|Year : 2012 | Volume
| Issue : 1 | Page : 52-54
Role of voriconazole in the management of invasive fungal sinusitis
TB Ramakrishna, B Kalyanchakravarthy, CR Vijay Bharatreddy
Department of Otolaryngology, Head and Neck Surgery, SVS Medical College, Yenugonda, Mahabubnagar, India
|Date of Web Publication||21-Mar-2012|
T B Ramakrishna
Professor and HOD, Department of Otolaryngology, Head and Neck Surgery, SVS Medical College, Yenugonda, Mahabubnagar - 509 002
Source of Support: None, Conflict of Interest: None
Chronic sinusitis is less often caused by fungal infections. In its clinical presentation, the "invasive' form of disease is turbulent in immunocompromised hosts like diabetics. In non-immunocompromised hosts, it rarely becomes invasive and often poses resistance to antifungal agents. We present here a case report of invasive fungal sinusitis, which has been treated surgically and with newer generation antifungal agent, "voriconazole" subsequently. A 1½-year follow-up showed complete resolution of symptoms.
Keywords: Voriconazole, invasive fungal sinusitis, medial maxillectomy
|How to cite this article:|
Ramakrishna T B, Kalyanchakravarthy B, Vijay Bharatreddy C R. Role of voriconazole in the management of invasive fungal sinusitis. J NTR Univ Health Sci 2012;1:52-4
|How to cite this URL:|
Ramakrishna T B, Kalyanchakravarthy B, Vijay Bharatreddy C R. Role of voriconazole in the management of invasive fungal sinusitis. J NTR Univ Health Sci [serial online] 2012 [cited 2019 Nov 18];1:52-4. Available from: http://www.jdrntruhs.org/text.asp?2012/1/1/52/94177
| Introduction|| |
Fungal infections of the sinuses have recently been implicated for causing a large number of cases of chronic rhinosinusitis. The evidence, though, is still controversial.  Most fungal sinus infections are benign or noninvasive, except when they occur in individuals who are immunocompromised.  Several reports are available that have shown invasive fungal infections in immunocompetent individuals. ,
The management of invasive fungal sinusitis is mainly surgical, in the form of debridement. It is essential to treat medically with suitable antifungal agents to prevent any recurrences. Amphotericin B is the gold standard in invasive forms, especially in immunocompromised states (diabetes, cancer chemotherapy, irradiation, long-term steroid usage, and renal transplant recipients).  However, invasive fungal sinusitis is increasingly reported in immunocompetent hosts.  Along with surgery, the need for orally effective antifungal agents has been felt and newer molecules have been developed.
Voriconazole is a recent systemic antifungal agent, belonging to the azoles chemical family. Voriconazole is increasingly used for the treatment of adult and pediatric patients with invasive aspergillosis, those with fluconazole-resistant invasive Candida infections, non-neutropenic patients with candidemia, and those with emerging infections caused by Scedosporium spp. and = Fusarium spp. 
| Case Report|| |
A 25-year-old young man presented to the ENT outpatient services in the first week of February 2010 with chief complaints of progressively increasing swelling of right cheek of 5 years' duration. He had two bouts of bleeding from the right nasal cavity 3 months ago. He underwent endoscopic sinus surgery in 2005 and once again in 2008. The biopsy report after the second surgery was in favor of fungal polyposis. He had watering of the right eye for 1 year. He used to have a dull ache in the cheek region during night time. He had no visual disturbances or loosening of teeth. He was non-diabetic and had never received steroids earlier.
Clinical evaluation showed a 3 cm × 3 cm hard, non-tender, immobile swelling over the right maxilla with proptosis of the right eye. There was no mass seen in the nasal cavities. He had no trismus or loss of sensation over the cheek. His vision was 6/6 in both eyes, without any restriction of orbital movements. His right nasolacrimal duct was found to be blocked. A provisional diagnosis of inverted papilloma/invasive fungal sinusitis has been made and CT scan of paranasal sinuses has been obtained. The CT findings showed a nonhomogenous mass occupying entire right maxillary sinus with bony erosion of anterolateral wall, with thickening of soft tissues of the cheek. In view of bony erosion and extensive disease, a radical surgical approach has been decided. Medial maxillectomy by lateral rhinotomy incision was done on 18-2-2010 [Figure 1].
|Figure 1: Lateral rhinotomy approach exposure of thickened granulomatous tissue|
Click here to view
The mass was completely excised, both from maxillary sinus and from undersurface of the cheek [Figure 2].
Histopathology examination confirmed fungal granuloma. The tissue was not sent for any fungal culture. The patient was kept on voriconazole 100 mg twice daily for a period of 3 months. His hematological and liver functions were closely monitored once in 30 days during the course of treatment. He was free of disease at the end of
| Discussion|| |
Fungal infections of the paranasal sinuses are often increasingly reported due to their occurrence in immunocompromised patients, especially diabetics. Earlier, they were labeled as "Mucormycosis." But as many other species of fungi were found to be causative organisms, the current nomenclature has been revised and the term "Zygomycosis" has been adopted. The pathophysiology in such patients is vasculitis and resulting necrosis of turbinates, palate, orbits, and skull base. Hence, the management in such patients has to be aggressive (orbital exenteration, palatal excisions, or skull base debridement). 
The invasive fungal sinusitis in immunocompetent patients is often a subject of dilemma. An aggressive debridement is not warranted, as there is no necrosis of palate or orbit. However, a complete surgical excision is mandatory. Similarly, an intravenous antifungal agent (Amphotericin), with systemic side effects like renal and hepatic toxicity on long-term usage, is not an ideal situation. Hence, a moderate approach is required in managing such cases.
There are many orally effective antifungal agents (fluconazole, itraconazole) available today. However, their efficacy is not proven significantly over amphotericin.  Voriconazole acts as an enzyme inhibitor, blocking the synthesis of ergosterol, a constituent of fungal membranes, and thereby the growth of the microorganism. As with other triazoles (fluconazole, itraconazole), voriconazole binds the active site of the P450-dependent enzyme, lanosterol 14alpha-demethylase (CYP51 or Erg11p), and ligates the iron heme cofactor through a nitrogen atom. This inhibition leads to depletion of ergosterol and accumulation of 14alpha-methyl sterols such as lanosterol, affecting the integrity and function of the fungal membrane. 
Voriconazole is a broad-spectrum antifungal showing in vitro activity against Candida spp. including fluconazole-resistant C. albicans and C. krusei, Aspergillus spp. Including itraconazole- and amphotericin B-resistant Aspergillus fumigatus, and emerging pathogens such as Scedosporium spp. and Fusarium spp. Efficacy of voriconazole in fungal sinusitis has been studied recently. 
In the present case study, there was no disease recurrence at the end of 1-year follow-up. The main drawback in the management is its high cost. We feel at least a 3-month course of voriconazole is necessary to prevent recurrence. Further studies are required to evaluate long-term efficacy of the drug.
| Conclusion|| |
Voriconazole is a new antifungal agent that showed promising result in a case of recurrent invasive fungal sinusitis.
| Acknowledgements|| |
We thank Dr. Srinath, Medical Superintendent, for permitting to use the hospital records, and Dr. K. J. Reddy, FRCS, Medical Director, for support and encouragement.
| References|| |
|1.||Blitzer A, Lawson W. Mycotic infections of the nose and paranasal sinuses. In: English G, editor. Otolaryngology. St. Louis, Mo: J. B. Lippincott; 1992: p. 1-23. |
|2.||Blitzer A, Lawson W, Meyer BR, Biller JF. Patient survival factors in paranasal sinus mucormycosis. Laryngoscope 1980;90:635-8. |
|3.||Hussain S, Salahuddin N, Ahmad I, Salahuddin I, Jooma R. Rhinocerebral invasive mycosis: Occurrence in immunocompetent individuals. Eur J Radiol 1995;20:151-5. |
|4.||Scharf JL, Soliman AM. Chronic rhizopus invasive fungal rhinosinusitis in an immunocompetent host. Laryngoscope 2004;114:1533-5. |
|5.||Kaplan AH, Poza-Juncal E, Shapiro R, Stapleton JT. Cure of mucormycosis in a renal transplant patient receiving cyclosporine with maintenance or immunosupression. Am J Nephrol 1988;8:139. |
|6.||Siddiqui AA, Shah AA, Bashir SH. Craniocerebral aspergillosis of sinonasal origin in immunocompetent patients: Clinical spectrum and outcome in 25 cases. Neurosurgery 2004;55:602-11. |
|7.||Gillespie MB, O'Malley BW Jr, Francis HW. An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host. Arch Otolaryngol Head Neck Surg 1998;124:520-6. |
|8.||Anselmo-Lima WT, Lopes RP, Valera FC, Demarco RC. Invasive fungal rhinosinusitis in immunocompromised patients. Rhinology 2004;4:141-4. |
|9.||Schwarz S, Milatovic D, Thiel E. Successful treatment of cerebral aspergillosis with a novel triazole (voriconazole) in a patient with acute leukaemia. Br J Haematol 1997;97:663-5. |
|10.||Ho A, McGarry G, Peters E. Treatment of chronic invasive fungal sinusitis with Voriconazole in an HIV patient, J Int AIDS Soc 2010;13(Suppl 4):190. |
|11.||deShazo RD, Chapin K, Swain RE. Fungal Sinusitis. N Engl J Med 1997;337:254-9. |
|12.||Erwin GE Jr, Fitzgerald JE. Allergic bronchopulmonary aspergillosis and allergic fungal sinusitis successfully treated with voriconazole. J Asthma 2007;44:891-5. |
[Figure 1], [Figure 2]