記述言語：英語  

DOI： 10.1111/1346-8138.17396

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Medknow  

DOI： 10.4103/ijd.ijd_281_24

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1111/1346-8138.17324

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記述言語：英語  

DOI： 10.1111/1346-8138.17322

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出版者・発行元：Cold Spring Harbor Laboratory  

Abstract

Epstein-Barr virus induced 3 (EBI3) is a gene induced by stimulation of toll-like receptors (TLRs) and functions as a component of a heterodimer cytokine IL-27. IL-27 regulates both innate and acquired immune responses; however, their functionin vivois still largely unknown. Splenomegaly, an enlargement of the spleen, is known to be induced by chronic infectious diseases, including infectious mononucleosis due to EB virus infection. Repeated treatment of imiquimod (IMQ; a TLR7 agonist) has been reported to induce splenomegaly and cytopenia due to increased splenic function. Although immune cell activation is speculated to be involved in the pathogenesis of chronic infection-mediated splenomegaly, the detailed molecular mechanism is unknown. Here, we demonstrated that IMQ induced marked splenomegaly and severe bicytopenia (anemia and thrombocytopenia) in the wild-type mice. Myeloid cells, not lymphoid cells, were increased in the enlarged spleen. Extramedullary hematopoiesis was observed in the enlarged spleen of the IMQ-treated mice. RNA-seq analysis revealed that type I interferon (IFN)-related genes were upregulated in the spleen and peripheral blood in IMQ-treated mice.Ebi3deficiency partially retrieved these IMQ-induced pathological changes. We found thatIl27as well asEbi3genes were elevated by IMQ in the spleen and peripheral blood. Further, IL-27 stimulation upregulated type I IFN-related genes in bone marrow-derived macrophage culture in the absence of type I IFN. Collectively, EBI3 contributes to TLR7-induced splenomegaly and bicytopenia, presumably via IL-27.

DOI： 10.1101/2024.06.10.598101

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Selective activator protein (AP)-1 inhibitors are potentially promising therapeutic agents for atopic dermatitis (AD) because AP-1 is an important regulator of skin inflammation. However, few studies have investigated the effect of topical application of AP-1 inhibitors in treating inflammatory skin disorders. METHODS: Immunohistochemistry was conducted to detect phosphorylated AP-1/c-Jun expression of skin lesions in AD patients. In the in vivo study, 1 % T-5224 ointment was topically applied for 8 days to the ears of 2,4 dinitrofluorobenzene challenged AD-like dermatitis model mice. Baricitinib, a conventional therapeutic agent Janus kinase (JAK) inhibitor, was also topically applied. In the in vitro study, human epidermal keratinocytes were treated with T-5224 and stimulated with AD-related cytokines. RESULTS: AP-1/c-Jun was phosphorylated at skin lesions in AD patients. In vivo, topical T-5224 application inhibited ear swelling (P < 0.001), restored filaggrin (Flg) expression (P < 0.01), and generally suppressed immune-related pathways. T-5224 significantly suppressed Il17a and l17f expression, whereas baricitinib did not. Baricitinib suppressed Il4, Il19, Il33 and Ifnb expression, whereas T-5224 did not. Il1a, Il1b, Il23a, Ifna, S100a8, and S100a9 expression was cooperatively downregulated following the combined use of T-5224 and baricitinib. In vitro, T-5224 restored the expression of FLG and loricrin (LOR) (P < 0.05) and suppressed IL33 expression (P < 0.05) without affecting cell viability and cytotoxicity. CONCLUSIONS: Topical T-5224 ameliorates clinical manifestations of AD-like dermatitis in mice. The effect of this inhibitor is amplified via combined use with JAK inhibitors.

DOI： 10.1016/j.alit.2023.12.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: With the development of novel therapies for advanced malignant melanoma (MM), biomarkers that can accurately reflect the progression of MM are needed. Serum levels of melanin-related indole metabolites such as 5-hydroxy-6-methoxyindole-2-carboxylic acid (5H6MI2C) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) are potential biomarkers for MM. Here, we describe the development of a mass spectrometry (MS)-based assay to determine serum levels of 5H6MI2C and 6H5MI2C. MATERIALS AND METHODS: We developed a stable isotope dilution-selective reaction monitoring-MS protocol using liquid chromatography tandem mass spectrometry (LC-MS/MS) to measure human serum 5H6MI2C and 6H5MI2C levels. Analytical evaluations of the method were performed and the method was applied to serum samples from MM patients (n = 81). RESULTS: The method established in this study showed high reproducibility and linearity. This novel method also found that serum 6H5MI2C levels were significantly elevated in patients with metastatic MM compared to those with non-metastatic MM. Unfortunately, 5H6MI2C did not show a comparable significant difference. CONCLUSION: We successfully established measurement methods for serum 5H6MI2C and 6H5MI2C levels using LC-MS/MS. Serum 6H5MI2C levels offer a potential marker for MM.

DOI： 10.1016/j.cca.2024.117873

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

The effect of persistent skin inflammation on extracutaneous organs and blood is not well studied. Patients with recessive dystrophic epidermolysis bullosa (RDEB), a severe form of the inherited blistering skin disorder, have widespread and persistent skin ulcers, and they develop various complications including anaemia, hyperglobulinaemia, hypoalbuminaemia and secondary amyloidosis. These complications are associated with the bioactivities of IL‐6, and the development of secondary amyloidosis requires the persistent elevation of serum amyloid A (SAA) level. We found that patients with RDEB had significantly higher serum levels of IL‐6 and SAA compared to healthy volunteers and patients with psoriasis or atopic dermatitis. Both IL‐6 and SAA were highly expressed in epidermal keratinocytes and dermal fibroblasts of the skin ulcer lesions. Keratinocytes and fibroblasts surrounding the ulcer lesions are continuously exposed to Toll‐like receptor (TLR) ligands, pathogen‐associated and damage‐associated molecular pattern molecules. In vitro, TLR ligands induced IL‐6 expression via NF‐κB in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs). SAA further induced the expression of IL‐6 via TLR1/2 and NF‐κB in NHEKs and NHDFs. The limitation of this study is that NHEKs and NHDFs were not derived from RDEB patients. These observations suggest that TLR‐mediated persistent skin inflammation might increase the risk of IL‐6‐related systemic complications, including RDEB.

DOI： 10.1111/exd.15040

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記述言語：英語  

DOI： 10.1111/1346-8138.17029

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記述言語：英語  

DOI： 10.1111/1346-8138.16974

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記述言語：英語  

DOI： 10.1111/1346-8138.16918

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記述言語：英語  

DOI： 10.1111/1346-8138.16919

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

A 43‐year‐old woman developed angioedema‐like eyelid edema on day +6 after the second NVX‐CoV2373 vaccination. Short‐term oral prednisolone treatment resulted in complete resolution of the eyelid edema.

DOI： 10.1002/cia2.12314

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1007/s12185-023-03599-7

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掲載種別：研究論文（学術雑誌）  

Previous studies on family history of psoriasis showed that patients with a family history have an earlier onset of the disease, but such studies in Japan are still limited. To elucidate the characteristics of patients with familial psoriasis, we studied the family history of patients with psoriasis using the West Japan Psoriasis Registry, a multi-institutional registry operated by 26 facilities in the western part of Japan, including university hospitals, community hospitals, and clinics. This study enrolled 1847 patients registered between September 2019 and December 2021, with 199 (10.8%) having a family history of psoriasis. Patients with a family history of psoriasis had significantly earlier onset of the disease than those without a family history. Furthermore, patients with a family history of psoriasis had significantly longer disease duration. Psoriatic arthritis (PsA) was significantly more common in patients with a family history (69/199, 34.7%) than in those without a family history (439/1648, 26.6%) (adjusted P = 0.023). A subanalysis of patients with PsA revealed a significant difference in the patient global assessment (PaGA) score in Fisher's exact test and adjusted test. The numbers of patients with PaGA 0/1 were 29 (43.3%) and 172 (39.9%) in patients with PsA with and without family history of psoriasis, respectively, whereas the numbers of patients with PaGA 3/4 were 13 (19.4%) and 145 (33.6%) in patients with PsA with and without family history of psoriasis, respectively. Other disease severity variables did not show a difference between the two groups. Our findings suggest that genetics play a larger role in the development of PsA than in the development of psoriasis vulgaris. Most cases of PsA occur in patients who already have psoriasis, therefore dermatologists should pay attention to joint symptoms, especially in patients with psoriasis who have a family history of psoriasis.

DOI： 10.1111/1346-8138.16733

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Clinical studies have suggested a bidirectional association between non-alcoholic steatohepatitis (NASH) and psoriasis, affecting each other's development and severity. Here, we explored bidirectional causal linkages between NASH and psoriasis using a murine model. METHODS: NASH was induced in mice by streptozotocin injection at 2 days of age and by high-fat diet feeding (STAM™ model). Psoriasis was induced by topical application of imiquimod (IMQ) on the ear. The severities of liver damage and psoriatic skin changes were determined using histological analysis. Gene expression in the skin tissues was evaluated using quantitative PCR analysis. Serum cytokine levels were determined using enzyme-linked immunosorbent assay. To examine the innate immune responses of normal human epidermal keratinocytes (NHEKs), the cells were treated with interleukin (IL)-17A, tumor necrosis factor (TNF)-α, and AdipoRon, an adiponectin receptor agonist. RESULTS AND DISCUSSION: There were no differences in the degree of liver tissue damage (fat deposition, inflammation, and fibrosis) between NASH mice with and those without psoriasis. Conversely, the co-occurrence of NASH significantly augmented psoriatic skin changes, represented by epidermal hyperplasia, in psoriatic mice. Pro-inflammatory cytokines were expressed in the inflamed skin of psoriatic mice, and the expression of genes, especially Il23a, Il1b, Il36g, and Mip2, was significantly upregulated by the co-occurrence of NASH. The expression of keratinocyte activation marker genes Defb4b and Krt16 was also upregulated by the co-occurrence of NASH. The serum TNF-α and IL-17 levels were increased by the co-occurrence of NASH and psoriasis. The serum adiponectin levels decreased in NASH mice compared with that in non-NASH mice. In NHEK culture, TNF-α and IL-17A synergistically upregulated CXCL1, CXCL8, and IL1B expression. The upregulated pro-inflammatory gene expression was suppressed by AdipoRon treatment, reflecting the anti-inflammatory capacity of adiponectin. CONCLUSION: The co-occurrence of NASH exacerbated psoriatic skin changes associated with increased serum inflammatory cytokine levels and decreased serum adiponectin levels. Combined with in vitro findings, increased inflammatory cytokine levels and decreased adiponectin levels likely promote innate immune responses in epidermal keratinocytes in psoriatic skin lesions. Overall, therapeutic intervention for co-occurring NASH is essential to achieve a favorable prognosis of psoriasis in clinical practice.

DOI： 10.3389/fimmu.2023.1214623

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Considering the role of epidermal keratinocytes, they occupy more than 90% of the epidermis, form a physical barrier, and also function as innate immune barrier. For example, epidermal keratinocytes are capable of recognizing various cytokines and pathogen-associated molecular pattern, and producing a wide variety of inflammatory cytokines, chemokines, and antimicrobial peptides. Previous basic studies have shown that the immune response of epidermal keratinocytes has a significant impact on inflammatory skin diseases. The purpose of this review is to provide foundation of knowledge on the cytokines which are recognized or produced by epidermal keratinocytes. Since a number of biologics for skin diseases have appeared, it is necessary to fully understand the relationship between epidermal keratinocytes and the cytokines. In this review, the cytokines recognized by epidermal keratinocytes are specifically introduced as "input cytokines", and the produced cytokines as "output cytokines". Furthermore, we also refer to the existence of biologics against those input and output cytokines, and the target skin diseases. These use results demonstrate how important targeted cytokines are in real skin diseases, and enhance our understanding of the cytokines.

DOI： 10.3389/fimmu.2023.1239598

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記述言語：英語  

DOI： 10.1111/cod.14210

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is rare and fatal when diagnosed late in the disease course. Random skin biopsy (RSB) is useful for early diagnosis, but criteria for its application are not well established. OBJECTIVE: To develop an IVLBCL-probability scoring system for stratifying patients and investigate its feasibility and capability for RSB application. METHODS: A retrospective cohort of 77 consecutive patients with suspected IVLBCL who underwent RSB was included in this study. All patients were classified into 3 IVLBCL-probability groups according to the IVLBCL-probability scoring system comprising the following 4 components: general symptoms, organ-specific symptoms, serum soluble-interleukin-2 receptor levels, and serum lactate-dehydrogenase levels. RESULTS: The high (score 7-10), intermediate (score 4-6) and low (score 1-3) IVLBCL-probability groups contained 32, 30, and 15 patients, respectively. All 5 patients with IVLBCL were stratified into the high IVLBCL probability group. Accuracies in the diagnosis of IVLBCL were 100%, 100%, and 93.8% for the low, intermediate, and high IVLBCL-probability groups. The positive detection rate in the high IVLBCL-probability group increased to 9.4% from 3.9% across all groups. CONCLUSIONS: The newly-developed IVLBCL-probability scoring system has good capability for stratification of patients and could allow limiting application of RSB for diagnosis only to high-probability groups.

DOI： 10.1016/j.jdin.2022.09.005

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記述言語：英語  

DOI： 10.1111/1346-8138.16646

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Self-healing collodion baby (SHCB), also called "self-improving collodion baby", is a rare mild variant of autosomal recessive congenital ichthyosis and is defined as a collodion baby who shows the nearly complete resolution of scaling within the first 3 months to 1 year of life. However, during the neonatal period, it is not easy to distinguish SHCB from other inflammatory forms of autosomal recessive congenital ichthyosis, such as congenital ichthyosiform erythroderma. Here, we report a case study of two Japanese SHCB patients with compound heterozygous mutations, c.235G>T (p.(Glu79*))/ c.1189C>T (p.(Arg397Cys)) and c.1295A>G (p.(Tyr432Cys))/ c.1138delG (p.(Asp380Thrfs*3)), in CYP4F22, which encodes cytochrome P450, family 4, subfamily F, polypeptide 22 (CYP4F22). Immunohistochemically, inflammation with the strong expression of IL-17C, IL-36γ, and TNF-α was seen in the skin at birth. CYP4F22 is an ultra-long-chain fatty acid (FA) ω-hydroxylase responsible for ω-O-acylceramide (acylceramide) production. Among the epidermal ceramides, acylceramide is a key lipid in maintaining the epidermal permeability barrier function. We found that the levels of ceramides with ω-hydroxy FAs including acylceramides and the levels of protein-bound ceramides were much lower in stratum corneum samples obtained by tape stripping from SHCB patients than in those from their unaffected parents and individuals without SHCB. Additionally, our cell-based enzyme assay revealed that two mutants, p.(Glu79*) and p.(Arg397Cys), had no enzyme activity. Our findings suggest that genetic testing coupled with non-invasive ceramide analyses using tape-stripped stratum corneum samples might be useful for the early and precise diagnosis of congenital ichthyoses, including SHCB.

DOI： 10.1016/j.jlr.2022.100308

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/ijd.16460

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ijd.16460

記述言語：英語  

DOI： 10.1111/1346-8138.16601

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Western Japan Division of JDA  

DOI： 10.2336/nishinihonhifu.84.337

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記述言語：英語   出版者・発行元：ELSEVIER IRELAND LTD  

Atopic dermatitis (AD) is a chronic inflammatory skin disease; the three major factors responsible for AD, i.e., epidermal barrier dysfunction, allergic inflammation, and itching, interact with each other to form a pathological condition. Excessive protease activities are characteristic abnormalities that affect the epi-dermal barrier in patients with AD. In normal skin, epidermal serine protease activities are controlled by kallikrein-related peptidases (KLKs) and their inhibitors, including lympho-epithelial Kazal-type-related inhibitor (LEKTI). In AD lesions, KLKs are excessively expressed, which results in the enhancement of epi-dermal serine protease activities and facilitates the invasion by allergens and microorganisms. In addition, some KLKs can activate protease-activated receptor 2 (PAR2) in epidermal keratinocytes and peripheral nerves, resulting in the induction of inflammation and itching. Furthermore, in AD patients with single nucleotide polymorphism (SNP) such as E420K and D386N of SPINK5 which encodes LEKTI, LEKTI function is attenuated, resulting in the activation of KLKs and easy invasion by allergens and microorganisms. Further analysis is needed to elucidate the detailed mechanism underlying the control of serine protease activities, which may lead to the development of new therapeutic and prophylactic agents for AD.(c) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jdermsci.2022.06.004

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Western Japan Division of JDA  

DOI： 10.2336/nishinihonhifu.84.202

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記述言語：英語  

DOI： 10.1111/1346-8138.16442

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and Apoe-deficient dyslipidemic mice, and administered a high-fat diet for 10 weeks to induce obesity. Imiquimod was applied to the ear for 5 days to induce psoriatic dermatitis. To examine the innate immune responses of NHEKs, we cultured and stimulated NHEKs using IL-17A, TNF-α, palmitic acid, and leptin. We found that obesity and dyslipidemia synergistically aggravated psoriatic dermatitis associated with increased gene expression of pro-inflammatory cytokines and chemokines. Treatment of NHEKs with palmitic acid and leptin amplified pro-inflammatory responses in combination with TNF-α and IL-17A. Additionally, pretreatment with palmitic acid and leptin enhanced IL-17A-mediated c-Jun N-terminal kinase phosphorylation. These results revealed that obesity and dyslipidemia synergistically exacerbate psoriatic skin inflammation, and that metabolic-disorder-associated inflammatory factors, palmitic acid, and leptin augment the activation of epidermal keratinocytes. Our results emphasize that management of concomitant metabolic disorders is essential for preventing disease exacerbation in patients with psoriasis.

DOI： 10.3390/ijms23084312

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掲載種別：研究論文（学術雑誌）  

Generalized pustular psoriasis (GPP) is a rare and severe subtype of psoriasis. Because of its rarity, GPP studies with a large sample size have been scarce. We studied the characteristics of GPP and pustular psoriasis using data from the West Japan Psoriasis Registry that had been registered until the end of December 2020. The dataset included 104 patients with pustular psoriasis and 1290 patients with other subtypes of psoriasis. Multivariate analysis revealed a significantly greater number of female patients, a significantly lower mean body mass index, and a significantly lower ratio of habitual drinkers in pustular psoriasis, compared to other subtypes of psoriasis. Of the 104 patients, 102 had GPP, including 88 von Zumbusch, 10 juvenile-onset, and four annular pustular psoriasis. Although the male : female ratio of GPP with psoriasis vulgaris (GPP+PsV) (47/20) was similar to that of psoriasis in Japan, the GPP without PsV (GPP−PsV) group highlighted a female predominance (13/22). The mean age at GPP onset was 45.3 years, and the mean interval from PsV onset to GPP onset was 12.5 years. Four of nine patients with GPP had an IL36RN gene mutation. Infection, medicine, and pregnancy were the precipitating factors for GPP. A family history of psoriasis was present in eight (7.8%) patients with GPP. Twenty-four patients with GPP had psoriatic arthritis. Biologics were used in 76.5% of patients with GPP, followed by etretinate (37.3%), cyclosporine (24.5%), methotrexate (13.7%), apremilast (8.8%), and granulocyte and monocyte adsorption apheresis (6.9%). Etretinate was used in 17 (51.5%) of 33 patients with GPP with less than 10-year history. Thus, etretinate remains a good treatment option for GPP even in the era of biologics. Hypertension was the most commonly identified comorbidity, followed by diabetes. We believe that the characteristics revealed in this study can further contribute to effective GPP management.

DOI： 10.1111/1346-8138.16217

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記述言語：英語  

DOI： 10.1111/1346-8138.16285

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記述言語：英語  

DOI： 10.1111/jdv.17890

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/cia2.12189

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Interleukin (IL) 23 (p19/p40) plays a critical role in the pathogenesis of psoriasis and is upregulated in psoriasis skin lesions. In clinical practice, anti-IL-23Ap19 antibodies are highly effective against psoriasis. IL-39 (p19/ Epstein-Barr virus-induced (EBI) 3), a newly discovered cytokine in 2015, shares the p19 subunit with IL-23. Anti-IL-23Ap19 antibodies may bind to IL-39; also, the cytokine may contribute to the pathogenesis of psoriasis. To investigate IL23Ap19- and/or EBI3-including cytokines in psoriatic keratinocytes, we analyzed IL-23Ap19 and EBI3 expressions in psoriasis skin lesions, using immunohistochemistry and normal human epidermal keratinocytes (NHEKs) stimulated with inflammatory cytokines, using quantitative real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-electrospray tandem mass spectrometry (LC-Ms/Ms). Immunohistochemical analysis showed that IL-23Ap19 and EBI3 expressions were upregulated in the psoriasis skin lesions. In vitro, these expressions were synergistically induced by the triple combination of tumor necrosis factor (TNF)-α, IL-17A, and interferon (IFN)-γ, and suppressed by dexamethasone, vitamin D3, and acitretin. In ELISA and LC-Ms/Ms analyses, keratinocyte-derived IL-23Ap19 and EBI3, but not heterodimeric forms, were detected with humanized anti-IL-23Ap19 monoclonal antibodies, tildrakizumab, and anti-EBI3 antibodies, respectively. Psoriatic keratinocytes may express IL-23Ap19 and EBI3 proteins in a monomer or homopolymer, such as homodimer or homotrimer.

DOI： 10.3390/ijms222312659

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掲載種別：研究論文（学術雑誌）  

The efficacy and safety of new psoriatic treatments are confirmed in clinical trials, but such clinical trial data are limited by the number and heterogeneity of patients. Furthermore, the prevalence and characteristics of psoriasis differ among racial groups. Therefore, it is important to obtain real-world evidence in specific regions. To identify the optimal systemic treatment for psoriatic patients in Western Japan, we established the Western Japan Psoriasis Registry (WJPR). This registry is led by a neutral physicians’ league associated with university hospitals, general hospitals, and clinics that specialize in treatment of psoriasis. Systemically treated psoriatic patients who provided written informed consent were enrolled, and data were collected on their background information, several patient-reported outcomes, dermatologists’ objective evaluations, and treatment regimens. Patient enrollment began in 2019, and 1394 patients had been recruited by the end of 2020. The prevalence of psoriatic arthritis was 27.2% and that of pustular psoriasis was 7.5%. The mean body mass index was 24.1 kg/m2, and 12% of patients had severe obesity (body mass index ≥30 kg/m2). Major comorbidities were hypertension (35.0%), diabetes (14.1%), and hyperlipidemia (12.2%). Serological data showed that hepatitis B virus surface antigen, anti-hepatitis B virus core antibody, anti-hepatitis C virus antibody, and human T-cell leukemia virus type 1 antibody were detected in 1.1%, 18.0%, 3.1%, and 3.7% of patients, respectively. The most frequently used small-molecule-systemic intervention was apremilast (18.0%), followed by methotrexate (7.7%), etretinate (4.2%), and cyclosporin (3.7%). The most frequently used biologics were interleukin (IL)-17 inhibitors (31.8%), followed by IL-23 inhibitors (including IL-12/23 inhibitors) (26.7%), and tumor necrosis factor inhibitors (11.1%). The WJPR is the first Japanese prospective observational cohort of psoriatic patients. Annual WJPR updates may provide the incidences of comorbidities such as cardiovascular events or onset of arthritis in systemically treated patients, identify rare complications, and identify the optimal treatment regimens for various psoriatic patients.

DOI： 10.1111/1346-8138.16092

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記述言語：英語  

DOI： 10.1111/1346-8138.16195

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記述言語：英語  

DOI： 10.1111/1346-8138.16186

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Anti-programmed cell death protein-1 (PD-1) antibodies have become a standard treatment for advanced melanoma. However, a predictive biomarker for assessing the efficacy of anti-PD-1 antibodies has not been identified. In cancer, CD8+ T cells specific for tumor antigens undergo repeated T-cell receptor stimulation due to the persistence of cancer cells and gradually lose their ability to secrete interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). We aimed to evaluate multi-cytokine production and immune exhaustion of peripheral CD8+ T cells in melanoma patients treated with anti-PD-1 antibodies. Twenty-four melanoma patients treated with nivolumab were included. Effector cytokine production (IL-2, TNF-α, and IFN-γ) and expression of an exhaustion marker (PD-1) in patients' CD8+ cells were analyzed with flow cytometry. The relationships between parameters such as the neutrophil-to-lymphocyte ratio (NLR) and clinical response to nivolumab were examined. Immunohistochemistry for programmed death-ligand 1 (PD-L1) expression in tumor cells and tumor-infiltrating lymphocytes (TILs) and analysis of their association with clinical response were performed. The clinical response rate to nivolumab was 29%. Regarding TILs, NLR, and several other parameters, no significant difference was found between responders and non-responders. The responder group showed an increase in the percentage of PD-1+ CD8+ /TNF-α+ IFN-γ+ or PD-1+ CD8+ /IFN-γ+ IL-2+ TNF-α+ T cells compared to non-responders. Positivity for PD-L1 expression was significantly higher in the responder group than the non-responder group. In advanced melanoma, the percentage of multifunctional CD8+ PD-1+ T cells and PD-L1 expression in the tumors may be a biomarker for a good response to anti-PD-1 antibody monotherapy.

DOI： 10.1111/1346-8138.15904

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

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

DOI： 10.1111/1346-8138.16057

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記述言語：英語  

DOI： 10.1111/1346-8138.15896

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記述言語：英語  

DOI： 10.1016/j.jdermsci.2021.06.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.5946-20

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記述言語：英語  

DOI： 10.1111/1346-8138.15870

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1111/1346-8138.15729

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

It has recently been shown that bi-allelic mutations in the lanosterol synthase (LSS) gene, which was originally reported as a causative gene for congenital cataracts, underlie a non-syndromic form of hypotrichosis. Furthermore, it has also been revealed that mutations in the LSS gene can cause syndromic forms of hypotrichosis. To date, however, clear genotype-phenotype correlations have not completely been characterized. In this study, we identified two Japanese patients who had severe congenital hypotrichosis without any other associated findings. Their scalp hairs were extremely short and thin, and were able to be plucked easily. Observation of the plucked hairs showed aberrantly-miniaturized anagen hair follicles. Genetic analysis demonstrated that both patients carried bi-allelic mutations in the LSS gene in a compound heterozygote state. Our findings further underscore the crucial roles of the LSS gene in hair follicle development and hair growth in humans.

DOI： 10.1111/1346-8138.15679

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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.13820

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記述言語：英語  

DOI： 10.1111/1346-8138.15687

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 41-year-old man presented with itching of the skin surrounding his tattoos, blurred vision, fever, general fatigue, and arthralgia. Physical examination revealed skin bulges confined to the tattoo ink lines. Histological analyses of the skin revealed non-caseating granulomas surrounding the tattoo inks. Together with other clinical manifestations including uveitis, lymph nodes swelling, and elevated serum angiotensin-converting enzyme and lysozyme, he was diagnosed with systemic sarcoidosis. The administration of prednisolone alleviated the sarcoidosis-related symptoms, including skin changes. This case illustrates that skin changes on tattoos can be a presenting manifestation of systemic sarcoidosis and that skin biopsy is useful in early diagnosis.

DOI： 10.1080/24725625.2020.1816645

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Western Division of Japanese Dermatological Association  

DOI： 10.2336/NISHINIHONHIFU.83.431

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Western Division of Japanese Dermatological Association  

DOI： 10.2336/NISHINIHONHIFU.83.417

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Western Division of Japanese Dermatological Association  

DOI： 10.2336/NISHINIHONHIFU.83.120

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Our Dermatology Online  

DOI： 10.7241/ourd.20204.28

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.15542

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.15497

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.15513

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Smartphones have become essential devices in modern society. The coverage rate of smartphones in 2017 in Japan was 75% according to the Ministry of Internal Affairs and Communications. The iPhone is one of the most well-known smartphone brands. According to the manufacturer of iPhones (Apple), more than 200 million iPhones had been sold worldwide by 2017. These devices are often charged at night-time, especially while being used in bed. There are only three reports of smartphone charger-induced skin damage. We present two new cases of skin ulcers induced by an iPhone charger. The iPhone's "lightning cable" has electrodes outside, and we found that this can present a higher risk of causing a skin injury compared with other types of phone chargers. We also investigated the mechanism of the skin ulcers caused by the iPhone charger. The results indicated that these ulcers were chemical burns rather than an electrical injury or heat-induced burn.

DOI： 10.1111/1346-8138.15475

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Several virulence factors of Aeromonas such as hemolysin, proteases and lipases have been characterized. The relationship between these virulence factors and disease remains unclear. A 71-year-old man underwent thoracoscopic esophagectomy, lymph node dissection and Roux-en-Y reconstruction for esophageal cancer. On postoperative day 1, redness around the wound on the thoracic abdominal wall gradually enlarged and necrosis became apparent with septic shock. Necrotizing soft tissue infection was suspected and emergency surgical debridement was performed. Blood and wound cultures were positive for Aeromonas hydrophila. The strain was found to have hemolytic activity, proteolytic activity and extremely high elastolytic activity. In addition, the strain actively produced elastolytic metalloprotease, which may contribute to extensive tissue necrosis.

DOI： 10.1111/1346-8138.15323

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1002/jmv.25811

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.15248

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although rare, tuberculosis has been reported with biologic treatment against psoriasis in Japan, a tuberculosis medium-burden country. Mycobacterial infection often develops after a long incubation period and might not have been adequately identified in clinical trials or post-marketing surveillance. To determine the real-world incidence of tuberculosis in psoriatic patients treated with biologics, we conducted a retrospective, multicenter, observational study in 18 facilities in Western Japan. Psoriatic patients who visited a participating facility between 2010 and March 2017 and received biologic reagents were enrolled. Information on sex, age at first biologic treatment, results of interferon-γ release assay (IGRA) for Mycobacterium tuberculosis, treatment history with isoniazid, and onset of active and/or latent tuberculosis was collected. A total of 1117 patients (830 men and 287 women) were enrolled. The mean duration of biologic treatment was 3.54 years. Sixty-five patients (5.8%) showed positive IGRA results at screening. Active tuberculosis developed in two patients after the administration of tumor necrosis factor inhibitors (both involved miliary tuberculosis). Latent tuberculosis was observed in two patients treated with anti-interleukin-12/23p40 antibody. The incidence rate of tuberculosis, including latent tuberculosis, in this survey was 0.36%. Although the incidence rate of tuberculosis was low considering the observation period of biologic treatment, active tuberculosis was found in both the screening-negative group and a screening-positive subject after isoniazid prophylaxis (both miliary tuberculosis), concluding that negative screening or isoniazid treatment does not always assure that an individual has no tuberculosis. Hence, dermatologists still need to pay careful attention to tuberculosis at every patient visit.

DOI： 10.1111/1346-8138.15156

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.3390/ijms21030913

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Immunoglobulin A (IgA) vasculitis (IgAV) is a small vessel vasculitis presenting cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis caused by deposition of the IgA1-mediated immune complex. Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterised by eosinophil-rich and granulomatous inflammation in small to medium-sized vessels. Both IgAV and EGPA are classified as autoimmune systemic vasculitis, but the pathogenesis of immune complex-mediated IgAV and that of pauci-immune EGPA are different. Here we report a rare case of simultaneous development of IgAV and EGPA presenting palpable purpura and numbness in a patient with a history of asthma. Histological examination revealed leukocytoclastic vasculitis with deposition of IgA, IgM and C3 in the upper dermis and necrotising vasculitis with eosinophilic infiltration and granulomatous formation in the lower dermis and subcutaneous fat, indicating the existence of IgAV and EGPA. Our case provides evidence of concurrent development of two different types of vasculitis, which may affect disease-associated complications, therapeutic strategy and prognosis.

DOI： 10.1080/24725625.2019.1673528

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: With the recent developments in novel molecular targeted therapy such as immune-checkpoint blockades, serine/threonine-protein kinase B-Raf, and mitogen-activated protein kinase kinase inhibitors, the prognosis of advanced malignant melanoma has been improving. 5-S-cysteinyl-dopa (5-S-CD), a precursor of pheomelanin, has been previously revealed to be a useful biomarker for advanced-stage malignant melanoma, especially in patients with distant metastases. Here, we aimed to assess and compare the utility of serum 5-S-CD and lactate dehydrogenase levels as markers for predicting the effects of nivolumab in advanced malignant melanoma. METHODS: Baseline serum 5-S-CD and lactate dehydrogenase levels in patients with unresectable stage IIIC and IV malignant melanoma treated with nivolumab (n = 21) were analyzed to determine their utility as predictive markers for survival. We also analyzed the prognostic value of these markers among patients with only stage IV malignant melanoma (n = 17). RESULTS: Our analysis showed that patients with baseline serum 5-S-CD levels >25.0 nmol/L had significantly poor prognosis. In contrast, serum lactate dehydrogenase levels at the upper limit of the normal range did not exhibit such changes. CONCLUSIONS: Serum 5-S-CD levels have the potential to be an excellent predictive marker for the efficacy of nivolumab therapy in patients with advanced malignant melanoma.

DOI： 10.1177/1724600819883658

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.15078

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cutaneous angiosarcoma is a rare aggressive malignant tumor. Concurrent chemoradiation (CCRT) with maintenance chemotherapy using taxanes is one of the primary treatments. The aim of the present study was to retrospectively analyze the efficacy of CCRT with maintenance chemotherapy using taxanes in localized angiosarcoma of the scalp without cervical lymph node metastases. A total of 19 patients treated with radiation therapy for localized angiosarcomas of the scalp without cervical lymph node metastases were enrolled. The overall survival (OS), progression-free survival (PFS), and local control (LC) rates were calculated using Kaplan-Meier analysis. Univariate analyses were performed for various potential prognostic factors for OS, PFS, and LC. The median radiation dose was 70 Gy (range, 60-70 Gy), and the fractional dose was 2 Gy. Radiation therapy alone, radiation therapy + interleukin-2, surgery + CCRT with maintenance chemotherapy, CCRT with maintenance chemotherapy, and CCRT without maintenance chemotherapy were administered to 2, 4, 2, 9 and 2 patients, respectively. The 1- and 3-year OS, PFS, and LC rates were 88 and 52%, 47 and 33%, and 74 and 56%, respectively. CCRT with maintenance chemotherapy and surgery were significant prognostic factors for PFS (P=0.036 and 0.025, respectively). Therefore, CCRT with maintenance chemotherapy using taxanes might be effective in treating localized angiosarcomas of the scalp without cervical lymph node metastases.

DOI： 10.3892/mco.2019.1918

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記述言語：英語  

DOI： 10.1111/1346-8138.14896

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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.2019.08.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1111/1346-8138.15049

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.15049.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.14756

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.14745.

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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/ijd.14141

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

Excessive protease activity is a characteristic abnormality that affects the epidermal barrier in patients with atopic dermatitis (AD). Kallikrein-related peptidases (KLKs) are excessively expressed in AD lesions, and it is suggested that the abnormal action of KLKs is involved in the skin barrier dysfunction in AD. In other words, overexpressed KLKs disrupt the normal barrier function, and due to that breakdown, external substances that can become antigens of AD easily invade the epidermis, resulting in dermatitis, coupled with the induction of Th2 cytokines. Further investigations are required to elucidate the role of KLKs in AD; this knowledge could contribute to the design of new therapeutic and prophylactic drugs for AD.

DOI： 10.18926/AMO/56452

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.14694.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.14756.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2336/nishinihonhifu.81.396

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1111/1346-8138.14694

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Toll-like receptors (TLRs) play critical roles in innate immune response by sensing pathogen- or damage-associated molecular patterns. Epidermal keratinocytes and dermal fibroblasts also produce proinflammatory cytokines and chemokines under stimulation with TLR ligands. Serum amyloid A (SAA) is an essential factor in the pathogenesis of secondary amyloidosis, and also has immunomodulatory functions. SAA are produced mainly by hepatocytes but also by a variety of cells, including immune cells, endothelial cells, synoviocytes, and epidermal keratinocytes. However, SAA expression in human dermal fibroblasts has not been shown to date. AIM: To investigate the effect of TLR ligands on SAA expression in epidermal keratinocytes and dermal fibroblasts. METHODS: We investigated whether TLR ligands induce the expression of SAA in normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) by real-time quantitative PCR and ELISA. The effect of SAA on its own expression in NHDFs was also studied. RESULTS: SAA expression was induced via nuclear factor-κB by TLR1/2, 3, 5 and 2/6 ligands in NHEKs. In NHDFs, TLR1/2 and TLR2/6 ligands increased SAA expression. SAA further induced its own expression via TLR1/2 and NF-κB in NHDFs, as previously reported for NHEKs. CONCLUSIONS: Our results provide new evidence that the skin's innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa.

DOI： 10.1111/ced.13604

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report the case of an 88-year-old Japanese man with erythrodermic involvement of T-cell prolymphocytic leukemia (T-PLL). He had a history of pharyngeal diffuse large B-cell lymphoma successfully treated with polychemotherapy including cyclophosphamide and epirubicin, 6 years before the current illness. He presented with numerous reddish, coalescing, flat-topped papules on the trunk and extremities, sparing the skin folds of the abdomen, the features of which mimicked those of papuloerythroderma. Immunohistochemistry showed perivascular and epidermotropic infiltration of CD3+ CD4+ T cells in the cutaneous lesion. However, flow cytometric analysis revealed that the skin infiltrating T cells were negative for surface CD4, and that CD3+ CD4- CD8- cells made up 92% of the T-cell fraction of peripheral blood. The circulating atypical T cells had a round or oval nucleus and prominent nucleoli, and the deletion of chromosomes 6q, 13 and 17. These cytological profiles were consistent with those of T-PLL and distinct from those of Sézary cells. The same T-cell clone was detected in the cutaneous lesion and peripheral blood, but the expression of CD62L was absent in the skin infiltrates and present in the circulating cells. No specific mutation was detected in STAT3 or STAT5B. Although low-dose oral etoposide had a beneficial effect on the skin rash, a fatal crisis of marked leukocytosis (169 × 103 /μL) occurred 19 months after the illness onset. CD62L-leukemic cells of T-PLL may infiltrate the skin to form papuloerythroderma-like cutaneous lesions.

DOI： 10.1111/1346-8138.14702

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Lympho-epithelial Kazal-type inhibitor (LEKTI) tightly controls the activities of serine proteases such as kallikrein-related peptidase (KLK) 5 and KLK7 in the epidermis. LEKTI is known to be an essential molecule for the epidermal skin barrier, as demonstrated by SPINK5 nonsense mutation, which results in Netherton syndrome. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns or damage-associated molecular patterns and produce inflammatory cytokines, chemokines, and antimicrobial peptides. However, the effect of TLR signaling on the expression of LEKTI is not clear. OBJECTIVE: To investigate whether TLR signaling can affect expression of LEKTI in epidermal keratinocytes. METHODS: We stimulated a panel of TLR ligands and investigated the expression of LEKTI in normal human epidermal keratinocytes (NHEKs). We further measured trypsin or chymotrypsin-like serine protease activity in NHEK cultured media under stimulation with TLR3 ligand, poly (I:C). Immunostaining for LEKTI was performed using skin samples from skin infectious diseases. RESULTS: TLR1/2, 3, 5, and 2/6 ligands induced the expression of LEKTI in NHEKs. The trypsin or chymotrypsin-like serine protease activity in NHEKs was up-regulated with the stimulation of poly (I:C). The gene expressions of KLK6, KLK10, KLK11, and KLK13 were also increased by poly (I:C). An immunohistochemical analysis demonstrated that the expression of LEKTI was up-regulated in the lesions of varicella, pyoderma, and rosacea. CONCLUSIONS: TLR signaling induces the expression of LEKTI in epidermal keratinocytes, which might contribute to the control of aberrant serine protease activities in inflammatory skin diseases.

DOI： 10.1016/j.jdermsci.2018.09.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1001/jamadermatol.2018.1601

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記述言語：英語  

DOI： 10.1111/bjd.16443

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記述言語：英語  

DOI： 10.1111/bjd.16319

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a large multidomain serine protease inhibitor that is expressed in epidermal keratinocytes. Nonsense mutations of the SPINK5 gene, which codes for LEKTI, cause Netherton syndrome, which is characterized by hair abnormality, ichthyosis, and atopy. A single nucleotide polymorphism (SNP) of SPINK5, p.K420E, is reported to be associated with the pathogenesis of atopic dermatitis (AD). We studied all 34 exons of the SPINK5 gene in Japanese 57 AD patients and 50 normal healthy controls. We detected nine nonsynonymous variants, including p.K420E; these variants had already been registered in the SNP database. Among them, p.R654H (n=1) was found as a heterozygous mutation in the AD patients, but not in the control. No new mutation was detected. We next compared the data of the AD patients with data from the Human Genetic Variation Database provided by Kyoto University; a significant difference was found in the frequency of the p.S368N genotype distribution. PolyPhen-2 and SIFT, two algorithms for predicting the functional effects of amino acid substitutions, showed significant scores for p.R654H. Therefore, R654H might be a risk factor for epidermal barrier dysfunction in some Japanese AD patients.

DOI： 10.18926/AMO/56073

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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.2018.3234

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記述言語：英語  

DOI： 10.1111/1346-8138.14127

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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 common chronic inflammatory skin disorder that is characterized by scaly, erythematous, sharply demarcated plaques. The treatment for psoriasis has dramatically changed over the last 10 years with the introduction of biologics. However, the risk of cancer induced by biologics for psoriasis has not been fully analyzed, since these agents have such a short history of use. Here we report the case of a 74-year-old woman with psoriasis vulgaris and psoriatic arthritis complicated by breast cancer after systemic treatments including etretinate, cyclosporine, methotrexate, adalimumab, and ustekinumab.

DOI： 10.18926/AMO/55860

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Double-stranded RNA (dsRNA) sensors including TLR3, MDA5 and RIG-I are expressed in epidermal keratinocytes and play an important immunological role by enhancing various innate and adaptive immune responses. Although the role of elevated extracellular calcium concentration in keratinocyte differentiation is well understood, the effect of high calcium on dsRNA sensors is not well studied. We investigated alterations in dsRNA sensor expression and antiviral activity induced by a high extracellular concentration of calcium in epidermal keratinocytes. Normal human epidermal keratinocytes (NHEKs) were stimulated with high calcium and/or synthetic dsRNA, poly (I:C). TLR3, IFIH1 (MDA5) and DDX58 (RIG-I) expression were measured via qPCR, and IFN-β and human beta-defensin 2 (HBD2) levels were measured using ELISA. TLR3 localization was evaluated with immunocytofluorescence. Antiviral activity was quantified with virus plaque assays using herpes simplex virus type 1 (HSV-1). High calcium significantly upregulated mRNA expression of TLR3, IFIH1 and DDX58 in NHEKs. In addition, high calcium significantly enhanced poly (I:C)-induced anti-HSV-1 activity in NHEKs. The antiviral molecule HBD2 but not IFN-β induction by poly (I:C) was enhanced by high calcium. Our findings indicate that high levels of extracellular calcium enhance the expression of dsRNA sensors and augment antiviral activity in epidermal keratinocytes.

DOI： 10.1111/exd.13456

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記述言語：英語  

DOI： 10.1684/ejd.2017.3147

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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/exd.13361

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記述言語：英語  

DOI： 10.1093/annonc/mdx325

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記述言語：英語  

DOI： 10.1016/j.jid.2016.10.016

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記述言語：英語  

DOI： 10.1684/ejd.2016.2889

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1016/j.jdermsci.2016.10.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We previously reported a positive feedback loop between S100A8/A9 and proinflammatory cytokines mediated by extracellular matrix metalloproteinase inducer, an S100A9 receptor. Here, we identify neuroplastin-β as an unreported S100A8 receptor. Neuroplastin-β and extracellular matrix metalloproteinase inducer form homodimers and a heterodimer, and they are co-localized on the surface of cultured normal human keratinocytes. Knockdown of both receptors suppressed cell proliferation and proinflammatory cytokine induction. Upon stimulation with S100A8, neuroplastin-β recruited GRB2 and activated extracellular signal-regulated kinase, resulting in keratinocyte proliferation. Keratinocyte proliferation in response to inflammatory stimuli was accelerated in involucrin promoter-driven S100A8 transgenic mice. Further, S100A8 and S100A9 were strongly up-regulated and co-localized in lesional skin of atopic dermatitis patients. Our results indicate that neuroplastin-β and extracellular matrix metalloproteinase inducer form a functional heterodimeric receptor for S100A8/A9 heterodimer, followed by recruitment of specific adaptor molecules GRB2 and TRAF2, and this signaling pathway is involved in activation of both keratinocyte proliferation and skin inflammation in atopic skin. Suppression of this pathway might have potential for treatment of skin diseases associated with chronic inflammation such as atopic dermatitis.

DOI： 10.1016/j.jid.2016.06.617

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1016/j.jdermsci.2016.03.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Thymic stromal lymphopoietin (TSLP) initiates the Th2-type allergic inflammation, and is thought to play an important role in the pathogenesis of atopic dermatitis (AD). TNF-α is a key cytokine which is involved in the pathophysiology of various inflammatory diseases, and the expression level is elevated in the sera and skin of patients with AD. In addition, TNF-α has been reported to induce TSLP expression in epidermal keratinocytes. Topical glucocorticoids and calcineurin inhibitors are safe and effective agents for AD, but the effects of these agents on TNF-α-induced TSLP expression are not fully understood. OBJECTIVE: To investigate whether the glucocorticosteroid dexamethasone and the calcineurin inhibitor tacrolimus could affect TSLP expression induced by TNF-α in lesional keratinocytes of AD. METHODS: The effects of topical dexamethasone and tacrolimus on TSLP expression were evaluated in an AD mouse model induced by repeated 2,4,6-trinitro-1-chlorobenzene application. Co-immunostaining for TSLP and TNF-α was performed using skin samples from AD patients and the mouse model. Normal human epidermal keratinocytes (NHEKs) were cultured with dexamethasone or tacrolimus in the presence of TNF-α to analyze TSLP expression. RESULTS: Topical application of dexamethasone but not tacrolimus repressed TSLP expression in the mouse model. TSLP and TNF-α showed similar distribution pattern in epidermal keratinocytes of AD lesions and the mouse model. TSLP expression was induced by TNF-α via NF-κB in a dose-dependent and an autocrine and/or paracrine manner in NHEKs, which was significantly suppressed by dexamethasone but not by tacrolimus. Similarly to TSLP expression, IL-6, TNF-α, IL-8, and IL-36γ expression induced by TNF-α were significantly suppressed by dexamethasone but not by tacrolimus in NHEKs. CONCLUSION: Dexamethasone but not tacrolimus suppresses the TSLP expression induced by TNF-α in lesional keratinocytes of AD model. Our observations uncover the unreported functional difference between topical glucocorticosteroids and calcineurin inhibitors in cutaneous inflammatory diseases.

DOI： 10.1016/j.jdermsci.2015.06.016

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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 SCIENCE INC  

Toll-like receptors (TLRs) recognize specific microbial products in the innate immune response. TLR3, a double-stranded RNA sensor, is thought to have an important role in viral infections, but the regulation of TLR3 expression and its function in keratinocytes are not fully understood. Here we show the Th1 cytokine IFN-γ increased the TLR3 expression via STAT1 in cultured normal human epidermal keratinocytes (NHEKs). Co-stimulation with IFN-γ and the TLR3 ligand poly (I:C) synergistically increased the expression of IFN-β, IL-6, IL-8, and human β-defensin-2 in NHEKs compared with poly (I:C) or IFN-γ alone. These synergistic inductions were significantly inhibited by an endosomal acidification inhibitor, chloroquine, and by TLR3 siRNA. Co-stimulation with IFN-γ and poly (I:C) also significantly enhanced the anti-viral activity against herpes simplex virus type-1 in NHEKs compared with poly (I:C) or IFN-γ alone. In addition to the in vitro findings, an immunohistochemical analysis revealed IFN-γ-positive cells surrounding herpetic vesicles. These findings indicate that IFN-γ might contribute to the innate immune response to cutaneous viral infections by enhancing TLR3 expression and function in keratinocytes.

DOI： 10.1038/jid.2015.125

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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)  

DOI： 10.1111/bjd.13411

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1111/1346-8138.12695

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記述言語：英語  

Background Cathelicidin antimicrobial peptide LL-37 has the capacity to kill a wide range of microbes and to modify host immunity. Recently, our group observed that the activation of keratinocytes by LL-37 and DNA greatly increases interferon (IFN)-beta through Toll-like receptor (TLR) 9. However, the effect of LL-37 on the induction of IFN-beta through TLR3, a sensor of double-stranded (ds) RNA, in keratinocytes is not well known. Objectives To investigate whether LL-37 could affect TLR3 signalling and antiviral activity in normal human epidermal keratinocytes (NHEKs). Methods We investigated the production of IFN-beta in NHEKs stimulated with a TLR3 ligand, poly (I:C), in the presence of LL-37. To examine the effect of LL-37 and poly (I:C) on antiviral activity, a virus plaque assay using herpes simplex (HS) virus type-1 was carried out. The uptake of poly (I:C) conjugated with fluorescein isothiocyanate (FITC) into the keratinocytes was observed in the presence of LL-37. Immunostaining for TLR3 and LL-37 was performed using skin samples from HS. Results LL-37 and poly (I:C) synergistically induced the expression of IFN-beta in NHEKs. Furthermore, co-stimulation with LL-37 and poly (I:C) significantly decreased the viral plaque numbers compared with poly (I:C) or LL-37 alone. LL-37 enhanced the uptake of FITC-conjugated poly (I:C) into cells. Immunohistochemical analysis demonstrated that the expression of TLR3 and LL-37 is up-regulated in HS lesions. Conclusions Our findings suggest that LL-37 augments the antiviral activity induced by dsRNA in keratinocytes, which may contribute to the innate immune response to cutaneous viral infections such as HS.

DOI： 10.1111/bjd.12942

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掲載種別：研究論文（学術雑誌）   出版者・発行元：John Libbey Eurotext  

DOI： 10.1684/ejd.2014.2270

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Nonpathogenic anti-desmoglein (Dsg) 3 antibodies can be found in pemphigus vulgaris (PV) patients' sera. Previously, ethylenediaminetetraacetic acid (EDTA)-treated enzyme-linked immunosorbent assay (ELISA) was found to detect only nonpathogenic anti-Dsg3 antibodies against the non-calcium (Ca(2+))-dependent epitopes. OBJECTIVE: We examined whether the calculated anti-Dsg3 antibody titer for Ca(2+)-dependent epitopes, using the conventional and EDTA-treated ELISAs, correlated better with the disease activity of PV. METHODS: We analyzed 123 serum samples from 19 PV patients. Of these samples, there were 52 samples from 15 PV patients obtained in asymptomatic phases. The difference between conventional Dsg3 ELISA index and EDTA-treated Dsg3 ELISA index was calculated as the anti-Dsg3 antibody activity for Ca(2+)-dependent conformational epitopes (conformational Dsg3 ELISA index). We analyzed the correlation between Dsg3 ELISA index values and the pemphigus disease area index (PDAI). Moreover, we examined whether the conformational Dsg3 ELISA index fluctuated in parallel with the disease activity during clinical courses of 6 PV patients. We evaluated the pathogenicity of anti-Dsg3 antibodies detected in remission phases using a dissociation assay. RESULTS: The conventional Dsg3 ELISA index showed a high positive rate in the asymptomatic phase of PV. By contrast, the conformational Dsg3 ELISA index showed a much closer correlation to the disease activity when monitored in individual cases. Nonpathogenic anti-Dsg3 antibodies were detected in these cases. CONCLUSION: The conformational Dsg3 ELISA index reflected the pathogenicity of anti-Dsg3 antibodies more accurately than the conventional Dsg3 ELISA index. Using both conventional and EDTA-treated ELISAs would be useful in monitoring the disease activity of PV.

DOI： 10.1016/j.jdermsci.2013.02.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Human papillomavirus-associated warts (HPV-warts) are persistent, evading host immune surveillance. However, these warts sometimes disappear spontaneously, following inflammation. Non-inflamed HPV-warts demonstrated decreased numbers of epidermal Langerhans cells (LCs), low expression levels of MIP3α and E-cadherin, and no apoptotic cells. In the inflamed HPV-warts, on the other hand, various dendritic cell (DC) subsets and many CD8+ cytotoxic T lymphocytes (CTLs) were recruited in association with epidermal MIP3α expression. Many apoptotic keratinocytes were observed in the dermo-epidermal junction. Cellular events were different in HPV-induced Bowen disease (HPV-Bowen): a few LCs were retained in the lesional epidermis, and considerable numbers of B-cells and plasma cells were also observed in the infiltrates, with little or no infiltration of plasmacytoid DCs or dermal/mature DCs. Multiple HPV16-Bowen diseases in the same individuals showed the presence of different sizes of E6/E7-containing cellular transcripts, which indicated that HPV genomes were integrated into the different sites of chromosomes. Toll-like receptor (TLR) 3 was expressed by the lesional keratinocytes even in the non-inflamed HPV-warts, and type 1 interferons (IFNs) were produced in cultured keratinocytes by TLR3 stimulation. HPV-warts are protected from host immune responses and apoptotic signals because they are surrounded by LC-depleted epidermal walls, and viral anti-apoptotic molecules. The up-regulation of epidermal TLR3 signaling might inhibit further HPV spreading.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Eccrine poroma frequently occurs as a solitary tumour, and only a few reports have described the occurrence of multiple lesions. Multiple eccrine poromas, or eccrine poromatosis, may occur in patients who have undergone radiotherapy and/or polychemotherapy. We report here four cases of multiple eccrine poromas in patients who were either undergoing, or had undergone, intensive chemotherapy (from 6 months to 16 years prior to onset). Three patients had non-Hodgkin's lymphoma and one had malignant fibrous histiocytosis. The number of lesions varied from 3 to > 20 in each patient, and all the lesions occurred on non-irradiated skin. The histopathological features were consistent with those of eccrine poroma, Pinkus type. In addition to radiation therapy, intensive chemotherapy may play a role in the pathogenesis of multiple eccrine poromas even many years after treatment.

DOI： 10.2340/00015555-1279

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Epithelial keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by keratinocytes is induced by interleukin-17 (IL-17) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis.

DOI： 10.1016/j.immuni.2012.04.010

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記述言語：英語  

DOI： 10.1016/j.jaci.2012.03.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1038/jid.2011.461

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

One characteristic abnormality of lesional skin in psoriasis is the excessive production of antimicrobial peptides and proteins (AMPs). AMPs typically are small (12-50 amino acids), have positive charge and amphipathic structure, and are found in all living organisms including mammals, insects, plants and invertebrates. These peptides are best known for their integral role in killing pathogenic microorganisms; however, in vertebrates, they are also capable of modifying host inflammatory responses by a variety of mechanisms. In psoriatic lesions, many AMPs are highly expressed, and especially the associations between psoriasis and cathelicidin, β-defensins or S100 proteins have been well studied. Among them, a cathelicidin peptide, LL-37, has been highlighted as a modulator of psoriasis development in recent years. AMPs had been thought to worsen psoriatic lesions but recent evidence has also suggested the possibility that the induction of AMPs expression might improve aspects of the disease. Further investigations are needed to uncover a previously underappreciated role for AMPs in modulating the immune response in psoriasis, and to improve disease without the risks of systemic immunosuppressive approaches.

DOI： 10.1111/j.1346-8138.2011.01483.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Here we show that keratinocytes in psoriatic lesional skin express increased Toll-like receptor (TLR) 9 that similarly localizes with elevated expression of the cathelicidin antimicrobial peptide LL-37. In culture, normal human keratinocytes exposed to LL-37 increased TLR9 expression. Furthermore, when keratinocytes were exposed to LL-37 and subsequently treated with TLR9 ligands, such as CpG or genomic DNA, they greatly increased production of type I IFNs. This response mimicked observations in the epidermis of psoriatic lesional skin as keratinocytes in psoriatic lesions produce greater amounts of IFN-β than normal skin lacking LL-37. The mechanism for induction of type I IFNs in keratinocytes was dependent on TLR9 expression but not on a DNA-LL-37 complex. These findings suggest that keratinocytes recognize and respond to DNA and can actively participate in contributing to the immunological environment that characterizes psoriasis.

DOI： 10.1038/jid.2011.259

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Human papilloma virus (HPV)-related warts persist, evading host immune surveillance, but sometimes disappear with inflammation. OBJECTIVES: To elucidate the immune evasion mechanisms of HPV, we have examined the density, dynamics, and subsets of dendritic cell (DC) types in non-inflammatory or inflammatory HPV-related skin lesions such as warts and Bowen's disease (HPV-Bowen), and compared the epidermal expression levels of macrophage inflammatory protein (MIP)-3α and E-cadherin. METHODS: The expression of various DC markers, MIP-3α, and E-cadherin in the tissue samples obtained from patients with warts, HPV-Bowen and HPV-unrelated skin diseases was evaluated by immunohistochemistry. MIP-3α gene expression levels were examined in warts and HPV-Bowen by in situ hybridization (ISH) and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The numbers of Langerhans cells (LCs) and the expression levels of MIP-3α and E-cadherin were decreased in non-inflammatory warts and HPV-Bowen, as compared with normal skin. Both epidermal LCs and MIP-3α expression reappeared in inflammatory warts, associated with dermal infiltrates composed of many cytotoxic T cells and various subsets of DCs, while cellular infiltrates in HPV-Bowen contained many B cells and plasma cells with sparse infiltration of DCs. The upregulation of MIP-3α gene expression was confirmed in the inflammatory warts and HPV-Bowen by ISH and RT-qPCR. CONCLUSIONS: The depletion of LCs in the non-inflammatory warts and HPV-Bowen is associated with a down-regulation of expression levels of MIP-3α and E-cadherin in the lesional keratinocytes. MIP-3α expression is upregulated in lesional keratinocytes of inflammatory warts, with the subsequent recruitment of various DC subsets and cytotoxic T cells, whereas plasma cell-rich infiltration was induced in HPV-Bowen.

DOI： 10.1016/j.jdermsci.2011.05.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A diverse environment challenges skin to maintain temperature, hydration, and electrolyte balance while also maintaining normal immunological function. Rosacea is a common skin disease that manifests unique inflammatory responses to normal environmental stimuli. We hypothesized that abnormal function of innate immune pattern recognition could explain the enhanced sensitivity of patients with rosacea, and observed that the epidermis of patients with rosacea expressed higher amounts of Toll-like receptor 2 (TLR2) than normal patients. Increased expression of TLR2 was not seen in other inflammatory skin disorders such as atopic dermatitis or psoriasis. Overexpression of TLR2 on keratinocytes, treatment with TLR2 ligands, and analysis of TLR2-deficient mice resulted in a calcium-dependent release of kallikrein 5 from keratinocytes, a critical protease involved in the pathogenesis of rosacea. These observations show that abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli and can act as a critical element in the pathogenesis of rosacea.

DOI： 10.1038/jid.2010.351

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The purpose of this study is to report on a patient who developed conjunctival lesions of blastic plasmacytoid dendritic cell neoplasm (BPDCN) after radiation to skin lesions of the same pathological type. A 79-year-old man developed salmon-pink lesions in the lower fornix of the conjunctiva of both eyes and biopsy revealed BPDCN. One and a half years previously, he noticed an erythematous plaque with a 30-mm diameter, which later became multiple, on the left chest, and the biopsy revealed BPDCN. The bone marrow was negative for CD56-positive cells, but fluorescence-activated cell sorting analysis of peripheral blood cells revealed a group of cells positive for CD4 and CD56, or CD4 and CD123. The monocyte fraction, in an increased percentage of white blood cell counts, did contain atypical cells positive for the three markers. Whole-body 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography demonstrated no abnormal uptake lesions. He received 30 Gy of radiation to the chest lesions, and later, the same dose of radiation to novel skin lesions on the back, waist, and chest, and also to pharyngeal lesions. In conclusion, the conjunctiva could be involved with BPDCN and pathological differential diagnosis by biopsy is mandatory to establish the correct diagnosis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cathelicidin has dual functions in the skin, acting as an innate antibiotic and as an immunomodulator in diseases such as rosacea and psoriasis. The serine proteases kallikrein 5 (KLK5) and kallikrein 7 (KLK7) control enzymatic processing of cathelicidin precursor in the skin and regulate the eventual function of the final forms of these peptides. We analyzed factors that control expression of KLK5 and KLK7 in normal human epidermal keratinocytes to better understand how these may influence cathelicidin processing and function. Increased extracellular calcium-induced KLK5 and KLK7 mRNA expression and protein release in a time-dependent manner that is similar to induction of differentiation markers such as keratin 10 and involucrin. However, 1,25(OH)(2) vitamin D(3), 9-cis retinoic acid (RA), and 13-cis RA also induced the KLKs, but the timing and pattern of KLK induction for each were different and distinct from changes in differentiation markers. Increased protease activity and differential processing of cathelicidin accompanied increased KLK expression. These findings show that the expression and activity of KLK are under fine control and can be distinctly influenced by variables such as differentiation, calcium, vitamin D, and RA. Thus, these variables may further control the functions of antimicrobial peptides in the skin.

DOI： 10.1038/jid.2009.435

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tumor surveillance requires the interaction of multiple molecules and cells that participate in innate and the adaptive immunity. Cathelicidin was initially identified as an antimicrobial peptide, although it is now clear that it fulfills a variety of immune functions beyond microbial killing. Recent data have suggested contrasting roles for cathelicidin in tumor development. Because its role in tumor surveillance is not well understood, we investigated the requirement of cathelicidin in controlling transplantable tumors in mice. Cathelicidin was observed to be abundant in tumor-infiltrating NK1.1(+) cells in mice. The importance of this finding was demonstrated by the fact that cathelicidin knockout mice (Camp(-/-)) permitted faster tumor growth than wild type controls in two different xenograft tumor mouse models (B16.F10 and RMA-S). Functional in vitro analyses found that NK cells derived from Camp(-/-) versus wild type mice showed impaired cytotoxic activity toward tumor targets. These findings could not be solely attributed to an observed perforin deficiency in freshly isolated Camp(-/-) NK cells, because this deficiency could be partially restored by IL-2 treatment, whereas cytotoxic activity was still defective in IL-2-activated Camp(-/-) NK cells. Thus, we demonstrate a previously unrecognized role of cathelicidin in NK cell antitumor function.

DOI： 10.4049/jimmunol.0902110

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Innate immune responses involve the production of antimicrobial peptides (AMPs), chemokines, and cytokines. We report here the identification of B-cell leukemia (Bcl)-3 as a modulator of innate immune signaling in keratinocytes. In this study, it is shown that Bcl-3 is inducible by the Th2 cytokines IL-4 and IL-13 and is overexpressed in lesional skin of atopic dermatitis (AD) patients. Bcl-3 was shown to be important to cutaneous innate immune responses as silencing of Bcl-3 by small-interfering RNA (siRNA) reversed the downregulatory effect of IL-4 on the HBD3 expression. Bcl-3 silencing enhanced vitamin D3 (1,25D3)-induced gene expression of cathelicidin AMP in keratinocytes, suggesting a negative regulatory function on cathelicidin transcription. Furthermore, 1,25D3 suppressed Bcl-3 expression in vitro and in vivo. This study identified Bcl-3 as an important modulator of cutaneous innate immune responses and its possible therapeutic role in AD.

DOI： 10.1038/jid.2009.49

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Malignant lymphoma is occasionally complicated by ichthyosiform eruptions. OBJECTIVES: To analyse histopathologically the ichthyosiform eruptions associated with cutaneous lymphomas. METHODS: We reviewed the files of patients with malignant lymphoma seen in our dermatology department between January 2001 and May 2006 to search for patients with ichthyosiform eruptions. RESULTS: In our series, nine of 106 patients with malignant lymphomas had ichthyosiform eruptions during their clinical courses, including three (30%) of 10 patients with anaplastic large cell lymphoma (ALCL) and six (14%) of 44 patients with mycosis fungoides (MF). None of the 18 patients with cutaneous B-cell lymphoma had ichthyosiform eruptions. The three patients with ALCL had ichthyosiform eruptions histopathologically consistent with acquired ichthyosis (AI) in which packed horny layers and thin granular layers were present without lymphocytic infiltration. In contrast, four of the six patients with MF (stages Ib and IIb) had ichthyosiform eruptions with epidermotropic infiltration of atypical lymphocytes, as observed in ichthyosiform MF (IMF). Of the remaining two patients, one showed histopathological features overlapping AI and IMF, and the other had AI alone. These two patients (stages IVa and IIb) had tumours composed of CD30+ cells. Filaggrin expression was markedly diminished in both AI and IMF-like eruptions, similar to that of inherited ichthyosis vulgaris. CONCLUSIONS: Ichthyosiform eruptions are often associated with ALCL and MF and can be classified into three groups: AI associated with ALCL and MF expressing CD30, IMF, and their overlap.

DOI： 10.1111/j.1365-2133.2009.09109.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cathelicidin is strongly expressed in lesional skin in psoriasis and may play an important role as both an antimicrobial peptide and as an autoinflammatory mediator in this chronic skin disease. The mechanism of increased cathelicidin in psoriatic keratinocytes is not known, but recent observations have found that psoriasis has abundant Th17 cells that produce IL-17A and IL-22. We found that human keratinocytes stimulated with supernatants from T cells isolated from lesional psoriatic skin increased expression of cathelicidin when stimulated in the presence of 1,25-dihydroxyvitamin D(3) (1,25D(3)). This increase was signaled through the IL-17RA. In vitro, IL-17A, but not IL-22, enhanced cathelicidin mRNA and peptide expression in keratinocytes dependent on the presence of 1,25D(3). At the same time, coincubation with 1,25D(3) blocked induction of human beta-defensin 2 (HBD2), IL-6, and IL-8, which are other target genes of IL-17A. Act1, an adaptor associated with IL-17RA and essential for IL-17A signaling, mediated cathelicidin induction, as its suppression by small interfering RNA inhibited HBD2 and cathelicidin. Both, 1,25D(3) and IL-17A signaled cathelicidin induction through MEK-ERK. These results suggest that increased IL-17A in psoriatic skin increases cathelicidin through a vitamin D(3)-, Act1-, and MEK-ERK-dependent mechanism. Therapy targeting this cathelicidin-regulating system might be beneficial in patients suffering from psoriasis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recalcitrant pyodermic lesions and neutrophilic dermatoses are often associated with subclinical myelodysplastic syndrome (MDS). In this case series, we assessed the diagnostic importance of karyotypic analysis of bone marrow cells in 4 patients with MDS-associated pyodermic eruptions treated at our university hospital. Karyotypic analysis was performed in bone marrow cells and peripheral blood lymphocytes obtained. Serum levels of granulocyte colony-stimulating factor were measured. OBSERVATIONS: Four patients with pyodermic eruptions or neutrophilic dermatosis had chromosomal abnormalities in bone marrow cells, including del(20)(q11;q13.3) in 2 patients, trisomy 8 in 1 patient, and t(11;22)(q23;q11) in 1 patient. Three patients without morphologic findings suggestive of MDS were diagnosed as having refractory anemia. One female patient had refractory anemia with ringed sideroblasts associated with del(20). Two patients with refractory anemia had a normal karyotype in peripheral blood lymphocytes. Two patients with elevated serum levels of granulocyte colony-stimulating factor had more active or widespread cutaneous diseases. CONCLUSIONS: Karyotypic analysis of bone marrow cells, but not of peripheral blood lymphocytes, is essential in proving a diagnosis of MDS-associated pyodermic lesions. The overexpression of granulocyte colony-stimulating factor, which may compensate for impaired hematopoiesis in patients with MDS, seems to be a key cytokine leading to neutrophilic infiltration.

DOI： 10.1001/archderm.144.5.643

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To establish a new diagnostic method for Epstein-Barr virus (EBV)-associated cutaneous disorders. DESIGN: Skin biopsy is usually required to confirm the latent EBV infections in cutaneous lesions of EBV-associated NK/T-cell lymphoproliferative disorders, including hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). We have devised a novel, noninvasive method to detect EBV-encoded small RNA (EBER), BamHI A rightward transcripts (BARTs) in the skin crusts and scales of such patients. PATIENTS: Six patients with EBV-associated cutaneous lesions were enrolled in the present study, including three patients with HV, one with HV-like eruptions and chronic active EBV infection, and two with EBV-associated cutaneous lymphoma. MAIN OUTCOME MEASURES: RNA was extracted from the crusts obtained from the cutaneous lesions by forceps, converted to cDNA, and processed for polymerase chain reaction (PCR) amplification with a specific set of primers. The PCR products were assayed by a DNA sequencer. RESULTS: Intact RNAs were successfully extracted from the crusts as well as control materials. EBER1 and BARTs RNAs were detected in all 7 crusts, and in 6 of 7 crusts of EBV-associated cutaneous diseases, respectively. One of 23 crusts from non EBV-associated diseases was positive for EBER1 RNA. The sensitivity and specificity of our assay for latent EBV infection were 100% and 95.8% for EBER1 RNA, and 85.7% and 100% for BARTs mRNA, respectively. The correct DNA sequence for EBER1 and BARTs was confirmed in the PCR products by a direct sequencing method. CONCLUSIONS: Our procedure may be of use as a biomarker for EBV-associated cutaneous lesions, including HV, HMB, and NK/T-cell lymphomas.

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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.mimet.2006.09.025

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Staphylococcal infections cause a variety of cutaneous and systemic infections, including impetigo, furuncle, subcutaneous abscess, staphylococcal scalded skin syndrome (SSSS), toxic shock syndrome (TSS) and neonatal toxic shock syndrome-like exanthematous disease (NTED), in association with microbial virulence factors. The virulence factors produced by Staphylococcus aureus have a wide array of biological properties, including disruption of the epithelial barrier, inhibition of opsonization by antibody and complement, interference with neutrophil chemotaxis, cytolysis of neutrophils, and inactivation of antimicrobial peptides. Exfoliative toxins (ETs) induce the 'acantholytic' infection of S. aureus due to the disruption of cell-to-cell cohesion, which allows the pathogenic organisms to spread within the epithelium. Furthermore, S. aureus expresses exotoxins with biological properties of superantigens that induce T-cell activation with subsequent anergy and immunosuppression. Of the S. aureus leukotoxins, Panton-Valentine leukocidin (PVL) is involved in the development of multiple furuncles with more intense erythema, particularly in healthy young adults. TSS is an acute life-threatening illness caused by TSS toxin-1 (TSST-1) and is usually classified into two categories; menstrual TSS, originally described in association with tampon use, and nonmenstrual TSS with a variety of clinical settings. NTED is a neonatal disease induced by TSST-1 although clinical symptoms are much milder than those of TSS. In TSS and NTED, the expansion of TSST-1-reactive Vbeta2-positive T cells is observed. The production of pathogenic S. aureus exotoxins and biofilm formation is regulated by the accessory gene regulator (agr) locus in the quorum-sensing signaling pathway. There is no doubt that targeting the quorum-sensing signaling pathway or anti-toxin therapy is a promising therapeutic approach supportive of primary antibiotic therapy.

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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 the pathogenic association of latent Epstein-Barr virus (EBV) infections with both typical hydroa vacciniforme (HV) and severe HV-like eruptions, and to survey the complications and outcomes of patients. DESIGN: Case series. PATIENTS: Twenty-nine patients with HV or severe HV-like eruptions. INTERVENTIONS: In situ hybridization and immunostaining of biopsy specimens; extraction of DNA samples from cutaneous lesions and/or peripheral blood mononuclear cells for EBV DNA assay. MAIN OUTCOME MEASURES: Clinicopathologic manifestations, hematologic findings, complications, and outcomes; presence of latent EBV infection. RESULTS: T cells positive for EBV-encoded small nuclear RNA (EBER) were detected, to various degrees, in cutaneous infiltrates in 28 (97%) of 29 patients, including all 6 patients with definite HV with a positive phototest reaction, 11 of 12 patients with probable HV without evidence of photosensitivity, and all 11 patients with severe HV associated with systemic symptoms. In addition to EBER-positive T cells, many cytotoxic T lymphocytes expressing T-cell intracellular antigen 1 and granzyme B were present in the cutaneous lesions. Natural killer (NK) cells were absent or at a background level. The UV-induced cutaneous lesions showed histopathologic findings consistent with those of HV, containing many EBER-positive cells. Although no hematologic abnormalities were found in the definite and probable HV groups, the amounts of EBV DNA were increased in the peripheral blood mononuclear cells. By contrast, the severe HV group had markedly increased levels of EBV DNA associated with NK-cell lymphocytosis, and complications including chronic active EBV infection, hypersensitivity to mosquito bites, and hemophagocytic syndrome. Five patients with severe disease died of EBV-associated NK/T-cell lymphomas or hemophagocytic syndrome 2 to 14 years after onset. CONCLUSION: Both typical and severe HV are included within the spectrum of cutaneous disorders mediated by EBV-infected T cells, and the severe HV group may have overt EBV-associated NK/T-cell lymphoproliferative disorders with a frequently fatal outcome.

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記述言語：英語  

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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)  

DOI： 10.1111/j.1365-2133.2005.06849.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.1365-2133.2005.06470.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Panton-Valentine leukocidin (PVL) is mainly associated with necrotic suppurative lesions, such as furuncles and abscesses in the skin and subcutaneous tissue, but it has also been isolated from patients with community-acquired, severe, necrotizing pneumonia. However, the clinical manifestations of furuncles caused by PVL-producing Staphylococcus aureus and the role of patients' background are not fully understood. METHODS: We used polymerase chain reaction amplification to test for the PVL gene in 161 strains of S. aureus isolated from suppurative skin lesions. For all PVL gene-positive strains isolated from furuncles, we analyzed cutaneous manifestations, patient background characteristics, and bacteriological markers, including coagulase types, presence of the mecA gene, and toxin profiles, and we compared these results with those for PVL gene-negative strains. RESULTS: PVL genes were detected in 16 (40%) of the 40 S. aureus strains isolated from furuncles, 2 (28%) of the 7 strains isolated from carbuncles, 1 (14%) of the 7 strains isolated from abscesses, and 1 (5%) of the 20 strains isolated from folliculitis. PVL gene-positive S. aureus usually causes multiple (rather than single) furuncles, and such furuncles are usually associated with more-intense erythema around the lesions. PVL gene-positive strains were isolated from young adults without underlying diseases, whereas PVL gene-negative strains were isolated from patients with various systemic complications, including diabetes, leukemia, and autoimmune diseases. CONCLUSIONS: PVL gene-positive S. aureus strains are involved in the development of multiple furuncles with more-intense erythema, particularly in healthy young adults. An understanding of the characteristics of furuncles due to PVL gene-positive strains might be useful for preventing the development of the severe systemic infections.

DOI： 10.1086/427290

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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：BLACKWELL PUBLISHING LTD  

BACKGROUND: Granulysin is a recently identified antimicrobial protein expressed on cytotoxic T cells, natural killer (NK) cells and NKT cells. It has been shown that granulysin contributes to the defence mechanisms against mycobacterial infection. Superficial microbial folliculitis is a common skin disease. In a previous report, we showed that, as a first line of defence, alpha-defensin, a human neutrophil peptide, and beta-defensin (human beta-defensin-2) were expressed in infiltrating neutrophils and in lesional epidermal keratinocytes, respectively, in superficial folliculitis. As we also observed many infiltrating lymphocytes in lesional dermis, we hypothesized that infiltrating lymphocytes may possess antimicrobial substances, such as granulysin, and play a role in the defence mechanism as a second line of defence. OBJECTIVES: Seven specimens of superficial microbial folliculitis diagnosed clinically and histologically were examined by means of immunohistochemistry. To identify the phenotype of cells expressing granulysin, confocal laser microscopic examination was performed. RESULTS: A dense lymphoid cell infiltrate was observed in pustules, in the perivascular regions. A large number of these lymphoid cells were positive for granulysin. Phenotypically, cells consisted of CD3+ T cells, CD8+ T cells and UCHL-1+ T cells. CD20+ cells and CD56+ cells were not observed. Microscopic examination with a confocal laser showed that the lymphocytes producing granulysin were CD3+ and CD4+ T cells but not CD8+ T cells. CONCLUSIONS: We showed that many granulysin-bearing T cells infiltrated affected follicles and perilesional dermis in superficial microbial folliculitis. However, few granulysin-positive lymphoid cells were observed in sterile pustular lesions. Our observations indicated that adaptive immunity such as granulysin, a lymphocyte-produced antimicrobial protein, may play an important role in the cutaneous defence mechanism.

DOI： 10.1111/j.0007-0963.2004.05925.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：ELSEVIER SCI IRELAND LTD  

BACKGROUND: Streptococcus pyogenes and Staphylococcus aureus are often simultaneously detected from many cases of non-bullous impetigo with atopic dermatitis. OBJECTIVES: Using confocal laser scanning microscopy (CLSM), to investigate formation of S. pyogenes microcolonies in skin lesions. METHODS: The S. pyogenes cells in the stationary growth phase alone were strongly stained with fluorescein isothiocyanate-concanavalin A (FITC-ConA), and this staining was reduced by pretreatment with amylase. Although the components of sugars in glycocalyx produced by S. pyogenes cells are unknown, we suggested that the materials stained by FITC-ConA were consistent with the presence of ConA-reactive sugars in glycocalyx produced by S. pyogenes cells. RESULTS: S. pyogenes cells associated with streptococcal impetigo skin and croton-oil inflamed mouse skin formed microcolonies encircled by materials (glycocalyx) that stained strongly with FITC-ConA, and these findings were consistent with those in biofilms. In croton-oil inflamed mouse skin, polymorphonuclear leukocytes (PMNs) infiltrated to just below the epidermis in the cefdinir-treated group but only to the middle dermis in the cefdinir-non-treated group. In this case S. pyogenes and S. aureus cells formed separate microcolonies and existed independently in the outer walls of pustule lesions of streptococcal impetigo. CONCLUSION: In skin infections, S. pyogenes and S. aureus formed aggregates of microcolonies (similar to that in biofilms) encircled by glycocalyx, which can make the infection hard to eradicate using an antimicrobial agent alone. The effect of conventional antimicrobial agents against biofilm is mainly due to the increase of the invasion of PMNs into the biofilm.

DOI： 10.1016/S0923-1811(03)00096-3

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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：(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：(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：(NPO)日本皮膚外科学会  

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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：(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：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：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：(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：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：金原出版(株)  

＜文献概要＞67歳,女性。初診1.5ヵ月前より体重減少と口唇・口腔内にびらんが出現した。上肢と体幹には爪甲大の痂皮と紅斑を認めた。CTで後腹膜と鼠径部に腫瘤を認め,生検にて濾胞性リンパ腫と診断した。皮膚生検では苔癬型反応を認め,血清中の抗Dsg3抗体,抗エンボプラキン抗体,抗ペリプラキン抗体が陽性で腫瘍随伴性天疱瘡と診断した。オビヌツズマブ,ベンダムスチンを投与し腫瘍,皮膚粘膜症状ともに改善していたが,閉塞性細気管支炎を合併した。発症10ヵ月後に肺気胸と肺炎により死亡した。腫瘍随伴性天疱瘡に合併する閉塞性細気管支炎は腫瘍縮小,皮膚粘膜病変改善後も発症・進行し致死的な経過をたどる傾向があり,呼吸状態の変化に留意する必要がある。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01266&link_issn=&doc_id=20230524110025&doc_link_id=10.18888%2Fhi.0000003905&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000003905&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：金原出版(株)  

＜文献概要＞71歳,男性。乾癬性関節炎に対してアダリムマブで加療するも二次無効となり,紅皮症化したためブロダルマブを開始した。その後皮膚症状,関節症状ともに速やかに改善したが,2ヵ月間の自己中断後に発熱,関節痛,皮疹の膿疱化を認めた。ブロダルマブを再開し,速やかに皮疹は改善した。今後も治療を自己中断する懸念があり,ブロダルマブをグセルクマブに変更した。しかし,関節症状が再燃したため,さらにセルトリズマブペゴルに変更し,皮膚,関節症状ともに改善した。抗IL-17受容体A抗体であるブロダルマブは,中止後にリバウンド現象として膿疱化が出現することがあるため,治療を自己中断しないよう厳格に指導する必要がある。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01266&link_issn=&doc_id=20230524110011&doc_link_id=10.18888%2Fhi.0000003891&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000003891&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：金原出版(株)  

症例は47歳女性で、左鼠径部に3cm大の皮下腫瘤を自覚し、CTでリンパ節腫脹を指摘されたため前医外科を受診した。その後、原発不明悪性黒色腫の疑いで当院を紹介受診し、左鼠径リンパ節郭清を全身麻酔下で施行した。約6時間後に夕食を摂取し、その30分後に両耳介周囲の腫脹が出現、麻酔科、耳鼻科と併診した。麻酔科では手技や術後経過は麻酔科的に問題がないと考えられ、アナフィラキシーのような全身症状や皮膚症状もなく、限局した腫脹のみで使用した薬剤との関連は明らかではなかった。耳鼻科では臨床症状、採血結果から細菌感染症、ウイルス感染症の可能性は低いと判断された。アレルギー性耳下腺炎を疑われベポタスチンの内服を開始し、発症から3日で症状が軽快し、血清アミラーゼ値も正常化したためベポタスチンの内服は終了とした。以降症状の再燃はなかった。鼠径リンパ節の病理診断は悪性黒色腫の転移であった。

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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：日本皮膚科学会-西部支部  

71歳,女性。1年前に右膝と両側前腕に皮下硬結を自覚し,その後左臀部にも皮下硬結が出現した。右膝に20×10cm,左臀部に10×7cm,右前腕に10×7cm,左前腕に2個の7×5cmの板状皮下硬結がみられた。皮膚生検では皮下脂肪組織に非乾酪壊死性類上皮細胞肉芽腫を認め,sIL-2Rは1697.0U/mlと高値であった。胸部CTでは縦隔リンパ節の軽度腫大があり,Gaシンチグラフィーでは四肢と左臀部の皮下硬結部に高度な集積を認め,extensive subcutaneous sarcoidosisと診断した。膝関節屈曲制限が生じる懸念があったためプレドニゾロン25mg/day内服を開始したところ,皮下病変は速やかに縮小し,sIL-2Rは418.3U/mlまで低下した。皮下型サルコイドーシスではトラニラストやミノサイクリン内服で軽快する症例や,無治療で軽快する症例もあるが,本症例では,右膝部皮下病変の拡大による歩行障害が懸念されたため,ステロイド内服による治療を選択した。広範な皮下型病変を呈するサルコイドーシスでは,sIL-2Rや皮膚病変のサイズなどを総合的に評価し,病勢を検討することが必要である。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01003&link_issn=&doc_id=20230516250006&doc_link_id=10.2336%2Fnishinihonhifu.85.109&url=https%3A%2F%2Fdoi.org%2F10.2336%2Fnishinihonhifu.85.109&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  

DOI： 10.4103/ijd.ijd_645_22

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J-GLOBAL

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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：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：日本皮膚科学会-西部支部  

59歳,女性。初診の9年前より前頭部右側に徐々に増大する硬化性局面を認めた。限局性強皮症と考えられ経過観察されていたが,同部位に潰瘍を生じ皮膚生検にて基底細胞癌と診断された。下床の頭蓋骨を含めて広範囲切除し,前外側大腿遊離皮弁による再建術を施行した。病理組織学的所見では斑状強皮症型/破壊型であり,頭蓋骨内部への浸潤が認められた。切除断端陰性であったが,約半年後に第5胸椎左横突起転移を生じ切除術を施行した。その約1年後右大腿骨内側顆に転移が出現し,切除・人工関節置換術後にシスプラチン・ドキソルビシン療法を施行した。その約2年後,右肺門部転移が出現しカルボプラチン・パクリタキセル療法を施行した。その後,特発性器質化肺炎を生じたため化学療法を中止し,プレドニゾロン投与にて加療した。その後は化学療法の再開を希望されなかったため,緩和的放射線療法を施行した。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01003&link_issn=&doc_id=20221110410016&doc_link_id=10.2336%2Fnishinihonhifu.84.443&url=https%3A%2F%2Fdoi.org%2F10.2336%2Fnishinihonhifu.84.443&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：金原出版(株)  

＜文献概要＞80歳,男性。2001年より夏季に下腿に水疱が出現した。病理組織像では好酸球浸潤を混じる表皮下水疱を認め,水疱性類天疱瘡を疑ったが,抗BP180 NC16a部位抗体,蛍光抗体法と全長BP180 ELISAは陰性だった。経過中,蛍光抗体間接法のみ表皮側に陽性となった。2018年に四肢・体幹にびらんと緊満性水疱が生じ,蛍光抗体直接法で表皮基底膜部にIgGが線状に沈着し,全長BP180 ELISAは陽性,免疫ブロット法でBP180 C末端部リコンビナント蛋白と120kDa LAD-1に対する抗体陽性,ELISAでBP230に対する抗体も陽性となり,水疱性類天疱瘡と診断した。症状を繰り返すなかでepitope spreading現象がおきたと考えた。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01266&link_issn=&doc_id=20220914050025&doc_link_id=10.18888%2Fhi.0000003535&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000003535&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：日本皮膚科学会-西部支部  

47歳,女性。肺腺扁平上皮癌に対してドセタキセル(DTX)とラムシルマブ(RAM)の併用療法を開始3ヵ月後から,頭頸部・体幹・上肢に2～6mmの紅色丘疹が多発した。増大傾向で出血もみられたため,初診時から3ヵ月の間に合計8ヶ所の病変を切除した。病理組織学的に,いずれも毛細血管の増生がみられ毛細血管拡張性肉芽腫(Pyogenic Granuloma:PG)の診断であった。その後原病の増悪のためRAMは中止となったが,PGの新生はみられず,切除せず残存していたPGはすべて消退した。RAM投与中にPGが生じた報告は自験例を含めて15例報告されており,通常のPGと比較して一部異なる経過もみられた。出血を伴うこともあるため慎重な経過観察が必要であり,症状増悪があれば外科的切除すべきであると考えた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01003&link_issn=&doc_id=20220902400013&doc_link_id=10.2336%2Fnishinihonhifu.84.337&url=https%3A%2F%2Fdoi.org%2F10.2336%2Fnishinihonhifu.84.337&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：(NPO)日本皮膚外科学会  

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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  

症例1:67歳,女性。X-23年関節リウマチ(RA)を発症した。アバタセプトからトシリズマブ(TCZ)へ変更1ヵ月後,四肢体幹に紅色丘疹や膿疱が出現した。生検では表皮内に好中球浸潤,真皮浅層に白血球破砕性血管炎を認めた。プレドニゾロン(PSL)3mg/日から7.5mg/日へ増量し,ステロイド外用で改善したためTCZを継続したが皮疹は再燃しなかった。症例2:65歳,女性。X-15年RAを発症した。PSL20mg/日,タクロリムス3mg/日併用で症状は改善したが,PSL10mg/日から9mg/日へ減量,インフリキシマブをTCZに変更1ヵ月後に両下腿に小潰瘍が多発し,急激に拡大した。痂疲を伴う紫斑が散在し,最大8cmまでの黄白色壊死組織を付す皮膚潰瘍がみられた。生検では表皮内膿疱,真皮浅層に白血球破砕性血管炎を認めた。TCZを中止し,PSL50mg/日に増量し,シクロホスファミドパルスを6回施行したところ潰瘍は上皮化し治癒した。自験例はいずれもTCZ初回投与後に皮膚症状が出現し,病理組織学的に白血球破砕性血管炎を呈した。TCZは血管炎治療にも用いられるが,今回TCZ投与後に血管炎を伴う皮疹が生じたため,paradoxical reactionの可能性を考えた。文献的にはTCZのparadoxical reaction 10例中4例で投与継続可能であり,症例1でも投与を継続した。TCZはRAに有効な薬剤であり,その副作用としての皮疹には十分注意した上で継続可否の判断をすることが重要である。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01003&link_issn=&doc_id=20220707470008&doc_link_id=10.2336%2Fnishinihonhifu.84.202&url=https%3A%2F%2Fdoi.org%2F10.2336%2Fnishinihonhifu.84.202&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：(株)協和企画  

＜文献概要＞症例のポイント ・二次感染を契機に皮膚症状が増悪したが,モガムリズマブが奏効し長期に寛解維持している.・皮膚T細胞リンパ腫患者において,細菌感染症などの増悪因子除去も重要である.

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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  

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

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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：日本皮膚科学会-西部支部  

症例1:72歳,女性。子宮平滑筋肉腫の多発肺転移に対して投与されたトラベクテジンの血管外漏出があり,右胸部CVポート刺入部を中心に広範囲の組織壊死を来した。適宜デブリドマンを施行し,4×8cmの範囲に全層植皮術を行い漏出後71日目に略治を得た。症例2:67歳,女性。子宮平滑筋肉腫の多発リンパ節転移,肺転移に対して投与されたトラベクテジンの血管外漏出があり,右胸部CVポート刺入部を中心に広範囲の組織壊死を来した。適宜デブリドマンを施行し,5×5cmの範囲に全層植皮術を行い漏出後96日目に略治を得た。紅斑部の病理所見では,いずれも表皮,真皮には炎症所見は目立たず,皮下組織の広範囲な壊死があった。表皮・真皮の温存ができると考え,皮下組織のみのデブリドマンによって植皮範囲を縮小できた。トラベクテジンの血管外漏出に遭遇した際は感染やさらなる壊死の拡大を防ぎ,創部の縮小を目指して加療することが必要である。また医原性の障害であり,自験例のように数回のデブリドマンと植皮術が必要で,傷閉鎖までは長期間を要することを慎重に説明していくことが重要である。(著者抄録)

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記述言語：日本語   出版者・発行元：金原出版(株)  

29歳女性。右乳頭の黒色斑の精査目的で当科へ紹介となった。所見では右乳頭部に8×5mmのやや不整形な黒褐色斑が認められた。生検を行ったところ、melanosis of the nipple and areolaと診断され、患者と相談の上、整容的観点から切除せず、経過観察とした。

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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＞乾癬に関する研究は世界中で精力的に行われており,病態の理解も飛躍的に進歩している。その目覚ましい研究の成果が臨床応用され,乾癬に対する新しい薬剤や治療法が毎年のように登場している。本稿では乾癬の病態理解の進歩と最新の治療について詳説する。

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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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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 ・健常人のPanton-Valentine leukocidin(PVL)産生の市中型MRSA(methicillin-resistant Staphylococcus aureus)感染によるせつ腫症であり,再発を繰り返し治療に難渋した.・せつ,せつ腫症の典型の病理組織像では毛包周囲の壊死,好中球の浸潤を認めるが,著明な好酸球の浸潤を認めた.

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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  

91歳,男性。既往にハンセン病,尿管癌がある。ADLが悪く,ほぼ寝たきり状態。2年前に顔面神経麻痺のある左頬にびらんと痂皮が散在し,日光角化症として液体窒素などで加療されていたが,腫瘤になり徐々に増大し,生検で有棘細胞癌と診断された。他院では手術や放射線治療が検討されたが保存的治療の方針となっていた。創部を触る動作が増えたためアセトアミノフェン内服,潰瘍面より出血がありモーズ療法を行っていた。その後さらに腫瘤は増大し,当科を紹介受診した。左頬に中央に潰瘍を伴う12×10cmの淡紅褐色,広基性の腫瘤があった。CTではリンパ節,遠隔転移は認めなかった。超高齢でADLが悪く,低アルブミン血症,胸水があり,腫瘤が大きく輸血が必要でハイリスク症例であった。局所制御目的で全身麻酔下に切除,植皮を行った。しかし術後5ヵ月後に肺炎で永眠された。(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=J02197&link_issn=&doc_id=20210719270014&doc_link_id=10.5227%2Fskincancer.36.71&url=https%3A%2F%2Fdoi.org%2F10.5227%2Fskincancer.36.71&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  

乾癬治療における生物学的製剤使用時の結核スクリーニングの現状について西日本の18施設を調査した。事前の検査ではinterferon gamma release assay(IGRA)が全施設で行われ、画像検査はCTが15施設、胸部レントゲンが3施設であった。フォローアップでは検査の結果や画像所見により頻度が異なっていた。全患者1,117例のうち、IGRA陽性で抗結核薬を投与されていた例は64例、IGRA陰性で抗結核薬を投与されていた例は103例であり、副作用を認めた患者は23例15%であった。これらの適切な検査と治療により、結核の発生頻度が低く抑えられていると考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：(NPO)日本皮膚外科学会  

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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  

68歳,女性。半年前に舌痛および口腔内違和感が生じ,口腔外科にて口腔扁平苔癬と診断され,その後下腿に暗紅色の紅斑が出現した。金属パッチテストで,亜鉛陽性となり,該当歯科金属を除去したところ,数日後より頭皮にそう痒を伴う脱毛が多発した。初診時,頭部に淡紅色の紅斑を伴う脱毛斑が9ヶ所みられ,病理組織学的に毛包漏斗部および峡部上皮のリンパ球浸潤と周囲間質の線維化および正常毛球の残存を認めた。下腿紅斑は表皮真皮境界部の空胞変性と真皮の帯状リンパ球浸潤の像であった。脱毛斑に対しステロイド局注を開始し,約2ヵ月後にそう痒と紅斑は改善し,約8ヵ月後に,小型の脱毛斑2ヶ所は治癒した。その後脱毛瘢痕部にエキシマライトを約1.5年間照射し脱毛斑はさらに3ヶ所治癒した。口腔粘膜部のびらんや下腿紅斑は出没を繰り返し,初診より1.5年後,腟周囲にびらんおよび白色局面が出現し,いずれもステロイド外用を継続中である。自験例は歯科金属除去後に扁平苔癬の一部として毛包性扁平苔癬が生じ,既存の口腔や下腿病変の増悪と腟周囲にも病変が生じた経過が特徴的であった。当院で過去2年間のうち金属パッチテスト陽性の扁平苔癬は15例あり,年齢は39歳から84歳までの男性4名,女性11名で,粘膜型13例,皮膚型1例,皮膚粘膜毛孔性扁平苔癬型1例(自験例)であった。該当金属を除去したのは4例で,経過不明の2例をのぞき,自験例を含めいずれも症状は改善しなかった。(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  

20歳代の在日外国人男性。右手疼痛を主訴に整形外科を受診した際に皮疹を指摘され、当科を受診した。顔面・四肢末梢・腰腹部に光沢のある境界明瞭な結節を多数認め、臨床症状、皮膚スメア検査、組織所見、らい菌特異的PCR陽性よりLL型ハンセン病と診断した。ハンセン病およびらい反応は、治療が遅れると後遺症を残しうるため早期診断・早期治療が重要である。自験例は多剤併用療法開始後に皮膚症状の悪化や神経・眼症状、発熱、関節痛など多彩ならい性結節性紅斑の症状が出現し、その後慢性化したが、ほとんど後遺症なく経過している。(著者抄録)

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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  

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

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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  

25歳,女性。初診の約6ヵ月前より右上腕に紅色結節が出現し,急速に増大した。肉眼所見では5×10mmの境界明瞭な紅色扁平結節が存在しそれと隣接して2mmの黒褐色の小色素斑が認められた。病理組織学的に結節部はSpitz母斑,小色素斑は黒子様色素細胞母斑であった。さらに,免疫組織化学的に結節部にはROS1蛋白の過剰発現が,色素斑にはBRAF V600E変異蛋白が検出され,両者は発生機序の異なる病変であることが示された。(著者抄録)

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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  

71歳,男性。2018年8月上旬に,瀬戸内海での漁で網にかかったナルトビエイ(Aetobatus narutobiei)を外していた時に,尻尾の棘が左小指の基部に刺さった。直後に海水で洗浄し,しばらく自宅で様子をみていたが,同部位が次第に腫脹してきたため,1ヵ月半後に当科を受診した。初診時,左小指MP関節の背側に中心がクレーター状に陥凹し,潰瘍化している15×14mmの紅色結節を認めた。組織片を2%小川培地に接種し,30℃と35℃の条件下で培養を行ったところ,いずれの条件下でも28日目に灰白色のコロニー形成を認め,MALDI-TOF MSのマススペクトルのパターンからMycobacterium marinumと診断した。皮膚病変はミノサイクリン塩酸塩(200mg/日内服を3ヵ月間)を投与して完治した。エイ刺傷は,その鋭利な尾棘による損傷と刺毒による炎症を特徴とし,創部感染のリスクもある。近年ナルトビエイの瀬戸内海での生息域の拡大が問題視されている。そのため,エイ刺傷への対応を知ることは大切である。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

微生物の侵入から身体を守る皮膚のバリア機構においては、「抗菌ペプチド」が重要な役割を果たしている。抗菌ペプチドは広域の抗菌活性をもつのみならず、炎症誘導、創傷治癒促進、血管新生促進など、さまざまな機能を有していることも報告され、アラーミン(alarmin)の一種とも考えられている。一方、皮膚のバリア形成には、その場に存在する常在菌も重要な役割を果たしていることがわかってきた。常在菌叢を構成する個々の細菌種のゲノムの集合体を「マイクロバイオーム」と呼ぶ。近年のシークエンス技術の発展によって、正常皮膚および皮膚疾患病変部のマイクロバイオームに関しても、さまざまな新知見が得られている。(著者抄録)

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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：(株)医学書院  

＜文献概要＞73歳,男性.4年前に肺アスペルギルス症の治療のためボリコナゾールを内服開始した.2年前から頭部,顔面,両手背に角化性の丘疹,紅斑が多発した.病理組織所見は,顔面は有棘細胞癌,頭部・手背は日光角化症であった.ボリコナゾール内服中止とイミキモド外用により皮疹は改善した.ボリコナゾールは,その代謝物が紫外線を吸収して活性酸素を産生し,表皮のDNA損傷を惹起する.さらにボリコナゾールそのものがCOX-2の転写活性を誘導することで発癌を促進させる可能性が示されており,長期内服中に光線過敏症状を経て日光角化症,有棘細胞癌を生じうる.ボリコナゾールの光線関連皮膚障害は本邦ではまだ報告が少ないものの,十分な遮光指導を受けていない肺アスペルギルス症の患者に多い.ボリコナゾール内服患者には具体的な遮光指導と慎重な皮膚症状の経過観察を行うことで,光線関連皮膚障害を最小限に抑えることが期待できる.

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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=J01559&link_issn=&doc_id=20200929210011&doc_link_id=10.11477%2Fmf.1412206182&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1412206182&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)協和企画  

＜文献概要＞症例のポイント ・イミキモドは単球および形質細胞様樹状細胞を主体としたTLR7に作用し,その結果IL-17/IL-23の産生を促し,乾癬のマウスモデルとして使用されている.・日光角化症の患者に対するイミキモドクリーム外用により,外用部位以外にも角化性紅斑が出現し,乾癬が誘発された.・患者は乾癬の既往はなかったが,イミキモドクリームにより強い紅斑反応を示していた.

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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  

58歳,男性。右外耳道有棘細胞癌に対してepidermal growth factor receptor(EGFR)阻害剤のセツキシマブとパクリタキセルの併用療法を6ヵ月間,合計14回施行した。最終投与日から13日後に四肢に一部血疱や浸潤を伴う点状紫斑が多発し,腎機能障害も認めた。皮膚病理所見では真皮全層の血管周囲に好中球や好酸球の浸潤と核塵を認め,真皮浅層から中層の毛細血管に血管壁のフィブリノイド変性があり,leukocytoclastic vasculitis(LCV)に矛盾しない所見であった。蛍光抗体直接法では真皮上層の血管周囲にC3の沈着が認められたが,IgAの沈着は認めなかった。セツキシマブ・パクリタキセルを休薬し,プレドニゾロン(PSL)20mg/日内服と細胞外液の補液を開始したところ,皮疹,腎機能ともに速やかに改善した。しかし,蛋白尿と尿潜血が持続して検出されたため,PSL8.0mg/日を維持量として継続した。その後外耳道癌が再び増大し,4ヵ月後にセツキシマブ・パクリタキセルを再投与したが皮疹の再燃は認めなかった。EGFR阻害剤投与中に,血管周囲にC3の沈着を伴うLCVの報告が本症例以外にも3例ある。そのうち1例では潰瘍化や壊死を伴う臨床像を呈し,1例では下血を合併していた。本症例ではEGFR阻害剤がLCV発症の直接の誘因になったかどうかは不明だが,EGFR阻害剤によりLCVが重症化した可能性が考えられる。(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=2020&ichushi_jid=J01003&link_issn=&doc_id=20200911420006&doc_link_id=130007905518&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007905518&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

記述言語：日本語   出版者・発行元：大道学館出版部  

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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=J01556&link_issn=&doc_id=20200827450019&doc_link_id=%2Fam3daidc%2F2020%2F009708%2F020%2F1042-1046%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fam3daidc%2F2020%2F009708%2F020%2F1042-1046%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：日本皮膚科学会-西部支部  

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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：Wiley-Blackwell Publishing Ltd  

DOI： 10.1002/cia2.12102

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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＞頭部血管肉腫に対して,放射線療法とタキサン系抗癌剤による化学放射線療法が主流となっており,有害事象や合併症により入院が長期化することがある。しかしながら,高齢の患者が治療について十分に理解できていないことも多く,治療のコンプライアンス低下につながる。そこで患者への正確な情報提供を目的として,頭部血管肉腫の入院中の有害事象について検討した。入院期間は中央値57日,化学放射線療法による有害事象は放射線皮膚炎94%,皮膚びらんからの感染41%,脱毛53%,血球減少53%であり,発現時期と期間を明確にできた。事前に主なスケジュールと有害事象について十分説明することが重要である。

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記述言語：日本語   出版者・発行元：大道学館出版部  

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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=J01556&link_issn=&doc_id=20200407480008&doc_link_id=%2Fam3daidc%2F2020%2F009703%2F008%2F0309-0314%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fam3daidc%2F2020%2F009703%2F008%2F0309-0314%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：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：日本皮膚科学会-西部支部  

61歳,男性。2013年5月に多発性筋炎と診断され,プレドニゾロン(PSL)で治療が開始された。治療開始前のCTで左頸部と左腋窩リンパ節腫脹を認め経過観察されていたが,リンパ節は増大傾向を呈し,リンパ節生検で悪性黒色腫と診断された。精査では原発巣は認められなかった。DTIC療法とDAC-Tam-Feron療法を受けたが効果に乏しく,2015年3月からベムラフェニブを開始し転移巣は速やかに縮小したが,転移巣が増大してきたため,2015年11月にニボルマブ2mg/kgを3週間間隔で投与開始した。ニボルマブ2回目投与後から筋原性酵素の上昇や疲労感を認め,多発性筋炎の増悪と考えた。ニボルマブを継続しつつ,PSLを5mgから20mgに増量したところ,筋症状は改善した。しかし転移巣は増大傾向にあったため,ニボルマブは5回で中止した。イピリムマブも効果がなく,2016年6月からダブラフェニブとトラメチニブの併用療法を開始した。転移巣は速やかに縮小したが,次第に耐性を示すようになった。2017年7月に多発転移により全身状態が悪化し,永眠した。免疫チェックポイント阻害薬により既存の自己免疫疾患が悪化したが,自己免疫疾患悪化時も適切な対応を行うことにより免疫チェックポイント阻害薬は継続可能であった。(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=2019&ichushi_jid=J01003&link_issn=&doc_id=20191004380009&doc_link_id=10.2336%2Fnishinihonhifu.81.396&url=https%3A%2F%2Fdoi.org%2F10.2336%2Fnishinihonhifu.81.396&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：金原出版(株)  

＜文献概要＞65歳,女性。4年前より左耳前部に紅斑が出現した。近医皮膚科でステロイド外用を開始されるも難治であった。生検で真皮内に類上皮細胞肉芽腫を認め,サルコイドーシスの疑いで精査・加療目的に当科を紹介受診した。初診時,左耳前部に鱗屑を付す4×5cm大の円板状紅斑,耳介部に潰瘍形成,頭頂部に15×20mm大の瘢痕様紅斑を認めた。単純CTで両側縦隔リンパ節に加え,両鼠径リンパ節など全身のリンパ節腫脹を認めた。皮膚生検,鼠径リンパ節生検,気管支鏡検査でいずれも非乾酪性肉芽腫を認めたため,サルコイドーシスと確定診断した。自験例は感染症との鑑別を要する非典型的臨床像であったが,鼠径リンパ節生検により診断を裏づけることができた。また,Th2優位に移行した成熟期のサルコイドーシスであったと推測する。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01266&link_issn=&doc_id=20191024130009&doc_link_id=10.18888%2Fhi.0000001619&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000001619&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：日本皮膚科学会-西部支部  

表皮のバリア形成に重要な役割を果たす表皮角化細胞産生カリクレイン関連ペプチダーゼとアトピー性皮膚炎(AD)との関連性について述べた。多くのカリクレイン(KLKs)はAD病変部において発現が増強されており、表皮バリア機能を低下させることによって病態形成と関連している可能性がある。表皮角化細胞はKLKsの阻害因子であるリンパ上皮Kazal型関連阻害因子(LEKTI)、さらにSLPI、PI3、SPINK6、SPINK9なども発現するため、AD病変部の過剰なプロテアーゼ活性については酵素のみならず、阻害因子の発現量および機能、さらにはpHの変化も含めて総合的に酵素活性増強機構を検討する必要がある。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01003&link_issn=&doc_id=20191004380003&doc_link_id=10.2336%2Fnishinihonhifu.81.367&url=https%3A%2F%2Fdoi.org%2F10.2336%2Fnishinihonhifu.81.367&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：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：(NPO)日本皮膚外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本皮膚外科学会  

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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)  

＜文献概要＞75歳,男性。狭心症で冠動脈ステント留置後3ヵ月目頃より右肩甲部に痒みを伴う紅斑が出現し,1年後に潰瘍化した。デブリードマンと外用療法で約1年半加療されるも難治であったため,精査・加療目的に当科を紹介受診した。初診時,右肩甲部に3×3cm大の深い潰瘍があり周囲8×7cm大の範囲に板状硬結,暗褐色色素沈着と血管拡張を認めた。MRIでは筋層まで達していた。冠動脈造影による放射線性皮膚潰瘍と考え,潰瘍,硬結を切除,有茎広背筋皮弁術を施行した。術後は機能面,整容面ともに良好であった。右肩甲部皮膚潰瘍の患者に遭遇した場合,冠動脈造影の既往を問診することが重要である。また再建方法としては有茎広背筋皮弁術が治療選択肢となる。

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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＞52歳,男性。2年前より下口唇の口腔粘膜部に自覚症状のない粘膜下結節が出現した。超音波検査では,境界明瞭な10mm大の粘膜下結節を認め,内部不均一な低エコー像を示した。カラードプラ像では豊富な血流信号を認めた。結節を全摘出したところ,病理組織では異型に乏しい長紡錘形細胞が特定の配列をとることなく増殖し,間質に不規則に分枝した鹿角様血管を認めた。免疫染色ではCD34とbcl-2がびまん性に陽性で,CD31とfactorVIIIは陰性であった。また,抗STAT6抗体による免疫染色では,核に陽性であった。以上の所見からsolitary fibrous tumor(SFT)と診断した。臨床所見ではmucous cystとの鑑別を要したが,超音波検査で血流を確認することがSFTの診断の一助となると考えた。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01266&link_issn=&doc_id=20190722170009&doc_link_id=10.18888%2Fhi.0000001479&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000001479&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：金原出版(株)  

＜文献概要＞69歳,女性。神経線維腫1型に伴うびまん性神経線維腫と特発性血小板減少性紫斑病(ITP)を合併。宗教的輸血拒否患者。25年前より右下腹部の腫瘤が徐々に増大してきていた。2016年当科を初診し,手術を計画したが,宗教上の輸血療法不能を理由に中止となった。2017年腫瘤の増大と表面の紫斑が出現した。腫瘤表面に拳大の紫斑と内部に硬結を触知,貧血の進行を認め,腫瘤内出血が疑われ緊急入院した。医療安全上の対応と周術期の対策を各科・各部署の協力で検討した。ITPに対してプレドニゾロン内服,術前に動脈塞栓術を施行後,術中の閉鎖回路による希釈式自己血灌流のうえ,術中出血は200mlで腫瘍を切除できた。院内の医療連携システムの充実が重要である。

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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：(一社)日本皮膚悪性腫瘍学会  

症例1:60歳、男性。2015年、食道悪性黒色腫と診断された。BRAF変異陰性。後腹膜、腸間膜に多発転移あり。ニボルマブ投与を開始し、腹膜播種病変は画像上消失した。原発巣と近傍のリンパ節転移は残存したため、食道亜全摘+所属リンパ節郭清術を施行した。術後、ニボルマブ投与を再開したが、脳転移が出現。イピリムマブ投与に変更し、全脳照射を施行したが、永眠された。症例2:72歳、女性。2015年、食道悪性黒色腫と診断された。BRAF変異陰性。PET/CTにてL2椎体に転移あり。ニボルマブ投与により転移巣は画像上消失し、原発巣は色素沈着のみとなった。ニボルマブ投与継続していたが、食道原発巣の再発を認め、食道亜全摘+所属リンパ節郭清術を施行した。術後、無治療で経過観察中であるが、現在のところ再発、転移はない。進行期の食道悪性黒色腫にニボルマブが奏効した2例を経験したので、報告した。(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=2019&ichushi_jid=J02197&link_issn=&doc_id=20190703420006&doc_link_id=130007666722&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007666722&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

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：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：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：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：(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：科学評論社  

CiNii Article

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その他リンク： http://search.jamas.or.jp/link/ui/2017265401

記述言語：日本語   出版者・発行元：科学評論社  

CiNii Article

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その他リンク： http://search.jamas.or.jp/link/ui/2017265401

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：日本皮膚科学会  

DOI： 10.14924/dermatol.126.1709

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その他リンク： http://search.jamas.or.jp/link/ui/2016400626

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：岡山医学会  

DOI： 10.4044/joma.125.217

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その他リンク： http://ousar.lib.okayama-u.ac.jp/51888

記述言語：日本語   出版者・発行元：医学書院  

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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  

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

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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：日本皮膚科学会大阪地方会・日本皮膚科学会京滋地方会  

セリンプロテアーゼである組織カリクレインは表皮角層のバリア機能に影響を与える。表皮角化細胞では特にカリクレイン5（トリプシン型セリンプロテアーゼ）とカリクレイン7（キモトリプシン型セリンプロテアーゼ）が高発現している。これらの組織カリクレインは，正常皮膚においては表皮角層の剥離を促す。アトピー性皮膚炎では組織カリクレインが過剰発現し，制御因子との均衡が崩れ，接着分子の分解がおこり微生物やアレルゲンが侵入しやすい表皮に変化すると考えられる。我々の研究では Th2 サイトカインが表皮における組織カリクレインとプロテアーゼインヒビターとの均衡を変化させ，アトピー性皮膚炎のバリア機能低下に関与する可能性が示唆された。(皮膚の科学，増16: 29-33, 2011)

DOI： 10.11340/skinresearch.10.Suppl.16_29

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記述言語：日本語   出版者・発行元：金原出版  

CiNii Article

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その他リンク： http://search.jamas.or.jp/link/ui/2011264530

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J-GLOBAL

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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)日本研究皮膚科学会  

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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：山口大学医学会  

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記述言語：日本語   出版者・発行元：医学書院  

DOI： 10.11477/mf.1412100540

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その他リンク： http://search.jamas.or.jp/link/ui/2006166156

記述言語：日本語   出版者・発行元：日本小児皮膚科学会  

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記述言語：日本語   出版者・発行元：金原出版(株)  

9ヵ月女児.生後2週間後から後頭部に爪甲大の紅色局面が出現し,近医にてレーザー治療,ステロイド外用を受けていたが紅斑は増大,腫瘤を形成し,出血を伴うようになった.後頭部右側から後頸部にかけて広基性に隆起する腫瘤を有し,腫瘤頂部からは物理的刺激により容易に出血した.Factor VIII,CD34,glucose transporter protein 1(GLUT1)は,いずれも増生する血管内皮細胞に染色された.血液検査上,出血傾向はなく,増大傾向もなくなっていたが,頻回に出血を繰返すため,治療としてステロイドの内服を選択した.その結果,腫瘤の色調の退色,容積の減少がみられ,漸減中も腫瘤の再増大はみられず,投与開始から6ヵ月後にステロイドを終了した.ステロイド内服は,本症例のように腫瘤を形成し,易出血性を伴うような場合には,早期でなくても試みられるべき治療法と考えられた

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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：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：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：日本皮膚科学会-西部支部  

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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：(一社)日本研究皮膚科学会  

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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：金原出版(株)  

49歳女(症例1).4年前に感冒症状で塩酸ミノサイクリン点滴を受けたところ,開始直後に呼吸困難,意識レベル低下を来たした.薬剤アレルギーの精査で,濃度1mg/mlのスクラッチテストを左前腕内側に施行した.15分後に同部位に15×27mmの紅斑が出現し,30分後には6×7mmの膨疹となった.更に45分後,腰仙部に手掌大の膨疹が出現した.膨疹は数時間で消失し,呼吸困難,意識レベル消失はなかった.61歳男(症例2).ミノマイシン内服で30〜40分後,全身に紅斑が出現し,数時間後に消失した.塩酸ミノサイクリン1mg/mlの皮内テストを施行したところ,15分後に同部位に15×10mmの膨疹を伴う35×40mmの紅斑が出現し,30分後には30×35mmに縮小した.濃度0.05mg/mlでは15分後に8×7mmの膨疹を伴う15×20mmの紅斑が出現した

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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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開催年月日： 2023年6月24日

記述言語：日本語   会議種別：口頭発表（招待・特別）  

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開催年月日： 2021年5月

記述言語：日本語  

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開催年月日： 2021年5月

記述言語：日本語  

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開催年月日： 2021年5月

記述言語：日本語  

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開催年月日： 2021年5月

記述言語：日本語  

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開催年月日： 2021年5月

記述言語：日本語  

researchmap

開催年月日： 2021年5月

記述言語：日本語  

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開催年月日： 2021年5月

記述言語：日本語  

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開催年月日： 2021年2月

記述言語：日本語  

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開催年月日： 2021年2月

記述言語：日本語  

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開催年月日： 2021年2月

記述言語：日本語  

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開催年月日： 2021年2月

記述言語：日本語  

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開催年月日： 2019年3月30日

記述言語：日本語   会議種別：口頭発表（招待・特別）  

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開催年月日： 2019年3月23日

記述言語：日本語   会議種別：口頭発表（招待・特別）  

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開催年月日： 2019年3月17日

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2019年3月10日

記述言語：日本語   会議種別：口頭発表（招待・特別）  

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開催年月日： 2019年2月25日

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2019年2月9日

記述言語：日本語   会議種別：口頭発表（招待・特別）  

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開催年月日： 2019年1月26日

記述言語：日本語   会議種別：口頭発表（招待・特別）  

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開催年月日： 2019年1月19日

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2019年1月19日

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2019年1月19日

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2019年1月19日