今日の臨床サポート

副鼻腔真菌症

著者: 竹野幸夫 広島大学大学院 耳鼻咽喉科学・頭頸部外科学

監修: 森山寛 東京慈恵会医科大学附属病院

著者校正済:2022/02/16
現在監修レビュー中
参考ガイドライン:
  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. 協和企画 , 東京 ; 2014: p.88-90.
  1. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik J-A, Wingard JR, Patterson TF, Infectious Diseases Society of America. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis [Internet]. 2008 Feb 1 [cited 2018 Dec 6];46(3):327–60. Available from: https://academic.oup.com/cid/article-lookup/doi/10.1086/525258 PMID: 18177225
  1. Fadda GL, Allevi F, Rosso C, Martino F, Pipolo C, Cavallo G, Felisati G, Saibene AM. Treatment of Paranasal Sinus Fungus Ball: A Systematic Review and Meta-Analysis. Ann Otol Rhinol Laryngol. 2021 Nov;130(11):1302-1310. doi: 10.1177/00034894211002431. Epub 2021 Mar 18. PMID: 33733891.
患者向け説明資料

概要・推奨   

  1. 非浸潤型には内視鏡下鼻内手術が有用である。成功率98.4%と良好な成績[1]。抗真菌薬の術後投与は原則不要であった(推奨度1)
  1. 浸潤性の場合は手術による病巣の清掃と抗真菌薬の全身投与が推奨されている。抗真菌薬としては、ボリコナゾール(ブイフェンド)、イトラコナゾール(イトリゾール)、リポソーム封入アムホテリシンB(アムビゾーム)、の点滴静注での使用が提唱されている(推奨度C1)
 
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:
竹野幸夫 : 特に申告事項無し[2022年]
監修:森山寛 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 定期レビューを行い、手術・薬物治療について新たに判明した推奨度・エビデンスなどについて加筆修正した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 耳鼻咽喉科領域においても日常の外来診察において真菌症に遭遇する機会は増加しつつある[2][3]
  1. 背景として、抗菌薬の使用による菌交代現象としての真菌感染症といった感染側の要因がある。
  1. また免疫機能の低下した患者の増加(副腎皮質ホルモン、免疫抑制薬など)、糖尿病罹患率の増加、患者の高齢化など宿主側の要因もある[3]
  1. CTやMRIの発達と普及による副鼻腔内部の診断技術の向上、といった医療技術の進歩も要因である。
  1. 副鼻腔真菌症は病態的に、重篤な症状を呈する浸潤型(破壊型)と、限局した病変を呈する非浸潤型(寄生型)に大別される。浸潤型はさらに急性(電撃性)と慢性に分けられる。
 
副鼻腔真菌症の分類

副鼻腔真菌症は病態的に、真菌の病原性により発症する浸潤型と非浸潤型真菌症、並びに真菌の抗原性によって発症するアレルギー性真菌性副鼻腔炎に分類される。

出典

img1:  著者提供
 
 
 
  1. 真菌の抗原性によって発症するアレルギー性真菌性副鼻腔炎(allergic fungal sinusitis、AFRS)が、新たな疾患カテゴリーとして注目されている。(→ 好酸球性副鼻腔炎)
  1. 発症の誘因としては、副鼻腔自然口周囲の狭小化が大気中に浮遊している真菌の繁殖しやすい嫌気性環境を醸成し、換気不全を来す。さらに真菌塊形成(fungus ball)が物理的に副鼻腔の排泄機能と粘液線毛クリアランスの障害を引き起こし、真菌増殖を容易にするという悪循環サイクルが考えられている。
  1. 臨床で経験する副鼻腔真菌症のほとんどは非浸潤型であり、年齢分布では60歳代にピークが存在する。性差については女性のほうが、男性より多いとされている。
  1. 原因真菌としてはAspergillus属が過半数を占めており、次いでCandidaMucor属もそれぞれ約10%程度を占めている。浸潤型ではAspergillusfumigatus, flavusやMucorales目のRhizopus属などによる報告が多い。
問診・診察のポイント  
ポイント:
  1. 鼻閉、鼻漏(粘膿性、血性)などの鼻症状の有無、その経緯

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文献 

Gian Luca Fadda, Fabiana Allevi, Cecilia Rosso, Federica Martino, Carlotta Pipolo, Giovanni Cavallo, Giovanni Felisati, Alberto Maria Saibene
Treatment of Paranasal Sinus Fungus Ball: A Systematic Review and Meta-Analysis.
Ann Otol Rhinol Laryngol. 2021 Nov;130(11):1302-1310. doi: 10.1177/00034894211002431. Epub 2021 Mar 18.
Abstract/Text OBJECTIVES: Paranasal sinus fungus ball is a common non-invasive mycosis with excellent long-term surgical treatment results. The present systematic review and meta-analysis were undertaken to define current treatment concepts and success rates in paranasal sinus fungus ball treatment.
METHODS: Systematic searches were performed in multiple databases with criteria designed to include all studies published until May 2020 focusing on paranasal sinuses fungus ball treatment in humans. We selected studies including at least 10 patients, specifying treatment modalities, providing a minimum 6-month follow-up, and objectivating treatment success. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for treatment modalities and success rates. Success rates were pooled in a random effect meta-analysis and compared according to the use of intraoperative sinus lavages and postoperative antibiotics.
RESULTS: Among 740 unique citations, 14 studies were deemed eligible. Most (n = 11) were retrospective case series. All studies relied on endoscopic sinus surgery. Intraoperative lavages were proposed in 10 studies and postoperative antibiotics in 7 (for all patients in 5 studies and for selected patients in 2). No significant heterogeneity was observed between results (Cochran's Q P = .639, I2 test = 0). Treatment success rate was 98.4% (95% confidence interval 97.4%-99.3%). Intraoperative sinus toilette and postoperative antibiotics didn't significantly improve the success rate.
CONCLUSION: Endoscopic sinus surgery shows excellent results in fungus ball treatment. Further prospective studies might help further reducing antibiotics prescriptions in these patients and improve their management.

PMID 33733891
Casey Vaughan, Amanda Bartolo, Nimisha Vallabh, Samuel C Leong
A meta-analysis of survival factors in rhino-orbital-cerebral mucormycosis-has anything changed in the past 20 years?
Clin Otolaryngol. 2018 Dec;43(6):1454-1464. doi: 10.1111/coa.13175. Epub 2018 Aug 8.
Abstract/Text BACKGROUND: Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon yet potentially lethal fungal infection. Although most cases originate from developing countries, an ageing population and increased prevalence of chronic illness may mean some clinicians practicing in developed countries will encounter ROCM cases in their careers. Yohai et al published a systematic review of 145 case reports from 1970 to 1993 assessing prognostic factors for patients presenting with ROCM. We present an updated review of the literature and assess whether survival outcomes have changed in the two decades since that seminal paper.
SEARCH STRATEGY: An extensive Medline literature search was performed for case reports published between 1994 and 2015.
RESULTS: In total, 210 published cases were identified from the literature review, of which 175 patients from 140 papers were included in this review. Fifty-five were female, with an overall mean age of 43 years. Overall survival rate was 59.5%, which was not significantly better than the previous series reported (60%) reported by Yohai et al. Survival rates in patients with chronic renal disease had improved, from 19% to 52%, and in patients with leukaemia (from 13% to 50%). Facial necrosis and hemiplegia remained poor prognostic indicators (33% and 39% survival rates, respectively). Early commencement of medical treatment related to better survival outcomes (61% if commenced within first 12 days of presentation, compared to 33% if after 13 days). Timing of surgery had less of an effect on overall survival. However, in 28 cases that did not receive any surgical treatment, survival was only 21%.
CONCLUSIONS: Although overall survival rates have not improved, survival in patients with renal disease were better, potentially due to the introduction of liposomal amphotericin B which is less nephrotoxic. Prompt recognition of ROCM, reversal of predisposing co-morbidities and aggressive medical treatment remain the cornerstone of managing this highly aggressive disease.

© 2018 John Wiley & Sons Ltd.
PMID 29947167
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
D W Denning, J Y Lee, J S Hostetler, P Pappas, C A Kauffman, D H Dewsnup, J N Galgiani, J R Graybill, A M Sugar, A Catanzaro
NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis.
Am J Med. 1994 Aug;97(2):135-44.
Abstract/Text BACKGROUND: Invasive aspergillosis is the most common invasive mould infection and a major cause of mortality in immunocompromised patients. Response to amphotericin B, the only antifungal agent licensed in the United States for the treatment of aspergillosis, is suboptimal.
METHODS: A multicenter open study with strict entry criteria for invasive aspergillosis evaluated oral itraconazole (600 mg/d for 4 days followed by 400 mg/d) in patients with various underlying conditions. Response was based on clinical and radiologic criteria plus microbiology, histopathology, and autopsy data. Responses were categorized as complete, partial, or stable. Failure was categorized as an itraconazole failure or overall failure.
RESULTS: Our study population consisted of 76 evaluable patients. Therapy duration varied from 0.3 to 97 weeks (median 46). At the end of treatment, 30 (39%) patients had a complete or partial response, and 3 (4%) had a stable response, and in 20 patients (26%), the protocol therapy was discontinued early (at 0.6 to 54.3 weeks) because of a worsening clinical course or death due to aspergillosis (itraconazole failure). Twenty-three (30%) patients withdrew for other reasons including possible toxicity (7%) and death due to another cause but without resolution of aspergillosis (20%). Itraconazole failure rates varied widely according to site of disease and underlying disease group: 14% for pulmonary and tracheobronchial disease, 50% for sinus disease, 63% for central nervous system disease, and 44% for other sites; 7% in solid organ transplant, 29% in allogeneic bone marrow transplant patients, and 14% in those with prolonged granulocytopenia (median 19 days), 44% in AIDS patients, and 32% in other host groups. The relapse rates among those who completed therapy and those who discontinued early for possible toxicity were 12% and 40%, respectively; all were still immunosuppressed.
CONCLUSION: Oral itraconazole is a useful alternative therapy for invasive aspergillosis with response rates apparently comparable to amphotericin B. Relapse in immunocompromised patients may be a problem. Controlled trials are necessary to fully assess the role of itraconazole in the treatment of invasive aspergillosis.

PMID 8059779
Thwe Phyo Kan Nyunt, Joaquim Mullol, Kornkiat Snidvongs
Predictive factors for invasive fungal rhinosinusitis in diabetic patients: Systematic review and data re-analysis.
Asian Pac J Allergy Immunol. 2021 Mar;39(1):1-8. doi: 10.12932/AP-250720-0929.
Abstract/Text This systematic review aims to identify prognostic factors for the overall survival of invasive fungal rhinosinusitis (IFRS) in patients with diabetes using original data from the existing published articles. Systematic searches of Medline, EMBASE, and Cochrane Library databases were performed to include articles from 1988 to 2019 using the terms: "fung*" AND "rhinosinusitis" AND "invasive" AND "diabetes OR ketoacidosis". Data from 258 diabetic patients with IFRS (mean age 55.9 years, 55.6% male, 124 studies) were extracted for data analysis. The mortality rate was 31.8%. Seven variables: plasma glucose level, HbA1C, ketoacidosis, leukopenia, serum creatinine level, duration of diabetes, and the cavernous sinus extension were assessed. Univariate analysis was done for each variable and revealed that the cavernous sinus extension was a significant risk factor. Multivariable logistic regression analysis confirmed that the cavernous sinus extension independently predicted mortality in patients with diabetes (hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.2 to 5.4, p = 0.01). Kaplan Meier curve and Log-rank test were used for analyzing survival outcomes. The twelve-month overall survival rate of the patients with the cavernous sinus extension was 43.9% compared to 73.9% for the patients without the cavernous sinus extension (p = 0.01). Appropriate treatment of this condition could enhance the survival outcomes.

PMID 33274958
Xavier Dufour, Catherine Kauffmann-Lacroix, Jean-Claude Ferrie, Jean-Michel Goujon, Marie-Helene Rodier, Alexandre Karkas, Jean-Michel Klossek
Paranasal sinus fungus ball and surgery: a review of 175 cases.
Rhinology. 2005 Mar;43(1):34-9.
Abstract/Text OBJECTIVE: To analyze the surgical results after Functional Endoscopic Sinus Surgery (FESS) in patients with paranasal sinus fungus ball.
MATERIAL AND METHODS: Retrospective analysis of the results of FESS performed in 175 patients suffering from paranasal sinus fungus balls.
RESULTS: All maxillary (n = 150), sphenoidal (n = 20), and ethmoidal (n = 4) locations have been treated exclusively by FESS to obtain a wide opening of the affected sinuses, allowing a careful extraction of all fungal material without removal of the inflamed mucous membrane. No major complication occurred. Postoperative care was reduced to nasal lavage with topical steroids for 3 to 6 weeks. Only 1 case of local failure have been observed (maxillary sinus, n = 1), and 6 cases of persisting of fungus ball (maxillary sinus, n = 4; frontal sinus, n = 2) with a mean follow-up of 5 years. No medical treatment (antibiotic, antifungal) was required.
CONCLUSION: Surgical treatment of a fungus ball consists in opening the infected sinus cavity at the level of its ostium and removing fungal concretions while sparing the normal mucosa. No antifungal therapy is required. Finally, through this 175 patients study, FESS appears a reliable and safe surgical treatment with a low morbidity.

PMID 15844500

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