記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although biologic agents have significantly improved therapeutic outcomes for psoriasis, their long-term use can be burdensome for patients due to high costs, parenteral administration, and safety concerns. Consequently, some patients in remission wish to switch to alternative maintenance therapies to reduce this treatment burden. Based on our prior survey, the present prospective, open-label, single-arm, multicenter clinical study focused on patients with plaque psoriasis with or without psoriatic arthritis (PsA) who had achieved remission with biologics but were hesitant to continue this therapy. We evaluated the efficacy and safety of transitioning to apremilast, a phosphodiesterase 4 inhibitor, for maintaining remission. Among 209 patients initially surveyed, 46 were enrolled, and 44 were included in the efficacy analysis. The study cohort comprised 30 males and 16 females, with a mean disease duration of 19.2 years, a mean Psoriasis Area and Severity Index (PASI) score of 0.36, and a mean Dermatology Life Quality Index (DLQI) score of 0.30 at baseline. At 24 weeks, the Kaplan-Meier (KM) median time to relapse was not reached overall; the KM remission-maintenance rate was 63.6% (95% CI, 48.8-76.3) when adverse event related discontinuations were counted as events, and 75.7% (59.7-86.8) when censored. The corresponding restricted mean survival time through 24 weeks was 20.31 and 22.03 weeks, respectively. Patients who maintained remission consistently demonstrated low scores (≤ 1) across PASI, Body Surface Area, DLQI, and American College of Rheumatology components throughout the observation period. A total of 34 adverse events occurred in 23 patients, most commonly diarrhea, vomiting, and headache. All were mild, no serious events were observed, and all resolved without sequelae. In conclusion, for patients with plaque psoriasis with or without PsA who have achieved remission but are concerned about the burdens of long-term biologic therapy, transitioning to apremilast represents an effective and viable strategy.

DOI： 10.1111/1346-8138.17968

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tocilizumab (TCZ) is effective for inducing remission in adult-onset Still's disease (AOSD), but its use may occasionally trigger macrophage activation syndrome (MAS). The rationale for re-introducing TCZ in patients with a history of MAS is not well established. Here, we report a case of successful re-administration of TCZ for an AOSD relapse in a patient with a prior history of MAS during TCZ therapy. A 67-year-old woman, initially treated with TCZ for polyarthritis, developed MAS associated with AOSD. MAS was resolved with glucocorticoid pulse therapy, high-dose glucocorticoids, and cyclosporine A. However, AOSD relapsed during glucocorticoid tapering. Methotrexate, cyclosporine A, and repeated glucocorticoid pulses failed to control the disease. Following another glucocorticoid pulse, TCZ (8 mg/kg weekly) was re-introduced intravenously. This approach allowed successful glucocorticoid tapering and long-term remission. This case highlights the complexities of managing AOSD: while the initial TCZ therapy may have contributed to the onset of MAS, the subsequent re-introduction of TCZ enabled effective disease control and sustained remission.

DOI： 10.1093/mrcr/rxaf020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cutaneous angiosarcoma (cAS) is a rare and aggressive malignant vascular tumor that arises from endothelial cells lining the blood vessels. It can occur in any part of the body, but most commonly, it affects the skin and soft tissues. cAS has a poor prognosis with a 5-year survival rate of only 9%. This review summarizes the current understanding of angiosarcoma pathogenesis, clinical presentation, diagnosis, and treatment approaches. Recent advances in molecular characterization have identified recurrent genetic alterations that may lead to the development of novel targeted therapies. Multidisciplinary management combining surgery, radiation, and systemic therapy remains the mainstay of treatment; however, outcomes remain poor for metastatic disease. Ongoing research into the molecular drivers of cAS and immunotherapeutic approaches offers hope for improving the outcomes of this challenging malignancy.

DOI： 10.1093/jjco/hyaf071

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記述言語：英語  

DOI： 10.1016/j.alit.2025.06.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare, severe, and chronic inflammatory skin disease characterized by widespread pustules that leads to unpredictable and potentially serious disease flares. Information regarding treatment status for GPP and treatment patterns for flares is important but limited as a result of the rarity of the condition. We conducted a 10-year, retrospective, longitudinal chart review of treatment patterns at GPP referral hospitals in Japan. METHODS: Eligible patients with GPP had at least 6 months of continuous observation data within 10 years after the date of protocol approval. Data were collected from patient records and annual patient reports. Patient characteristics and treatment details, including in relation to flare occurrence, were analyzed. RESULTS: The median age of patients (N = 205) was 53 years; 48.3% were female and most had mild or moderate GPP (66.8%). Patients commonly received nonbiologic systemic therapy (86.3%) and a similar proportion received biologics (79.5%); 95.1% received topical treatment and 22.4% received systemic adrenal corticosteroids. Use of nonbiologic systemic therapy decreased, and use of biologics increased, over the study period. During the observation period, the proportion of patients receiving biologic therapy increased after a flare (from 41.4% receiving biologics when flares occurred to 62.9% initiating a new biologic post flare). CONCLUSION: In Japanese clinical practice, the evolution of treatment practices for GPP has seen an increased use of biologic therapies over time. Biologic use was common after flares; however, some flares occurred during biologic therapy, indicating a need for improved treatment options to maintain stable disease and prevent flares.

DOI： 10.1007/s13555-025-01429-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.17703

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND & AIMS: Low muscle mass is associated with poor immune checkpoint inhibitor (ICI) efficacy in patients with melanoma; however, whether this is true in all populations remains to be explored. The current study aimed to investigate the effect of low muscle mass on overall survival (OS) and progression-free survival (PFS) of patients with advanced melanoma treated with ICI. METHODS: muscle index (SMI) at the third lumbar spine was calculated from computed tomography (CT) images, and SMI values < 42 cm2/m2 for men and <38 cm2/m2 for women diagnosed low muscle mass. The association of low muscle mass, OS, and PFS with ICI treatment in patients was investigated. RESULTS: Seventy-six patients with advanced melanoma were assessed retrospectively at our institution; 32 were in the low muscle mass group, while 44 were in the normal muscle mass group. The median OS in patients with and without low muscle mass was 7.1 and 26.6 months (hazard ratio [HR] 3.12, 95 % confidence interval [Cl], 1.65-5.89; p < 0.001) and median PFS was 2.1 and 14.8 months, respectively (HR, 3.10; 95 % Cl 1.74-5.54, p < 0.001). Multivariate analysis showed significantly poor differences in OS (HR, 2.46; 95 % CI, 1.20-5.03; p = 0.01) and significant differences in PFS independently in the low muscle mass group (HR, 3.10; 95 % CI, 1.74-5.54; p < 0.001). CONCLUSIONS: Low muscle mass may be a poor prognostic factor for patients with advanced melanoma treated with ICI.

DOI： 10.1016/j.clnesp.2025.02.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Generalized pustular psoriasis (GPP) is a chronic, inflammatory disease characterized by the sudden and recurrent development of widespread sterile pustules on the skin. The treatment of GPP includes non-biologic and biologic therapies. In Japan, biologic agents are being increasingly used as first-line treatment, with more biologics approved in Japan than in other countries. A previous secondary data-based study utilizing data in the Medical Data Vision database and the Japan Medical Data Center in Japan demonstrated heterogeneity in real-world biologic treatment patterns, with at least one switch during the follow-up period (mean n switches 3.8; mean length of follow-up 3.3 years) for approximately one third of patients with GPP treated with a biologic drug. The aim of this study was to evaluate where consensus lies among experts regarding switching biologic treatments for patients with GPP in Japan. METHODS: A Delphi exercise that consists of three survey rounds was performed with ten Japanese dermatologists. Participants were asked to respond to questions related to experts' experience with specific biologics, experience with switching, timing of switches and importance of specific criteria (drivers) when making the decision to switch. The consensus threshold was 70%. RESULTS: Based on the results of the Delphi exercise, most experts rarely (60%) or never (20%) switch a biologic agent and only 20% switch often during acute symptoms/GPP flare driven by the short time of the flare; this result may be different during the maintenance phase. Lack of efficacy, loss of efficacy due to long-term use, side effects, contraindications, new products with better efficacy and safety evidence, risk of infection, and lack of adherence play an important role in making the decision to switch. CONCLUSION: Switches may occur for patients on biologics when flares occur (loss of effectiveness) or when there is insufficient response (lack of effectiveness). The decision to switch a biologic is impacted by several other criteria, including safety and the availability of more efficacious and better tolerated therapies. Overall, there is still an unmet need for robust evidence to inform GPP treatment choice.

DOI： 10.1007/s13555-025-01377-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Drug-induced hypersensitivity syndrome (DIHS) is one of the severe drug eruptions accompanied by fever and multiple organ dysfunction, and it is induced by a relatively limited range of drugs, including anticonvulsants. A distinctive feature of this condition is its association with the reactivation of herpes viruses, particularly human herpesvirus 6. The pathogenesis involves two key factors: drug allergy and herpesvirus reactivation. DIHS is often challenging to diagnose in its early stages, and its clinical course varies widely, ranging from relatively mild to life-threatening cases. Additionally, unexpected complications, such as autoimmune diseases, may occur during the convalescent phase. As a result, diagnosing, treating, and predicting the prognosis of DIHS remain complex issues. In response to these challenges, the Ministry of Health, Labour and Welfare Study Group on Severe Erythema Multiforme has taken the lead in developing new guidelines for the management of DIHS. These guidelines aim to support clinical practice by providing up-to-date, evidence-based information on the diagnosis, treatment, and prognosis of DIHS.

DOI： 10.1111/1346-8138.17609

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A psoriasis (PSO) diagnosis may pose specific treatment challenges for women of childbearing age (WoCBA) who are considering pregnancy, are pregnant, or have just given birth. OBJECTIVE: To report perspectives of WoCBA with PSO regarding pregnancy and dermatologists about the disease management of these women in Australia and Japan. METHODS: Online surveys were completed by women aged 18 to 45 years who were pregnant within the past 5 years with moderate to severe PSO and dermatologists. RESULTS: In Japan (n = 31) and Australia (n = 27), most WoCBA with PSO did not feel adequately informed about pregnancy planning and had concerns regarding the safety of tumor necrosis factor inhibitors (TNFi) when used during pregnancy. Dermatologists (Australia: n = 40; Japan: n = 97) also had safety concerns around prescribing TNFi during pregnancy, and most were impartial toward or not at all comfortable with prescribing TNFi to women who were pregnant or actively planning pregnancy. Dermatologists felt that more safety data on pregnancy, lactation, and pediatric outcomes 5 years postdelivery would increase their comfort with prescribing TNFi. LIMITATIONS: Limitations included small respondent size, a lack of formal validation for questionnaires, recall bias among participants, and generalizability of results to all WoCBA with PSO. Response rates of survey participants were also not collected. CONCLUSION: Additional safety information can help address concerns about biologic use (including TNFi) in WoCBA, enabling dermatologists to make informed treatment recommendations in such patients.

DOI： 10.1097/JW9.0000000000000189

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jvc2.583

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記述言語：英語  

DOI： 10.1111/1346-8138.17440

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jid.2025.01.016

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(株)Gakken  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(株)Gakken  

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記述言語：英語  

DOI： 10.1016/j.jaad.2024.11.030

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: We aimed to gather real-world clinical evidence of detailed disease activity, treatments, remission rates, and adverse events (AEs) associated with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome in a prospective study. METHODS: Patients in Japan suspected of having VEXAS syndrome were enrolled in a registry study. A novel disease activity measure (VEXASCAF) assessing 11 symptoms associated with VEXAS syndrome was evaluated at enrolment and after 3 months. AEs, survival, CRP levels, and treatments were also recorded at enrolment and 3 months after enrolment. All exons of UBA1 were sequenced using a next-generation sequencer to determine the variant allele frequencies of pathogenic variants in the peripheral blood of all patients. RESULTS: Of the 55 registered patients, 30 patients were confirmed to have pathogenic variants of UBA1. All patients were male, with a median age of 73.5 years. VEXASCAF and CRP levels decreased significantly at 3 months post-enrolment, but the oral prednisolone dose did not change. Only two patients achieved complete remission according to FRENVEX at 3 months after enrolment. During the observation period of 6 months, 28 AEs were observed, including 3 deaths, 4 malignancies from two cases, 2 thromboses, and 13 infections (including 4 mycobacterial infections). Inflammation of the lung and cervical region (i.e. parotid and submandibular gland swelling, tonsillitis, cervical swelling, and pain) were the most common AEs. CONCLUSIONS: Patients with VEXAS syndrome required high-dose glucocorticoids to achieve remission, and complications-such as malignancy, thrombosis, and infection-occurred frequently within a short observation period.

DOI： 10.1093/rheumatology/keae530

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The plasma membrane protein caveolin-1 (CAV-1) regulates signaling by inhibiting a wide range of kinases and other enzymes. Our previous study demonstrated that the downregulation of CAV-1 in psoriatic epidermal cells contributes to inflammation by enhancing JAK/STAT signaling, cell proliferation, and chemokine production. Administration of the CAV-1 scaffolding domain (CSD) peptide suppressed imiquimod (IMQ)-induced psoriasis-like dermatitis. To identify an optimal therapeutic peptide derived from CAV-1, we have compared the efficacy of CSD and subregions of CSD that have been modified to make them water soluble. We refer to these modified peptides as sCSD, sA, sB, and sC. In IMQ-induced psoriasis-like dermatitis, while all four peptides showed major beneficial effects, sB caused the most significant improvements of skin phenotype and number of infiltrating cells, comparable or superior to the effects of sCSD. Phosphorylation of STAT3 was also inhibited by sB. Furthermore, sB suppressed angiogenesis both in vivo in the dermis of IMQ-induced psoriasis mice and in vitro by blocking the ability of conditioned media derived from CAV-1-silenced keratinocytes to inhibit tube formation by HUVEC. In conclusion, sB had similar or greater beneficial effects than sCSD not only by cytokine suppression but by angiogenesis inhibition adding to its ability to target psoriatic inflammation.

DOI： 10.1038/s41598-024-71350-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：日本語   出版者・発行元：(一社)日本組織適合性学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

Abstract

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a severe spectrum of rare mucocutaneous reactions, primarily drug-induced and characterized by significant morbidity and mortality. These conditions manifest through extensive skin detachment, distinguishing them from other generalized skin eruptions. The rarity and severity of SJS/TEN underscore the importance of accurate diagnostic criteria and effective treatments, which are currently lacking consensus. This review proposes new diagnostic criteria to improve specificity and global applicability. Recent advancements in understanding the immunopathogenesis of SJS/TEN are explored, emphasizing the role of drug-specific T cell responses and HLA polymorphisms in disease onset. The review also addresses current therapeutic approaches, including controversies surrounding the use of immunosuppressive agents and the emerging role of TNF-α inhibitors. Novel therapeutic strategies targeting specific pathogenic mechanisms, such as necroptosis and specific immune cell pathways, are discussed. Furthermore, the development of new drugs based on these insights, including targeted monoclonal antibodies and inhibitors, are examined. The review concludes by advocating for more robust and coordinated efforts across multidisciplinary medical fields to develop effective treatments and diagnostic tools for SJS/TEN, with the aim of improving patient outcomes and understanding of the disease and its mechanisms.

DOI： 10.1093/bjd/ljae321

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床免疫学会  

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記述言語：日本語   出版者・発行元：日本皮膚科学会-西部支部  

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記述言語：日本語   出版者・発行元：(株)協和企画  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J01268&link_issn=&doc_id=20240529440017&doc_link_id=10.24733%2Fpd.0000003839&url=https%3A%2F%2Fdoi.org%2F10.24733%2Fpd.0000003839&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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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: Dermatological 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. Ophthalmological 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 < 0.001) and specific year in the survey (P < 0.001). 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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Anti-SS-A/Ro antibody (anti-SSA), the diagnostic marker of Sjögren's syndrome (SS), is often detected in systemic sclerosis (SSc). Some patients are diagnosed with SSc/SS overlap syndromes, while there are anti-SSA-positive SSc cases without SS. In this study, we investigated the clinical characteristics of SSc with anti-SSA and clarified the clinical impact of this antibody in SSc. METHODS: A retrospective chart review was conducted of 156 patients with SSc at Yokohama City University Hospital from 2018 to 2021. Clinical data, laboratory data, imaging, and autoantibody positivity status were collected and analysed to assess the association between these variables and anti-SSA using multivariable logistic regression analysis. RESULTS: This cohort included 18 men and 138 women with SSc (median age, 69.0 years). Thirty-nine patients had diffuse cutaneous SSc (dcSSc) (25%), and 117 patients had limited cutaneous SSc (75%). Forty-four patients were anti-SSA-positive. Among them, 24 fulfilled the SS criteria. Multivariable logistic regression revealed that anti-SSA was statistically associated with interstitial lung disease (ILD; odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.14-6.3; P = 0.024). Meanwhile, anti-SSA positivity tended to increase the development of digital ulcer (OR = 2.18; 95% CI, 0.99-4.82, P = 0.054). In the comparative analysis of the autoantibody single-positive and anti-SSA/SSc-specific autoantibody double-positive groups, the anti-SSA single-positive group showed a significantly increased risk of ILD (OR = 12.1; 95% CI, 2.13-140.57; P = 0.003). Furthermore, patients with SSc and anti-SSA indicated that anti-SSA-positive SSc without SS was strongly associated with dcSSc when compared to that in patients with SS (OR = 6.45; 95% CI, 1.23-32.60; P = 0.024). CONCLUSIONS: Anti-SSA positivity increases the risk of organ involvement, such as ILD, in patients with SSc. Additionally, the anti-SSA-positive SSc without SS population may have more severe skin fibrosis than others. Anti-SSA may be a potential marker of ILD and skin severity in SSc.

DOI： 10.1186/s13075-024-03325-6

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：日本臨床皮膚科医会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jaip.2024.02.041

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記述言語：日本語   出版者・発行元：(株)協和企画  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01440&link_issn=&doc_id=20231026170011&doc_link_id=10.11477%2Fmf.1402229265&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1402229265&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

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jid.2023.09.282

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記述言語：日本語   出版者・発行元：(株)協和企画  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jaad.2023.09.061

PubMed

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記述言語：日本語   出版者・発行元：(株)南江堂  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00764&link_issn=&doc_id=20230829290019&doc_link_id=issn%3D0030-5901%26volume%3D74%26issue%3D9%26spage%3D991&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0030-5901%26volume%3D74%26issue%3D9%26spage%3D991&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

PubMed

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記述言語：英語  

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

PubMed

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jvc2.113

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.16644

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Osteopontin (OPN) was initially described as a protein involved in bone metabolism, but the roles played by OPN in the immune system and allergic reactions have attracted increasing attention. Here, we clarify the OPN-related dynamics of severe cutaneous adverse drug reactions, and assess whether the OPN level has utility for classifying such reactions and serving as a biomarker of severity. Serum OPN levels in patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and erythema multiforme-type drug reaction (EM-DR) were quantified by ELISA. The OPN sources were analyzed by dual immunofluorescence assay of DIHS, SJS/TEN and EM-DR biopsy specimens. The serum OPN levels of DIHS/DRESS patients (489.1 ± 37.0 ng/mL) and SJS/TEN patients (508.5 ± 47.8 ng/mL) were significantly higher compared with controls (314.4 ± 14.3 ng/mL; p < 0.001). After treatment, the serum OPN level of DIHS/DRESS patients decreased to that of controls. In addition, OPN levels in DIHS/DRESS patients and SJS/TEN patients were higher than in patients with EM-DR (Mann-Whitney U test, p < 0.05). However, when the Kruskal-Wallis test was used to compare the OPN levels among the three groups of patients, the difference was not significant (p = 0.055). Dual immunofluorescence assay revealed that T lymphocytes and macrophages were the main OPN sources in DIHS, SJS/TEN and EM-DR patients. These data suggest that the OPN level can be used to evaluate the severity of inflammation in patients experiencing drug reactions.

DOI： 10.1111/1346-8138.16670

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Enhanced circulating blood periostin levels positively correlate with disease severity in patients with systemic sclerosis (SSc). Monocytes/macrophages are predominantly associated with the pathogenesis of SSc, but the effect of periostin on immune cells, particularly monocytes and macrophages, still remains to be elucidated. We examined the effect of periostin on monocytes and monocyte-derived macrophages (MDM) in the pathogenesis of SSc. The modified Rodnan total skin thickness score in patients with dcSSc was positively correlated with the proportion of CD80-CD206+ M2 cells. The proportion of M2 macrophages was significantly reduced in rPn-stimulated MDMs of HCs compared to that of SSc patients. The mRNA expression of pro-fibrotic cytokines, chemokines, and ECM proteins was significantly upregulated in rPn-stimulated monocytes and MDMs as compared to that of control monocytes and MDMs. A similar trend was observed for protein expression in the respective MDMs. In addition, the ratio of migrated cells was significantly higher in rPn-stimulated as compared to control monocytes. These results suggest that periostin promotes inflammation and fibrosis in the pathogenesis of SSc by possible modulation of monocytes/macrophages.

DOI： 10.1371/journal.pone.0281881

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block key mediators of tumor-mediated immune evasion. The frequency of its use has increased rapidly and has extended to numerous cancers. ICIs target immune checkpoint molecules, such as programmed cell death protein 1 (PD-1), PD ligand 1 (PD-L1), and T cell activation, including cytotoxic T-lymphocyte-associated protein-4 (CTLA-4). However, ICI-driven alterations in the immune system can induce various immune-related adverse events (irAEs) that affect multiple organs. Among these, cutaneous irAEs are the most common and often the first to develop. Skin manifestations are characterized by a wide range of phenotypes, including maculopapular rash, psoriasiform eruption, lichen planus-like eruption, pruritus, vitiligo-like depigmentation, bullous diseases, alopecia, and Stevens-Johnson syndrome/toxic epidermal necrolysis. In terms of pathogenesis, the mechanism of cutaneous irAEs remains unclear. Still, several hypotheses have been proposed, including activation of T cells against common antigens in normal tissues and tumor cells, increased release of proinflammatory cytokines associated with immune-related effects in specific tissues/organs, association with specific human leukocyte antigen variants and organ-specific irAEs, and acceleration of concurrent medication-induced drug eruptions. Based on recent literature, this review provides an overview of each ICI-induced skin manifestation and epidemiology and focuses on the mechanisms underlying cutaneous irAEs.

DOI： 10.3389/fimmu.2023.1071983

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Systemic sclerosis (SSc) is a chronic, heterogenous disease of connective tissue characterized by organ fibrosis together with vascular injury and autoimmunity. Transforming growth factor (TGF)-β plays a central role in generating fibrosis, including SSc. Periostin is a matricellular protein playing a key role in the generation of fibrosis by amplifying the TGF-β signals. SOX (SRY-related HMG box) 11 is a transcription factor playing several important roles in organ development in embryos. We have previously shown that SOX11 induces periostin expression. However, the roles of the interactions among the TGF-β signals, periostin, and SOX11 remain unknown in the pathogenesis of SSc. In this study, we found that most clones of dermal fibroblasts derived from SSc patients showed constitutive, high expression of SOX11, which is significantly induced by TGF-β1. SOX11 forms a positive loop with periostin to activate the TGF-β signals in SSc dermal fibroblasts. Genetic deletion of Sox11 in Postn-expressing fibroblasts impairs dermal fibrosis by bleomycin. Moreover, using the DNA microarray method, we identified several fibrotic factors dependent on the TGF-β/SOX11/periostin pathway in SSc dermal fibroblasts. Our findings, taken together, show that a positive loop formed by SOX11 and periostin in fibroblasts upregulates the TGF-β signals, leading to skin fibrosis.

DOI： 10.1016/j.jid.2022.12.008

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記述言語：英語   出版者・発行元：(一社)日本研究皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/cia2.12233

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is a member of the genus Betacoronavirus. This virus was first detected in December 2019, and the situation quickly escalated to cause a global pandemic within a few months. COVID-19 had caused more than 5.5 million deaths as of January 2022. Hence, the urgency of effective vaccination contributed to the fastest rate of vaccine development seen to date (i.e., within 1.5 years). Despite reports of good vaccine efficacy without severe systemic reactions at the clinical trial stage, hypersensitivity reactions have been reported following worldwide vaccination campaigns. We provide a brief review regarding the structure of SARS-CoV-2. We also review the most acceptable types of vaccines in terms of safety profiles, namely the BNT162b2, mRNA-1273, and AZD1222 vaccines. This review aims to facilitate an understanding of the possible immune mechanisms regarding COVID-19-vaccination-related hypersensitivity reactions, such as thrombosis and thrombocytopenia, cutaneous adverse reactions, myocarditis, and perimyocarditis.

DOI： 10.3390/biomedicines10071641

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1016/j.alit.2022.02.001

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier {BV}  

DOI： 10.1016/j.ejca.2022.01.020

PubMed

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記述言語：英語  

DOI： 10.1016/j.alit.2022.02.003

PubMed

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記述言語：英語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：日本脊椎関節炎学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1093/rheumatology/keac519.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0260730

Scopus

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記述言語：英語  

DOI： 10.1016/j.jdermsci.2021.10.005

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.16014

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01174&link_issn=&doc_id=20210728470005&doc_link_id=10.14924%2Fdermatol.131.1841&url=https%3A%2F%2Fdoi.org%2F10.14924%2Fdermatol.131.1841&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To determine clinical and genetic features of individuals with relapsing polychondritis (RP) likely caused by pathogenic somatic variants in ubiquitin-like modifier activating enzyme 1 (UBA1). METHODS: Fourteen patients with RP who met the Damiani and Levine criteria were recruited (12 men, 2 women; median onset age (IQR) 72.1 years (67.1-78.0)). Sanger sequencing of UBA1 was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue. Droplet digital PCR (ddPCR) and peptide nucleic acid (PNA)-clamping PCR were used to detect low-prevalence somatic variants. Clinical features of the patients were investigated retrospectively. RESULTS: UBA1 was examined in 13 of the 14 patients; 73% (8/11) of the male patients had somatic UBA1 variants (c.121A>C, c.121A>G or c.122T>C resulting in p.Met41Leu, p.Met41Val or p.Met41Thr, respectively). All the variant-positive patients had systemic symptoms, including a significantly high prevalence of skin lesions. ddPCR detected low prevalence (0.14%) of somatic variant (c.121A>C) in one female patient, which was subsequently confirmed by PNA-clamping PCR. CONCLUSIONS: Genetic screening for pathogenic UBA1 variants should be considered in patients with RP, especially male patients with skin lesions. The somatic variant in UBA1 in the female patient is the first to be reported.

DOI： 10.1136/annrheumdis-2021-220089

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Monocytes and macrophages may be involved in the pathogenesis of systemic sclerosis (SSc); however, its etiology and regulation of monocyte and macrophage function in SSc remain unknown. Interferon regulatory factor (IRF) 8 is a transcriptional regulator that is essential for the differentiation and function of monocytes and macrophages, and thus may be involved in the regulation of macrophage phenotypes in SSc fibrosis. In this study, we measured IRF8 levels in circulating monocytes of 26 SSc patients (diffuse cutaneous SSc (dcSSc), n = 11; limited cutaneous SSc (lcSSc), n = 15) and 14 healthy controls. IRF8 levels were significantly suppressed in monocytes of dcSSc patients and correlated negatively with the modified Rodnan total skin thickness score. Next, we assessed cell surface markers, cytokine profiles, and extracellular matrix (ECM) expression levels in IRF8-silenced monocyte-derived macrophages (siIRF8-MDMs). siIRF8-MDMs displayed an M2 phenotype and significantly upregulated mRNA and protein levels of pro-fibrotic factors and ECM components. Finally, we assessed skin fibrosis in myeloid cell-specific IRF8 conditional knockout (IRF8flox/flox; Lyz2Cre/+) mice and found upregulated ECM mRNA levels and increased bleomycin-induced skin fibrosis. In conclusion, altered IRF8 regulation in monocytes and macrophages may be involved in SSc pathogenesis.

DOI： 10.1016/j.jid.2021.02.015

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記述言語：英語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 42-year-old man with a history of surgery for tongue cancer was referred to our hospital due to an abnormal chest shadow. High-resolution computed tomography showed lower lobe reticulation. A physical examination revealed nail dystrophy, oral leukoplakia, and reticulated hypopigmentation. Lung biopsy revealed subpleural and perilobular fibrosis, suggestive of usual interstitial pneumonia. However, multiple pathological findings, including homogenous fibrosis and cell infiltration in the centrilobular region, which were compatible with nonspecific interstitial pneumonia, and bronchiolitis were also seen. Genetic testing showed a hemizygous missense mutation in the DKC1 gene, and the patient was diagnosed with dyskeratosis congenita. Although anti-fibrotic therapy was initiated, the patient's respiratory function has continued to decrease.

DOI： 10.2169/internalmedicine.5143-20

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Previous clinical studies have shown that efficacy and serum brodalumab levels are dose dependent in patients with psoriasis receiving the same dose of brodalumab during the study. This study aimed to investigate the association between dosage, serum levels, and efficacy of brodalumab in Japanese patients with plaque psoriasis with dosage variations during the study. This was a post hoc exploratory analysis of a 108-week, multicenter, open-label extension study, which changed into a post-marketing surveillance study following brodalumab approval in Japan. Eligible patients with plaque psoriasis (n = 129) received brodalumab 140 mg every 4 weeks on Day 1; dosage change at physician's discretion from 140 mg every 8 weeks to 210 mg every 2 weeks was permitted; patients switched to 210 mg every 2 weeks during the post-marketing surveillance study. Exploratory endpoints included serum brodalumab levels at Weeks 28 and 108, its association with Psoriasis Area and Severity Index score, and Psoriasis Area and Severity Index score in patients receiving brodalumab 210 mg every 2 weeks at end of study. Median brodalumab trough levels were significantly higher (P < 0.05) at higher vs. lower dosages at Weeks 28 (n = 126) and 108 (n = 111) except for 140 mg every 2 weeks vs. 210 mg every 2 weeks at Week 108 and higher in patients with lower Psoriasis Area and Severity Index scores-significantly different only for Psoriasis Area and Severity Index score 0 vs. >2 at Week 28 (P = 0.0153). Of 100 patients receiving 210 mg every 2 weeks at end of study, 89% had a Psoriasis Area and Severity Index score ≤2. In patients with plaque psoriasis, brodalumab efficacy may depend upon sustained serum trough levels and can be restored by using the approved dose.

DOI： 10.1111/1346-8138.15690

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/rheumatology/keaa112

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1016/j.jdermsci.2020.09.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1111/1346-8138.15467

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The medical comorbidities including skin diseases are associated with male infertility. The most common cause of male infertility is the inability of testes to produce sperm; however, the influence of persistent dermatitis on testicular function has not been elucidated so far. We investigated the relationship between skin inflammation and impaired sperm production using a spontaneous dermatitis mouse model. We examined the breeding records of dermatitis mice and their wild-type littermates. Sperm count, motility, and viability were analyzed by direct microscopic observation and flow cytometry. In addition, testis and epididymis were histologically examined. Finally, sperm viability was evaluated in another dermatitis mouse model and in wild-type mice in which inflammatory cytokines were intraperitoneally administered. Compared to wild-type littermate mice, the number of children born was lower in mice with dermatitis. The body weight and testis size were decreased age-dependently. In the skin disease group, the sperm count and movement ratio were clearly decreased, and reduced sperm viability was observed. Histological examination revealed the detachment of Sertoli cells and reduced spermatogenesis. The fibrosis of epididymal stroma was severe, and it might affect defective sperm maturation in the epididymis. In addition, this phenomena was reproduced by a hapten applied dermatitis mouse model and the intraperitoneal administration of inflammatory cytokines. Once the skin is inflamed, inflammatory cytokines are produced and released, which may affect testicular and sperm function. Additional studies are needed to determine the relationship between male infertility and severe dermatitis in human.

DOI： 10.3390/biomedicines8090293

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記述言語：英語  

DOI： 10.1111/1346-8138.15535

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jid.2019.12.025

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0234523

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.15343

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

: Adipose tissue (AT) is the largest endocrine organ, producing bioactive products called adipocytokines, which regulate several metabolic pathways, especially in inflammatory conditions. On the other hand, there is evidence that chronic inflammatory skin disease is closely associated with vascular sclerotic changes, cardiomegaly, and severe systemic amyloidosis in multiple organs. In psoriasis, a common chronic intractable inflammatory skin disease, several studies have shown that adipokine levels are associated with disease severity. Chronic skin disease is also associated with metabolic syndrome, including abnormal tissue remodeling; however, the mechanism is still unclear. We addressed this problem using keratin 14-specific caspase-1 overexpressing transgenic (KCASP1Tg) mice with severe erosive dermatitis from 8 weeks of age, followed by re-epithelization. The whole body and gonadal white AT (GWAT) weights were decreased. Each adipocyte was large in number, small in size and irregularly shaped; abundant inflammatory cells, including activated CD4+ or CD8+ T cells and toll-like receptor 4/CD11b-positive activated monocytes, infiltrated into the GWAT. We assumed that inflammatory cytokine production in skin lesions was the key factor for this lymphocyte/monocyte activation and AT dysregulation. We tested our hypothesis that the AT in a mouse dermatitis model shows an impaired thermogenesis ability due to systemic inflammation. After exposure to 4 °C, the mRNA expression of the thermogenic gene uncoupling protein 1 in adipocytes was elevated; however, the body temperature of the KCASP1Tg mice decreased rapidly, revealing an impaired thermogenesis ability of the AT due to atrophy. Tumor necrosis factor (TNF)-α, IL-1β and interferon (INF)-γ levels were significantly increased in KCASP1Tg mouse ear skin lesions. To investigate the direct effects of these cytokines, BL/6 wild mice were administered intraperitoneal TNF-α, IL-1β and INF-γ injections, which resulted in small adipocytes with abundant stromal cell infiltration, suggesting those cytokines have a synergistic effect on adipocytes. The systemic dermatitis model mice showed atrophy of AT and increased stromal cells. These findings were reproducible by the intraperitoneal administration of inflammatory cytokines whose production was increased in inflamed skin lesions.

DOI： 10.3390/ijms21093367

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記述言語：英語  

DOI： 10.1016/j.ejca.2020.02.044

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.15284

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(公社)日本皮膚科学会  

DOI： 10.1111/1346-8138.15273

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.resinv.2019.12.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The European League Against Rheumatism/American College of Rheumatology classification criteria for inflammatory myopathies are able to classify patients with skin-predominant dermatomyositis (DM). However, approximately 25% of patients with skin-predominant DM do not meet two of the three hallmark skin signs and fail to meet the criteria. OBJECTIVES: To develop a set of skin-focused classification criteria that will distinguish cutaneous DM from mimickers and allow a more inclusive definition of skin-predominant disease. METHODS: An extensive literature review was done to generate items for the Delphi process. Items were grouped into categories of distribution, morphology, symptoms, antibodies, histology and contextual factors. Using REDCap™, participants rated these items in terms of appropriateness and distinguishing ability from mimickers. The relevance score ranged from 1 to 100, and the median score determined a rank-ordered list. A prespecified median score cut-off was decided by the steering committee and the participants. There was a pre-Delphi and two rounds of actual Delphi. RESULTS: There were 50 participating dermatologists and rheumatologists from North America, South America, Europe and Asia. After a cut-off score of 70 during the first round, 37 of the initial 54 items were retained and carried over to the next round. The cut-off was raised to 80 during round two and a list of 25 items was generated. CONCLUSIONS: This project is a key step in the development of prospectively validated classification criteria that will create a more inclusive population of patients with DM for clinical research. What's already known about this topic? Proper classification of patients with skin-predominant dermatomyositis (DM) is indispensable in the appropriate conduct of clinical/translational research in the field. The only validated European League Against Rheumatism/American College of Rheumatology criteria for idiopathic inflammatory myopathies are able to classify skin-predominant DM. However, a quarter of amyopathic patients still fail the criteria and does not meet the disease classification. What does this study add? A list of 25 potential criteria divided into categories of distribution, morphology, symptomatology, pathology and contextual factors has been generated after several rounds of consensus exercise among experts in the field of DM. This Delphi project is a prerequisite to the development of a validated classification criteria set for skin-predominant DM.

DOI： 10.1111/bjd.18096

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記述言語：英語  

DOI： 10.1111/1346-8138.15142

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1165/rcmb.2019-0245OC

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12931-020-1299-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/rheumatology/kez238

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000504429

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1001/jamadermatol.2019.1668

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.14913

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.14802

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jaci.2019.01.004

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記述言語：英語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-018-36767-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.14237

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s13075-018-1613-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jdermsci.2018.02.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s10038-017-0408-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1684/ejd.2017.3174

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.alit.2017.06.016

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/rheumatology/key060

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jdermsci.2017.09.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.13711

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.13975

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12576-016-0480-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jdermsci.2016.11.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.13434

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0174547

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.13177

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.alit.2015.09.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/bjd.14426

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/jid.2015.249

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.alit.2014.06.001

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1684/ejd.2015.2622

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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-BLACKWELL  

Background Recent findings indicate that periostin, an extracellular matrix protein induced by T helper 2 cytokines, plays a critical role in the pathogenesis of atopic dermatitis (AD).
Objectives To determine whether serum periostin level is associated with clinical phenotype in adult patients with AD.
Methods An enzyme-linked immunosorbent assay was performed to determine serum periostin levels in 257 adult patients with AD, 66 patients with psoriasis vulgaris (PV) as a disease control and 25 healthy controls. Serum periostin levels were analysed together with clinical characteristics and laboratory parameters, including thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), blood eosinophil count and total IgE. Immunohistochemical analysis evaluated the expression of periostin in association with various clinical phenotypes of AD. The effect of treatment on serum periostin level was also assessed.
Results Serum periostin was significantly higher in patients with AD than in patients with PV and healthy controls. Periostin level was found to be positively correlated with disease severity, TARC level, LDH level and eosinophil count, but not with IgE level. Higher serum periostin level was observed in patients with extrinsic AD compared with patients with intrinsic AD; the positive correlation of disease severity disappeared in patients with intrinsic AD. Robust expression of periostin was detected in the dermis of patients with AD with erythroderma, lichenification and, to a lesser extent, scaly erythema. Serial measurement of serum periostin revealed decreased levels of periostin after treatment for AD.
Conclusions Periostin may play a critical role in disease severity and chronicity in the pathogenesis of AD.

DOI： 10.1111/bjd.12943

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Extracellular matrix (ECM) is not only involved in the maintenance of normal physiological tissue but also in interactions with other ECM components, tissue remodeling, and modulating immune responses. The skin provides a distinctive environment characterized by rich fibroblasts producing various ECM proteins, epithelial-mesenchymal interactions, and immune responses induced by external stimuli. Recently, periostin-a matricellular protein-has been highlighted for its pivotal functions in the skin. Analysis of periostin null mice has revealed that periostin contributes to collagen fibrillogenesis, collagen cross-linking, and the formation of ECM meshwork via interactions with other ECM components. Periostin expression is enhanced by mechanical stress or skin injury; this is indicative of the physiologically protective functions of periostin, which promotes wound repair by acting on keratinocytes and fibroblasts. Along with its physiological functions, periostin plays pathogenic roles in skin fibrosis and chronic allergic inflammation. In systemic sclerosis (SSc) patients, periostin levels reflect the severity of skin fibrosis. Periostin null mice have shown reduced skin fibrosis in a bleomycin-induced SSc mouse model, indicating a key role of periostin in fibrosis. Moreover, in atopic dermatitis (AD), attenuated AD phenotype has been observed in periostin null mice in a house dust mite extract-induced AD mouse model. Th2 cytokine-induced periostin acts on keratinocytes to produce inflammatory cytokines that further enhance the Th2 response, thereby sustaining and amplifying chronic allergic inflammation. Thus, periostin is deeply involved in the pathogenesis of AD and other inflammation-related disorders affecting the skin. Understanding the dynamic actions of periostin would be key to dissecting pathogenesis of skin-related diseases and to developing novel therapeutic strategies.

DOI： 10.2332/allergolint.13-RAI-0685

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1684/ejd.2014.2442

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0087754

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Extracellular matrix (ECM) is not only involved in the maintenance of normal physiological tissue but also in interactions with other ECM components, tissue remodeling, and modulating immune responses. The skin provides a distinctive environment characterized by rich fibroblasts producing various ECM proteins, epithelial-mesenchymal interactions, and immune responses induced by external stimuli. Recently, periostin-a matricellular protein-has been highlighted for its pivotal functions in the skin. Analysis of periostin null mice has revealed that periostin contributes to collagen fibrillogenesis, collagen cross-linking, and the formation of ECM meshwork via interactions with other ECM components. Periostin expression is enhanced by mechanical stress or skin injury; this is indicative of the physiologically protective functions of periostin, which promotes wound repair by acting on keratinocytes and fibroblasts. Along with its physiological functions, periostin plays pathogenic roles in skin fibrosis and chronic allergic inflammation. In systemic sclerosis (SSc) patients, periostin levels reflect the severity of skin fibrosis. Periostin null mice have shown reduced skin fibrosis in a bleomycin-induced SSc mouse model, indicating a key role of periostin in fibrosis. Moreover, in atopic dermatitis (AD), attenuated AD phenotype has been observed in periostin null mice in a house dust mite extract-induced AD mouse model. Th2 cytokine-induced periostin acts on keratinocytes to produce inflammatory cytokines that further enhance the Th2 response, thereby sustaining and amplifying chronic allergic inflammation. Thus, periostin is deeply involved in the pathogenesis of AD and other inflammation-related disorders affecting the skin. Understanding the dynamic actions of periostin would be key to dissecting pathogenesis of skin-related diseases and to developing novel therapeutic strategies.

DOI： 10.2332/allergolint.13-RAI-0685

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recent findings indicate that periostin, an extracellular matrix protein induced by T helper 2 cytokines, plays a critical role in the pathogenesis of atopic dermatitis (AD). OBJECTIVES: To determine whether serum periostin level is associated with clinical phenotype in adult patients with AD. METHODS: An enzyme-linked immunosorbent assay was performed to determine serum periostin levels in 257 adult patients with AD, 66 patients with psoriasis vulgaris (PV) as a disease control and 25 healthy controls. Serum periostin levels were analysed together with clinical characteristics and laboratory parameters, including thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), blood eosinophil count and total IgE. Immunohistochemical analysis evaluated the expression of periostin in association with various clinical phenotypes of AD. The effect of treatment on serum periostin level was also assessed. RESULTS: Serum periostin was significantly higher in patients with AD than in patients with PV and healthy controls. Periostin level was found to be positively correlated with disease severity, TARC level, LDH level and eosinophil count, but not with IgE level. Higher serum periostin level was observed in patients with extrinsic AD compared with patients with intrinsic AD; the positive correlation of disease severity disappeared in patients with intrinsic AD. Robust expression of periostin was detected in the dermis of patients with AD with erythroderma, lichenification and, to a lesser extent, scaly erythema. Serial measurement of serum periostin revealed decreased levels of periostin after treatment for AD. CONCLUSIONS: Periostin may play a critical role in disease severity and chronicity in the pathogenesis of AD.

DOI： 10.1111/bjd.12943

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：4  

DOI： 10.1186/ar4251

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：2  

DOI： 10.14670/HH-28.175

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2177/jsci.36.452

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掲載種別：研究論文（学術雑誌）   出版者・発行元：4  

DOI： 10.1111/bjd.12117

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：136  

DOI： 10.1126/scitranslmed.3003421

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：2  

DOI： 10.1016/j.jdermsci.2012.02.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00403-011-1198-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：8  

DOI： 10.1371/journal.pone.0043049

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：10  

DOI： 10.1111/j.1346-8138.2011.01262.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：4  

DOI： 10.1111/j.1582-4934.2010.01063.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1365-2133.2010.10145.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：6  

DOI： 10.1186/ar3180

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：3  

DOI： 10.1186/ar3005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：2  

DOI： 10.1165/rcmb.2008-0211OC

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掲載種別：研究論文（学術雑誌）   出版者・発行元：4 Suppl 50  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2174/1874312900802010017

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：13  

DOI： 10.1182/blood-2007-07-100008

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：Blackwell Publishing Ltd  

DOI： 10.1111/jdv.16851

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）  

DOI： 10.1002/cia2.12138

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：日本臨床皮膚科医会  

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）  

DOI： 10.1002/cia2.12101

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(株)学研メディカル秀潤社  

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記述言語：日本語   出版者・発行元：金原出版(株)  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01266&link_issn=&doc_id=20200123100010&doc_link_id=10.18888%2Fhi.0000001750&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000001750&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(株)学研メディカル秀潤社  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(株)新興医学出版社  

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：日本皮膚科学会-西部支部  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：公益社団法人 日本皮膚科学会  

<p>本邦における皮膚動脈炎（皮膚型結節性多発動脈炎）の現状を把握するため，日本皮膚科学会血管炎・血管障害診療ガイドライン改訂委員会に所属している全国12施設にアンケート調査を行った．対象は，2012年1月から2016年12月までの5年間である．平均約3年間の観察期間において，発熱・脳出血・脳梗塞が1割強の症例でみられた．また，関節痛・関節炎ありが37％，筋痛・筋炎ありが21％，末梢神経障害ありが33％に認められた．加えて，ステロイド全身投与治療が半数症例で施行されていた．随伴症状を呈した症例は，皮膚限局とは必ずしも言えず，全身性の結節性多発動脈炎への移行の可能性を推測させた．</p>

DOI： 10.14924/dermatol.129.1901

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記述言語：日本語   出版者・発行元：(株)協和企画  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

CiNii Books

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記述言語：日本語   出版者・発行元：(株)学研メディカル秀潤社  

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記述言語：日本語   出版者・発行元：日本皮膚科学会-西部支部  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：金原出版(株)  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01266&link_issn=&doc_id=20180524170032&doc_link_id=10.18888%2Fhi.0000000732&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000000732&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語  

DOI： 10.3390/ijms19041102

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記述言語：日本語   出版者・発行元：(公社)日本栄養・食糧学会  

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記述言語：日本語   出版者・発行元：(公社)日本栄養・食糧学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：日本脊椎関節炎学会  

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記述言語：日本語   出版者・発行元：(株)日本医事新報社  

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記述言語：日本語   出版者・発行元：(株)北隆館  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚アレルギー・接触皮膚炎学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚アレルギー・接触皮膚炎学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚アレルギー・接触皮膚炎学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：金原出版(株)  

70歳女。右側頭部の皮疹を主訴とした。ペット飼育歴はなく、糖尿病、関節リウマチにて内服加療中であり、外用薬と抗真菌薬、抗菌薬の内服を併用するも皮疹は改善しなかった。紹介受診時には右前頭部に血痂を伴うやや隆起した紅色局面と軽度の脱毛がみられ、グロコット染色では毛周囲に黒色に染色される線毛状の菌糸を認めた。培養所見では表面は白みがかった粗い綿毛状、周辺部は淡い黄色色素と放射状の溝を認め、裏面は黄色調であり、スライドカルチャーでは紡錘形で厚い隔壁に分画され、先端の尖った大分生子と棍棒状の小分生子を認めた。以上よりMicrosporum canisによる頭部白癬と診断してテルビナフィン塩酸塩を開始し、3ヵ月後には皮疹は消退した。自験例は動物との接触がなく、原因菌や感染経路の推察において真菌培養の重要性が示された。

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(株)北隆館  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

CiNii Books

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DOI： 10.14924/dermatol.126.2419

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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