous cell carcinoma antigen 2 in patients with psoriasis: associations with disease severity and response to the treatment Reviewed

    Y. Watanabe, Y. Yamaguchi, N. Komitsu, S. Ohta, Y. Azuma, K. Izuhara, M. Aihara

    BRITISH JOURNAL OF DERMATOLOGY   174 ( 6 )   1327 - 1336   2016.6

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    DOI： 10.1111/bjd.14426

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  • Retrospective analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in 87 Japanese patients - Treatment and outcome Reviewed

    Yumiko Yamane, Setsuko Matsukura, Yuko Watanabe, Yukie Yamaguchi, Kazuko Nakamura, Takeshi Kambara, Zenro Ikezawa, Michiko Aihara

    ALLERGOLOGY INTERNATIONAL   65 ( 1 )   74 - 81   2016.1

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    DOI： 10.1016/j.alit.2015.09.001

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  • Decreased Expression of Caveolin-1 Contributes to the Pathogenesis of Psoriasiform Dermatitis in Mice Reviewed

    Yukie Yamaguchi, Yuko Watanabe, Tomoya Watanabe, Noriko Komitsu, Michiko Aihara

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   135 ( 11 )   2764 - 2774   2015.11

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    DOI： 10.1038/jid.2015.249

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  • The serum level of HMGB1 (high mobility group box 1 protein) is preferentially high in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms Reviewed

    H. Fujita, S. Matsukura, T. Watanabe, N. Komitsu, Y. Watanabe, Y. Takahashi, T. Kambara, Z. Ikezawa, M. Aihara

    BRITISH JOURNAL OF DERMATOLOGY   171 ( 6 )   1585 - 1588   2014.12

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    DOI： 10.1111/bjd.13162

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  • A Case of Toxic Epidermal Necrolysis Induced by Allopurinol with Human Herpesvirus-6 Reactivation Reviewed

    Yuko Watanabe, Setsuko Matsukura, Yuji Isoda, Akiko Morita, Michiko Aihara, Takeshi Kambara

    ACTA DERMATO-VENEREOLOGICA   93 ( 6 )   731 - 732   2013

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    DOI： 10.2340/00015555-1610

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  • O41-3 アトピー性皮膚炎の入院における教育効果の検討(アトピー性皮膚炎2,口演,第62回日本アレルギー学会秋季学術大会)

    松倉 節子, 中村 和子, 守田 亜希子, 大野 真梨恵, 渡邉 裕子, 磯田 祐士, 相原 道子, 蒲原 毅

    アレルギー   61 ( 9 )   1517 - 1517   2012

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    Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

    DOI： 10.15036/arerugi.61.1517_3

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  • MS14-1 過去8年間に横浜市立大学附属市民総合医療センター皮膚科を受診した薬疹患者の統計的観察(MS14 薬物アレルギー,ミニシンポジウム,第24回日本アレルギー学会春季臨床大会)

    渡邉 裕子, 松倉 節子, 大野 真梨恵, 久田 恭子, 磯田 祐士, 守田 亜希子, 蒲原 毅, 池澤 善郎, 相原 道子

    アレルギー   61 ( 3 )   496 - 496   2012

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  • Therapeutic Effects for Infliximab in Psoriatic Uveitis; Case Report and Review of the Literature in Japan

    Watanabe Yuko, Kambara Takeshi, Sano Saori, Hakuta Amiko, Onoda Masahito, Ikezawa Zenro, Aihara Michiko

    The Japanese Journal of Dermatology   122 ( 9 )   2321 - 2327   2012

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    DOI： 10.14924/dermatol.122.2321

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  • O55-4 横浜市立大学附属市民総合医療センターにおける分子標的薬による薬疹症例の検討(O55 薬物アレルギー2,口演,第61回日本アレルギー学会秋季学術大会)

    松倉 節子, 池澤 優子, 高村 直子, 三津山 信治, 渡邊 裕子, 守田 亜希子, 磯田 祐士, 相原 道子, 蒲原 毅

    アレルギー   60 ( 9 )   1447 - 1447   2011

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    Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

    DOI： 10.15036/arerugi.60.1447_1

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  • O51-4 当科における小麦アレルギー14症例の検討(O51 小麦アレルギー2,口演,第61回日本アレルギー学会秋季学術大会)

    守田 亜希子, 大野 真梨恵, 久田 恭子, 磯田 祐士, 渡邊 裕子, 池澤 優子, 松倉 節子, 蒲原 毅, 相原 道子

    アレルギー   60 ( 9 )   1441 - 1441   2011

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    Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

    DOI： 10.15036/arerugi.60.1441_2

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  • Statistical analysis of Stevens-Johnson syndrome caused by Mycoplasma pneumonia infection in Japan Reviewed

    Yuko Kunimi, Yuko Hirata, Michiko Aihara, Yuko Kunimi, Zenro Ikezawa

    Allergology International   60 ( 4 )   525 - 532   2011

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

    DOI： 10.2332/allergolint.11-OA-0309

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  • Drug-induced hypersensitivity syndrome associated with a marked increase in anti-paramyxovirus antibody titers in a scleroderma patient. International journal

    Taio Naniwa, Shinji Maeda, Hiroo Sawada, Yuko Watanabe, Tomoyo Osawa, Yoshihito Hayami, Shogo Banno, Akimichi Morita, Ryuzo Ueda

    Allergology international : official journal of the Japanese Society of Allergology   56 ( 3 )   303 - 8   2007.9

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MISC

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Awards

  • YCU Frontier Research Fellow

    2025.1  

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  • UCB Research Grant Award 2024

    2024.8  

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  • 優秀演題賞 銅賞

    2020.12   日本皮膚免疫アレルギー学会  

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Research Projects

  • 乾癬併存症におけるCaveolin-1を介した病態的関与と発現制御

    Grant number：23K07789  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    山口 由衣, 渡邊 友也, 渡邉 裕子, 奥山 朋子

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • Significance of anti-SS-A antibody in Stevens-Johnson syndrome and toxic epidermal necrolysis

    Grant number：23K15289  2023.4 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • 重症薬疹の病態におけるγ-chain の役割

    Grant number：19K17779  2019.4 - 2023.3

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    渡邉 裕子

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    Stevens-Johnson症候群(SJS)および中毒性壊死症(TEN)の患者血清を用いてγ-chain subunit値をELISA測定したところ、血清γ-chain subunit値は健常人コントロール群および通常の薬疹群と比較してSJS/TEN患者で有意に高く、特により重症なTEN患者で高値であった。臨床的特徴と血清γ-chain subunit値の解析では、SJS/TENの重症度と血清γ-chain subunit値が相関することが明らかとなった。SJS/TENの後遺症・死亡といった予後不良歴では、予後良好例と比較してγ-chain subunit値が有意に高値であった。また、皮疹の改善に伴い血清γ-chain subunit値も低下することから重症度や病勢のバイオマーカーとして有用な可能性が示唆された。SJS/TEN患者の皮膚組織においても、健常人と比較してSJS/TEN患者の表皮ではγ-chain subunitが有意に強く発現していることが明らかとなった。現在、in vitroの研究として、プライマリーケラチノサイトを用いて、γ-chain subunitおよびIL-2ファミリーサイトカインの共刺激実験を含むγ-chain subunitの機能実験を行っている。その他の細胞障害性因子との相互作用についても検討中である。健常人から採取したPBMCを用いた、γ-chain subunitの機能解析を準備中である。

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Social Activities

  • 神奈川乾癬友の会 相談医

    Role(s)： Advisor,　Organizing member,　Contribution

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