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

DOI： 10.1016/j.ajo.2024.05.011

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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.jaip.2024.02.041

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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.jid.2023.09.282

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/cia2.12306

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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

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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

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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

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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

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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）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1111/1346-8138.16644

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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

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

DOI： 10.1016/j.jdermsci.2022.07.003

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

DOI： 10.1016/j.jdermsci.2022.07.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1016/j.alit.2021.12.002

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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}  

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

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1111/1346-8138.15963

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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  

DOI： 10.1016/j.alit.2020.12.001

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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）   出版者・発行元：JOHN WILEY & SONS LTD  

DOI： 10.1002/cia2.12138

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.15535

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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  

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）   出版者・発行元：Wiley  

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

DOI： 10.1111/bjd.19133

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記述言語：英語   出版者・発行元：JOHN WILEY & SONS LTD  

Toxic epidermal necrolysis (TEN) is a life-threatening cutaneous reaction with several complications. Although acute respiratory distress syndrome (ARDS) is rare, it can cause rapid and potentially fatal pulmonary dysfunction. Here, we present a case of TEN with ARDS attributed to acetaminophen.

DOI： 10.1002/cia2.12101

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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 rare condition, causing life-threatening adverse cutaneous reactions. TEN occurrence after bone marrow transplantation (BMT) is a well-known phenomenon; however, to date, only a few cases have been reported in the published work. Here, we describe the case of a 53-year-old woman who experienced TEN after undergoing allogenic BMT for malignant lymphoma. Skin erosion spread across a maximum of 70% of the body surface area and severe mucosal lesions developed. Steroid pulse therapy, plasma apheresis and immunoglobulin therapy were administrated, which resulted in the complete resolution of TEN. However, she developed hemophagocytic lymphohistiocytosis and died 38 days after BMT, owing to rupture of the lower digestive tract complicated by multi-organ failure. In our case, engraftment failure occurred, and the peripheral white blood cell count was less than 100/μL during the TEN course, suggesting that the presence of only a few immune cells could cause TEN. Our findings showed that high mortality rates and widespread skin erosion could be regarded as the most important characteristics of TEN occurring after BMT.

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）  

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

DOI： 10.1111/1346-8138.14895

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Caveolin-1 (CAV-1) is the principal component of caveolae that regulates a variety of signaling molecules and receptors. Our previous study revealed CAV-1 reduction in the epidermis of patients with psoriasis, which leads to enhanced Janus kinase/signal transducer and activator of transcription activation and cytokine production, suggesting that aberrant CAV-1 expression may contribute to psoriatic inflammation. This study aimed to investigate whether abnormal modulation of CAV-1 on immune cells is involved in the pathogenesis of psoriasis. We observed that CAV-1 level in psoriasis patients was apparently reduced in peripheral blood mononuclear cells (PBMCs) and it was prominent in CD14+ monocytes. CAV-1 silencing in monocytes represented elevated levels of interleukin (IL)-1β and IL-6, and those had enhanced chemotaxis activity. In a murine model of psoriasis-like inflammation induced by imiquimod, we observed a significant CAV-1 reduction in PBMCs. Systemic administration of CAV-1 scaffolding domain peptide significantly improved the skin phenotype with less macrophage infiltration. Taken together, aberrant CAV-1 expression in monocytes may be involved in the pathogenesis of psoriasis.

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/cod.13088

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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 Squamous cell carcinoma antigen (SCCA) belongs to the ovalbuminserpin family and is a known tumour marker. Expression of SCCA is upregulated in the serum and skin of patients with psoriasis. Objectives The aim of this study was to determine SCCA2 levels in association with disease severity and treatment efficacy in patients with psoriasis.
Materials and methods Patients with psoriasis (n = 123) and healthy controls (n = 25) were enrolled in this prospective cross-sectional study. Enzyme-linked immunosorbent assay (ELISA) analysis was performed to determine serum SCCA2 levels. SCCA2 expression in skin was evaluated using immunohistochemical analysis. Serum SCCA2 levels were compared with Psoriasis Area Severity Index (PASI) scores. The effect of treatment on serum SCCA2 levels was assessed using serial examinations. Induction of SCCA2 by several psoriatic cytokines in human keratinocytes was evaluated.
Results The serum levels of SCCA2 were significantly higher in patients with psoriasis than healthy controls and correlated well with disease severity. Increased SCCA2 staining was observed in lesional skin but not in nonlesional skin of patients with psoriasis. In addition, SCCA2 expression levels in skin correlated with serum concentrations of SCCA2. SCCA2 significantly decreased according to improvement of PASI scores. Interleukin (IL)-17 and IL-22 synergistically increased the production of SCCA2 at both mRNA and protein levels in human keratinocytes.
Conclusions Significant elevation of SCCA2 is associated with disease severity and reflects treatment efficacy. SCCA2 may be a useful biomarker in psoriasis, reflecting T-helper 17-type inflammation - the main determinant of the severity of psoriasis.

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）   出版者・発行元：JAPANESE SOCIETY ALLERGOLOGY  

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality.
Methods: To present the clinical characteristics of SJS and TEN in Japan and evaluate the efficacy of treatments, we retrospectively analyzed cases of SJS and TEN treated in 2 university hospitals during 2000-2013.
Results: Fifty-two cases of SJS (21 males and 31 females; average age, 55.1 years) and 35 cases of TEN (17 males and 18 females; average age, 56.6 years) were included in this study. Twenty-eight cases of SJS (53.8%) and all cases of TEN were caused by drugs. Hepatitis was the most common organ involvement in both SJS and TEN. Renal dysfunction, intestinal disorder, and respiratory disorder were also involved in some cases. The major complication was pneumonia and sepsis. All cases except for 3 cases were treated systemically with corticosteroids. Steroid pulse therapy was performed in 88.6% of TEN. Plasmapheresis and/or immunoglobulin therapy was combined with steroid therapy mainly in TEN after 2007. The mortality rate was 6.9% and the rates for SJS and TEN were 1.9% and 14.3%, respectively. These were much lower than predicted mortality according to a severity-of-illness scoring system for TEN prognosis (SCORTEN) score. When comparing the mortality rate between 2000-2006 and 2007-2013, it was decreased from 4.5% to 0.0% in SJS and from 22.2% to 5.3% in TEN.
Conclusions: Treatment with steroid pulse therapy in combination with plasmapheresis and/or immunoglobulin therapy seems to have contributed to prognostic improvement in SJS/TEN. Copyright (C) 2015, Japanese Society of Allergology. Production and hosting by Elsevier B.V.

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）   出版者・発行元：NATURE PUBLISHING GROUP  

Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal keratinocyte development, in which T helper type 17 cells and signal transducer and activator of transcription 3 (STAT3) activation have pivotal roles. Moreover, caveolin-1 (CAV-1) has been implicated in the regulation of signal transduction, and aberrant CAV-1 expression is involved in a variety of diseases. However, whether CAV-1 is involved in psoriasis is unknown. Here we examined CAV-1 expression in the psoriatic epidermis and investigated its role in the pathogenesis of psoriasis. CAV-1 was markedly reduced in lesional epidermis of psoriasis patients. CAV/ silencing in keratinocytes in vitro revealed significant activation of STAT3, leading to increased expression of keratin 16 and several cytokine/chemokines, such as IL-6, C-X-C chemokine ligand 8 (CXCL8), CXCL9, and C-C chemokine ligand 20. In addition, psoriasis-related cytokines, including tumor necrosis factor-a (TNF-a), decreased CAV-1 expression in keratinocytes. Finally, administration of CAV-1 scaffolding domain peptide in a murine model of psoriasis-like skin inflammation induced by imiquimod improved the skin phenotype and reduced epidermal thickness and infiltrating cell counts. Furthermore, expression of TNF-a, IL-17A, and IL-23 was significantly suppressed by this treatment. Collectively, our study indicated that CAV-1 participates in the pathogenesis of psoriasis by regulating the STAT3 pathway and cytokine networks.

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）   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/bjd.13162

Web of Science

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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：ACTA DERMATO-VENEREOLOGICA  

DOI： 10.2340/00015555-1610

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.61.1517_3

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.61.496_3

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記述言語：日本語   出版者・発行元：Japanese Dermatological Association  

58歳，男性．25歳時に尋常性乾癬が発症し，33歳時に霧視の自覚と共に非肉芽腫性前部ぶどう膜炎がみられ乾癬性ぶどう膜炎と診断された．シクロスポリン内服で加療されたが治療に難渋し，58歳時に膿疱性乾癬が発症した．シクロスポリンを中止しインフリキシマブを開始後，皮膚症状と共に眼症状の著明な改善が得られた．再発性，難治性の乾癬性ぶどう膜炎に対しインフリキシマブは有効な治療法と考えられた．自験例および本邦における乾癬性ぶどう膜炎のまとめでは，初発症状は，視力低下が最も多く，次いで霧視，充血，眼痛の順に多くみられた．ぶどう膜炎発症時の乾癬の臨床病型は，関節症性乾癬が31例中13例（42%）と最も多く，次いで尋常性乾癬が31例中10例（32%），膿疱性乾癬が31例中7例（23%）であった．乾癬性ぶどう膜炎患者の25例中23例（92%）で関節症状がみられ，23例中22例（96%）でHLA-A2がみられた．ぶどう膜炎に対し皮疹出現の先行例が約90%にみられ，皮疹出現から長期経過後にぶどう膜炎が生じている例が多かった．関節症状とHLA-A2を有する乾癬では，ぶどう膜炎を合併する危険性があり注意が必要と考えられた．

DOI： 10.14924/dermatol.122.2321

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.60.1447_1

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.60.1441_2

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

Background: Stevens-Johnson syndrome (SJS) associated with Mycoplasma pneumoniae (M. pneumoniae) infection is mainly observed in children. In adults, drugs are a major cause of SJS, but some adult patients with SJS are infected with M. pneumoniae. We analyzed patients with SJS associated with M. pneumoniae infection to elucidate the differences between drug-induced SJS and M. pneumoniae-associated SJS and also to study differences between M. pneumoniae-associated SJS in children and adults. Methods: This is a retrospective review of Japanese patients who have been reported as M. pneumoniaeassociated SJS in medical Journals published from 1981 to 2009, compared with data of Japanese patients with drug-induced SJS reported from 2000 to 2009. Results: Thirty-eight cases of M. pneumoniae-associated SJS and 78 cases of drug-induced SJS were analyzed in this study. Ocular lesions were observed more frequently in M. pneumoniae-associated SJS than in drug-induced SJS (p &lt
0.01), and adult patients showed a higher ratio of sequelae in their eyes than did patients under 20 years of age (p &lt
0.01). Sixty-six percent of adult patients with M. pneumoniae-associated SJS developed fever/respiratory symptoms and mucocutaneous lesions on the same day. In contrast, most of the patients under 20 years of age developed fever/respiratory symptoms before mucocutaneous involvement. This means that these adult patients were infected and immunized previously and developed allergic reactions to M. pneumoniae soon after the later infection. Conclusions: In order to prevent ocular sequelae in adult patients when M. pneumoniae infection is suspected, more intensive treatment may be needed in adult patients than in younger patients. © 2011 Japanese Society of Allergology.

DOI： 10.2332/allergolint.11-OA-0309

Scopus

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記述言語：英語  

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is characterized by a severe multiorgan hypersensitivity reaction that usually appears after prolonged exposure to certain drugs and may be related to reactivation of herpes viruses. There have been few reports regarding the clinical association of DIHS with pathogens other than herpes viruses. CASE SUMMARY: We report a case of scleroderma with DIHS associated with paramyxovirus infection. A 61-year-old man with early diffuse cutaneous scleroderma with myositis and progressive interstitial pneumonia developed generalized erythema with high fever 3 weeks after taking sulfamethoxazole/trimethoprim. The diagnosis of DIHS was made based on the patient's history of using an offending drug, clinical manifestations and laboratory data showing peripheral eosinophilia with the presence of atypical lymphocytes. Virological tests showed significant increases of antibody titers against mumps virus and parainfluenza virus type 2, which strongly suggested that paramyxovirus infection occurred during the clinical course of DIHS. DISCUSSION: These findings suggest that paramyxovirus infection had contributed to the development of DIHS in this patient and that there is a need to seek evidence of other viral infections in some cases of DIHS, especially those without herpes virus reactivation/infection.

DOI： 10.2332/allergolint.C-06-49

Scopus

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：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)日本アフェレシス学会  

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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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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：(株)全日本病院出版会  

薬疹診療において,その臨床型を鑑別し,重症度を予測することは重要な課題である.そのためには,皮疹の分布や個疹の性状を単独で捉えるのではなく,時間経過に伴う変化を踏まえた総合的な判断が求められる.本稿では,特にStevens-Johnson症候群,中毒性表皮壊死症,薬剤性過敏症症候群といった見逃してはならない重症薬疹に焦点を当て,これらの疾患に特徴的な皮疹と,それらが示唆する臨床的意義について解説する.(著者抄録)

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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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：(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  

近年,新規がん治療薬の登場に伴って,従来のがん治療薬では見られなかった新しい皮膚障害がみられるようになった。特に免疫チェックポイント阻害剤や分子標的薬は高頻度に皮膚障害を生じ,その臨床は軽症～重症まで非常に多彩である。特定のがん治療薬の効果と皮膚障害の関連性は注目すべき点であり,時に治療薬の効果を予測する有用な指標となり得る。したがって,臨床医はこれらの薬剤による皮膚障害についての最新の知識をアップデートし,適切に評価することが極めて重要である。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)協和企画  

＜文献概要＞症例のポイント ・左腎細胞癌術後の局所再発,リンパ節転移に対するニボルマブ/イピリムマブ(NIVO/IPI)初回投与後に水疱を伴う難治性扁平苔癬型薬疹(lichenoid drug eruption:LDE)を生じた.・全身性ステロイド投与にて皮疹は改善したが,ステロイド中止から2ヵ月後に誘因なく同症状が再燃し,最終的に長期のステロイド投与を要した.・再燃時の皮膚障害はGrade 3と重症であり,永続的にNIVO/IPIは中止となった.・NIVO/IPIは初回投与以降中止されたが,原疾患に対する追加治療なしにすべての癌病巣は消失し,2年間完全奏効を維持している.

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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  

J-GLOBAL

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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  

免疫チェックポイント阻害薬(ICI)の適応拡大に伴い,免疫関連有害事象(irAE)としての皮膚障害(cirAE)の発生が増加している.cirAEの多くは軽症で管理可能であるが,稀にStevens-Johnson症候群(SJS)や中毒性表皮壊死症(TEN),薬剤性過敏症症候群(DIHS)といった重症薬疹が発生することがある.ICIの使用はこれらの重症薬疹の発症リスクや重症度を高めることが示されている.これらの重症薬疹では,皮膚科医による迅速な診断と治療介入が患者の生命に直結するため,その管理が極めて重要である.また,cirAEの発症は治療効果や予後にも影響を与えることが示唆されており,特定のcirAEがICI治療の効果指標となる可能性が報告されている.本稿ではcirAEの基礎および最新の知見を概説したあとに,cirAEとしてのSJS/TEN発症メカニズム,臨床的特徴,鑑別診断,および治療法についても解説する.(著者抄録)

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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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：(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

記述言語：日本語   出版者・発行元：(一社)日本アフェレシス学会  

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記述言語：日本語   出版者・発行元：(株)協和企画  

＜文献概要＞症例のポイント ・生物学的製剤投与中の乾癬患者に生じたIgA腎症を経験した.・乾癬患者が腎障害を合併する頻度は高いが,さらに生物学的製剤投与によりIgA腎症が誘発されることがある.・生物学的製剤投与中に尿所見に変化がみられた場合にはIgA腎症も念頭に精査を行う必要がある.

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記述言語：日本語   出版者・発行元：(株)南江堂  

＜文献概要＞はじめに 乾癬および掌蹠膿疱症(palmoplantar pustulosis:PPP)は,ともに皮疹と骨関節症状を合併しうる炎症性皮膚疾患である.乾癬に末梢関節炎,体軸関節炎および付着部炎を伴う場合は乾癬性関節炎(psoriatic arthritis:PsA)に,PPPの皮疹に骨関節炎を伴う場合は掌蹠膿疱症性骨関節炎(pustulotic arthro-osteitis:PAO)に診断される.PsA,PAO患者の中には,複数の科を受診しているにもかかわらず,皮疹と骨関節症状が同一疾患による症状と認識されずに骨関節症状が進行してしまうケースが散見される.本稿ではPsAとPAOの早期発見・早期診断に有用な臨床的特徴を整理し,皮膚科へ連携すべきポイントについて考えていきたい.また,皮膚科での診療の実際について併せて概説する.

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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：(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：(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：(公社)日本皮膚科学会  

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J-GLOBAL

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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：(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：金原出版(株)  

＜文献概要＞薬疹の臨床型は軽症から重症までさまざまであり,それぞれの病態に対応した治療選択が求められる。特に重症薬疹では初期治療が患者の予後に大きく影響するため,病態を理解したうえで迅速かつ適切な治療介入が必要である。本稿では遅延型薬疹の病態について概説したのち,重症薬疹であるStevens-Johnson症候群(Stevens-Johnson syndrome,以下SJS)/中毒性表皮壊死症(toxic epidermal necrolysis,以下TEN),薬剤性過敏症症候群(drug-induced hypersensitivity syndrome,以下DIHS)の治療薬にフォーカスして,近年の知見を交えて解説する。

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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)診断と治療社  

＜産婦人科医におさえてほしいポイント＞・抗悪性腫瘍薬による手足症候群について、原因薬剤毎にその病態や症状、経過が異なることを理解する。特にリポソーマルドキソルビシンやマルチキナーゼ阻害薬による手足症候群は重症化しやすいため、しばしば休薬や追加治療が必要となる。・手足症候群は、薬剤投与前からの予防・軽症時の対応が重症化の回避につながるため、患者への生活指導、適切なタイミングでの皮膚科コンサルトが重要である。・ICIによる皮膚障害の大部分は軽症例だが、多彩な皮疹や予期せぬ経過をたどるため早期に皮膚科にコンサルトしていただくことをお勧めする。(著者抄録)

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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：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：(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：(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  

免疫チェックポイント阻害薬による皮膚障害の重症化因子および皮膚障害の臨床型分類を検討する目的で、免疫チェックポイント阻害薬の使用経過で皮膚障害を発症した163人に対してアンケート形式の調査を行った。本研究では、有意な重症化因子は同定されなかったが、対象疾患と臨床型の検討で悪性黒色腫と白斑、肺癌と扁平苔癬様皮疹に関連がみられ、対象疾患により特徴的な臨床型を呈する可能性が考えられた。皮膚障害の重症群は全体の約10%であったがTENが2症例あり、免疫チェックポイント阻害薬投与中の重症薬疹に注意すべきと考えられた。(著者抄録)

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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  

免疫チェックポイント阻害薬による皮膚障害の重症化因子および皮膚障害の臨床型分類を検討する目的で、免疫チェックポイント阻害薬の使用経過で皮膚障害を発症した163人に対してアンケート形式の調査を行った。本研究では、有意な重症化因子は同定されなかったが、対象疾患と臨床型の検討で悪性黒色腫と白斑、肺癌と扁平苔癬様皮疹に関連がみられ、対象疾患により特徴的な臨床型を呈する可能性が考えられた。皮膚障害の重症群は全体の約10%であったがTENが2症例あり、免疫チェックポイント阻害薬投与中の重症薬疹に注意すべきと考えられた。(著者抄録)

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その他リンク： https://search.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：(一社)日本皮膚悪性腫瘍学会  

免疫チェックポイント阻害薬はさまざまな有害事象が出現することが知られている。内分泌系の副作用は,投与開始後遅れて出現することや継続的なホルモン補充療法が必要になるため,注意が必要である。下垂体機能低下症は,自覚症状が非典型的で発見が難しいが,放置すると副腎クリーゼを起こし致死的となる危険性もある。今回当科にて経験した下垂体機能低下症5例の臨床的特徴を検討した。全例で強い倦怠感がみられ,3例で低ナトリウム血症がみられた。全例ステロイドホルモンの補充療法を行い速やかに改善した。転帰はprogressive diseaseが20%,partial responseが20%,残り60%がstable diseaseであった。下垂体機能低下症は早期発見し速やかにステロイドホルモン補充を行えば改善する。初発症状として倦怠感と低ナトリウム血症が高頻度にみられることから,この所見に注目することが早期発見につながると考えられる。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J02197&link_issn=&doc_id=20210719270009&doc_link_id=10.5227%2Fskincancer.36.44&url=https%3A%2F%2Fdoi.org%2F10.5227%2Fskincancer.36.44&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：(一社)日本皮膚悪性腫瘍学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚悪性腫瘍学会  

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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：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  

J-GLOBAL

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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  

J-GLOBAL

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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  

J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本皮膚悪性腫瘍学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚悪性腫瘍学会  

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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：金原出版(株)  

＜文献概要＞75歳,女性。結核性リンパ節炎に対するHERZ療法開始13日後に発熱とともに粘膜疹と全身の多形滲出性紅斑が出現しStevens-Johnson症候群と診断した。ステロイドパルス療法と免疫グロブリン大量静注療法にて治癒した。リファンピシンとエタンブトール塩酸塩の再投与にて皮疹が誘発され,原因薬剤と考えられた。抗結核薬による薬疹では薬剤中止が原疾患の増悪を招き,致死的になることも多い。Stevens-Johnson症候群の再投与試験は本来禁忌であるが,自験例は結核再燃により治療の再開が必要となり,原因薬決定のため再投与を行った。再投与に際しては,薬疹の重症度を勘案して用量を決定し,十分に経過観察しながら行うことが重要である。

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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=20200827140021&doc_link_id=10.18888%2Fhi.0000002131&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000002131&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  

2000年1月から2019年3月までに当大学2施設で経験したStevens-Johnson症候群(SJS)と中毒性表皮壊死症(TEN)132例を解析した。死亡率はSJSで1.3%、TENで12.5%であった。ステロイド投与に加え、免疫グロブリン大量静注療法や血漿交換療法との集学的治療が確立された直近7年間では、TENの死亡率は3.8%と予後の改善が認められた。また、TENの発症から2病院受診までの期間が死亡群に比べ、生存群で有意に短く、早期診断・早期治療の重要性が再確認された。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)じほう  

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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)  

＜文献概要＞90歳,女性。高血圧,胸部大動脈瘤で降圧薬と抗血小板薬を内服していた。初診時,体表面積50%のびらんがあり,中毒性表皮壊死症(TEN)と診断した。高用量ステロイドの全身投与を開始したが,びらんが拡大したため免疫グロブリン大量静注療法を追加し,治癒した。その後再発を認め,皮疹は改善したが,原疾患の大動脈瘤破裂で死亡した。高齢発症のTENの臨床的特徴を調べるため,当科で過去19年間に経験したTEN 25例について検討した。70歳以上の高齢者では,70歳未満と比較し受診が遅れる傾向があり,またTEN治療中の感染症・敗血症のリスクが有意に高いことがわかった。高齢発症例ではより慎重な治療選択が重要と考えられた。

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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=20200324060008&doc_link_id=10.18888%2Fhi.0000001828&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000001828&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：(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：(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)  

＜文献概要＞69歳,男性。52歳時に尋常性乾癬を発症し,66歳時に当科を初診した。各種生物学的製剤で効果を維持できず,69歳時にブロダルマブへ変更し,皮疹は改善した。変更6ヵ月後に左上眼瞼の浮腫,疼痛が出現した。頭部CTで左篩骨洞から左眼窩内に突出する膿瘍を認め,眼窩蜂窩織炎と診断した。耳鼻科にて切開排膿,抗菌薬投与,プレドニゾロン40mg/日を投与し改善した。一時ブロダルマブを中止していたが,中止1ヵ月後より乾癬が再燃したため投与を再開した。眼窩蜂窩織炎は,慢性副鼻腔炎から進展する,高リスクの疾患である。生物学的製剤投与中,副鼻腔炎の発症リスクが増加する可能性も報告されており,生物学的製剤投与中の患者において副鼻腔炎のコントロールも重要である。

CiNii Books

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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：(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：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)日本臨床社  

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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：(公社)日本医師会  

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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：(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：(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：(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)日本臨床社  

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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=J01205&link_issn=&doc_id=20171226160013&doc_link_id=%2Fag6niria%2F2018%2F007601%2F013%2F0074-0079%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag6niria%2F2018%2F007601%2F013%2F0074-0079%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE INC  

Web of Science

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記述言語：日本語   出版者・発行元：(株)南山堂  

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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：医学書院  

70歳,男性.右上顎洞悪性黒色腫術後に全身の紅斑が出現した.皮疹出現より4日目に発熱と皮疹が急速に増悪し,Stevens-Johnson症候群と診断した.被疑薬はすべて中止し,ベタメタゾン8mg/日の点滴を開始し,翌日よりステロイドパルス療法を施行したが病勢が進行し,表皮剥離が進行したため,中毒性表皮壊死症(toxic epidermal necrolysis:TEN)と診断した.集中治療室に転棟し,全身処置を行いながら血漿交換療法,大量免疫グロブリン静注療法を併用した.最大表皮剥離面積は80%に及んだが,16日目より皮疹の改善がみられ,32日目には完全に上皮化し,後遺症を残さず治癒した.TENの急速進行期では,各種の免疫調整効果を組み合わせた治療が有効であると考えた.(著者抄録)

CiNii Books

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）   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：国家公務員共済組合連合会  

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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）   出版者・発行元：NATURE PUBLISHING GROUP  

Web of Science

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記述言語：日本語   出版者・発行元：(株)自然科学社  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：南江堂  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2015060282

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：NATURE PUBLISHING GROUP  

Web of Science

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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）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：日本語   出版者・発行元：日本皮膚科学会  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2012371857