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Fungal Sinusitis

Editor: Venkat Rajasurya Updated: 7/3/2023 11:35:18 PM


There are several types of fungal sinusitis. The classification depends on the degree of invasion of the sinuses. The overarching categories are non-invasive and invasive fungal sinusitis.

There are three subtypes of non-invasive fungal sinusitis (FS): Fungal ball (FB), saprophytic fungal sinusitis (SFS), and allergic fungal rhinosinusitis (AFRS). Similarly, there are three subtypes of invasive fungal sinusitis (IFS): acute invasive rhinosinusitis (AIRS), chronic invasive rhinosinusitis (CIRS), and granulomatous invasive sinusitis (GIFS). To accurately diagnose fungal sinusitis, a physician must take into account several variables, including patient history and clinical presentation, imaging, endoscopic biopsy with histopathology, and lab work.

For this activity and to ease following the material, we classify the infections into allergic fungal sinusitis, fungal ball, invasive fungal sinusitis, and granulomatous sinusitis. 

The other categorization of fungal sinusitis has its basis on the immune-competence profile of patients. The broad understanding is that immunocompromised patients are the primary victims of fungal sinusitis. The non-invasive fungal sinusitis tends to primarily occur in immunocompetent individuals as opposed to invasive sinusitis's which is more prevalent in immunodeficiency. Invasive fungal sinusitis could be fatal in that the infection could spread into the intracerebral space; this correlates with an increase in mortality and morbidity of victims.[1][2] Immunocompromised patients should take special precautions and should be aggressively treated should there be any suspicion of fungal sinusitis.[1]


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Most published literature suggests that the etiology of fungal sinusitis is not well understood. However, there have been increasing cases of fungal sinusitis reported in recent years, possibly due to our increasing use of immune-suppressants and antibiotics, or simply the growing number of chronic diseases that suppress the immune system.[3][4] One example is mucormycosis, a rare but life-threatening disease that is most common in diabetic patients.[5]

The two main categories of fungi that are responsible for causing diseases in humans are molds and yeasts, although fungal sinusitis is attributed to molds more than it is to yeasts.[1] Molds have hyphae and are multicellular, but the yeast is unicellular. There are multiple types of fungi that humans are exposed to in the air, since the fungi are omnipresence, and they usually have no adverse effect on the sinonasal tract and are not causing ailments or diseases. Colonization of the sinuses with fungi is not a rare phenomenon and does not confirm an infection. The immune fitness of the individual often plays a more central role in determining whether those atmospheric fungi lead to the pathology of the sinuses or not.[3][4] Diabetes, chemotherapy, use of corticosteroids, and immune-suppression, in general, predispose individuals to fungal infections of the sinuses.

The most frequent cause of allergic fungal sinusitis (AFS) and invasive fungal sinusitis (IFS) is Aspergillus.[6][7] The other common organisms responsible for fungal sinusitis are Mucor and Rhizopus, also known as mucormycosis.[8] A key feature of mucormycosis is necrosis of the turbinates.[8] 

Allergic fungal rhinosinusitis is the most common form of fungal sinusitis. 


Geographical location is one key difference in the prevalence of fungal sinusitis around the globe. For example, granulomatous invasive sinusitis is often a complication of chronic fungal sinusitis and is more common in India, Sudan, and Pakistan.[2] One study reports trauma to be the most common cause of mucormycosis in Asian countries, while immune-suppression accounts for most cases in developed countries.[5]


The exact pathophysiology of saprophytic fungal sinusitis is still somewhat unclear. Otherwise, it is that of evolving infection for other forms.[9] 


1) In allergic fungal sinusitis (AFS), the microscopic findings of tissue obtained from surgical debridement reveal Charcot-Layden crystals, much like those seen in patients with asthma. Besides, patients have notable polyposis, “eosinophilic appearing mucin” inside the sinuses, and elevated serum IgE levels.[7] Histologically, when observing samples from AFS patients, inflammatory cells are seen inside mucin. Furthermore, samples from AFS patients show “tide lines” or “tree rings” in addition to the characteristics mentioned above.[6][7][9]

2) In the fungus ball, as the name indicates, an “entangled mass of fungal organisms in fibrinous, necrotic exudate” is seen.[9] Fungal balls could resemble allergic fungal rhinosinusitis when using low-powered microscopes, but this confusion could be eliminated by using high-powered microscopes.[9] 

3) As discussed above, invasive fungal sinusitis (IFS) most commonly presents among immunocompromised patients. Necrotic vascular thrombosis of the mucosa could be visible on histopathology of acute IFS likely secondary to the vascular thrombosis that the fungi create as they invade the sinuses.[9]

4) Submucosal granulomatous inflammation is a feature in granulomatous invasive fungal sinusitis (GIFS), which most commonly presents in immunocompetent patients. Some studies suggest that a significant number of chronic fungal sinusitis cases progress to GIFS, and this transformation requires routine checking through biopsy.[2]

History and Physical

Clinicians should have a high index of suspicion for invasive fungal sinusitis in patients who present with congestion, headache, dizziness, swelling of eyes, periorbital cellulitis, vertigo, personality/behavioral changes, as well as recurrent vomiting.[3][5][7] Proptosis or diplopia of the eyes could also present in some cases of fungal sinusitis. Patients typically have a fever [1] and could be tachycardic if at the early stages of infection. In the cases of sphenoidal fungal sinusitis, a diagnosis could be delayed due to vague symptoms, with headache as the most common presentation.[3] There is often pain on palpation of the site of the facial sinuses, i.e. maxillary, ethmoidal, sphenoid, and frontal. The maxillary sinus is almost always the affected sinus in fungal balls, accounting for approximately 94% of the cases.[4] These symptoms could be confused for other ENT, neurological, or gastroenterological etiologies, so further investigation is necessary.

Saprophytic fungal sinusitis is often asymptomatic and could be hard to detect.[4] Invasive fungal sinusitis passes the mucosa and attacks the nerves, vessels, and bone. Therefore the symptoms are more pronounced. Anesthesia, cranial nerve palsies, proptosis, headache and facial pain, nose casts, and drainage can all be part of the presentation. 


The mainstay of diagnosis in patients with fungal rhinosinusitis is functional endoscopic sinus surgery followed by histopathological analysis of the sample.[6] Although a sample should be taken from the affected tissue visualized in the nasal septum, it is often taken from the middle turbinate when there is no apparent tissue on the septum.[8] This sample is cultured and mixed with KOH for visualization under a microscope.[8] "Cheesy and claylike” mucous found during intranasal endoscopy is suggestive of fungus ball and is highly sensitive as well as specific for this pathology. However, diagnosis confirmation is by histology.[4] 

The other technology used for the histopathological analysis of fungal sinusitis is polymerase chain reaction (PCR). One study found PCR to be the most sensitive method with a high Negative Predictive Value (NPV), which makes it also ideal for ruling out the disease.[10]

A technology used in the diagnosis of invasive fungal sinusitis is frozen sectioning, in which debridement-tissue from infected sinuses get frozen (usually around -28 degrees Celsius), sectioned into small fragments, and stained with hematoxylin and eosin for evaluation under a microscope.[1] This technique is a widely used procedure for the diagnosis of invasive infection and is known to yield a rapid diagnosis. There is a mortality benefit for this procedure as well due to early detection compared to other methods.[1] For patients with mucormycosis, necrotic tissue could be hard to visualize under the frozen section, so researchers have found that the addition of Periodic Acid Schiff (PAS) helps enhance its outcomes.[8]

Touch preparation (TP) is an alternative method of diagnosing invasive sinusitis and was found to yield comparatively rapid as well as accurate diagnosis.[2] This approach involves sampling the tissues of interest at the margins, plating them on a glass slide, staining with Diff-quick stain, and visualizing under a microscope. TP is suitable in cases where the sample is limited, or whenever there is a high laboratory workload.

Computed tomography (CT) of the head is also utilized to visualize the thickened sinus walls and opacifications, ring-enhancing lesions, or bony erosions created by the fungal growth.[6][7]

1) Diagnosing allergic fungal sinusitis is dependant on major criteria presence of type 1 hypersensitivity, nasal polyps, eosinophilic mucin presence, positive fungal stain, and positive CT findings. Minor criteria of unilateral disease, asthma, and Charcot-Leyden crystals in mucin can further confirm the diagnosis. These patients are young (20 to 30) and have dark-colored rubbery nasal casts. The most common sinus involved is ethmoids. On CT, they show a "double density" sign: thick fungal mucin surrounded by hyperplasia.   

2) Fungus balls usually happen in immunocompetent females in the maxiallry sinus (95%). Although inhalation of the spores can be the cause, the presence of mucosal injury might facilitate the process, as it happens in dental work or sinus surgery; this is usually asymptomatic and found incidentally in a CT. At times there is facial pain or postnasal discharge and crusting in the nasal cavity. 

3) Invasive fungal sinusitis is rare but aggressive and with a high mortality rate of around 50%. The difference is an invasion of the vessels, nerves, and bones (rather than just the sinus mucosa). Zygomycetes causing mucormycosis in an uncontrolled diabetic is a classic example. Aspergillus causing infection in AIDS patients or other immunocompromised states is another example. Pain, pressure, or fever happen gradually, but after several weeks, the invasion happens, and the symptoms will exacerbate acutely, which can be confusing diagnostically. Facial nerve palsies, swelling, diplopia, proptosis are all possible. Nerve invasion causes anesthesia, and vessel invasion caused emboli, necrosis, and blackened turbinates and nares. CT will confirm the deep invasion. 

4) Granulomatous sinusitis is more common outside the US in the middle east and north Africa. It is an invasive form of infection that happens more slowly and is showing a pathology of non-caseating granuloma. 

Treatment / Management

Surgical debridement is the treatment of choice for most cases of fungal sinusitis,[11][8][3] as it is both diagnostic and therapeutic. Sometimes craniotomy could be preferred if complications arise before and during surgical debridements, such as infections that spread to involve the cavernous sinus.[6] Functional endoscopic sinus surgery will enable the operator to observe the pathology and anatomy, biopsy the lesions, clear and wash the sinuses, fix any underlying problems (fistula, foreign body, etc.). Polypectomy should take place if indicated. (B2)

Oral corticosteroids are beneficial in many acute and chronic fungal sinusitis (AFS) and improve symptoms by suppressing inflammation and lowering circulating IgE levels, although their prolonged use is discouraged.[7][4]  An exact regimen for corticosteroid use is not available, and the duration of treatment should be individually tailored. Nasal topical steroids should probably not be used alone but have a place in combination with systemic steroids. One study showed benefits in reducing the recurrence rate after two years.[12]

Systemic antifungals are not ideal therapy for AFS but can be an adjunct treatment for invasive fungal rhinosinusitis. Amphotericin B may be the first drug of choice in the treatment of invasive fungal sinusitis because of its broad coverage of Mucor species and Aspergillus. The use of some azole antifungals could also be beneficial, but concurrent management by an infectious disease specialist is warranted.[7][4] Topical antifungals have been used with little success and are not recommended. 

Fungal immunotherapy is also an alternative treatment for AFS as it can desensitize the body to fungal antibodies.[7][4] It is a costly treatment modality, and its short-term benefits are more significant than long-term benefits. It might reduce the need for corticosteroids and therefore prevent side effects of long-term corticosteroid use.[13](B3)

As mentioned above, most cases of invasive fungal sinusitis are secondary to the deficient immune system. Therefore, one must address the cause of the immunodeficiency for optimal care.

Saprophytic fungal sinusitis does not require surgical intervention. It is manageable through nasal douching, which is cleansing of the nasal sinuses with saline.[7][4]

Differential Diagnosis

Bacterial, viral, allergic, and other kinds of sinusitis are in the differential. 


Prognosis is usually good for AFS, but can be dire for IFS, particularly if the underlying immune status cannot be restored

1) Allergic fungal sinusitis is typically responsive to surgical treatment, and recurrence can be controlled successfully as well. Functional endoscopy in the office is the follow-up method. Local debridement is possible during the same procedure. Untreated cases can rarely erode into adjacent structures via mass-effect in longstanding, untreated disease.[7]

2) Invasive fungal sinusitis is potentially life-threatening and carries a poor prognosis. Invasion causes complications such as cavernous sinus thrombosis and central nervous system infections with mortality of around 50%; therefore, urgent treatment is necessary. Complications can occur fast, and recurrence of disease is not unusual, and repeated debridements are often required. Survivers might have facial deformities, nerve damage, and chronic pain. The principal prognostic factor is the patient's immune status. If it can be normalized, the prognosis can be better. If the immune status cannot be restored, the prognosis is very grave and often fatal.[14]

3) Granolumatose sinusitis can be a manifestation of systemic diseases such as Wegener granulomatosis, and prognosis will depend upon the management of the systemic disease.  


A rare but fatal complication of invasive fungal rhinosinusitis is cavernous sinus or orbital apex aspergillosis. When both parts are affected, it is known as cavernous sinus-orbital apex syndrome. Patients may experience headaches, acute unilateral visual loss, or pain in the eye.[11] This situation is usually the result of thrombosis of the cavernous sinus or carotid-cavernous fistula. Despite the recent expansion in the research and analysis of fungal sinusitis, this disease is not well understood and remains challenging to diagnose and treat.[2][15]

Enhancing Healthcare Team Outcomes

Fungal sinusitis is a rare infection of facial sinuses, and it often affects people who are immunocompromised, though it can also occur in immunocompetent patients. Most researchers attribute the recent increase in the prevalence of fungal sinusitis to immunodeficiency secondary to cancer therapy, diabetes mellitus, post-transplant therapy, as well as the vast use of antibiotics in modern societies.

Although more studies and discoveries have been conducted on the topic recently, the subject remains largely under-studied. One of the significant complications of invasive fungal sinusitis is the ability to spread to the cavernous sinuses and cause systemic manifestations with potentially fatal complications. As such, clinicians must recognize presentations suspicious for invasive fungal sinusitis and treat them as rapidly as possible; this is one of the incentives behind the discovery of diagnostic modalities that allow for quick recognition and treatment of fungal sinusitis.

It is essential to distinguish invasive fungal sinusitis (which must be treated emergently) from allergic fungal sinusitis (which has a benign course and can be managed electively).

Surgical debridement is by far the mainstay of treatment for most forms of fungal sinusitis. It is, at times, followed by systemic antifungal therapy to prevent the recurrence of infection. Most patients require multiple surgical therapies to obtain long-term relief for invasive disease.

Interprofessional work between internists, infectious disease specialists, ENT surgeons, and nurses is essential for accurate diagnosis and timely treatment. Whatever course of treatment the clinician chooses, it would be wise to consult with a  board-certified infectious disease pharmacist - they can recommend antifungals to accompany debridement and verify dosing on steroids. Nursing will participate in patient care before, during, and following any procedure and can administer medication as well as perform monitoring and counsel the patient. Both the pharmacist and nurses need to inform the treating clinician of any concerns they may encounter. These types of interprofessional interventions are necessary to drive optimal outcomes with fungal sinusitis infections. [Level 5]



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