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MPA、GPAの治療アルゴリズム

出典
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1: 厚生労働科学研究費補助金 難治性疾患等政策研究事業難治性血管炎の医療水準・患者のQOL向上に資する研究班 針谷正祥ほか編:ANCA関連血管炎診療ガイドライン2023、p.xv、診断と治療社、2023

厚生労働省多発血管炎性肉芽腫症診断基準

日本では最も標準的な診断基準であるとともに、公費補助の基準となっている。
出典
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1: 難病情報センターホームページhttps://www.nanbyou.or.jp/(2023年9月現在)から引用

原発性全身性血管炎分類アルゴリズムによるGPAの分類

Wattsらが提唱した血管炎分類のアルゴリズム。主に疫学研究への使用を目的としたアルゴリズムであるが、ACR分類基準、チャペルヒル(Chapel Hill)分類、GPAの肉芽腫性炎症および腎血管炎の代用マーカー、ANCA所見を用いて分類できる。表はGPA分類の部分を抜粋したもの。
 
参考文献:
Watts R, Lane S, Hanslik T,et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies.Ann Rheum Dis. 2007 Feb;66(2):222-7. (PMID : 16901958 改変あり)

肺胞出血のCT画像

a:GPA活動期の胸部CT。肺胞出血がみられる。
b:ステロイドとシクロホスファミドで治療後のCT、治療開始後約2週間で呼吸困難とX線画像は改善した。
出典
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1: Overview of Vasculitis Merkel, Peter A., Vascular Medicine: A Companion to Braunwald's Heart Disease, Chapter 41, 507-519

GPAの眼病変

左眼窩内に腫瘤を形成し、眼球突出と視神経圧迫による視力障害を起こしている。
出典
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1: Rheumatology , Fifth Edition Marc C. Hochberg, Alan J. Silman, Josef S. Smolen, Michael E. Weinblatt, and Michael H. Weisman. 153 , 1547-1558.e1 (改変あり)

GPAの肺結節、空洞

a:GPA患者の単純X線写真。左上肺野に5.5 cm径の内部に空洞を伴う結節影を認める。右上肺野に結節影が2つ。右下肺野に1つ。右肺に石灰化を伴う結節影があり、肺門リンパ節にも石灰化を認める。
b:同じ患者の上葉CT。左肺の巨大な空洞結節影の周囲に石灰化を伴う結節を認め、慢性の肉芽腫と考えられる。右上葉にも約1 cm径の結節影を認める。
出典
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1: Epistaxis due to Wegener's granulomatosis in a pediatric patient.
著者: Don Hayes, Joseph A Iocono, Jeffery S Bennett, David Corey Lachman, Hubert O Ballard
雑誌名: Am J Otolaryngol. 2010 Sep-Oct;31(5):368-71. doi: 10.1016/j.amjoto.2009.05.001. Epub 2009 Jun 30.
Abstract/Text: Epistaxis is a common problem in children that typically is not severe and seldom requires hospitalization. The nose is a highly vascular structure with a large surface area; subsequently, it is highly predisposed to bleeding. Childhood vasculitides are very rare and are commonly diagnosed by characteristic lesions on imaging studies along with syndrome recognition by clinicians. We present a case of recurrent epistaxis that persisted over 3 months due to Wegener's granulomatosis in an adolescent that was misdiagnosed as a benign hemorrhage from Kiesselbach's plexus.

Copyright 2010 Elsevier Inc. All rights reserved.
Am J Otolaryngol. 2010 Sep-Oct;31(5):368-71. doi: 10.1016/j.amjoto.200...

GPAの腎病理組織糸球体像

GPA患者の腎生検。糸球体に線維細胞性半月体を認める。
出典
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1: Husain,Aliya N.MD: High-Yield Thoracic Pathology,578-579

ANCA関連血管炎性中耳炎(OMAAV)診断基準2015(ANCA関連血管炎性中耳炎(OMAAV)診療の手引き2016年度版)

出典
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1: 日本耳科学会:ANCA関連血管炎性中耳炎(OMAAV)診療の手引き 2016年版. 金原出版、2016

GPAおよびOMAAVの耳病変

出典
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1: Propylthiouracil-induced Otitis Media with Antineutrophil Cytoplasmic Antibody-associated Vasculitis. Intern Med. Figure.3 (DOI: 10.2169/internalmedicine.0944-18)

PEXIVAS試験における減量プロトコール

出典
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1: Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis.
著者: Michael Walsh, Peter A Merkel, Chen-Au Peh, Wladimir M Szpirt, Xavier Puéchal, Shouichi Fujimoto, Carmel M Hawley, Nader Khalidi, Oliver Floßmann, Ron Wald, Louis P Girard, Adeera Levin, Gina Gregorini, Lorraine Harper, William F Clark, Christian Pagnoux, Ulrich Specks, Lucy Smyth, Vladimir Tesar, Toshiko Ito-Ihara, Janak Rashme de Zoysa, Wojciech Szczeklik, Luis Felipe Flores-Suárez, Simon Carette, Loïc Guillevin, Charles D Pusey, Alina L Casian, Biljana Brezina, Andrea Mazzetti, Carol A McAlear, Elizabeth Broadhurst, Donna Reidlinger, Samir Mehta, Natalie Ives, David R W Jayne, PEXIVAS Investigators
雑誌名: N Engl J Med. 2020 Feb 13;382(7):622-631. doi: 10.1056/NEJMoa1803537.
Abstract/Text: BACKGROUND: More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
METHODS: We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD).
RESULTS: Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups.
CONCLUSIONS: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).

Copyright © 2020 Massachusetts Medical Society.
N Engl J Med. 2020 Feb 13;382(7):622-631. doi: 10.1056/NEJMoa1803537.

本邦のLoVAS試験における減量プロトコール

出典
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1: Effect of Reduced-Dose vs High-Dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-Associated Vasculitis: A Randomized Clinical Trial.
著者: Shunsuke Furuta, Daiki Nakagomi, Yoshihisa Kobayashi, Masaki Hiraguri, Takao Sugiyama, Koichi Amano, Takeshi Umibe, Hajime Kono, Kazuhiro Kurasawa, Yasuhiko Kita, Ryutaro Matsumura, Yuko Kaneko, Keita Ninagawa, Keiju Hiromura, Shin-Ichiro Kagami, Yosuke Inaba, Hideki Hanaoka, Kei Ikeda, Hiroshi Nakajima, LoVAS Collaborators
雑誌名: JAMA. 2021 Jun 1;325(21):2178-2187. doi: 10.1001/jama.2021.6615.
Abstract/Text: IMPORTANCE: The current standard induction therapy for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis is the combination of high-dose glucocorticoids and cyclophosphamide or rituximab. Although these regimens have high remission rates, they are associated with considerable adverse events presumably due to high-dose glucocorticoids.
OBJECTIVE: To compare efficacy and adverse events between a reduced-dose glucocorticoid plus rituximab regimen and the standard high-dose glucocorticoid plus rituximab regimen in remission induction of ANCA-associated vasculitis.
DESIGN, SETTING, AND PARTICIPANTS: This was a phase 4, multicenter, open-label, randomized, noninferiority trial. A total of 140 patients with newly diagnosed ANCA-associated vasculitis without severe glomerulonephritis or alveolar hemorrhage were enrolled between November 2014 and June 2019 at 21 hospitals in Japan. Follow-up ended in December 2019.
INTERVENTIONS: Patients were randomized to receive reduced-dose prednisolone (0.5 mg/kg/d) plus rituximab (375 mg/m2/wk, 4 doses) (n = 70) or high-dose prednisolone (1 mg/kg/d) plus rituximab (n = 70).
MAIN OUTCOMES AND MEASURES: The primary end point was the remission rate at 6 months, and the prespecified noninferiority margin was -20 percentage points. There were 8 secondary efficacy outcomes and 6 secondary safety outcomes, including serious adverse events and infections.
RESULTS: Among 140 patients who were randomized (median age, 73 years; 81 women [57.8%]), 134 (95.7%) completed the trial. At 6 months, 49 of 69 patients (71.0%) in the reduced-dose group and 45 of 65 patients (69.2%) in the high-dose group achieved remission with the protocolized treatments. The treatment difference of 1.8 percentage points (1-sided 97.5% CI, -13.7 to ∞) between the groups met the noninferiority criterion (P = .003 for noninferiority). Twenty-one serious adverse events occurred in 13 patients in the reduced-dose group (18.8%), while 41 occurred in 24 patients in the high-dose group (36.9%) (difference, -18.1% [95% CI, -33.0% to -3.2%]; P = .02). Seven serious infections occurred in 5 patients in the reduced-dose group (7.2%), while 20 occurred in 13 patients in the high-dose group (20.0%) (difference, -12.8% [95% CI, -24.2% to -1.3%]; P = .04).
CONCLUSIONS AND RELEVANCE: Among patients with newly diagnosed ANCA-associated vasculitis without severe glomerulonephritis or alveolar hemorrhage, a reduced-dose glucocorticoid plus rituximab regimen was noninferior to a high-dose glucocorticoid plus rituximab regimen with regard to induction of disease remission at 6 months.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02198248.
JAMA. 2021 Jun 1;325(21):2178-2187. doi: 10.1001/jama.2021.6615.

欧州リウマチ学会が推奨するIVCYならびに経口CYの投与量

参考文献:
Kallenberg CG, Merkel PA, Raspe H, Salvarani C, Scott DG, Stegeman C, Watts R, Westman K, Witter J, Yazici H, Luqmani R; European Vasculitis Study Group. EULAR recommendations for the management of primary small and medium vessel vasculitis.Ann Rheum Dis. 2009 Mar;68(3):310-7. PMID: 18413444
出典
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1: 筆者作成

MPA、GPAの治療アルゴリズム

出典
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1: 厚生労働科学研究費補助金 難治性疾患等政策研究事業難治性血管炎の医療水準・患者のQOL向上に資する研究班 針谷正祥ほか編:ANCA関連血管炎診療ガイドライン2023、p.xv、診断と治療社、2023

厚生労働省多発血管炎性肉芽腫症診断基準

日本では最も標準的な診断基準であるとともに、公費補助の基準となっている。
出典
img
1: 難病情報センターホームページhttps://www.nanbyou.or.jp/(2023年9月現在)から引用