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

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

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

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

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Language：Japanese   Publisher：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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Language：Japanese   Publisher：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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Other Link： 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

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

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DOI： 10.4103/ijd.ijd_645_22

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Language：Japanese   Publisher：日本皮膚科学会-西部支部  

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DOI： 10.1111/1346-8138.16442

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OBJECTIVE: While there are literature reporting increased incidence of hair loss in COVID-19 patients, insufficient evidence exists on the topic to date. This review aims to identify the existing evidence and clinical characteristics of hair loss with COVID-19 infection. METHODS: Following the PRISMA Extension for Scoping Reviews, MEDLINE and EMBASE were searched for all peer-reviewed articles with relevant keywords including "Alopecia," "Telogen Effluvium (TE)," and "COVID-19" from their inception to November 20, 2021. RESULTS: A total of 26 articles, with 9 observational studies and 17 case reports or series (a total of 58 cases), were included. Most studies dealt with TE. There were no clear trends between COVID-19 severity and the extent of hair loss. Analysis of the 58 cases also found similar results with most of the cases being female (82.8%), the median onset of hair loss of 2.0 months, and the median time to recovery of hair loss of 5.0 months with a resolution rate of 95%. CONCLUSION: While this systematic review revealed uncertainty and a lack of strong evidence regarding the association of COVID-19 and hair loss, hair loss in COVID-19 may mainly include TE and be reversible in nature. Future studies are warranted to determine the detailed pathophysiology and risk factors of hair loss in COVID-19, including possible roles of estrogen, progesterone, and pro-inflammatory cytokines.

DOI： 10.1111/jocd.15218

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Language：Japanese   Publisher：(NPO)日本皮膚外科学会  

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This study sought to confirm the homogeneity of BRAF V600E mutation status in melanoma. BRAF immunohistochemistry was performed on 102 lesions from 60 patients of melanoma with BRAF V600E mutation and 38 negative-control melanoma lesions from 38 patients, both of which were confirmed by real-time PCR or the MassARRAY System. In the positive-control lesions, 9 lesions from 7 patients with preceding BRAF-inhibitor therapy were included. Of the 102 BRAF-mutant lesions, 101 (99.0%) showed diffuse BRAF immunoexpression, but 39 (38.2%) of them showed various heterogeneous intensities. The heterogeneous intensity of immunostaining was due to necrosis (n = 10), minimal or clear cytoplasm (n = 5), tissue crush (n = 8), insufficient fixation (n = 24), or technical error (n = 4). Only 1 lesion (1.0%) with nondiffuse immunoexpression harbored 80% weakly BRAF-positive tumor area and 20% BRAF-negative area with tissue damage. Sanger sequencing performed on the weak or negative regions in 7 lesions revealed BRAF V600E mutation in all the tested lesions. By contrast, all 38 negative-control lesions demonstrated no BRAF immunoexpression. This study demonstrated intralesional homogeneity and interlesional concordance for BRAF V600E mutation status and intralesional frequent heterogeneity for BRAF immunoexpression. The abovementioned 5 phenomena caused substantial reduction in BRAF immunostaining intensity. In 9 lesions within this study, BRAF immunoexpression and BRAF V600E point mutation status were not affected by preceding BRAF inhibitor therapy. Our data would also support the position that it does not matter whether we select primary or metastatic samples for BRAF mutation analysis.

DOI： 10.1097/DAD.0000000000002146

PubMed

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Language：Japanese   Publisher：(NPO)日本皮膚外科学会  

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Language：Japanese   Publisher：(NPO)日本皮膚外科学会  

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Language：Japanese   Publisher：(一社)日本皮膚悪性腫瘍学会  

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

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Language：Japanese   Publisher：日本皮膚科学会-西部支部  

2012年11月から2020年1月までに当院では8例の進行期乳房外パジェット病に対して1次治療としてタキサン系化学療法を施行した。年齢中央値は75.5歳(67〜89歳),男性6例,女性2例で,原発部位は外陰部が5例,鼠径部が2例,肛門部が1例であった。初期手術施行例は4例であった。転移部位は遠隔リンパ節が8例,肝臓が3例,小脳が1例,治療開始前のPerformance Statusは0〜1であった。1次治療としてパクリタキセル(PTX)4例,ドセタキセル(DTX)4例を開始し,平均7.1コース施行した。3例でPR(部分奏効),1例がSD(安定),4例がPD(進行)となった。放射線療法の併用は4例であった。2次治療以降では,DTX4例,PTX1例,S-1が1例,DTXとトラスツズマブ(Tmab)の併用が1例,Tmab単剤が1例,low-dose FP(5-フルオロウラシル(5-FU)+シスプラチン)が2例,FECOM(エピルビシン塩酸塩+マイトマイシンC+ビンクリスチン硫酸塩+カルボプラチン+5-FU)が1例であった。乳房外パジェット病は手術が第一選択であり,外科的治療で病勢コントロールが望めない進行期症例に対して化学療法が適応となる。進行期乳房外パジェット病の予後は悪く,エビデンスの高い化学療法は確立されていない。今回自験例でPRとなった症例では平均7ヵ月効果が持続しており,タキサン系化学療法は一定の抗腫瘍効果を得られたと考えた。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01003&link_issn=&doc_id=20220517220012&doc_link_id=10.2336%2Fnishinihonhifu.84.131&url=https%3A%2F%2Fdoi.org%2F10.2336%2Fnishinihonhifu.84.131&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞69歳,男性.左中指先端の黒色結節が徐々に拡大し,悪性黒色腫(malignant melanoma:MM)が疑われ前医より当科を紹介受診した.左中指先端から爪甲下に10×6mm大の黒色結節を認め,小指側に淡い褐色斑を伴っていた.PET-CTでリンパ節転移・遠隔転移は認めず,病変部切除・センチネルリンパ節生検の方針となった.手術前日に背部を診察すると中央に大豆大の小結節を伴う14×14mm大の辺縁不整な黒色斑を認め,MMの多発疑いで同時に切除した.左中指は末端黒子型(acral lentiginous melanoma:ALM)で病期IIC,左上背部は表在拡大型(superficial spreading melanoma:SSM)で病期IIIBであった.術後補助療法の希望なく経過観察中で,術後1年再発・転移はない.海外での原発性多発性悪性黒色腫(multiple primary melanomas:MPMs)はMM全体の1.2〜8.2%だが,本邦でMPMsは非常に稀である.また,海外のMPMsはSSMが多いが,自験例は異なる部位にALMとSSMが合併した点が特徴的であった.日本人のMMでも多発の可能性を考慮し全身の皮膚を評価することが大切である.

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Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞18歳,男性。発熱,血圧低下,意識障害のためICUへ緊急入院した際に左臀部に発赤腫脹,周囲に紅斑とびらんを認めた。CTにて左臀部皮下膿瘍が疑われ,切開排膿したところ黄白色調で表面平滑な大小の大豆様の結節病変が多数浮遊していた。組織学的にnodular-cystic fat necrosisと診断した。膿培養ではMRSA陽性,TSST-1産生株であり,トキシックショック症候群として抗菌薬加療で軽快した。患者は高度肥満であり,慢性刺激などの外傷によりnodular-cystic fat necrosisが臀部に生じたと考えた。Nodular-cystic fat necrosisの発症と細菌感染症の関連についての報告はないが,同部位の皮下膿瘍からトキシックショック症候群を発症したまれな症例であった。

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01266&link_issn=&doc_id=20220422050037&doc_link_id=10.18888%2Fhi.0000003217&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000003217&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

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

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Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

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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Language：Japanese   Publisher：日本皮膚科学会-西部支部  

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

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

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

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

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

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

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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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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Western Division of Japanese Dermatological Association  

DOI： 10.2336/NISHINIHONHIFU.83.417

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DOI： 10.1111/1346-8138.15542

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Immune-related adverse events (irAE) were reported to be associated with better outcomes in various cancers treated with the immune checkpoint inhibitor nivolumab. Considering that their development depends on host immune activation, irAE may reflect antitumor response in mucosal melanoma (MM). This single-center retrospective study including patients with advanced MM receiving nivolumab monotherapy between August 2014 and September 2018 investigated whether the development of irAE was associated with clinical efficacy. The study patients were divided into those with and without irAE, and treatment efficacy and safety were evaluated. The study cohort of 27 patients included 20 (74%), six (22%) and one (4%) patient with primary MM in the head and neck, genitourinary and anorectal regions, respectively. The irAE onset was not significantly associated with the objective response rate in patients while it was significantly associated with the disease control rate. The median progression-free survival in patients with and without irAE was 301 and 63 days, respectively. The median overall survival (OS) in patients with and without irAE was 723 and 199 days, respectively. According to the timing of irAE onset, the OS was better in seven patients who developed irAE after 180 days than in nine patients who developed irAE within 180 days. Although 16 patients (59%) experienced any grade irAE, including three (11%) with grade 3 or more irAE, there were no treatment-related deaths. These results indicated that the development of irAE may correlate with improved survival in patients with MM treated with nivolumab monotherapy. Further studies are necessary to confirm these findings.

DOI： 10.1111/1346-8138.15246

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

Background: In human skin, the serine proteases kallikrein-related peptidase (KLK)5 and KLK7 degrade corneodesmosome proteins, leading to desquamation. Serine protease activity of the skin is tightly regulated by the interplay between such proteases and serine protease inhibitors, including lymphoepithelial Kazal-type related inhibitor (LEKTI), encoded by SPINK5
secretory leucocyte peptidase inhibitor (SLPI)
and elafin. Expression of KLK5 and KLK7 is controlled and upregulated by stimulants such as calcium, 1,25-dihydroxyvitamin D3 [1,25(OH)2VD3] and retinoic acid (RA). Objectives: To understand the effect of calcium, 1,25(OH)2VD3 and RA on the expression of serine protease inhibitors in epidermal keratinocytes. Methods: We stimulated normal human epidermal keratinocytes (NHEKs) with high calcium, 1,25(OH)2VD3 or RA, and then analysed the expression of serine protease inhibitors using quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and immunocytofluorescence. We also analysed trypsin- and chymotrypsin-like serine protease activities in stimulated NHEKs. Results: High calcium, but not 1,25(OH)2VD3 or RA, significantly induced the expression of LEKTI, SLPI and elafin at both transcript and protein levels in NHEKs. These inductions were time- and dose-dependent. The activities of trypsin- and chymotrypsin-like serine proteases were significantly up- and downregulated by high calcium, respectively, in NHEKs. Conclusions: High calcium, but not 1,25(OH)2VD3 or RA, increases the expression of serine protease inhibitors in epidermal keratinocytes. Our findings contribute to the understanding of the mechanisms by which serine protease activities are regulated by serine proteases and related inhibitors in epidermal keratinocytes.

DOI： 10.1111/bjd.15153

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Language：Japanese   Publisher：(一社)日本臨床微生物学会  

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Language：Japanese   Publisher：(NPO)日本皮膚外科学会  

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Language：Japanese   Publisher：(NPO)日本皮膚外科学会  

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