Medical Therapy
The treatment of choice for all types of fungal sinusitis is surgical. Medical therapy serves mainly as postoperative adjuvant treatment and depends on the type of infection and whether invasion has occurred.
Allergic fungal rhinosinusitis
The treatment of choice is generally endoscopic sinus surgery. Systemic steroids have a role pre-operatively and postoperatively. Some surgeons advocate the use of pre-operative high-dose oral prednisone (0.5-1 mg/kg/day, up to 60 mg/day) to improve blood loss during surgery. Most surgeons, however, use oral prednisone postoperatively in a tapering dose over a 1- to 3-month period, once surgery is performed and the diagnosis is confirmed.
Aggressive nasal salt-water irrigations and a topical nasal steroid (fluticasone or budesonide) are essential postoperatively to prevent recurrence. Immunotherapy for specific allergens is controversial; it is a safe adjunct therapy with unclear benefits, even though some reports suggest benefit from this treatment. [23, 24] Systemic antifungals are not indicated in the absence of invasion.
Biologic therapy (antibody-based therapy) holds promise in the treatment of allergic fungal rhinosinusitis. Dupilumab (anti–interleukin-4 [IL-4]/IL13) has been approved by the US Food and Drug Administration (FDA) for use in chronic rhinosinusitis with nasal polyps. Its effect in patients with allergic fungal rhinosinusitis has yet to be determined.
Sinus fungal ball (mycetoma)
The recommended treatment is surgical. Once the fungal ball is removed, no further medical treatment is indicated, except for the underlying condition. No antifungal treatment is necessary.
Acute invasive fungal sinusitis
Emergent treatment is necessary once this condition is suspected. Initiate systemic antifungal treatment after surgical débridement. This is usually guided by infectious-disease specialists. High doses of liposomal amphotericin B (3-6 mg/kg/day) are recommended, especially when Mucor species are found. Voriconazole and isavuconazole are alternative agents that can be considered in milder forms caused by Aspergillus species. Oral isavuconazole is the main long-term maintenance treatment after the acute infection is under control. Treatment and reversal of the underlying immune deficiency and aggressive control of blood glucose levels, if possible, are paramount to improving the prognosis.
Chronic invasive fungal sinusitis
Surgical treatment is mandatory. Initiate medical treatment with systemic antifungals once invasion is diagnosed. Liposomal Amphotericin B (3-6 mg/kg/day) is recommended; this can be replaced by ketoconazole, Isavuconazole, or itraconazole once the disease is under control.
A study by Mehta et al suggested that itraconazole may be as effective as amphotericin B in the treatment of chronic invasive fungal sinusitis. In a prospective, randomized, unblinded study of 26 immunocompetent patients, one group (10 patients) was treated with amphotericin B and the other (16 patients) with itraconazole. A complete cure was achieved in two patients in the amphotericin-B group and five in the itraconazole group, while four amphotericin-B patients and seven itraconazole patients experienced persistent disease, and one amphotericin-B patient and three itraconazole patients had relapses. In addition, three patients died, and one was lost to follow-up. Based on relative risk analysis, the investigators concluded that itraconazole and amphotericin B worked equally well against chronic invasive fungal sinusitis. [25]
Chronic granulomatous fungal sinusitis
Surgical débridement is the mainstay of treatment, followed by systemic antifungal medications. Recurrence of this condition is rare.
Surgical Therapy
Allergic fungal rhinosinusitis
Endoscopic sinus surgery is generally considered the treatment of choice. Goals of surgical therapy are complete débridement of the eosinophilic mucin, polyps (if present), and fungal debris, from the involved sinuses. This leads to restoration of sinus aeration. Leaving residual fungal and eosinophilic debris can lead to rapid and early recurrence. An external approach can be combined with the endoscopic approach if the lesion is not accessible endoscopically. Adequate ventilation of the sinus is essential to prevent relapse or recurrence of allergic fungal rhinosinusitis once the disease has been exenterated.
A retrospective study by Masterson et al found that in terms of treatment with surgical (endoscopic sinus surgery) and targeted medical intervention, quality-of-life benefits were more prolonged in patients with allergic fungal rhinosinusitis than in those with chronic rhinosinusitis without nasal polyposis (CRSsNP) at 9- and 12-month follow-up (over a 12-month follow-up period). The study, which included 154 patients with chronic rhinosinusitis with nasal polyposis, 72 patients with CRSsNP, and 24 patients with allergic fungal rhinosinusitis, measured quality of life using the 22-item Sino-nasal Outcome Test (SNOT-22). [26]
Sinus fungal ball (mycetoma)
Surgical removal of the fungal ball with aeration of the sinus is the only requirement. Once this is accomplished, no further medical treatment is indicated, except for the underlying condition. Endoscopic lesion removal can be performed when the lesion is accessible. Consider an external approach in patients in whom the mycetoma cannot be removed endoscopically.
Acute invasive fungal sinusitis
Perform emergency surgery once this condition is suspected. [27] Radical débridement of the necrotic tissue should be carried out until normal tissue is reached. Often, débridement is achieved via external approaches when the disease has progressed to adjacent structures. In some cases, neurosurgeons and/or oculoplastic surgeons should be involved.
Chronic invasive fungal sinusitis
This condition is usually less aggressive than the acute stage. Surgical débridement is still warranted and can be approached endoscopically in most patients. Consider an external approach when adequate débridement cannot be achieved endoscopically.
Chronic granulomatous fungal sinusitis
Surgical débridement is the treatment of choice. Endoscopic and external approaches can be considered.
Follow-up
Allergic fungal rhinosinusitis
Long-term follow-up care is required for maintenance of the sinus cavities; this may be achieved via endoscopic examination and débridement in the office. A short course of systemic steroids may be readministered if any signs of relapse or recurrence are seen. (Disease recurrence is common.) Surgical débridement may be necessary if systemic steroids fail to control the disorder. A meta-analysis found a 28.7% revision rate for surgery in allergic fungal rhinosinusitis. [28]
Sinus fungal ball (mycetoma)
Long-term follow-up care is not required once the lesions are healed and patency of the sinuses is maintained.
Acute invasive fungal sinusitis
This condition is rare and is usually associated with a high mortality rate. Survivors may have facial deformities and require long-term follow-up care by several specialists, including head and neck surgeons, infectious-disease specialists, and immunodeficiency specialists. Endoscopic surveillance is important to detect early recurrence.
Chronic invasive fungal sinusitis
This condition tends to recur. Therefore, long-term follow-up care is recommended.
Chronic granulomatous fungal sinusitis
Experience with this condition is limited. Prognosis is good, but a tendency toward recurrence exists.
Complications
Allergic fungal rhinosinusitis
Erosion and expansion of bony walls of adjacent structures may occur if the condition is left untreated, and orbital and intracranial complications can consequently result. Erosion is most often observed in individuals who present with proptosis and facial dysmorphia. Despite significant skull base compression, dural invasion and cerebrospinal fluid (CSF) leakage rarely occur.
Sinus fungal ball (mycetoma)
Fungal balls, if left untreated, cause worsening of sinusitis symptoms, with the potential for complicated sinusitis. This may predispose the patient to complications, such as those involving the orbit and CNS.
Acute invasive fungal sinusitis
Initiate emergency treatment once this condition is suspected. This is a rapidly progressive disease that invades adjacent structures, causing tissue damage and necrosis. Cavernous sinus thrombosis and invasion of the CNS are common and carry a mortality rate of 50-80%. [15]
Increased risk of developing mucormycosis (Mucorales infection) has been associated with coronavirus disease 2019 (COVID-19). This is owing to various factors, including lung scarring from COVID-19 and the use of steroids (which have an immunosuppressant effect) to treat COVID-19. A proliferation of mucormycosis cases in India as a result of the COVID-19 pandemic may be attributable to such elements as a large population with diabetes (because diabetes is a risk factor for mucormycosis) and the heavy use of steroids to manage COVID-19. As reported in literature published between December 2019 and the beginning of April 2021, about 71% of cases of mucormycosis found in COVID-19 patients around the world came from India. [29, 30, 31]
Chronic invasive fungal sinusitis
Invasion into adjacent structures is not as common as in the acute type. However, erosion into the orbit or CNS is likely if the disease is left untreated.
Chronic granulomatous fungal sinusitis
Erosion into the adjacent structures (eg, orbit, CNS) is likely. Initiate aggressive therapy to avoid erosion.
Outcome and Prognosis
Allergic fungal rhinosinusitis
This disorder carries a good prognosis following adequate surgical débridement and aeration of the sinuses. Close follow-up care is important. Long-term use of topical steroids controls relapses. Short-term systemic steroids may be required when relapses occur.
Sinus fungal ball (mycetoma)
This condition has an excellent prognosis once the fungal ball is removed and adequate aeration of the sinus is restored. No long-term follow-up care is required for most patients.
Acute invasive fungal sinusitis
This condition carries a poor prognosis. Mortality rate is reported at 50%, even with aggressive surgical and medical treatment. Relapses are common during subsequent episodes of neutropenia. Treatment with systemic antifungals as prophylaxis is indicated in cases of neutropenia.
A retrospective study by Green et al of 14 immunocompromised pediatric patients with invasive fungal sinusitis indicated that while absolute neutrophil count was a significant prognostic factor in these children, patient age and gender, cause of immunodeficiency, and fungal agent were not. [32]
A literature review by Smith et al suggested presentation with facial pain to be a negative predictor of overall mortality (odds ratio = 0.296) in pediatric patients with invasive fungal sinusitis. [33]
Chronic invasive fungal sinusitis
Good prognosis has been noted in patients who receive a prolonged course of systemic antifungals. Patients who receive shorter courses of systemic antifungals have more relapses, thereby requiring further treatment.
Chronic granulomatous fungal sinusitis
Experience with this condition is limited. Generally, prognosis is good, but a tendency toward recurrence exists.
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Axial CT scan of sinuses shows a right fungal maxillary sinusitis with an expanding mass (possibly aspergillosis).
