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Fungal Sinusitis
Updated: Feb 20, 2018
Author: Hassan H Ramadan, MD, MSc; Chief Editor: Arlen D Meyers, MD, MBA

Overview

Background
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 patient education information, see the Headache and Migraine Center. Also, visit the patient
education article Sinus Infection.

Axial CT scan of sinuses shows a right fungal maxillary sinusitis with an expanding mass (possibly aspergillosis).

History of the Procedure

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
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fungus. However, the fungus is usually suspected upon reviewing the CT scan result and is detected on removal of the
secretions from the sinus.

Problem
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.

Etiology
Noninvasive fungal sinusitis

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.[4]

Invasive fungal sinusitis

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.

Pathophysiology
Allergic 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.[5]

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

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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.[6]

Sinus mycetoma

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

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

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.

Granulomatous invasive fungal sinusitis

This condition has been reported almost exclusively in immunocompetent individuals from North Africa. Generally, proptosis is
associated with granulomatous invasive fungal sinusitis.

Preinvasive fungal sinusitis

A study by Paknezhad et al indicated that in addition to the invasive and noninvasive forms of fungal sinusitis, an intermediate,
or preinvasive, subtype exists. In this form, intramucosal fungal infiltration occurs, but neither direct angioinvasion nor wide
extension beyond the submucosa is found. The investigators reported that patients with preinvasive fungal sinusitis appear to
need only limited surgical débridement, rather than the extended and repeated débridement required in invasive fungal
sinusitis.[25]

Presentation
Allergic 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.

Sinus mycetoma

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.

Acute invasive fungal sinusitis

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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.

Chronic invasive fungal sinusitis

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.

Granulomatous invasive fungal sinusitis

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.

Indications
The treatment of choice for all types of fungal sinusitis is surgical (see Surgical therapy).

Relevant Anatomy
See Surgical therapy.

Contraindications
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.

Workup

Laboratory Studies
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.[7]

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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).[8]

Imaging Studies
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%.[11]

MRI with enhancement may be helpful in assessing patients with allergic fungal sinusitis and in patients in whom invasive fungal
sinusitis is suspected.[10] 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.

Histologic Findings
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.

A retrospective study by Melancon and Clinger indicated that in the diagnosis of acute invasive fungal sinusitis, frozen section
biopsies have a positive predictive value of 100%, a sensitivity of 87.5%, and a specificity of 100% and are therefore important
in the early diagnosis of this disease.[24]

Treatment

Medical Therapy
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.

Allergic fungal sinusitis

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-

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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.

Sinus mycetoma

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.

Chronic invasive fungal sinusitis

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.[12]

Acute 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.

Chronic granulomatous fungal sinusitis

Surgical debridement is the mainstay of treatment, followed by systemic antifungal medications. Recurrence of this condition is
rare.

Surgical Therapy
Allergic fungal sinusitis

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 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).[13]

Sinus mycetoma

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.

Acute invasive fungal sinusitis

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.

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Chronic invasive fungal sinusitis

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.

Chronic granulomatous fungal sinusitis

Surgical debridement is the treatment of choice. Endoscopic and external approaches can be considered.

Follow-up
Allergic fungal sinusitis
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.

Sinus 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.

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 sinusitis

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.

Sinus mycetoma
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.

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%.

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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 sinusitis
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.

Sinus mycetoma

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.

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.[14]

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.[15]

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.

Questions & Answers

Overview

What is fungal sinusitis?

What are the most common etiologic pathogens of fungal sinusitis?

What are the types of fungal sinusitis?

What is noninvasive fungal sinusitis?

What is invasive fungal sinusitis?

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What is the pathophysiology of allergic fungal sinusitis?

What is sinus mycetoma?

What is acute invasive fungal sinusitis?

What is chronic invasive fungal sinusitis?

What is granulomatous invasive fungal sinusitis?

What is preinvasive fungal sinusitis?

What are the symptoms of allergic fungal sinusitis display?

What are symptoms of sinus mycetoma?

What symptoms does acute invasive fungal sinusitis display?

What are symptoms of chronic invasive fungal sinusitis?

What are symptoms of granulomatous invasive fungal sinusitis?

What is the treatment of choice for fungal sinusitis?

What is the relevant anatomy of fungal sinusitis?

What are contraindications for the surgical management of fungal sinusitis?

Workup

What is the role of lab studies in the diagnosis of fungal sinusitis?

What is the role of imaging studies in the diagnosis of fungal sinusitis?

Which histologic findings are characteristic of fungal sinusitis?

Treatment

How is allergic fungal sinusitis treated?

How is sinus mycetoma treated?

How is chronic invasive fungal sinusitis treated?

How is acute invasive fungal sinusitis treated?

How is chronic granulomatous fungal sinusitis treated?

How is allergic fungal sinusitis treated surgically?

How is sinus mycetoma treated surgically?

How is acute invasive fungal sinusitis treated surgically?

How is chronic invasive fungal sinusitis treated surgically?

How is chronic granulomatous fungal sinusitis treated surgically?

What is included in follow up care for allergic fungal sinusitis?

What is included in follow up care for sinus mycetoma?

What is included in follow up care for acute invasive fungal sinusitis?

Why is follow-up care needed for chronic invasive fungal sinusitis?

Why is follow-up care needed for chronic granulomatous fungal sinusitis?

What are complications of allergic fungal sinusitis?

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What are complications of sinus mycetoma?

What are complications of acute invasive fungal sinusitis?

What are complications of chronic invasive fungal sinusitis?

What are complications of chronic granulomatous fungal sinusitis?

What is the prognosis of allergic fungal sinusitis?

What is the prognosis of sinus mycetoma?

What is the prognosis of acute invasive fungal sinusitis?

What is the prognosis of chronic invasive fungal sinusitis?

What is the prognosis of chronic granulomatous fungal sinusitis?

Contributor Information and Disclosures

Author

Hassan H Ramadan, MD, MSc Professor and Vice-Chair, Department of Otolaryngology-Head and Neck Surgery, Professor,
Department of Pediatrics, West Virginia University School of Medicine

Hassan H Ramadan, MD, MSc is a member of the following medical societies: American Academy of Otolaryngic Allergy,
American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Rhinologic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy;
Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Stephen G Batuello, MD Consulting Staff, Colorado ENT Specialists

Stephen G Batuello, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck
Surgery, American Association for Physician Leadership, American Medical Association, Colorado Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and
Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for:
Cerescan;RxRevu;Cliexa;Preacute Population Health Management;The Physicians Edge<br/>Received income in an amount
equal to or greater than $250 from: The Physicians Edge, Cliexa<br/> Received stock from RxRevu; Received ownership
interest from Cerescan for consulting; for: Rxblockchain;Bridge Health.

Additional Contributors

Lanny Garth Close, MD Chair, Professor, Department of Otolaryngology-Head and Neck Surgery, Columbia University College
of Physicians and Surgeons

Lanny Garth Close, MD is a member of the following medical societies: Alpha Omega Alpha, American Head and Neck Society,
American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck
Surgery, American College of Physicians, American Laryngological Association, New York Academy of Medicine

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Disclosure: Nothing to disclose.

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