今日の臨床サポート

アスペルギローマ

著者: 寺田教彦 筑波大学 医学医療系 臨床医学域 感染症内科学

監修: 具芳明 東京医科歯科大学大学院医歯学総合研究科 統合臨床感染症学分野

著者校正/監修レビュー済:2022/05/25
参考ガイドライン:
  1. 米国感染症学会:Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. PMID:27365388
  1. ヨーロッパ臨床微生物学会・ヨーロッパ感染症学会・ヨーロッパ呼吸器学会:Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. 2016 PMID: 26699723
  1. 深在性真菌症のガイドライン作成委員会:深在性真菌症の診断・治療ガイドライン2014
  1. 日本医真菌学会:アスペルギルス症の診断・治療ガイドライン2015
患者向け説明資料

概要・推奨   

  1. アスペルギローマの多くは無症状で経過するが、致死的な喀血が問題となる。
  1. 無症状で画像上も安定して経過している場合、治療は不要である。喀血例、大量の喀血が懸念される場合外科的治療を考慮する(推奨度2 G)
  1. 大量喀血時などには、外科的治療前に気管支動脈塞栓術により血行動態を安定させることもある(推奨度2)
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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。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※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、実際の保険適応の査定において保険適応及び保険適応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応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:
寺田教彦 : 未申告[2022年]
監修:具芳明 : 特に申告事項無し[2022年]

改訂のポイント:
  1.  本邦や欧州のガイドラインに基づき、病態・疫学・診察について改訂を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. アスペルギローマとは、アスペルギルス属による腐生寄生による疾患である。通常肺結核などの抗酸菌感染症、肺気腫、嚢胞性あるいは線維性肺疾患のあとにできた空洞に自然界に生息するアスペルギルス属の分生子が吸入された後到達して発育し、菌糸とフィブリン、気道粘液、細胞の残骸が絡み合って凝集してできたものである。同様の菌球は他の真菌でもみられることがあるとされているがアスペルギルス属によるものが圧倒的に多いとされる。実際の頻度は不詳である。
  1. 以前は、アスペルギローマのサイズと喀血の頻度は無関係と考えられていたが[1]、最近は空洞と真菌球のサイズが大きいほど喀血を来しやすいことが報告されている[2]
  1. 結核後に2.5cm以上の空洞性肺病変があった患者では、11%に真菌球があったという報告がある。さらに調査の3年後には17%に増加したと報告している[3]
  1. アスペルギローマは従来simple aspergillomaと呼ばれる、単一の空洞にできる独立した菌球による病変と、complex aspergillomaと呼ばれる複数の空洞にわたって寄生がみられるタイプの2つを含む概念であった。ところが現在後者は経過として慢性進行性肺アスペルギルス症(CPPA:Chronic progressive pulmonary aspergillosis)と呼ばれる侵襲性真菌症の範疇に入るとされ、治療も内科的治療が奏効する場合が多いということで別の疾患とされている。この項で扱うアスペルギローマは上述のsimple aspergillomaのことである。
  1. アスペルギローマには肺の空洞、あるいは拡張した気管支にアスペルギルスの菌糸、フィブリン、気道粘液、細胞の残骸が絡み合って凝集したものと定義づけられ[3]、基礎に空洞性の肺、気管支病変が存在することが前提となる。また、その空洞性の病変としては、肺結核後遺症、肺嚢胞を有する肺線維症、嚢胞形成性の肺気腫といったものが代表例となる。
  1. ほかに、Simple aspergillomaを欧州のガイドラインでは、「アスペルギルス属に関連する血清学的あるいは微生物学的な証明を伴い、真菌球を含む単一の肺の空洞病変を認める。症状は軽度あるいは無症状で、少なくとも3カ月の画像経過で進行が認められない免疫不全ではない患者。」と定義している[4]
  1. 多くの場合は無症状であるが、血痰、胸痛、咳、疲労感、発熱、体重減少がみられることがある[5]
  1. ときに喀血がみられ、致命的になる。程度の差はあるが、約90%で喀血のエピソードを経験するという[6]。また、その喀血がまれに致命的となるため根治療法として手術が必要となる。なお、内科的治療は有用ではないことが多い[3][7]
問診・診察のポイント  
  1. 病歴のみで鑑別疾患の上位に挙げることはやや難しい。

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文献 

Thomas J Walsh, Elias J Anaissie, David W Denning, Raoul Herbrecht, Dimitrios P Kontoyiannis, Kieren A Marr, Vicki A Morrison, Brahm H Segal, William J Steinbach, David A Stevens, Jo-Anne van Burik, John R Wingard, Thomas F Patterson, Infectious Diseases Society of America
Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America.
Clin Infect Dis. 2008 Feb 1;46(3):327-60. doi: 10.1086/525258.
Abstract/Text
PMID 18177225
David W Denning, Jacques Cadranel, Catherine Beigelman-Aubry, Florence Ader, Arunaloke Chakrabarti, Stijn Blot, Andrew J Ullmann, George Dimopoulos, Christoph Lange, European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society
Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management.
Eur Respir J. 2016 Jan;47(1):45-68. doi: 10.1183/13993003.00583-2015.
Abstract/Text Chronic pulmonary aspergillosis (CPA) is an uncommon and problematic pulmonary disease, complicating many other respiratory disorders, thought to affect ~240 000 people in Europe. The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), which untreated may progress to chronic fibrosing pulmonary aspergillosis. Less common manifestations include: Aspergillus nodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (<3 months) usually found in moderately immunocompromised patients, which should be managed as invasive aspergillosis. Few clinical guidelines have been previously proposed for either diagnosis or management of CPA. A group of experts convened to develop clinical, radiological and microbiological guidelines. The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence of Aspergillus infection (microscopy or culture from biopsy) or an immunological response to Aspergillus spp. and exclusion of alternative diagnoses, all present for at least 3 months. Aspergillus antibody (precipitins) is elevated in over 90% of patients. Surgical excision of simple aspergilloma is recommended, if technically possible, and preferably via video-assisted thoracic surgery technique. Long-term oral antifungal therapy is recommended for CCPA to improve overall health status and respiratory symptoms, arrest haemoptysis and prevent progression. Careful monitoring of azole serum concentrations, drug interactions and possible toxicities is recommended. Haemoptysis may be controlled with tranexamic acid and bronchial artery embolisation, rarely surgical resection, and may be a sign of therapeutic failure and/or antifungal resistance. Patients with single Aspergillus nodules only need antifungal therapy if not fully resected, but if multiple they may benefit from antifungal treatment, and require careful follow-up.

Copyright ©ERS 2016.
PMID 26699723
K J Hammerman, C S Christianson, I Huntington, G A Hurst, M Zelman, F E Tosh
Spontaneous lysis of aspergillomata.
Chest. 1973 Dec;64(6):679-9.
Abstract/Text
PMID 4760014
Young Tae Kim, Moon Chul Kang, Sook Whan Sung, Joo Hyun Kim
Good long-term outcomes after surgical treatment of simple and complex pulmonary aspergilloma.
Ann Thorac Surg. 2005 Jan;79(1):294-8. doi: 10.1016/j.athoracsur.2004.05.050.
Abstract/Text BACKGROUND: The long-term outcomes of pulmonary aspergilloma have been known to depend on the underlying lung disease. We analyzed the surgical long-term outcomes for both simple and complex aspergilloma.
METHODS: From 1981 to 1999, 90 surgical procedures were performed on 88 patients with pulmonary aspergilloma. The patients included 44 men and 44 women with a median age of 41 years (range, 12 to 69 years). The underlying lung diseases in the 72 complex aspergilloma cases were 57 tuberculosis (65%), 14 bronchiectases (16%), and 1 emphysema (1.1%). Sixteen (18%) had no underlying lung disease. The procedures performed were 52 lobectomies, 33 segmentectomies or wedge resections, 3 pneumonectomies, and 2 cavernostomies.
RESULTS: One case of operative mortality (1.1%) occurred in complex aspergilloma. Among the other patients, 24 complications developed (27%): 11 prolonged air leaks (longer than 7 days), 7 persistent spaces, 3 postoperative bleedings, 2 empyemas, 2 pneumonias, and 1 wound infection. Risk factor analysis revealed old age and complex aspergilloma as significant risk factors for postoperative complication. One simple and 13 complex aspergilloma patients died during the follow-up period. Only 4 deaths were caused by pulmonary problems. The 10-year actuarial survival rates of simple and complex aspergilloma were 80.0% and 79.6%, respectively. There was no difference between the long-term survival of simple and complex aspergilloma.
CONCLUSIONS: Although the postoperative morbidity rate was higher in complex aspergilloma, surgical treatment for both simple and complex aspergilloma could achieve satisfactory long-term outcomes in selected groups of patients.

PMID 15620961
Anne Lejay, Pierre-Emmanuel Falcoz, Nicola Santelmo, Olivier Helms, Evgenia Kochetkova, My Jeung, Romain Kessler, Gilbert Massard
Surgery for aspergilloma: time trend towards improved results?
Interact Cardiovasc Thorac Surg. 2011 Oct;13(4):392-5. doi: 10.1510/icvts.2011.265553. Epub 2011 Jul 5.
Abstract/Text Surgery of aspergilloma has been renowned to be technically challenging and has a high complication rate. We have already demonstrated an improved outcome as a result of a reduction in complex cases related to history of tuberculosis. In this paper we will evaluate whether this time trend has continued during recent years. Initial presentation and postoperative outcome of 33 patients who underwent surgical treatment between 1998 and 2009 were reviewed and compared with two previous reports (group 1: 55 patients from 1974 to 1991; group 2: 12 patients from 1992 to 1997). Underlying disease was tuberculosis in 15% of patients (57% in group 1, 17% in group 2), and 12% of patients had complex aspergillomas (80% in group 1, 41% in group 2). Postoperatively, there was no mortality (5% in group 1, 0% in group 2). Morbidity decreased progressively in terms of bleeding (44% in group 1, 9% in group 2, and 6% in recently, accrued patients), of pleural space problems (47%, 18% and 12%, respectively), and of prolonged hospital stay (32%, 8% and 6%, respectively). With a decreased postoperative complications rate after resection, contemporary surgery of aspergilloma is safe and offers satisfactory early and long-term results.

PMID 21729950
Qian-Kun Chen, Ge-Ning Jiang, Jia-An Ding
Surgical treatment for pulmonary aspergilloma: a 35-year experience in the Chinese population.
Interact Cardiovasc Thorac Surg. 2012 Jul;15(1):77-80. doi: 10.1093/icvts/ivs130. Epub 2012 Apr 11.
Abstract/Text The surgical treatment of pulmonary aspergilloma is challenging and controversial. This study was designed to evaluate the clinical profile, indications and surgical outcomes of pulmonary aspergilloma operated on in our institute. A total of 256 patients with pulmonary aspergilloma underwent surgical treatment from 1975 to 2010. The patients were divided into two groups: Group A (simple aspergilloma, n = 96) and Group B (complex aspergilloma, n = 160). The principal underlying lung disease was tuberculosis (71.1%). The surgical procedures consisted of 212 lobectomies in both groups; eight cavernoplasties, 10 bilobectomies, 16 pneumonectomies and six thoracoplasties in Group B; four segmentectomies and six wedge resections in Group A. Postoperative complications occurred in 40 patients (15.6%). The major complications were residual pleural space (3.9%), prolonged air leak (3.1%), bronchopleural fistula (1.6%), excessive bleeding (1.6%), respiratory insufficiency (1.9%) and empyema (1.2%). No intraoperative deaths occurred. The overall mortality within 30 days post-operation was 1.2%, occurring only in Group B. There was no statistically significant difference in the postoperative morbidity between Groups A and B (P = 0.27). With the good selection of patients, meticulous surgical techniques and good postoperative management, aggressive surgical treatment with anti-fungal therapy for pulmonary aspergilloma is safe and effective, and can achieve favourable outcomes.

PMID 22499801
Peter Corr
Management of severe hemoptysis from pulmonary aspergilloma using endovascular embolization.
Cardiovasc Intervent Radiol. 2006 Sep-Oct;29(5):807-10. doi: 10.1007/s00270-005-0329-0.
Abstract/Text PURPOSE: To determine the effectiveness of endovascular embolization as a temporizing measure in the management of severe hemoptysis caused by intracavitary pulmonary aspergilloma.
METHODS: Patients presenting with hemoptysis, estimated to be more than 300 ml in the preceding 24 hr, in whom a radiological diagnosis of pulmonary aspergilloma was made on chest radiographs and/or computed tomography of the chest were subjected to bronchial and systemic arteriography and embolization using triacryl microspheres.
RESULTS: Twelve patients with upper lobe intracavitary aspergillomas were managed with embolization. In 11 patients hemoptysis stopped within 24 hr and with no recurrence over the next 4 weeks. In 1 patient hemoptysis persisted and an upper lobe lobectomy was performed.
CONCLUSION: Embolization of bronchial and systemic arteries is an effective method for treating acute severe hemoptysis from intracavitary aspergillomas, allowing the patient time to recover for definitive surgical management.

PMID 16810459
Thomas F Patterson, George R Thompson, David W Denning, Jay A Fishman, Susan Hadley, Raoul Herbrecht, Dimitrios P Kontoyiannis, Kieren A Marr, Vicki A Morrison, M Hong Nguyen, Brahm H Segal, William J Steinbach, David A Stevens, Thomas J Walsh, John R Wingard, Jo-Anne H Young, John E Bennett
Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America.
Clin Infect Dis. 2016 Aug 15;63(4):e1-e60. doi: 10.1093/cid/ciw326. Epub 2016 Jun 29.
Abstract/Text It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
PMID 27365388
B Dupont
Itraconazole therapy in aspergillosis: study in 49 patients.
J Am Acad Dermatol. 1990 Sep;23(3 Pt 2):607-14.
Abstract/Text Itraconazole, 200 to 400 mg once daily, was administered to 49 patients with different types of aspergillosis: pulmonary aspergilloma (14 patients), chronic necrotizing pulmonary aspergillosis (14), and invasive aspergillosis (21). Itraconazole was prescribed alone or in combination or after treatment with amphotericin B and flucytosine. Of 14 aspergilloma patients, 2 were cured and 8 had symptomatic improvement. In chronic necrotizing pulmonary aspergillosis, 7 of 14 patients were cured and 6 improved significantly. In invasive aspergillosis treatment failed in 6 patients and 15 were cured. Itraconazole can be an alternative to amphotericin B in the treatment of invasive aspergillosis and chronic necrotizing pulmonary aspergillosis. In aspergilloma itraconazole may be useful in inoperable cases.

PMID 2170481
J H Campbell, J H Winter, M D Richardson, G S Shankland, S W Banham
Treatment of pulmonary aspergilloma with itraconazole.
Thorax. 1991 Nov;46(11):839-41.
Abstract/Text In a 12 month open study of itraconazole in pulmonary aspergilloma nine patients received oral itraconazole 200 mg daily for six months followed by further itraconazole or observation for a further six months. There was no change in the serum IgG specific for Aspergillus fumigatus (mean (SE) change -4% (10%)) or symptoms of chronic cough and haemoptysis. In two of the three patients who continued treatment beyond six months symptoms and radiographic appearances improved and a temporary reduction in A fumigatus specific IgG occurred in one patient. Further experience of the effects of longer treatment are needed before oral itraconazole can be recommended for aspergilloma.

PMID 1663275
J Giron, C Poey, P Fajadet, N Sans, D Fourcade, J P Senac, J J Railhac
CT-guided percutaneous treatment of inoperable pulmonary aspergillomas: a study of 40 cases.
Eur J Radiol. 1998 Oct;28(3):235-42.
Abstract/Text OBJECTIVE: To treat symptomatic pulmonary aspergilloma in patients who were not considered to be operable.
MATERIAL AND METHODS: Forty patients were treated by CT-guided percutaneous injection of amphotericin paste, the aim being to fill the cavity completely and create an anaerobic environment for the aspergillus. The aspergillomas had developed after bacillary infection and pulmonary fibrosis. Surgery was contra-indicated in these patients because of severe respiratory failure. The authors detail the method of preparation of the paste and the technique of percutaneous injection.
RESULTS: Hemoptysis ceased in all 40 patients, with a follow-up ranging from 6 to 28 months; six patients were also treated with bronchial embolization. In 26 patients, the aspergilloma disappeared and serum tests for aspergillus became negative. Complete disappearance of both the aspergilloma and the cavity was obtained in three patients.
CONCLUSION: This technique appears to be a valuable contribution to non-surgical treatment of inoperable patients with pulmonary aspergilloma, but study should be continued in a larger series to define the exact indications and the interaction with other treatments which have recently been introduced.

PMID 9881259

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