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

BACKGROUND: Endogenous DNA derived from nuclei or mitochondria is released into the blood circulation as cell-free DNA (cfDNA) following cell damage or death. cfDNA is associated with various pathological conditions; however, its clinical significance in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unclear. This study aimed to evaluate the clinical significance of cfDNA in AAV. METHODS: We enrolled 35 patients with AAV, including 10 with eosinophilic granulomatosis with polyangiitis (EGPA), 13 with microscopic polyangiitis, and 12 with granulomatosis with polyangiitis. Serum cf-nuclear DNA (cf-nDNA) and cf-mitochondrial DNA (cf-mtDNA) levels were measured by quantitative polymerase chain reaction before and after the initiation of immunosuppressive therapy. Tissue samples from EGPA patients were examined by immunofluorescence and transmission electron microscopy. The structure of eosinophil extracellular traps (EETs) and neutrophil extracellular traps (NETs) and stability against DNase were assessed in vitro. Platelet adhesion of EETs were also assessed. RESULTS: Serum cf-nDNA and cf-mtDNA levels were significantly higher in AAV than in healthy controls, with the highest levels in EGPA; however, serum DNase activities were comparable among all groups. cf-nDNA and cf-mtDNA decreased after treatment and were associated with disease activity only in EGPA. Blood eosinophil count and plasma D-dimer levels were significantly correlated with cf-nDNA in EGPA and cf-mtDNA. EGPA tissue samples showed lytic eosinophils and EETs in small-vessel thrombi. The structure of EETs showed bolder net-like chromatin threads in vitro and EETs showed greater stability against DNase than NETs. EETs provided a scaffold for platelet adhesion. CONCLUSION: cfDNA was increased in EGPA, associated with disease activity. The presence of DNase-resistant EETs in small-vessel thrombi might contribute to higher concentration of cfDNA and the occurrence of immunothrombosis in EGPA.

DOI： 10.3389/fimmu.2021.801897

PubMed

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Authorship：Corresponding author  

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Authorship：Corresponding author  

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

Eosinophilic granulomatosis with polyangiitis (EGPA; ie, Churg-Strauss syndrome) is one of the antineutrophil cytoplasmic antibody-associated vasculitis syndromes. Although extravascular granulomatoses are a well-known histopathological feature, the diverse histopathologic spectrum of cutaneous lesions has not been described in detail. Thus, this study sought to investigate the possible correlation between the clinical features and histopathology of cutaneous lesions in EGPA cases, focusing on systemic thrombogenic conditions, such as visceral infarction and deep vein thrombosis. Fourteen cases of EGPA diagnosed at the Department of Dermatology in Asahikawa Medical University from 1977 to 2017 were clinically and histopathologically reviewed. In 6 (43%) cases, skin lesions were the initial manifestation of EGPA. Among the cutaneous lesions, purpura and erythema were the most common. Persistent proteinuria and macrohematuria were observed in only 2 myeloperoxidase-antineutrophil cytoplasmic antibody-positive cases. Systemic thrombotic symptoms, such as cerebral infarction and deep vein thrombosis, were detected in 5 (36%) cases, and, in 3 of those cases, thromboses in dermal or subcutaneous vessels were observed histopathologically. Elevation of plasma D-dimer level (>2.5 μg/mL) was significantly correlated with concomitant systemic thrombotic symptoms (P = 0.0152, Fischer exact test). The histopathological finding of thrombotic features and increased plasma D-dimer were predictive factors of EGPA accompanied with systemic thromboses, such as deep vein thromboses and cerebral infarction.

DOI： 10.1097/DAD.0000000000001202

PubMed

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Language：English  

DOI： 10.1111/1346-8138.13738

PubMed

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

We report a 38-year-old male patient who presented with cutaneous lesions mimicking widespread discoid lupus erythematosus with high-grade fever, arthralgia and lymphadenopathy. Additional lymph node and skin biopsies, however, revealed karyorrhectic debris without neutrophils and numerous CD68-positive cells, a characteristic finding of Kikuchi's disease (KD). Comparing skin biopsies on different occasions, we could see different forms of histopathology. The histopathology of skin lesions of KD may vary during the clinical course, which may reflect the stage of the disease.

DOI： 10.1111/1346-8138.12557

PubMed

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A 60-year-old woman presented with a 13-day history of a generalized erythematous rash accompanied by fever, periorbital edema and axillary lymphadenopathy. Prior to the appearance of the rash, the patient had been treated with intermittent courses of oral minocycline for cystitis. The patient was diagnosed with drug-induced hypersensitivity syndrome (DIHS) due to minocycline. During the admission, infectious endocarditis was suspected and the patient was treated with i.v. gammaglobulin (0.4 g/kg per day). The following day, the patient suffered from systemic deterioration and symptomatic low blood pressure that prompted repeat echocardiography which revealed an ejection fraction of 10%. DIHS-associated myocarditis was suspected and management with circulation assistance devices and steroid pulse therapy were started, resulting in satisfactory resolution. A rise in titer of human herpesvirus-6, cytomegalovirus and Herpes simplex virus-1 antibodies was detected. Although minocycline-induced myocarditis is rare, this severe drug reaction should be considered with DIHS.

DOI： 10.1111/1346-8138.12378

PubMed

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

Kawasaki disease is an acute febrile disease predominantly seen in young children. We report a case of Kawasaki disease in a 32-year-old pregnant woman. She developed a generalized erythematous skin rash accompanied by high fever. Bilateral conjunctival congestion, tender cervical lymphadenopathy, an edematous lower lip and peripheral edema followed by desquamation were observed. She was successfully treated with aspirin and intravenous gammaglobulin (1 g/kg/day). Her course was not complicated by coronary artery aneurysm and she delivered a healthy baby. To the best of our knowledge, this is the first case of Kawasaki disease in a pregnant woman. We suggest that Kawasaki disease should be included in the differential diagnosis of a generalized, erythematous skin rash accompanied by high fever in adults.

DOI： 10.1159/000327937

PubMed

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Language：Japanese   Publisher：(株)医学書院  

42歳,男性.初診の1ヵ月前から体幹部に紅色皮疹が出現し四肢に拡大した.10年前から浸潤性胸腺腫があり化学療法を施行されていた.病理組織像で表皮上層の個細胞角化とリンパ球の表皮内浸潤がみられ,浸潤する細胞の多くはCD8陽性T細胞であった.胸腺腫の既往と移植片対宿主病(graft versus host disease:GVHD)様の皮膚症状,肝障害からthymoma-associated multiorgan autoimmunity(TAMA)と診断した.合併症の重症筋無力症の治療にγグロブリン大量療法(intravenous immunoglobulin:IVIG)を施行したところ皮膚症状の改善をみたが,その後消化器症状が出現した.ステロイドパルス療法およびステロイドの増量で改善したが,胸腺腫に対する化学療法を開始したところ侵襲性肺アスペルギルス症を発症し永眠された.TAMAは制御性T細胞が減少しGVHD様の症状がみられるが,確立した治療法がなく,免疫抑制治療による感染症で死亡する例が多い.自験例ではIVIGで皮疹の改善がみられ,ある一定の効果が得られたことから,考慮されるべき治療法と考えた.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01559&link_issn=&doc_id=20170609060007&doc_link_id=10.11477%2Fmf.1412205136&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1412205136&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

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70歳,女性.微熱,激しい頭痛,顎関節の疼痛および開口障害が出現し当院を受診した.耳鼻科,脳神経外科,歯科口腔外科を受診したが診断に至らず当科を紹介された.両側頭動脈の腫脹から側頭動脈炎が疑われ,病理組織学的に動脈壁内に肉芽腫性血管炎の像を認めた.アメリカリウマチ学会の診断基準5項目すべてを満たし,側頭動脈炎と診断し,プレドニゾロン40mg/日の内服を開始した.内服後,自覚症状は軽快し,約2週間後に開口障害も改善した.側頭動脈炎の約半数で顎跛行がみられるが,開口障害にまで至ることは稀である.開口障害をきたした症例は,調べえた限り本邦では自験例を含め15例で,そのうち視力障害をきたしたのは3例であった.開口障害や視力障害は血管炎が進行した所見と考えられるため早期診断,早期治療が重要である.(著者抄録)

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57歳男。10歳頃に右肩皮疹に気付き、20歳時に母斑の診断で皮膚剥削術を受けた。しかし、その後同部位に再発し、徐々に拡大して潰瘍を形成した。右肩甲骨部に10×7cmの浸潤を触れる淡紅色局面があり、表面に多数の白色小丘疹が散在し、周囲には紅斑、中央に痂皮付着を認めた。生検病理所見では真皮全層～皮下脂肪織に、小型で均一な腫瘍細胞から成る腫瘍塊が多数増殖し浸潤していた。表皮直下には角質嚢腫様構造が多数みられ、島状・索状の腫瘍塊は基底細胞様細胞、管腔形成部分は腺腔上皮様細胞で構成されていた。間質には豊富な線維化がみられ、壊死や核異型はなかった。免疫染色では全細胞AE1/AE3陽性、管腔を形成する病変部位の一部がCK7陽性、腫瘍辺縁の細胞の一部がS-100陽性であった。Microsystic adnexal carcinomaの診断で拡大切除術と植皮術を受け、摘出標本で腫瘍細胞は真皮深層から脂肪織にまで増生し、神経周囲浸潤もみられた。

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Language：Japanese   Publisher：(株)医学書院  

68歳女.7年前にSjogren症候群と診断されプレドニゾロン(PSL)5mg/日内服中であった.5年3ヵ月前から下肢に紫斑が出現し,足趾の凍瘡様皮疹を繰り返していたが2年前に紫斑が拡大したためPSLを25mg/日に増量した.その後,紫斑の改善を認めPSLを漸減していたが,今回紫斑が再発したため精査加療目的で入院となった.皮膚生検では表皮に著変なく真皮上層の血管周囲に好中球と単核球の浸潤を認め,核塵・赤血球の血管外漏出もみられ,蛍光抗体直接法では真皮浅層の血管周囲に顆粒状のC3沈着を認めた.血清免疫電気泳動検査にてIgA-κ型M蛋白を認め,胃内視鏡検索の結果,胃アミロイドーシスの合併も確認された.以上の所見からMGUS(monoclonal gammopathy of undetermined significance)を合併したSjogren症候群と診断しメルファラン-プレドニゾロン(MP)療法を1クール施行したところ,高γグロブリン血症は著明に改善し,それに伴い下腿の紫斑も消退し,その後皮疹の再発は認めておらず,血中クリオグロブリンも陰性化している

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2006&ichushi_jid=J01559&link_issn=&doc_id=20060713260010&doc_link_id=10.11477%2Fmf.1412100969&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1412100969&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

Language：Japanese   Publisher：金原出版(株)  

64歳女.特に誘因なく体幹,四肢に痒みを伴う紅色皮疹が出現した.痛風でアロプリノールを内服中であったためアロプリノールを中止したが,皮疹は拡大した.体幹,四肢に癒合傾向を伴い,一部環状を呈する暗赤色から淡紅色の紅斑が多発していた.紅斑の辺縁部には膿疱が集簇し,一部膿海を形成し,中心部から膜様に落屑していた.また,白血球増加,リンパ球減少,CRP高値,低蛋白血症,低カルシウム血症,抗核抗体陽性,抗SS-A抗体陽性,f-T3低値,抗サイログロブリン抗体陽性がみられた.HLAを検索したところ,A24,DR4,CW1,B35を検出した.膿疱性乾癬にSjoegren症候群,慢性甲状腺炎の合併が明らかとなり,皮疹はプレドニゾロン,エトレチナートの服用で改善し,Sjoegren症候群は塩酸セビメリン水和物内服を開始し,慢性甲状腺炎は経過観察とした

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2005&ichushi_jid=J01266&link_issn=&doc_id=20050715030003&doc_link_id=https%3A%2F%2Fasahikawa-med.repo.nii.ac.jp%2Frecords%2F2712&url=https%3A%2F%2Fasahikawa-med.repo.nii.ac.jp%2Frecords%2F2712&type=%E6%97%AD%E5%B7%9D%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%EF%BC%9A%E6%97%AD%E5%B7%9D%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%88%90%E6%9E%9C%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA_AMCoR&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80003_3.gif

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40歳女.顔面に痒みを伴う紅斑が出現し,その1ヵ月後から右手首の腫脹,疼痛が出現し,その後全身に浮腫性紅斑と弛張熱が出現した.リウマチ因子,抗核抗体,抗DNA抗体は陰性で,マイコプラズマ抗体320倍,ASLOが935U/mlと高値を示した.ウイルス抗体価はヒトパルボウイルスB19 IgG抗体高値,IgM抗体軽度上昇,風疹・麻疹・EB・サイトメガロウイルスは既感染パターンを示した.ASLOが高値であったためペニシリン(トシル酸スルタミシリン)を投与したが弛張熱が続いた.その後,直径1cm大までの皮下結節が両手背,足背に出現した.病理組織所見で典型的なリウマトイド結節の所見であった.Still病と診断しPSLの内服を開始したところ,速やかに解熱し関節症状も改善した

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2004&ichushi_jid=J01266&link_issn=&doc_id=20040329100038&doc_link_id=https%3A%2F%2Fasahikawa-med.repo.nii.ac.jp%2Frecords%2F2711&url=https%3A%2F%2Fasahikawa-med.repo.nii.ac.jp%2Frecords%2F2711&type=%E6%97%AD%E5%B7%9D%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%EF%BC%9A%E6%97%AD%E5%B7%9D%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%88%90%E6%9E%9C%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA_AMCoR&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80003_3.gif

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40歳女.2000年3月頃から顔面の紅斑が出現し,徐々に拡大して,5月には発熱した.皮疹は亜急性型紅斑でリンパ球減少,抗DNA抗体,抗核抗体陽性所見と合わせて全身性エリテマトーデスと診断した.検査上,抗リン脂質抗体症候群を合併していた.無疹部ループスバンドテストで基底膜部にIgG,IgMが沈着し,腎生検の結果,WHO分類class IVであった.プレドニゾロン(PSL)50mg/日を開始したところ,皮膚症状,検査所見は徐々に改善したが,3週間目頃から手指の痺れ,突っ張り感を自覚し,その後多弁,易刺激性を中心とする精神・神経症状が出現した.画像所見,脳波所見も合わせ,neuropsychiatric lupusと診断した.PSLは増量せずに向精神薬治療で速やかに精神症状改善した.その後は順調に経過し,現在外来観察中である.精神症状の再発はない

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