今日の臨床サポート

遺伝性血管性浮腫

著者: 堀内孝彦 九州大学病院 別府病院病院長/免疫・血液・代謝内科教授

監修: 上阪等 千葉西総合病院 膠原病リウマチセンター

著者校正/監修レビュー済:2021/10/27
参考ガイドライン:
  1. 一般社団法人日本補体学会:遺伝性血管性浮腫(HAE)ガイドライン 改訂2019年版.補体57(1): 3-12, 2020
  1. 世界アレルギー機構/欧州アレルギー臨床免疫学会:The international WAO/EAACI guideline for the management of hereditary angioedema- The 2017 revision and update. Allergy 73: 1575-1596, 2018
  1. カナダHAEネットワーク:The International/Canadian hereditary angioedema guideline. Allergy Asthma Clin Immunol 15: 72, 2019

概要・推奨   

  1. アレルギーなどの明らかな原因のない繰り返す浮腫をみたときには補体C1インヒビター(C1-INH)欠損のある遺伝性血管性浮腫(Hereditary angioedema with C1 inhibitor deficiency; HAE-C1-INHを疑い、補体C4C1-INH活性ならびにC1-INH蛋白量を測定する(推奨度1
  1. C1-INHが正常の場合にはC1-INH正常のHAEHAE with normal C1-INH; HAEnCIを疑う。HAEnCIには診断に役立つバイオマーカーがないため、確定診断には遺伝子解析が必要であ推奨度1)。
  1. HAEとの鑑別が重要な疾患として後天性血管性浮腫(acquired angioedema; AAE)がある。補体C4値、C1-INH活性はHAEと同様低下する補体C1qが鑑別に有用とされHAEでは正常、AAEでは低下するといわれる。しかし実際にはHAEC1qが低下する場合もあり、鑑別に有用とは必ずしもいえない(推奨度2
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
堀内孝彦 : 講演料(武田薬品工業(株))[2021年]
監修:上阪等 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 原因となる遺伝子異常の解明の進歩、それに伴う新たな疾患概念の確立を解説する。
  1. 新しい作用機序を有する新規治療薬を紹介する。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 遺伝性血管性浮腫(Hereditary angioedema; HAE)はC1-INH遺伝子(SERPING1)を代表とするいくつかの遺伝子異常を原因として、四肢、腸管、咽頭・喉頭など全身に発作性浮腫を繰り返す遺伝性疾患である。
 
HAEの病態

 HAEにおける血管性浮腫(angioedema)の主たるメディエーターはブラジキニン(Bradykinin)である。長い間、HAEの唯一の原因であると考えられていたC1-INHは、名前のようにC1を抑制して補体活性化を制御するのみならず、そのほかにも様々な分子を抑制してブラジキニン産生を制御する。ブラジキニン血管内皮細胞のブラジキニンB2受容体(Bradykinin B2 receptor)に結合して血管透過性を上げる。
アンギオポエチン1はブラジキニンB2受容体の機能を抑制している。ブラジキニンは高分子キニノーゲン(High Molecular Weight kininogen)がカリクレイン(Kallikrein)によって切断されて生じるが、その過程にはキニン系のほか、凝固XII因子やプラスミンなどの凝固・線溶系もかかわっている。ミオフェリン(MYOF)の変異によってVEGF受容体(VEGFR)の機能が亢進する。またHS3ST6の変異は細胞表面のヘパラン硫酸の異常を生じ結果的に高分子キニノーゲンからのブラジキニン産生を亢進させると推察されている。
補体活性化の結果生じるC3a、C5aなどの分解産物は炎症を強力に誘導する。HAEにおける血管性浮腫などの病態に何らかの役割を果たしている可能性も否定できない。HAEにおいて遺伝子異常が報告されている分子を緑色で示す。

 
  1. HAE with C1-INH deficiency (HAE-C1-INH)はすべての人種に男女の差なく報告されており、頻度は5万人に1人とされる[1]
  1. C1-INHに異常がないHAE(HAE with normal C1-INH; HAEnCI)はHAE-C1-INHに比べて少ないとされるが正確な頻度は不明である。原因遺伝子としては、凝固XII因子(F12)、プラスミノーゲン(PLG)、アンギオポエチン1(ANGPT1)、キニノーゲン1(KNG1)、ミオフェリン(MYOF)、HS3ST6遺伝子が報告されているが、原因遺伝子が不明の場合も多い。
  1. わが国でもHAEnCIが報告されているがPLG遺伝子異常のみ報告されている[2]。欧米のHAEnCI患者において約4分の1を占めるF12遺伝子異常はわが国ではまったく認めないことから、HAEnCIの病因には明らかな人種差が認められる[3]
  1. HAEの病態に共通する病態と考えられているのはブラジキニンの過剰産生であり、その結果血管透過性が亢進してさまざまな部位に発作性浮腫を生じる[4][5]
 
わが国のHAE患者の症状の頻度

1969~2010年のわが国のすべてのHAE症例報告(英文、和文で132報告)の発端者132例を検討した結果、症状別では皮膚症状(浮腫)が最も多く、約半数に消化器症状、喉頭浮腫を認めた。

出典

img1:  Hereditary angioedema in Japan: genetic analysis of 13 unrelated cases.
 
 Am J Med Sci. 2012 Mar;343(3):210-4. doi・・・
 
  1. 皮膚の場合は顔面や口唇、四肢に限局して生じる指圧痕を残さない浮腫(non-pitting edema)として気づかれる。
 
HAEによる手の突発性浮腫

30歳代女性、右手全体の圧痕を残さない突発性浮腫

出典

img1:  著者提供
 
 
 
HAEによる口唇の突発性浮腫

30歳代女性、突発性の口唇浮腫

出典

img1:  著者提供
 
 
 
  1. 腸管に浮腫が起きれば激烈な腹痛を生じ、喉頭に浮腫を生じると呼吸困難や窒息を来すため、救急を受診することもまれではない。
 
腹部CT所見

HAEの腸管浮腫による腹痛発作は激烈である。急性腹症の鑑別疾患の1つとして知っておくべきである。
a, b:造影CTで均質な壁肥厚と低吸収の粘膜下浮腫を伴う回腸領域を示す。
c:造影CTで著明な低吸収の粘膜下浮腫と空腸ループを含む周囲の腸間膜浸潤を伴う腸壁肥厚を示す。

 
下顎矯正術後に発症した喉頭浮腫

18歳男性、下顎矯正術施行後30時間で、重篤な顔面、咽頭、喉頭浮腫を呈し、緊急の気管挿管が行われた(a)。検査の結果HAEと診断された。CT検査にて、気管チューブ(矢印)と、その周囲の組織の広範な浮腫を認める(b)。
This article was published in Journal of oral and maxillofacial surgery, Vol.71, No.4, Cifuentes J, et al., e185-e188, Copyright © Elsevier 2013.

出典

img1:  Life-threatening complications following orthognathic surgery in a patient with undiagnosed hereditary angioedema.
 
 J Oral Maxillofac Surg. 2013 Apr;71(4):e・・・
 
  1. 適切に対処されなかった場合、喉頭浮腫の致死率は30%といわれる[6]
 
  1. 顔面浮腫を生じ、最終的に遺伝性血管性浮腫と診断された症例
  1. 病歴:30歳女性。16歳頃から四肢に突発性浮腫が出現。顔面浮腫にて当科受診。妹も同様の発作あり。
  1. 診察:顔面に圧迫してもあとの残らない浮腫(non-pitting edema)を認める。
  1. 診断のためのテストとその結果:C4 <2mg/dl(正常値11~34)、CH50 <8U/mL(正常値20~50)、C3 124mg/dL(正常値71~135)、C1-INH活性 <25%(正常値70~130)、C1-INH抗原 9mg/dL(正常値11~26)、C1q <2mg/dL(正常値8.8~15.3)
  1. 治療:ベリナートP静注用500を2バイアル静注
  1. 転帰:症状は軽快して帰宅
  1. コメント:この症例は、経過と検査結果、治療への反応性など典型的であるが、唯一C1q低下のみ非典型的であった。C1q低下は教科書的には後天性血管性浮腫の所見とされる。
    確定診断のため、遺伝子解析を施行、C1-INHに1アミノ酸置換の変異を認めHAE1型と診断した。
 
発作時と正常時の写真

出典

img1:  著者提供
 
 
問診・診察のポイント  
  1. 10~20歳代に顔面や四肢の浮腫、腹痛、喉頭浮腫などの症状が初めて出現し、その後繰り返すことが多い[7]
 
 
  1. 症状は発作性であり、通常は24時間で完成し、3日から数日で完全に治る。

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文献 

著者: Takahiko Horiuchi, Hiroyuki Ohi, Isao Ohsawa, Teizo Fujita, Misao Matsushita, Noriko Okada, Tsukasa Seya, Tetsuro Yamamoto, Yuichi Endo, Michiyo Hatanaka, Nobutaka Wakamiya, Masashi Mizuno, Miki Nakao, Hidechika Okada, Hiroshi Tsukamoto, Misako Matsumoto, Norimitsu Inoue, Masaru Nonaka, Taroh Kinoshita, Japanese Association for Complement Research
雑誌名: Allergol Int. 2012 Dec;61(4):559-62. doi: 10.2332/allergolint.12-RAI-0471. Epub 2012 Oct 25.
Abstract/Text This guideline was provided by the Japanese Association for Complement Research targeting clinicians for making an accurate diagnosis of hereditary angioedema (HAE), and for prompt treatment of the HAE patient in Japan. This is a 2010 year version and will be updated according to any pertinent medical advancements.

PMID 23093794  Allergol Int. 2012 Dec;61(4):559-62. doi: 10.2332/aller・・・
著者: Hiromasa Yakushiji, Chinami Hashimura, Kazuhito Fukuoka, Arito Kaji, Hisaaki Miyahara, Shinya Kaname, Takahiko Horiuchi
雑誌名: Allergy. 2018 Nov;73(11):2244-2247. doi: 10.1111/all.13550. Epub 2018 Aug 13.
Abstract/Text
PMID 29987869  Allergy. 2018 Nov;73(11):2244-2247. doi: 10.1111/all.13・・・
著者: Konrad Bork, Thomas Machnig, Karin Wulff, Guenther Witzke, Subhransu Prusty, Jochen Hardt
雑誌名: Orphanet J Rare Dis. 2020 Oct 15;15(1):289. doi: 10.1186/s13023-020-01570-x. Epub 2020 Oct 15.
Abstract/Text BACKGROUND: Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) (HAEnCI) is associated with skin swellings, abdominal attacks, and the risk of asphyxia due to upper airway obstruction. Several different gene mutations linked to the HAE phenotype have been identified. Our aim was to qualitatively assess and describe the clinical differentiators of these genetically identified HAEnCI types. To achieve this, we performed a systematic literature review of patients with angioedema symptoms and a genetically confirmed diagnosis of an HAEnCI type.
RESULTS: A systematic literature search, conducted in March 2020, returned 132 records, 43 of which describe patients with symptoms of angioedema and a genetically confirmed diagnosis of an HAEnCI type. Overall, this included 602 patient cases from 220 families. HAEnCI with a mutation in the coagulation factor XII gene (F12) (HAE-FXII) was diagnosed in 446 patients from 185 families (male:female ratio = 1:10). Estrogens (oral contraceptives, hormonal replacement therapy, and pregnancy) negatively impacted the course of disease in most female patients (252 of 277). Asphyxia occurred in 2 of 446 patients. On-demand and/or long-term prophylaxis treatment included C1-INH concentrates, icatibant, progestins, and tranexamic acid. HAEnCI with a specific mutation in the plasminogen gene (HAE-PLG) was diagnosed in 146 patients from 33 families (male:female ratio = 1:3). Estrogens had a negative influence on the course of disease in the minority of female patients (14 of 62). Tongue swelling was an important clinical feature. Asphyxia occurred in 3 of 146 patients. On-demand treatment with icatibant and C1-INH concentrate and long-term prophylaxis with progestins and tranexamic acid were effective. HAEnCI with a specific mutation in the angiopoietin-1 gene (HAE-ANGPT1) was diagnosed in 4 patients from 1 family and HAEnCI with a specific mutation in the kininogen-1 gene (HAE-KNG1) in 6 patients from 1 family.
CONCLUSIONS: A number of clinical differentiators for the different types of HAEnCI have been identified which may support clinicians to narrow down the correct diagnosis of HAEnCI prior to genetic testing and thereby guide appropriate treatment and management decisions. However, confirmation of the causative gene mutation by genetic testing will always be required.

PMID 33059692  Orphanet J Rare Dis. 2020 Oct 15;15(1):289. doi: 10.118・・・
著者: Allen P Kaplan, Kusumam Joseph
雑誌名: Ann Allergy Asthma Immunol. 2010 Mar;104(3):193-204. doi: 10.1016/j.anai.2010.01.007.
Abstract/Text OBJECTIVE: To review the mechanisms by which bradykinin is generated in hereditary angioedema (HAE) (C1 inhibitor deficiency), including the role of human plasma proteins and endothelial cells.
DATA SOURCES: Published articles in reviewed journals that address (1) the fundamentals of bradykinin formation, (2) interactions between kinin-forming proteins and endothelial cells, (3) clinical evidence that bradykinin causes swelling in HAE, and (4) therapeutic options focused on inhibition of the plasma kallikrein-kinin cascade.
STUDY SELECTION: Historical articles that have made fundamental observations. Recent articles that address evolving concepts of disease pathogenesis and treatment.
RESULTS: C1 inhibitor deficiency causes dysregulation of the plasma bradykinin-forming cascade with overproduction of bradykinin due to uninhibited effects of activated factor XII and plasma kallikrein. Swelling in HAE and production of bradykinin are localized (and may then disseminate); activation along the endothelial cell surface involves cell membrane ligands of factor XII and high-molecular-weight kininogen, release of endothelial cell heat shock protein 90, activation of the high-molecular-weight kininogen-prekallikrein complex, and endothelial cell activation at the B2 receptor. Attacks of swelling may be terminated by treatment with a kallikrein inhibitor or B2 receptor blockade. Replenishing C1 inhibitor can abort attacks of swelling and provide prophylaxis with intravenous administration.
CONCLUSIONS: Bradykinin is the mediator of swelling in types I and II HAE and is overproduced because of a deficiency in C1 inhibitor. Inhibition of bradykinin formation by novel agentscan provide targeted therapeutic approaches that address the pathophysiologic abnormalities.

PMID 20377108  Ann Allergy Asthma Immunol. 2010 Mar;104(3):193-204. do・・・
著者: Chinami Hashimura, Chikako Kiyohara, Jun-Ichi Fukushi, Tomoya Hirose, Isao Ohsawa, Tomoko Tahira, Takahiko Horiuchi
雑誌名: Allergy. 2021 Aug 3;. doi: 10.1111/all.15034. Epub 2021 Aug 3.
Abstract/Text
PMID 34343365  Allergy. 2021 Aug 3;. doi: 10.1111/all.15034. Epub 2021・・・
著者: Konrad Bork, Nina Ressel
雑誌名: Transfus Apher Sci. 2003 Dec;29(3):235-8. doi: 10.1016/j.transci.2003.08.007.
Abstract/Text Hereditary angioedema (HAE) is clinically characterized by recurrent and self-limiting skin, intestinal, and life-threatening laryngeal edema. This study describes the age at which laryngeal edema first occurred, the time between onset and full development, and the effectiveness of therapy and prophylaxis in 123 HAE patients. 61 (49.7%) patients experienced a total of 596 laryngeal edema episodes. The ratio of laryngeal edema episodes to skin swellings and abdominal pain attacks was approximately 1:70:54 in patients who had laryngeal edema. The mean (SD) age at the first laryngeal edema was 26.2 (15.3) years. Nearly 80% of the laryngeal edemas occurred between age 11 and 45. The mean interval between onset and maximum development of laryngeal edema was 8.3 hours. A total of 354 laryngeal edemas cleared spontaneously without treatment and 208 laryngeal edemas were successfully treated with C1 inhibitor concentrate. Despite long-term prophylactic treatment with danazol, 6 patients developed subsequent laryngeal edemas. Laryngeal edema may occur at any age, although young adults are at greatest risk. In adults, the interval between onset of symptoms and acute risk of asphyxiation is usually long enough to allow for use of appropriate emergency procedures. It is essential to instruct patients and their relatives about the first signs of laryngeal edemas and the necessary procedures to follow.

PMID 14572815  Transfus Apher Sci. 2003 Dec;29(3):235-8. doi: 10.1016/・・・
著者: Konrad Bork, Jochen Hardt, Karl-Heinz Schicketanz, Nina Ressel
雑誌名: Arch Intern Med. 2003 May 26;163(10):1229-35. doi: 10.1001/archinte.163.10.1229.
Abstract/Text BACKGROUND: Hereditary angioedema due to C1 esterase inhibitor deficiency is clinically characterized by recurrent and self-limiting skin, intestinal, and laryngeal edema. Asphyxiation by laryngeal edema is the main cause of death among patients who die of hereditary angioedema. This study describes the age at which laryngeal edema first occurs, the time between onset and full development, and the effectiveness of therapy and prophylaxis.
METHODS: Information on 123 patients with hereditary angioedema was obtained from medical histories and reports by the general practitioners, emergency physicians, and hospitals involved.
RESULTS: Sixty-one patients (49.6%) experienced a total of 596 laryngeal edema episodes. The ratio of laryngeal edema episodes to skin swellings and abdominal pain attacks was approximately 1:70:54 in patients who had laryngeal edema. The mean (SD) age at the first laryngeal edema was 26.2 (15.3) years. Nearly 80% of the laryngeal edemas occurred between the ages of 11 and 45 years. The mean interval between onset and maximum development of laryngeal edema was 8.3 hours. A total of 342 laryngeal edemas cleared spontaneously without treatment, and 208 laryngeal edemas were successfully treated with C1 esterase inhibitor concentrate. Despite long-term prophylactic treatment with danazol, 6 patients developed subsequent laryngeal edemas.
CONCLUSIONS: Laryngeal edema may occur at any age, although young adults are at greatest risk. In adults, the interval between onset of symptoms and acute risk of asphyxiation is usually long enough to allow for use of appropriate emergency procedures. To prevent a fatal outcome, it is essential to instruct patients and their relatives about the first signs of laryngeal edemas and the necessary procedures to follow.

PMID 12767961  Arch Intern Med. 2003 May 26;163(10):1229-35. doi: 10.1・・・
著者: Tom Bowen, Marco Cicardi, Henriette Farkas, Konrad Bork, Hilary J Longhurst, Bruce Zuraw, Emel Aygoeren-Pürsün, Timothy Craig, Karen Binkley, Jacques Hebert, Bruce Ritchie, Laurence Bouillet, Stephen Betschel, Della Cogar, John Dean, Ramachand Devaraj, Azza Hamed, Palinder Kamra, Paul K Keith, Gina Lacuesta, Eric Leith, Harriet Lyons, Sean Mace, Barbara Mako, Doris Neurath, Man-Chiu Poon, Georges-Etienne Rivard, Robert Schellenberg, Dereth Rowan, Anne Rowe, Donald Stark, Smeeksha Sur, Ellie Tsai, Richard Warrington, Susan Waserman, Rohan Ameratunga, Jonathan Bernstein, Janne Björkander, Kristylea Brosz, John Brosz, Anette Bygum, Teresa Caballero, Mike Frank, George Fust, George Harmat, Amin Kanani, Wolfhart Kreuz, Marcel Levi, Henry Li, Inmaculada Martinez-Saguer, Dumitru Moldovan, Istvan Nagy, Erik W Nielsen, Patrik Nordenfelt, Avner Reshef, Eva Rusicke, Sarah Smith-Foltz, Peter Späth, Lilian Varga, Zhi Yu Xiang
雑誌名: Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):24. doi: 10.1186/1710-1492-6-24. Epub 2010 Jul 28.
Abstract/Text BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema.
OBJECTIVE: To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010).
METHODS: The Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'angioédème héréditaire (RCAH) http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review.
RESULTS: This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference.
CONCLUSIONS: Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.

PMID 20667127  Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):24. doi: ・・・
著者: M D Tarzi, A Hickey, T Förster, M Mohammadi, H J Longhurst
雑誌名: Clin Exp Immunol. 2007 Sep;149(3):513-6. doi: 10.1111/j.1365-2249.2007.03438.x. Epub 2007 Jul 5.
Abstract/Text Reduced levels of serum C4 have been considered a ubiquitous finding in hereditary angio-oedema (HAE), and consequently low C4 is often used to 'request manage' access to C1 inhibitor assays in the United Kingdom. However, in our experience normal C4 may occasionally be compatible with HAE. We audited the results of serum C4, C1 inhibitor antigen (C1inhA) and C1 inhibitor function (C1inhF) in 49 HAE patients, compared to a control group of 58 unaffected subjects. The sensitivity of low serum C4 for HAE among untreated patients was 81%; levels of complement C4 were within the normal range on nine separate occasions in five untreated HAE patients. Molecular genetic analysis of these individuals demonstrated novel mutations in the C1 inhibitor gene. The supplied reference ranges for the Quidel C1inhF enzyme-linked immunosorbent assay (ELISA) system appear to be too low, with a sensitivity of just 57% for HAE. Following optimization of the reference ranges using receiver operating characteristic analysis, low C1inhF was found to be 78% sensitive and 100% specific for HAE. The diagnosis of HAE is not excluded by normal levels of complement C4. We conclude that C1 inhibitor studies should be performed regardless of serum C4 where a high index of clinical suspicion exists.

PMID 17614974  Clin Exp Immunol. 2007 Sep;149(3):513-6. doi: 10.1111/j・・・
著者: Marco Cicardi, Andrea Zanichelli
雑誌名: Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):14. doi: 10.1186/1710-1492-6-14. Epub 2010 Jul 28.
Abstract/Text Acquired angioedema (AAE) is characterized by acquired deficiency of C1 inhibitor (C1-INH), hyperactivation of the classical pathway of human complement and angioedema symptoms mediated by bradykinin released by inappropriate activation of the contact-kinin system. Angioedema recurs at unpredictable intervals, lasts from two to five days and presents with edema of the skin (face, limbs, genitals), severe abdominal pain with edema of the gastrointestinal mucosa, life-threateing edema of the upper respiratory tract and edema of the oral mucosa and of the tongue. AAE recurs in association with various conditions and particularly with different forms of lymphoproliferative disorders. Neutralizing autoantibodies to C1-INH are present in the majority of patients. The therapeutic approach to a patient with AAE should first be aimed to avoid fatalities due to angioedema and then to avoid the disability caused be angioedema recurrences. Acute attacks can be treated with plasma-derived C1-INH, but some patients become non-responsive and in these patients the kallikrein inhibitor ecallantide and the bradykinin receptor antagonist icatibant can be effective. Angioedema prophylaxis is performed using antifibrinolytic agents and attenuated androgens with antifibrinolytic agents providing somewhat better results. Treatment of the associated disease can resolve AAE in some patients.

PMID 20667117  Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):14. doi: ・・・
著者: Tetsuro Yamamoto, Takahiko Horiuchi, Hisaaki Miyahara, Shigeru Yoshizawa, Junichi Maehara, Eisuke Shono, Kazuto Takamura, Haruhisa Machida, Kaoru Tsujioka, Takehiko Kaneko, Naoki Uemura, Kenichi Suzawa, Norihiko Inagaki, Noriko Umegaki, Yoshihiro Kasamatsu, Akihito Hara, Yojiro Arinobu, Yasushi Inoue, Hiroaki Niiro, Yoichiro Kashiwagai, Shin-Ichi Harashima, Tomoko Tahira, Hiroshi Tsukamoto, Koichi Akashi
雑誌名: Am J Med Sci. 2012 Mar;343(3):210-4. doi: 10.1097/MAJ.0b013e31822bdb65.
Abstract/Text INTRODUCTION: The molecular bases and clinical features of hereditary angioedema (HAE) have not been systematically documented in Japan or in other Asian countries. Thus, the authors researched the genetic and clinical characteristics of Japanese patients with HAE.
METHODS: The authors analyzed the CIINH gene for mutations in 13 unrelated Japanese patients with HAE by means of the polymerase chain reaction and nucleotide sequencing. In addition, the authors searched the literature from January 1969 to October 2010 on Japanese patients with HAE.
RESULTS: Seven of the mutations found were novel, including 4 missense mutations (8728T>G, 8831C>A, 16661T>G and 16885C>A), 2 frameshift mutations (2281_2350del70, 14158delT) and 1 large deletion (at least 1 kb-length deletion including exon 4), whereas 6 mutations had previously been reported in European populations.
CONCLUSIONS: The genetic and clinical characteristics in Japanese patients with HAE may be similar to those in Western patients although our sample size is small and the authors identified 7 novel mutations.

PMID 21934598  Am J Med Sci. 2012 Mar;343(3):210-4. doi: 10.1097/MAJ.0・・・
著者: Timothy Craig, Emel Aygören-Pürsün, Konrad Bork, Tom Bowen, Henrik Boysen, Henriette Farkas, Anete Grumach, Constance H Katelaris, Richard Lockey, Hilary Longhurst, William Lumry, Markus Magerl, Immaculada Martinez-Saguer, Bruce Ritchie, Alexander Nast, Ruby Pawankar, Bruce Zuraw, Marcus Maurer
雑誌名: World Allergy Organ J. 2012 Dec;5(12):182-99. doi: 10.1097/WOX.0b013e318279affa.
Abstract/Text : Hereditary Angioedema (HAE) is a rare disease and for this reason proper diagnosis and appropriate therapy are often unknown or not available for physicians and other health care providers. For this reason we convened a group of specialists that focus upon HAE from around the world to develop not only a consensus on diagnosis and management of HAE, but to also provide evidence based grades, strength of evidence and classification for the consensus. Since both consensus and evidence grading were adhered to the document meets criteria as a guideline. The outcome of the guideline is to improve diagnosis and management of patients with HAE throughout the world and to help initiate uniform care and availability of therapies to all with the diagnosis no matter where the residence of the individual with HAE exists.

PMID 23282420  World Allergy Organ J. 2012 Dec;5(12):182-99. doi: 10.1・・・
著者: Timothy J Craig, Robyn J Levy, Richard L Wasserman, Againdra K Bewtra, David Hurewitz, Krystyna Obtułowicz, Avner Reshef, Bruce Ritchie, Dumitru Moldovan, Todor Shirov, Vesna Grivcheva-Panovska, Peter C Kiessling, Heinz-Otto Keinecke, Jonathan A Bernstein
雑誌名: J Allergy Clin Immunol. 2009 Oct;124(4):801-8. doi: 10.1016/j.jaci.2009.07.017. Epub 2009 Sep 19.
Abstract/Text BACKGROUND: Hereditary angioedema caused by C1 esterase inhibitor deficiency is a rare disorder.
OBJECTIVE: To compare the efficacy of pasteurized C1 esterase inhibitor concentrate (Berinert, CSL Behring) at intravenous doses of 10 or 20 U/kg body weight with placebo in the treatment of single, acute abdominal or facial attacks in patients with hereditary angioedema.
METHODS: This was a randomized, double-blind, placebo-controlled study in 125 patients with type I or II hereditary angioedema. The primary outcome was time from start of treatment to onset of symptom relief. Secondary outcomes were time to complete resolution, proportion of patients with worsened intensity of angioedema symptoms between 2 and 4hours after treatment, and number of vomiting episodes within 4 hours.
RESULTS: Median time to onset of relief was significantly shorter with C1 esterase inhibitor concentrate at a dose of 20 U/kg than with placebo (0.5 vs 1.5 hours; P = .0025), whereas with 10 U/kg, the time to onset of relief was only slightly shorter than with placebo (1.2 vs 1.5 hours; P = .2731). Compared with placebo, the reduction in time to onset of relief was greatest for severe attacks (0.5 vs 13.5 hours). The secondary outcomes consistently supported the efficacy of the 20 U/kg dose. C1 esterase inhibitor concentrate was safe and well tolerated. No seroconversions were observed for HIV, hepatitis virus, or human B19 virus.
CONCLUSION: C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief.

PMID 19767078  J Allergy Clin Immunol. 2009 Oct;124(4):801-8. doi: 10.・・・
著者: M Maurer, M Magerl, I Ansotegui, E Aygören-Pürsün, S Betschel, K Bork, T Bowen, H Balle Boysen, H Farkas, A S Grumach, M Hide, C Katelaris, R Lockey, H Longhurst, W R Lumry, I Martinez-Saguer, D Moldovan, A Nast, R Pawankar, P Potter, M Riedl, B Ritchie, L Rosenwasser, M Sánchez-Borges, Y Zhi, B Zuraw, T Craig
雑誌名: Allergy. 2018 Aug;73(8):1575-1596. doi: 10.1111/all.13384. Epub 2018 Mar 12.
Abstract/Text Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: (1) How should HAE-1/2 be defined and classified?, (2) How should HAE-1/2 be diagnosed?, (3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, (4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and (5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures?

© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
PMID 29318628  Allergy. 2018 Aug;73(8):1575-1596. doi: 10.1111/all.133・・・
著者: Stephen Betschel, Jacquie Badiou, Karen Binkley, Rozita Borici-Mazi, Jacques Hébert, Amin Kanani, Paul Keith, Gina Lacuesta, Susan Waserman, Bill Yang, Emel Aygören-Pürsün, Jonathan Bernstein, Konrad Bork, Teresa Caballero, Marco Cicardi, Timothy Craig, Henriette Farkas, Anete Grumach, Connie Katelaris, Hilary Longhurst, Marc Riedl, Bruce Zuraw, Magdelena Berger, Jean-Nicolas Boursiquot, Henrik Boysen, Anthony Castaldo, Hugo Chapdelaine, Lori Connors, Lisa Fu, Dawn Goodyear, Alison Haynes, Palinder Kamra, Harold Kim, Kelly Lang-Robertson, Eric Leith, Christine McCusker, Bill Moote, Andrew O'Keefe, Ibraheem Othman, Man-Chiu Poon, Bruce Ritchie, Charles St-Pierre, Donald Stark, Ellie Tsai
雑誌名: Allergy Asthma Clin Immunol. 2019;15:72. doi: 10.1186/s13223-019-0376-8. Epub 2019 Nov 25.
Abstract/Text This is an update to the 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of hereditary angioedema (HAE) patients worldwide. It is a collaboration of Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is to provide evidence-based recommendations, using the GRADE system, for the management of patients with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. New to the 2019 version of this guideline are sections covering the diagnosis and recommended therapies for acute treatment in HAE patients with normal C1-INH, as well as sections on pregnant and paediatric patients, patient associations and an HAE registry. Hereditary angioedema results in random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased health-related quality of life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada, as in many countries, continues to be neither optimal nor uniform. It lags behind some other countries where there are more organized models for HAE management, and greater availability of additional licensed therapeutic options. It is anticipated that providing this guideline to caregivers, policy makers, patients, and advocates will not only optimize the management of HAE, but also promote the importance of individualized care. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency and intensive care physicians, primary care physicians, gastroenterologists, dentists, otolaryngologists, paediatricians, and gynaecologists who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful.

© The Author(s) 2019.
PMID 31788005  Allergy Asthma Clin Immunol. 2019;15:72. doi: 10.1186/s・・・
著者: V Wahn, W Aberer, W Eberl, M Faßhauer, T Kühne, K Kurnik, M Magerl, D Meyer-Olson, I Martinez-Saguer, P Späth, P Staubach-Renz, W Kreuz
雑誌名: Eur J Pediatr. 2012 Sep;171(9):1339-48. doi: 10.1007/s00431-012-1726-4. Epub 2012 Apr 29.
Abstract/Text Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.

PMID 22543566  Eur J Pediatr. 2012 Sep;171(9):1339-48. doi: 10.1007/s0・・・
著者: Deniz Eyice Karabacak, Semra Demir, Osman Ozan Yeğit, Ali Can, Kadriye Terzioğlu, Derya Ünal, Müge Olgaç, Raif Coşkun, Bahauddin Çolakoğlu, Suna Büyüköztürk, Aslı Gelincik
雑誌名: Allergy. 2021 Aug;76(8):2535-2543. doi: 10.1111/all.14796. Epub 2021 May 15.
Abstract/Text BACKGROUND: Hereditary angioedema (HAE) attacks can be provoked with psychological factors. The aim of this study was to assess the effects of anxiety, depression and stress related to COVID-19 pandemic on disease activity of HAE patients during the quarantine period (QP) and the return to normal period (RTNP).
METHODS: This study was conducted between March 2020 and September 2020 in four allergy centres. Demographic, clinical features and mental health status were evaluated in QP (from March to the beginning of June) and RTNP (from June to the beginning of September) applied by the government. The 10-point visual analogue scale (VAS10) was used to define the severity of HAE attacks. Depression, Anxiety and Stress Scales-21 (DASS-21) and Fear of COVID-19 (FC-19) scale were performed to assess mental health status.
RESULTS: 139 HAE patients were included in the study. In QP, median attack numbers and median VAS10 scores were 5 (min-max: 0-45) and 6 (min-max: 0-10), respectively. HAE attack numbers, DASS-21 stress, anxiety, depression and total DASS-21 scores, and FC-19 scores were higher in QP than RTNP (p = 0.001, p < 0.001, p = 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). However, there was no difference in attack severity scores between the two periods (p > 0.05).
CONCLUSIONS: This study revealed that the restriction measures during COVID-19 outbreak cause an increase in the number of HAE attacks in relation to anxiety, depression, stress and fear of COVID-19 pandemic. Therefore, it is important to provide psychological support to HAE patients during the pandemic.

© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PMID 33650198  Allergy. 2021 Aug;76(8):2535-2543. doi: 10.1111/all.147・・・
著者: Giorgio Costantino, Giovanni Casazza, Ilaria Bossi, Piergiorgio Duca, Marco Cicardi
雑誌名: BMJ Open. 2012;2(4). doi: 10.1136/bmjopen-2011-000524. Epub 2012 Jul 11.
Abstract/Text OBJECTIVE: To systematically review the evidence regarding long-term prophylaxis in the prevention or reduction of attacks in hereditary angio-oedema (HAE).
DESIGN: Systematic review and meta-analysis.
DATA SOURCES: Electronic databases were searched up to April 2011. Two reviewers selected the studies and extracted the study data, patient characteristics and outcomes of interest.
ELIGIBILITY CRITERIA FOR SELECTED STUDIES: Controlled trials for HAE prophylaxis.
RESULTS: 7 studies were included, for a total of 73 patients and 587 HAE attacks. Due to the paucity of studies, a meta-analysis was not possible. Since two studies did not report the number of HAE attacks, five studies (52 patients) were finally included in the summary analysis. Four classes of drugs with at least one controlled trial have been proposed for HAE prophylaxis. All those drugs, except heparin, were found to be more effective than placebo. In the absence of direct comparisons, the relative efficacies of these drugs were determined by calculating a RR of attacks (drug vs placebo). The results were as follows: danazol (RR=0.023, 95% CI 0.003 to 0.162), methyltestosterone (RR=0.054, 95% CI 0.013 to 0.163), ε-aminocaproic acid (RR=0.095, 95% CI 0.025 to 0.356), tranexamic acid (RR=0.308, 95% CI 0.195 to 0.479) and C1-INH 0.491 (95% CI 0.395 to 0.607).
CONCLUSIONS: Few trials have evaluated the benefits of HAE prophylaxis, and all drugs but heparin seem to be effective in this setting. Since there are no direct comparisons of HAE drugs, it was not possible to draw definitive conclusions on the most effective one. Thus, to accumulate evidence for HAE prophylaxis, further studies are needed that consider the dose-efficacy relationship and include a head-to-head comparison between drugs, with the active group, rather than placebo, as the control.

PMID 22786946  BMJ Open. 2012;2(4). doi: 10.1136/bmjopen-2011-000524. ・・・
著者: Hilary Longhurst, Marco Cicardi, Timothy Craig, Konrad Bork, Clive Grattan, James Baker, Huamin H Li, Avner Reshef, James Bonner, Jonathan A Bernstein, John Anderson, William R Lumry, Henriette Farkas, Constance H Katelaris, Gordon L Sussman, Joshua Jacobs, Marc Riedl, Michael E Manning, Jacques Hebert, Paul K Keith, Shmuel Kivity, Sergio Neri, Donald S Levy, Maria L Baeza, Robert Nathan, Lawrence B Schwartz, Teresa Caballero, William Yang, Ioana Crisan, María D Hernandez, Iftikhar Hussain, Michael Tarzi, Bruce Ritchie, Pavlina Králíčková, Mar Guilarte, Syed M Rehman, Aleena Banerji, Richard G Gower, Debra Bensen-Kennedy, Jonathan Edelman, Henrike Feuersenger, John-Philip Lawo, Thomas Machnig, Dipti Pawaskar, Ingo Pragst, Bruce L Zuraw, COMPACT Investigators
雑誌名: N Engl J Med. 2017 Mar 23;376(12):1131-1140. doi: 10.1056/NEJMoa1613627.
Abstract/Text BACKGROUND: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks.
METHODS: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening. We randomly assigned the patients to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods: either 40 IU or 60 IU of CSL830 per kilogram of body weight twice weekly followed by placebo, or vice versa. The primary efficacy end point was the number of attacks of angioedema. Secondary efficacy end points were the proportion of patients who had a response (≥50% reduction in the number of attacks with CSL830 as compared with placebo) and the number of times that rescue medication was used.
RESULTS: Of the 90 patients who underwent randomization, 79 completed the trial. Both doses of CSL830, as compared with placebo, reduced the rate of attacks of hereditary angioedema (mean difference with 40 IU, -2.42 attacks per month; 95% confidence interval [CI], -3.38 to -1.46; and mean difference with 60 IU, -3.51 attacks per month; 95% CI, -4.21 to -2.81; P<0.001 for both comparisons). Response rates were 76% (95% CI, 62 to 87) in the 40-IU group and 90% (95% CI, 77 to 96) in the 60-IU group. The need for rescue medication was reduced from 5.55 uses per month in the placebo group to 1.13 uses per month in the 40-IU group and from 3.89 uses in the placebo group to 0.32 uses per month in the 60-IU group. Adverse events (most commonly mild and transient local site reactions) occurred in similar proportions of patients who received CSL830 and those who received placebo.
CONCLUSIONS: In patients with hereditary angioedema, the prophylactic use of a subcutaneous C1 inhibitor twice weekly significantly reduced the frequency of acute attacks. (Funded by CSL Behring; COMPACT EudraCT number, 2013-000916-10 , and ClinicalTrials.gov number, NCT01912456 .).

PMID 28328347  N Engl J Med. 2017 Mar 23;376(12):1131-1140. doi: 10.10・・・
著者: Teresa Caballero, Henriette Farkas, Laurence Bouillet, Tom Bowen, Anne Gompel, Christina Fagerberg, Janne Bjökander, Konrad Bork, Anette Bygum, Marco Cicardi, Caterina de Carolis, Michael Frank, Jimmy H C Gooi, Hilary Longhurst, Inmaculada Martínez-Saguer, Erik Waage Nielsen, Krystina Obtulowitz, Roberto Perricone, Nieves Prior, C-1-INH Deficiency Working Group
雑誌名: J Allergy Clin Immunol. 2012 Feb;129(2):308-20. doi: 10.1016/j.jaci.2011.11.025. Epub 2011 Dec 24.
Abstract/Text BACKGROUND: There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH).
OBJECTIVE: We sought to elaborate guidelines for optimizing the management of gynecologic/obstetric events in female patients with HAE-C1-INH.
METHODS: A roundtable discussion took place at the 6th C1 Inhibitor Deficiency Workshop (May 2009, Budapest, Hungary). A review of related literature in English was performed.
RESULTS: Contraception: Estrogens should be avoided. Barrier methods, intrauterine devices, and progestins can be used. Pregnancy: Attenuated androgens are contraindicated and should be discontinued before attempting conception. Plasma-derived human C1 inhibitor concentrate (pdhC1INH) is preferred for acute treatment, short-term prophylaxis, or long-term prophylaxis. Tranexamic acid or virally inactivated fresh frozen plasma can be used for long-term prophylaxis if human plasma-derived C1-INH is not available. No safety data are available on icatibant, ecallantide, or recombinant human C1-INH (rhC1INH). Parturition: Complications during vaginal delivery are rare. Prophylaxis before labor and delivery might not be clinically indicated, but pdhC1INH therapeutic doses (20 U/kg) should be available. Nevertheless, each case should be treated based on HAE-C1-INH symptoms during pregnancy and previous labors. pdhC1INH prophylaxis is advised before forceps or vacuum extraction or cesarean section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer: Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female patients, genetic counseling, infertility, abortion, lactation, menopause treatment, and endometrial cancer.
CONCLUSIONS: A consensus for the management of female patients with HAE-C1-INH is presented.

Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
PMID 22197274  J Allergy Clin Immunol. 2012 Feb;129(2):308-20. doi: 10・・・
著者: Ibolya Czaller, Beáta Visy, Dorottya Csuka, George Füst, Ferenc Tóth, Henriette Farkas
雑誌名: Eur J Obstet Gynecol Reprod Biol. 2010 Sep;152(1):44-9. doi: 10.1016/j.ejogrb.2010.05.008. Epub 2010 Jun 11.
Abstract/Text OBJECTIVE: The course of hereditary angioedema (HAE) and the efficacy and safety of human C1-INH concentrate were appraised during pregnancy and the postpartum period, in patients with HAE.
STUDY DESIGN: Retrospective analysis of clinical data on 118 pregnancies (82 full-term and 36 abortions) in 41 female patients, extracted from the National HAE Registry, medical charts and patient diaries.
RESULTS: HAE attack frequency increases in 48% of pregnancies, whereas 33% of pregnancies were associated with mitigation of clinical signs and 19% of the pregnancies had no influence on the course of HAE, as compared to disease severity seen during the 2-year period preceding the pregnancy. During 46 full-term pregnancies, 26 patients reported attacks; 52% of these occurred in the third trimester. Abdominal attacks are the most common presentation of HAE during pregnancy. Attack number was significantly higher in patients who had sustained their initial attack before 8 years of age. Attack number increased during the third trimester if the fetus was afflicted by HAE. During the postpartum period, attacks occurred in 6/82 pregnancies. Patients received 91 vials of C1-INH concentrate altogether for the relief of acute attacks and for short- or long-term prophylaxis during pregnancy. This therapy was effective in all instances; no adverse effects were observed.
CONCLUSIONS: Pregnancy can either aggravate or mitigate edematous attacks, or alternatively, it may have no influence on the severity of the disease. According to our experience, C1-INH concentrate is an effective and safe therapeutic option during pregnancy.

Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
PMID 20541309  Eur J Obstet Gynecol Reprod Biol. 2010 Sep;152(1):44-9.・・・

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ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから