Skip to main content

Advertisement

SpringerLink
Log in

Diagnosis and Treatment of Acute Invasive Fungal Sinusitis in Cancer and Transplant Patients

  • Transplant and Oncology (M Ison, N Theodoropoulos and S Pergam, Section Editors)
  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Modern advances in oncologic and end-organ therapies have led to an increase in immunocompromised patients and a corresponding rise in acute invasive fungal sinusitis (AIFS). Here, we present a comprehensive medical and surgical approach to the diagnosis and management of immunocompromised cancer and transplant patients with AIFS.

Recent Findings

Aspergillus and Mucorales are the most common fungi to cause AIFS, though atypical fungal pathogens have been implicated particularly among patients on azole prophylaxis. Symptoms present in the majority of AIFS cases include fever, nasal congestion, and facial swelling. Nasal endoscopy and radiology are adjuncts to clinical exam with the gold standard diagnostic test still being histopathology, though molecular testing such as panfungal PCR is playing a larger role. The treatment of AIFS requires surgery, antifungal therapy, and reversal of immunosuppression. We recommend initiation of liposomal amphotericin B as an empiric therapy for AIFS, transitioned to targeted therapy when/if a fungal pathogen is identified. Goals of surgery include diagnostic sampling and debridement of necrotic tissue. Equally, if not more important, is reversal of underlying immune suppression. Immune-stimulating therapies hold promise for reducing mortality, but require additional study.

Summary

Despite improvements in medical and surgical management of AIFS, mortality continues to approach 50%. Early diagnosis of this disease entity followed by aggressive surgical and medical management are important, including reversal of the underlying immunosuppression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Wilson AL, Plebanski M, Stephens AN. New trends in anti-cancer therapy: combining conventional chemotherapeutics with novel immunomodulators. Curr Med Chem. 2018;25(36):4758–84. https://doi.org/10.2174/0929867324666170830094922.

    Article  CAS  PubMed  Google Scholar 

  2. Transplant trends. https://unos.org/data/transplant-trends/. Accesed Jul 1 2019

  3. deShazo RD, Chapin K, Swain RE. Fungal sinusitis. N Engl J Med. 1997;337(4):254–9. https://doi.org/10.1056/NEJM199707243370407.

    Article  CAS  PubMed  Google Scholar 

  4. Turner JH, Soudry E, Nayak JV, Hwang PH. Survival outcomes in acute invasive fungal sinusitis: a systematic review and quantitative synthesis of published evidence. Laryngoscope. 2013;123(5):1112–8. https://doi.org/10.1002/lary.23912.

    Article  PubMed  Google Scholar 

  5. Wandell GM, Miller C, Rathor A, Wai TH, Guyer RA, Schmidt RA, et al. A multi-institutional review of outcomes in biopsy-proven acute invasive fungal sinusitis. Int Forum Allergy Rhinol. 2018;8(12):1459–68. https://doi.org/10.1002/alr.22172.

    Article  PubMed  Google Scholar 

  6. Montone KT. Pathology of fungal rhinosinusitis: a review. Head Neck Pathol. 2016;10(1):40–6. https://doi.org/10.1007/s12105-016-0690-0.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gillespie MB, O’Malley BW, Francis HW. An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host. Arch Otolaryngol Head Neck Surg. 1998;124(5):520–6 http://www.ncbi.nlm.nih.gov/pubmed/9604977.

    Article  CAS  PubMed  Google Scholar 

  8. Chen CY, Sheng WH, Cheng A, Chen YC, Tsay W, Tang JL, et al. Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan. BMC Infect Dis. 2011;11:1–9. https://doi.org/10.1186/1471-2334-11-250.

    Article  Google Scholar 

  9. Candoni A, Klimko N, Busca A, et al. Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases. Mycoses. 2019;November 2018:252–60. https://doi.org/10.1111/myc.12884.

    Article  CAS  Google Scholar 

  10. Husain S, Silveira FP, Azie N, Franks B, Horn D. Epidemiological features of invasive mold infections among solid organ transplant recipients: PATH Alliance® registry analysis. Med Mycol. 2017;55(3):269–77. https://doi.org/10.1093/mmy/myw086.

    Article  PubMed  Google Scholar 

  11. Davoudi S, Kumar VA, Jiang Y, Kupferman M, Kontoyiannis DP. Invasive mould sinusitis in patients with haematological malignancies: a 10 year single-centre study. J Antimicrob Chemother. 2015;70(10):2899–905. https://doi.org/10.1093/jac/dkv198.

    Article  CAS  PubMed  Google Scholar 

  12. Bakhshaee M, Bojdi A, Allahyari A, Majidi MR, Tavakol S, Najafzadeh MJ, et al. Acute invasive fungal rhinosinusitis: our experience with 18 cases. Eur Arch Oto-Rhino-Laryngology. 2016;273(12):4281–7. https://doi.org/10.1007/s00405-016-4109-z.

    Article  Google Scholar 

  13. Lamoth F, Chung SJ, Damonti L, Alexander BD. Changing epidemiology of invasive mold infections in patients receiving azole prophylaxis. Clin Infect Dis. 2017;64(11):1619–21. https://doi.org/10.1093/cid/cix130.

    Article  PubMed  Google Scholar 

  14. Fung M, Schwartz BS, Doernberg SB, Langelier C, Lo M, Graff L, et al. Breakthrough invasive fungal infections on isavuconazole prophylaxis and treatment: what is happening in the real-world setting? Clin Infect Dis. 2018;67(7):1142–3. https://doi.org/10.1093/cid/ciy260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Trief D, Gray ST, Jakobiec FA, Durand ML, Fay A, Freitag SK, et al. Invasive fungal disease of the sinus and orbit: a comparison between mucormycosis and Aspergillus. Br J Ophthalmol. 2016;100(2):184–8. https://doi.org/10.1136/bjophthalmol-2015-306945.

    Article  PubMed  Google Scholar 

  16. Orlowski HLP, McWilliams S, Mellnick VM, et al. Imaging spectrum of invasive fungal and fungal-like infections. Radiographics. 37(4):1119–34. https://doi.org/10.1148/rg.2017160110.

    Article  PubMed  Google Scholar 

  17. Choi YR, Kim J-H, Min HS, Won JK, Kim HJ, Yoo RE, et al. Acute invasive fungal rhinosinusitis: MR imaging features and their impact on prognosis. Neuroradiology. 2018;60(7):715–23. https://doi.org/10.1007/s00234-018-2034-0.

    Article  PubMed  Google Scholar 

  18. Kim JH, Kang BC, Lee J-H, Jang YJ, Lee B-J, Chung Y-S. The prognostic value of gadolinium-enhanced magnetic resonance imaging in acute invasive fungal rhinosinusitis. J Inf Secur. 2015;70(1):88–95. https://doi.org/10.1016/j.jinf.2014.07.027.

    Article  CAS  Google Scholar 

  19. Silveira MLC, Anselmo-Lima WT, Faria FM, Queiroz DLC, Nogueira RL, Leite MGJ, et al. Impact of early detection of acute invasive fungal rhinosinusitis in immunocompromised patients. BMC Infect Dis. 2019;19(1):310. https://doi.org/10.1186/s12879-019-3938-y.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Badawy MS, Badawy BS, Yousef LM, El Sherief N. Evaluation of pulmonary fungal diseases in patients with fungal rhino-sinusitis. Egypt J Chest Dis Tuberc. 2013;62(3):493–500. https://doi.org/10.1016/j.ejcdt.2013.06.004.

    Article  Google Scholar 

  21. Hennessy M, McGinn J, White B, Payne S, Warrick JI, Crist H. Frozen section as a rapid and accurate method for diagnosing acute invasive fungal rhinosinusitis. Otolaryngol Head Neck Surg. 2018;159(3):576–80. https://doi.org/10.1177/0194599818770615.

    Article  PubMed  Google Scholar 

  22. Mmg L, Yj D, Wang J, et al. Galactomannan detection for invasive Aspergillosis in immunocompromised patients (review). Summary of findings for the main comparison. 2017;12. https://doi.org/10.1002/14651858.CD007394.pub2 www.cochranelibrary.com.

  23. Mardani M, Faghani Y, Tabarraee M, Abolghasemi S. Clinical manifestation and diagnosis of invasive fungal sinusitis in patients with hematological malignancy. Arch Clin Infect Dis. 2016;11(4). https://doi.org/10.5812/archcid.36566.

  24. Melancon CC, Lindsey J, Russell GB, Clinger JD. The role of galactomannan Aspergillus antigen in diagnosing acute invasive fungal sinusitis. Int Forum Allergy Rhinol. 2019;9(1):60–6. https://doi.org/10.1002/alr.22225.

    Article  PubMed  Google Scholar 

  25. Karageorgopoulos DE, Vouloumanou EK, Ntziora F, Michalopoulos A, Rafailidis PI, Falagas ME. β-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011;52(6):750–70. https://doi.org/10.1093/cid/ciq206.

    Article  CAS  PubMed  Google Scholar 

  26. Payne SJ, Mitzner R, Kunchala S, Roland L, McGinn JD. Acute invasive fungal rhinosinusitis: a 15-year experience with 41 patients. Otolaryngol Head Neck Surg (United States). 2016;154(4):759–64. https://doi.org/10.1177/0194599815627786.

    Article  Google Scholar 

  27. Zaman K, Rudramurthy SM, Das A, et al. Molecular diagnosis of rhino-orbito-cerebral mucormycosis from fresh tissue samples. J Med Microbiol. 2017;66(8):1124–9. https://doi.org/10.1099/jmm.0.000560.

    Article  CAS  PubMed  Google Scholar 

  28. Gholinejad-Ghadi N, Shokohi T, Seifi Z, et al. Identification of Mucorales in patients with proven invasive mucormycosis by polymerase chain reaction in tissue samples. Mycoses. 2018;61(12):909–15. https://doi.org/10.1111/myc.12837.

    Article  CAS  PubMed  Google Scholar 

  29. Liberman J, Mathias P, Sengupta DJ, Cookson B, Schmidt RA, Bryan A. When speed counts: molecular diagnosis of invasive fungal sinusitis. Am J Pathol. 2018;149:S169–70.

    Google Scholar 

  30. De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) C. Clin Infect Dis. 2008;46(12):1813–21. https://doi.org/10.1086/588660.

    Article  PubMed  Google Scholar 

  31. Chamilos G, Lewis RE, Kontoyiannis DP. Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis. 2008;47(4):503–9. https://doi.org/10.1086/590004.

    Article  PubMed  Google Scholar 

  32. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408–15. https://doi.org/10.1056/NEJMoa020191.

    Article  CAS  PubMed  Google Scholar 

  33. Husain S, Camargo JF. Invasive Aspergillosis in solid-organ transplant recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transpl. 2019. https://doi.org/10.1111/ctr.13544.

  34. Patterson TF, Thompson GR, Denning DW, et al. Practice guidelines for the diagnosis and management of Aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1–e60. https://doi.org/10.1093/cid/ciw326.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Marr KA, Schlamm HT, Herbrecht R, Rottinghaus ST, Bow EJ, Cornely OA, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015;162(2):81–9. https://doi.org/10.7326/M13-2508.

    Article  PubMed  Google Scholar 

  36. Luong M-L, Al-Dabbagh M, Groll AH, et al. Utility of voriconazole therapeutic drug monitoring: a meta-analysis. J Antimicrob Chemother. 2016;71(7):1786–99. https://doi.org/10.1093/jac/dkw099.

    Article  CAS  PubMed  Google Scholar 

  37. Hamada Y, Seto Y, Yago K, Kuroyama M. Investigation and threshold of optimum blood concentration of voriconazole: a descriptive statistical meta-analysis. J Infect Chemother. 2012;18(4):501–7. https://doi.org/10.1007/s10156-011-0363-6.

    Article  CAS  PubMed  Google Scholar 

  38. Andes D, Kovanda L, Desai A, Kitt T, Zhao M, Walsh TJ. Isavuconazole concentration in real-world practice: consistency with results from clinical trials. Antimicrob Agents Chemother. 2018;62(7). https://doi.org/10.1128/AAC.00585-18.

  39. Van Der Linden JWM, Warris A, Verweij PE. Aspergillus species intrinsically resistant to antifungal agents. Med Mycol. 2011;49(S1):S82–9. https://doi.org/10.3109/13693786.2010.499916.

    Article  Google Scholar 

  40. van der Linden JWM, Arendrup MC, Warris A, Lagrou K, Pelloux H, Hauser PM, et al. Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus. Emerg Infect Dis. 2015;21(6):1041–4. https://doi.org/10.3201/eid2106.140717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lewis RE, Albert ND, Liao G, Hou J, Prince RA, Kontoyiannis DP. Comparative pharmacodynamics of amphotericin B lipid complex and liposomal amphotericin B in a murine model of pulmonary mucormycosis. Antimicrob Agents Chemother. 2010;54(3):1298–304. https://doi.org/10.1128/AAC.01222-09.

    Article  CAS  PubMed  Google Scholar 

  42. Lanternier F, Poiree S, Elie C, Garcia-Hermoso D, Bakouboula P, Sitbon K, et al. Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis. J Antimicrob Chemother. 2015;70(11):3116–23. https://doi.org/10.1093/jac/dkv236.

    Article  CAS  PubMed  Google Scholar 

  43. Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102(3):433–44. https://doi.org/10.3324/haematol.2016.152900.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Sipsas NV, Gamaletsou MN, Anastasopoulou A, Kontoyiannis DP. Therapy of mucormycosis. J Fungi. 2018;4(3):1–17. https://doi.org/10.3390/jof4030090.

    Article  CAS  Google Scholar 

  45. van Burik J-AH, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis. 2006;42(7):e61–5. https://doi.org/10.1086/500212.

    Article  PubMed  Google Scholar 

  46. Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016;16(7):828–37. https://doi.org/10.1016/S1473-3099(16)00071-2.

    Article  CAS  PubMed  Google Scholar 

  47. Reed C, Bryant R, Ibrahim AS, Edwards J Jr, Filler SG, Goldberg R, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008;47(3):364–71. https://doi.org/10.1086/589857.

    Article  CAS  PubMed  Google Scholar 

  48. Kyvernitakis A, Torres HA, Jiang Y, Chamilos G, Lewis RE, Kontoyiannis DP. Initial use of combination treatment does not impact survival of 106 patients with haematologic malignancies and mucormycosis: a propensity score analysis. Clin Microbiol Infect. 2016;22(9):811.e1–8. https://doi.org/10.1016/j.cmi.2016.03.029.

    Article  CAS  Google Scholar 

  49. Pagano L, Cornely OA, Busca A, Caira M, Cesaro S, Gasbarrino C, et al. Combined antifungal approach for the treatment of invasive mucormycosis in patients with hematologic diseases: a report from the SEIFEM and FUNGISCOPE registries. Haematologica. 2013;98(10):127–30. https://doi.org/10.3324/haematol.2012.083063.

    Article  CAS  Google Scholar 

  50. Rausch CR, Dipippo AJ, Bose P, Kontoyiannis DP. Breakthrough fungal infections in patients with leukemia receiving isavuconazole. Clin Infect Dis. 2018;67(10):1610–3. https://doi.org/10.1093/cid/ciy406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Tortorano AM, Richardson M, Roilides E, et al. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others. Clin Microbiol Infect. 2014;20(Suppl 3):27–46. https://doi.org/10.1111/1469-0691.12465.

    Article  CAS  PubMed  Google Scholar 

  52. Kasapoglu F, Coskun H, Ozmen OA, Akalin H, Ener B. Acute invasive fungal rhinosinusitis: evaluation of 26 patients treated with endonasal or open surgical procedures. Otolaryngol Head Neck Surg. 2010;143(5):614–20. https://doi.org/10.1016/j.otohns.2010.08.017.

    Article  PubMed  Google Scholar 

  53. Duggal P, Wise SK. Chapter 8: Invasive fungal rhinosinusitis. Am J Rhinol Allergy. 27(Suppl 1):S28–30. https://doi.org/10.2500/ajra.2013.27.3892.

  54. Zappasodi P, Rossi M, Castagnola C, Pagella F, Matti E, Cavanna C, et al. Resolution of invasive fungal sinusitis in immunocompromised patients: neutrophil count is crucial beside a combined medical and surgical approach. Ann Hematol. 2010;89(7):737–9. https://doi.org/10.1007/s00277-009-0854-z.

    Article  PubMed  Google Scholar 

  55. Yohai RA, Bullock JD, Aziz AA, Markert RJ. Survival factors in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol. 39(1):3–22 http://www.ncbi.nlm.nih.gov/pubmed/7974189.

    Article  CAS  PubMed  Google Scholar 

  56. Simmons JH, Zeitler PS, Fenton LZ, Abzug MJ, Fiallo-Scharer RV, Klingensmith GJ. Rhinocerebral mucormycosis complicated by internal carotid artery thrombosis in a pediatric patient with type 1 diabetes mellitus: a case report and review of the literature. Pediatr Diabetes. 2005;6(4):234–8. https://doi.org/10.1111/j.1399-543X.2005.00118.x.

    Article  PubMed  Google Scholar 

  57. Kennedy CA, Adams GL, Neglia JR, Giebink GS. Impact of surgical treatment on paranasal fungal infections in bone marrow transplant patients. Otolaryngol Head Neck Surg. 1997;116(6):610–6. https://doi.org/10.1016/S0194-5998(97)70236-5.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, 94143, USA

    Monica Fung & Jennifer Babik

  2. Department of Otolaryngology, University of Washington, Seattle, WA, USA

    Ian M. Humphreys & Greg E. Davis

Authors
  1. Monica Fung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer Babik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ian M. Humphreys
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Greg E. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Monica Fung.

Ethics declarations

Conflict of Interest

All authors declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Transplant and Oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fung, M., Babik, J., Humphreys, I.M. et al. Diagnosis and Treatment of Acute Invasive Fungal Sinusitis in Cancer and Transplant Patients. Curr Infect Dis Rep 21, 53 (2019). https://doi.org/10.1007/s11908-019-0707-4

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11908-019-0707-4

Keywords

Search

Navigation