Fungal infections of the sinuses have recently been blamed for causing most 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.[1, 2, 3]
Distinguishing invasive disease from noninvasive disease is important because the treatment and prognosis are different for each. Noninvasive disease has 2 varieties of presentations, and invasive disease has 3 varieties of presentations. This article reviews all 5 varieties. For excellent patient education resources, see eMedicineHealth's Headache and Migraine Center. Also, visit eMedicineHealth's patient education article Sinus Infection.
Axial CT scan of sinuses shows a right fungal maxillary sinusitis with an expanding mass (possibly aspergillosis).
Fungal infections of the paranasal sinuses are uncommon and usually occur in individuals who are immunocompromised. However, recently, the occurrence of fungal sinusitis has increased in the immunocompetent population.
The most common pathogens are from Aspergillus and Mucor species. Aspergillosis can cause noninvasive or invasive infections. Invasive infections are characterized by dark, thick, greasy material found in the sinuses. Invasive infections can cause tissue invasion and destruction of adjacent structures (eg, orbit, CNS). Noninvasive infections cause symptoms of sinusitis, and the sinus involved is opacified on radiographic studies. Routine cultures from the sinuses rarely demonstrate the fungus. However, the fungus is usually suspected upon reviewing the CT scan result and is detected on removal of the secretions from the sinus.
Fungal infections of the paranasal sinus can manifest as 2 distinct entities.
The more serious infection commonly occurs in patients with diabetes or in individuals who are immunocompromised and is characterized by its invasiveness, tissue destruction, and rapid onset. Early detection and treatment are vital for these infections because of the high mortality rate.
Noninvasive infections are chronic and are usually treated for extended periods as chronic sinusitis before the condition is recognized.
Two forms are described in this category: allergic fungal sinusitis and sinus mycetoma/ball.
Most commonly, Curvularia lunata,Aspergillus fumigatus, and Bipolaris and Drechslera species cause allergic fungal sinusitis.
A fumigatus and dematiaceous fungi most commonly cause sinus mycetoma.
A study by Lu-Myers et al found that socioeconomic factors differed between patients with allergic fungal rhinosinusitis and those with chronic rhinosinusitis, with the latter tending to be white and older, with a higher income and greater access to primary care. The study, which involved a total of 186 patients (93 patients in each group), also found that patients with allergic fungal rhinosinusitis tended to have greater quantitative serum immunoglobulin E (IgE) levels and higher Lund-Mackay scale scores than did patients with chronic rhinosinusitis.
Invasive fungal sinusitis includes the acute fulminant type, which has a high mortality rate if not recognized early and treated aggressively, and the chronic and granulomatous types.
Saprophytic fungi of the order Mucorales, including Rhizopus,Rhizomucor,Absidia,Mucor,Cunninghamella,Mortierella,Saksenaea, and Apophysomyces species, cause acute invasive fungal sinusitis.
A fumigatus is the only fungus associated with chronic invasive fungal sinusitis.
Aspergillus flavus exclusively has been associated with granulomatous invasive fungal sinusitis.
Allergic rhinitis is prevalent in this group and is considered to be the trigger mechanism behind allergic fungal sinusitis. Patients are immunocompetent and often have asthma, eosinophilia, and elevated total fungus-specific IgE concentrations.
Surgery reveals greenish black or brown material (ie, allergic mucin), which has the consistency of peanut butter mixed with sand and glue. Allergic mucin and polyps may form a partially calcified expansile mass that obstructs sinus drainage. Growth of the mass may cause pressure-induced erosion of bone, rupture of sinus walls, and occasional leakage of the sinus contents into the orbit or brain.
A study by Gupta et al indicated that allergic fungal rhinosinusitis tends to be more severe when granulomas are present. The study involved 57 patients with allergic fungal rhinosinusitis, including nine patients with granulomas, with the investigators finding that those with granulomas had a tendency toward orbital and skull base erosion, as well as telecanthus, diplopia, exophthalmos, and facial pain.
This condition is usually unilateral and involves the maxillary sinus. Mucopurulent, cheesy, or claylike material is present at the time of surgery. Patients with sinusitis mycetoma are immunocompetent. Allergic conditions and fungus-specific IgE are less common.
Acute invasive fungal sinusitis results from a rapid spread of fungi through vascular invasion into the orbit and CNS. It is common in patients with diabetes and in patients who are immunocompromised and has been reported in immunocompetent individuals. Typically, patients with acute invasive sinusitis are severely ill with fever, cough, nasal discharge, headache, and mental status changes. They usually require hospitalization.
Chronic invasive fungal sinusitis is a slowly progressive fungal infection with a low-grade invasive process and usually occurs in patients with diabetes.
Orbital apex syndrome, which is characterized by a decrease in vision and ocular immobility due to a mass in the superior portion of the orbit, is usually associated with this condition.
This condition has been reported almost exclusively in immunocompetent individuals from North Africa. Generally, proptosis is associated with granulomatous invasive fungal sinusitis.
Patients present with symptoms of chronic sinusitis, which may include facial pressure, headache, nasal stuffiness, discharge, and cough. The condition should be suspected in individuals with intractable sinusitis and nasal polyposis.
Some patients may present with proptosis or eye muscle entrapment. These patients usually have atopy and have had multiple surgeries by the time of diagnosis. CT scanning of the sinuses reveals opacification with concretions and/or calcifications.
Presentation of patients with sinus mycetoma is similar to that of patients with sinusitis. Examination may reveal polyposis with evidence of sinusitis, mainly on one side. The main report is blowing of gravel-like material from the nose. Usually, sinus mycetoma is found accidentally on CT scanning of the sinuses.
Patients are usually hospitalized and are very sick with fever, cough, nasal discharge, headache, and mental status changes. A high index of suspicion for early diagnosis is critical, especially in individuals who are immunocompromised.
Signs and symptoms include dark ulcers on the septum, turbinates, or palate. In the late stages, signs and symptoms of cavernous sinus thrombosis are present.
Patients present with symptoms of long-standing sinusitis. Symptoms are usually not acute, and fever and mental status changes are absent.
Orbital apex syndrome, which is characterized by a decrease in vision and ocular immobility due to a mass in the superior portion of the orbit, is usually associated with this condition.
Nasal examination findings can be minimal. However, findings from the eye examination can be positive.
Patients present with symptoms of chronic sinusitis associated with proptosis. Examination of the nasal cavity can be nonrevealing. However, findings from the eye examination are usually impressive.
The treatment of choice for all types of fungal sinusitis is surgical (see Surgical therapy).
See Surgical therapy.
All forms of fungal sinusitis require surgical treatment. The only contraindications to surgical management relate to the general condition of the patient. Before surgery is recommended, risks and benefits of the surgical procedure should be weighed against the risks of general anesthesia.
Elevated total fungus-specific IgE concentrations are often found in patients with allergic fungal sinusitis. This is less common in patients with sinus mycetoma.
Using enzyme-linked immunosorbent assays, one study examined the sinonasal tissue and secretions in patients with chronic rhinosinusitis for the presence of mycotoxins (ie, aflatoxin, deoxynivalenol, zearalenone, ochratoxin, and fumonisin) to determine their possible role, if any, in chronic rhinosinusitis. No mycotoxins were found, except ochratoxin in 4 of 18 samples. The clinical significance of these results has not been determined.
A study by Payne et al of 41 patients with acute invasive fungal rhinosinusitis reported that predictive variables for the disease include an absolute neutrophil count below 500/μL (sensitivity of 78%), abnormalities of the septal mucosa (specificity of 97%), and necrosis and mucosal abnormalities of the middle turbinate (specificities of 97% and 88%, respectively).
CT scanning of the paranasal sinuses in the coronal views is essential in the evaluation of patients in whom fungal sinusitis is suspected.[9, 10] Middlebrooks et al devised a seven-variable, computed tomography (CT) scan–based diagnostic model for acute invasive fungal rhinosinusitis. They reported that an abnormality associated with one of the model’s variables—which consist of periantral fat, bone dehiscence, orbital invasion, septal ulceration, the pterygopalatine fossa, the nasolacrimal duct, and the lacrimal sac—has a positive predictive value of 87%, a negative predictive value of 95%, a sensitivity of 95%, and a specificity of 86%, while the involvement of two variables gives the model a specificity of 100% and a positive predictive value of 100%.
MRI with enhancement may be helpful in assessing patients with allergic fungal sinusitis and in patients in whom invasive fungal sinusitis is suspected. MRI may show low signal intensity, suggesting a fungal process versus a solid mass in allergic fungal sinusitis. It is also helpful in evaluating CNS spread in invasive fungal sinusitis.
In allergic fungal sinusitis, allergic mucin contains intact and degenerated eosinophils, Charcot-Leyden crystals, cellular debris, and sparse hyphae. The sinus mucosa has mixed cellular infiltrate of eosinophils, plasma cells, and lymphocytes. The mucus membrane is not invaded by fungi.
No allergic mucin is present in sinus mycetoma. However, the sinus contains dense material that consists of hyphae separate from but adjacent to the mucosa. The sinus mucosa is not invaded.
Histopathologic studies in acute invasive fungal sinusitis reveal hyphal invasion of the mucosa, submucosa, and blood vessels, including the carotid arteries and cavernous sinuses; vasculitis with thrombosis; hemorrhage; and tissue infarction.
Necrosis of the mucosa, submucosa, and blood vessels, with low-grade inflammation, is observed in chronic invasive fungal sinusitis.
Granuloma with multinucleated giant cells with pressure necrosis and erosion is observed in granulomatous invasive fungal sinusitis.
The treatment of choice for all types of fungal sinusitis is surgical. Medical treatment depends on the type of infection and the presence of invasion.
The treatment of choice is generally surgery. Systemic steroids may be indicated once surgery is performed and the diagnosis is confirmed. Some authors suggest a low dose of prednisone (0.5 mg/kg) in a tapering dose with alternate-day dosage over a 3-month period. Topical nasal steroids are helpful postoperatively. Aggressive nasal salt-water washes are recommended. Immune therapy for specific allergens is controversial, even though some reports suggest benefit from this treatment. Systemic antifungals are not indicated in the absence of invasion.
The recommended treatment is surgical. Once the fungus ball is removed, no further medical treatment is indicated, except for the underlying condition. No antifungal treatment is necessary.
Surgical treatment is mandatory. Initiate medical treatment with systemic antifungals once invasion is diagnosed. Amphotericin B (2 g/d) is recommended; this can be replaced by ketoconazole 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.
Emergent treatment is necessary once this condition is suspected. Initiate systemic antifungal treatment after surgical debridement. High doses of amphotericin B (1-1.5 mg/kg/d) are recommended. Oral itraconazole (400 mg/d) can replace amphotericin B once the acute stage has passed. Treatment of the underlying immune deficiency, if possible, is desirable.
Surgical debridement is the mainstay of treatment, followed by systemic antifungal medications. Recurrence of this condition is rare.
Surgery is generally considered the treatment of choice. Goals of surgical therapy are conservative debridement of the allergic mucin and polyps (if present) from the involved sinuses and restoration of sinus aeration. Goals may be achieved endoscopically if possible. An external approach can be considered if the lesion is not accessible endoscopically. Adequate ventilation of the sinus is essential to prevent relapse or recurrence of the disease once the disease is exenterated.
A retrospective study by Masterson et al found that 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).
Surgical removal of the fungus 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.
Perform emergency surgery once this condition is suspected. Perform radical debridement of the necrotic tissue until normal tissue is reached. Often, debridement is achieved via external approaches. In some cases, the skull-base team should be involved.
This condition is usually less aggressive than the acute stage. Surgical debridement is still warranted and can be approached endoscopically in some patients. Consider an external approach when adequate debridement cannot be achieved endoscopically.
Surgical debridement is the treatment of choice. Endoscopic and external approaches can be considered.
Long-term follow-up care is required for maintenance of the sinus cavities; this may be achieved via endoscopic examination and debridement in the office. A short course of systemic steroids may be readministered if any signs of relapse or recurrence are seen. Surgical debridement may be necessary if systemic steroids fail to control the disease.
Long-term follow-up care is not required once the lesions are healed and patency of the sinuses is maintained.
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.
This condition tends to recur. Therefore, long-term follow-up care is recommended.
Experience with this condition is limited. Prognosis is good, but a tendency toward recurrence exists.
Erosion into the adjacent structures may occur if the condition is left untreated. Erosion is most often observed in individuals who present with proptosis. Sinusitis symptoms worsen and do not respond to routine antimicrobial therapy.
Fungus 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.
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%.
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.
Erosion into the adjacent structures (eg, orbit, CNS) is likely. Initiate aggressive therapy to avoid erosion.
This disorder carries a good prognosis following adequate surgical debridement 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.
This condition has an excellent prognosis once the fungus ball is removed and adequate aeration of the sinus is restored. No long-term follow-up care is required for most patients.
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.
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.
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.
Experience with this condition is limited. Generally, prognosis is good, but a tendency toward recurrence exists.