Tools
Fungal Sinusitis
Introduction
Fungal rhinosinusitis (FRS) encompasses a spectrum of immune and pathologic responses, including invasive, chronic, granulomatous, and allergic forms, yet consensus on terminology, pathogenesis, and optimal management remains lacking.[1] Fungal spores pervade the environment and frequently come into contact with sinonasal structures evaluated by otolaryngology specialists, with fungi detectable in the nasal cavity and paranasal sinuses of nearly all individuals. Ongoing controversy surrounds diagnostic criteria and overlap between allergic fungal rhinosinusitis (AFRS) and chronic rhinosinusitis (CRS).[2] Notably, the pathogenicity of these fungi arises only under favorable conditions, eg, prolonged antibiotic exposure, poor ventilation, dark and damp environments, and immunocompromised states, which disrupt normal immune defenses and increase susceptibility to infection.[3]
FRS is classified into noninvasive and invasive forms. Noninvasive disease includes saprophytic infestation, fungal ball, and AFRS, whereas invasive disease includes the subtypes acute invasive rhinosinusitis (AIRS), chronic invasive rhinosinusitis (CIRS), and granulomatous invasive fungal sinusitis (GIFS).[4] Noninvasive disease requires both medical and surgical management, while invasive forms carry high morbidity and mortality without timely treatment. Clinical presentation may be acute, with rapid progression of symptoms lasting less than 30 days; subacute, with a duration of 30 to 90 days; or chronic, with slowly progressing symptoms lasting more than 90 days.[5][1][6][7][8][9]
Evaluation begins with a detailed clinical history and comprehensive head and neck examination, including nasal endoscopy and, when indicated, mucosal biopsy. Imaging typically involves computed tomography (CT) of the sinuses, with T1- and T2-weighted magnetic resonance imaging reserved for select cases. Magnetic resonance imaging (MRI) demonstrates high specificity for AFRS, particularly when combined with CT.[10]
Diagnostic support includes Bent and Kuhn criteria and serum immunoglobulin E (IgE) levels, which often exceed 1000 U/mL.[11] Bent and Kuhn criteria serve as the diagnostic standard, requiring all major criteria for diagnosis, while minor criteria provide a supportive clinical context. Major criteria include type 1 hypersensitivity confirmed by history, skin testing, or in vitro testing; nasal polyposis; characteristic CT findings; eosinophilic mucin without tissue invasion; and positive fungal staining of sinus contents obtained during surgery. Minor criteria include asthma, unilateral disease predominance, radiographic bone erosion, positive fungal cultures, Charcot-Leyden crystals in surgical specimens, and serum eosinophilia.[12]
The pathogenesis of AFRS remains incompletely understood and continues to generate debate. Histopathologic evaluation remains essential for diagnosis. Hematoxylin-eosin–stained mucosal specimens typically show inflammatory infiltrates composed of eosinophils, lymphocytes, and plasma cells, along with mucosal hypertrophy and hyperplasia, without evidence of necrosis, granuloma formation, giant cells, or tissue invasion.[13]
Management strategies for allergic fungal sinusitis and other types of fungal sinusitis continue to evolve. Historically, surgical approaches emphasized aggressive mucosal removal, sometimes necessitating external procedures. Medical therapy includes oral corticosteroids, saline or combination nasal irrigations, topical intranasal corticosteroids, and immunotherapy, although the latter remains controversial. Dupilumab, an anti–interleukin-4/interleukin-13 (IL-4/IL-13) agent approved by the US Food and Drug Administration (FDA) for chronic rhinosinusitis with nasal polyps, shows uncertain efficacy in AFRS. Acute and chronic invasive fungal sinusitis (IFS) generally respond to systemic antifungal therapy following surgical intervention.[14]
Noninvasive fungal sinusitis primarily affects immunocompetent individuals, whereas invasive disease occurs more frequently in immunocompromised populations. IFS may progress to intracranial extension, contributing to increased morbidity and mortality.[15][16] Immunocompromised patients require heightened vigilance and prompt, aggressive management when fungal sinusitis is suspected.[15]
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
Most published literature indicates that the causes of fungal sinusitis are not well understood. Nonetheless, reported cases of fungal sinusitis have risen in recent years, which may be linked to increased use of immunosuppressants and antibiotics, or to the rise in chronic diseases that weaken the immune system.[17][18] One example is mucormycosis, a rare but life-threatening disease that is most common in diabetic patients.[19]
The 2 main categories of fungi that cause disease in humans are molds and yeasts. Fungal sinusitis is more often attributed to molds than to yeasts.[15] Molds have hyphae and are multicellular, whereas yeast is unicellular. Humans are exposed to multiple types of fungi in the air, as they are omnipresent, and these fungi usually have no adverse effects on the sinonasal tract and do not cause disease. Sinus colonization with fungi is not uncommon and does not confirm an infection. The individual's immune status often plays a central role in determining whether those atmospheric fungi cause sinus pathology.[17][18] Diabetes, chemotherapy, corticosteroid use, and immunosuppression, in general, predispose individuals to sinus fungal infections.[20]
Aspergillus is the most common cause of allergic fungal sinusitis (AFS) and IFS.[21][22] More recent studies show that Bipolaris and Curvularia are most commonly recovered. Other common organisms responsible for fungal sinusitis are Mucor and Rhizopus, which cause mucormycosis. A key feature of mucormycosis is necrosis of the turbinates.[23] AFRS is the most common type of fungal sinusitis.[20]
Epidemiology
Geographic location is a key factor in the global prevalence of fungal sinusitis. For example, granulomatous invasive sinusitis often complicates chronic fungal sinusitis and is more common in India, Sudan, and Pakistan.[16] One study reports that trauma is the most common cause of mucormycosis in Asian countries, whereas immunosuppression accounts for most cases in developed countries.[19]
Pathophysiology
The exact pathophysiology of saprophytic fungal sinusitis remains unclear, whereas other forms involve an evolving infection.[3] AFS is typically characterized by an allergic reaction to fungal antigens found in the sinuses, without any evidence of fungal invasion. Occasionally, granulomas are observed in AFS histopathology, raising suspicion of invasion. In these cases, the disease may behave similarly to IFS, even in the absence of histological evidence of actual invasion.[24]
Histopathology
In AFS, microscopic examination of tissue obtained during surgical debridement reveals Charcot-Leyden crystals, similar to findings in patients with asthma. Patients also demonstrate marked nasal polyposis, eosinophilic-appearing mucin within the sinuses, and elevated serum IgE levels.[22] Histologic analysis shows inflammatory cells embedded within mucin, along with characteristic “tide lines” or “tree ring” patterns in tissue samples.[21][22][3]
In fungus ball disease, an entangled mass of fungal organisms within fibrinous, necrotic exudate characterizes the pathology.[3] Low-power microscopy may resemble AFRS; however, high-power microscopy allows clear differentiation between these entities.[3] IFS most often occurs in immunocompromised patients. Histopathologic evaluation in acute IFS may demonstrate necrotic vascular thrombosis of the mucosa, likely resulting from fungal invasion and associated vascular compromise.[3] Submucosal granulomatous inflammation defines GIFS, which most commonly affects immunocompetent individuals. Evidence from some studies suggests progression of a substantial proportion of chronic fungal sinusitis cases to GIFS, necessitating routine biopsy for accurate diagnosis.[16]
History and Physical
AFS and sinus fungal ball (mycetoma) often present with symptoms similar to chronic rhinosinusitis. Some patients report expelling green, yellow, or brown gravel-like material from the nose. Fungal debris may be visualized during nasal endoscopy, identified intraoperatively during functional endoscopic sinus surgery, or incidentally detected on computed tomography of the sinuses. A high index of suspicion for IFS remains essential in patients presenting with congestion, headache, dizziness, periorbital cellulitis, vertigo, personality or behavioral changes, and recurrent vomiting.[17][19][22]
Patients with AFS may exhibit malar flattening, proptosis, diplopia, or telecanthus, and early stages of infection may include fever and tachycardia.[15] Sphenoidal fungal sinusitis often presents with nonspecific symptoms, frequently delaying diagnosis; headache is the most common complaint.[17] Palpation of the maxillary, ethmoidal, sphenoid, and frontal sinuses may elicit pain, although tenderness remains subjective. The maxillary sinus represents the most frequently involved site in fungal balls, accounting for approximately 94% of cases.[18]
Saprophytic fungal sinusitis often remains asymptomatic and may evade detection.[18] In contrast, IFS involves mucosal invasion with extension into nerves, blood vessels, and bone, leading to more severe clinical manifestations. Presenting features may include anesthesia, cranial nerve palsies, proptosis, headache, facial pain, nasal casts, and drainage.
Evaluation
Evaluation of fungal sinusitis does not include specific diagnostic tests. Most patients with noninvasive fungal sinusitis are diagnosed based on clinical suspicion. Clinicians should be particularly alert for fungal sinusitis in patients who experience chronic sinus congestion or related symptoms that do not improve with standard treatment. During nasal endoscopy or functional endoscopic sinus surgery, signs of potential fungal material may be visible. The presence of “cheesy and clay-like” mucus during intranasal endoscopy is highly sensitive and specific for a fungus ball. However, a histological examination is necessary to confirm the diagnosis.[18][25] Otolaryngologists should always confirm a histopathological diagnosis of rhinosinusitis before initiating any treatment.[16]
Patients with a sinus fungal ball typically have normal serum IgE levels, while those with allergic fungal sinusitis may have elevated serum levels of fungus-specific IgE. The presence of mycotoxins in sinonasal tissues and secretions, as well as any potential connection to CRS, remains inconclusive.[26]
Patients with AIFRS typically have worsening signs and symptoms, particularly in high-risk populations, eg, those who are immunocompromised. In one study, disease-predictive variables included absolute neutrophil count less than 500/μL (P < .0001; sensitivity 78%), mucosal abnormalities of the middle turbinate (P < .0001; specificity 88%) and septum (P < .0001; specificity 97%), and, specifically, necrosis of the middle turbinate (P < .0001; specificity 97%).[27]
Frozen-section biopsy has high diagnostic accuracy for AIFRS and may enable earlier diagnosis and treatment.[15] Debrided tissue from infected sinuses is frozen (usually at -28 °C), sectioned into small fragments, and stained with hematoxylin and eosin for evaluation under a microscope.[15] A morbidity and mortality benefit of this procedure exists due to earlier detection compared with other methods.[15] Frozen-section biopsies positive for invasive fungal pathology are universally consistent with the definitive diagnosis.[28] However, frozen section interpretation is often difficult, and diagnosis is sometimes not possible.[23] Vascular invasion, degree of necrosis, pigmentation, and spores are valuable factors in distinguishing fungal agents of AIFRS.[29] For patients with mucormycosis, necrotic tissue can be difficult to visualize on frozen sections, so researchers have found that adding Periodic Acid-Schiff (PAS) staining improves outcomes.[23][30]
Several protocols are available for detecting bacteria and fungi in various clinical samples. However, FESS specimens are not suitable for nested PCR because environmental contaminants accumulate in the specimens. This limitation poses a challenge for diagnosing specimens collected from the nasal cavity. Since this issue cannot be overlooked, the use of nested PCR to detect fungal respiratory infections in the upper airways is considerably limited.[31] Serum galactomannan, an Aspergillus antigen, has been shown to correlate with a diagnosis of invasive pulmonary aspergillosis. However, given its low sensitivity, clinicians must exercise caution when relying on galactomannan as a screening tool for AIFS diagnosis.[32]
CT imaging can show asymmetric dense material in 1 sinus or nasal polyps in cases of noninvasive fungal sinusitis. Additionally, a CT scan of the head is used to visualize thickened sinus walls, opacifications, ring-enhancing lesions, or bony erosions caused by fungal growth.[21][22][33] Key points to consider include:
- Diagnosing allergic fungal sinusitis relies on the presence of major criteria, which include type 1 hypersensitivity, nasal polyps, eosinophilic mucin, a positive fungal stain, and confirmatory findings on a CT scan. Additionally, minor criteria, eg, unilateral disease, asthma, and the presence of Charcot-Leyden crystals in the mucin, can help further support the diagnosis. Typically, affected patients are young adults, usually between 20 and 30, and may have dark-colored, rubbery nasal casts. The ethmoid sinuses are the most commonly involved. On CT scans, a characteristic "double density" sign can be observed, indicating thick fungal mucin surrounded by hyperplasia.[34]
- Fungal balls typically occur in immunocompetent females, predominantly in the maxillary sinus, accounting for 95% of cases. While inhaling spores can lead to their formation, mucosal injury, often resulting from dental procedures or sinus surgery, may also contribute to the process. These cases are usually asymptomatic and are often discovered incidentally through a CT scan. However, some individuals may experience symptoms such as facial pain, postnasal discharge, and nasal cavity crusting.[35][36][35]
- IFS is a rare but aggressive condition with a mortality rate of approximately 50%. This type of sinusitis is characterized by the invasion of blood vessels, nerves, and bones, rather than just the sinus mucosa. A classic example is mucormycosis, which Zygomycetes often cause in individuals with uncontrolled diabetes.[37][38] Aspergillus can cause infections in AIDS patients or others with weakened immune systems. Initially, symptoms, eg, pain, pressure, or fever, develop gradually. However, after several weeks, the infection can invade deeper tissues, leading to a sudden worsening of symptoms that may complicate diagnosis. Potential symptoms include facial nerve palsies, swelling, double vision (diplopia), and bulging eyes (proptosis). If the infection invades the nerves, it can lead to a loss of sensation (anesthesia). At the same time, invasion of blood vessels can result in emboli, tissue death (necrosis), and blackened nasal turbinates and nostrils. A CT scan will confirm the extent of the deep tissue invasion.[33][38]
- GIFS is more prevalent outside the US, particularly in the Middle East and North Africa, and is an invasive infection that progresses more slowly and is characterized by noncaseating granulomas on pathology.[39]
Before sinonasal surgery, high-resolution CT and MRI can provide valuable information to guide surgical strategies.[40] Opacification is frequently observed on radiographs of fungal sinus infections. Invasive fungal lesions show T2 signal voids on MRI, corresponding to CT opacification and to intrasinus or nasal fungal components.[41]
Treatment / Management
Surgical debridement is the treatment of choice for most cases of fungal sinusitis because it is both diagnostic and therapeutic.[37][23][17] Not only should sinus aeration be restored, but removing all residual fungal and eosinophilic debris is vital to prevent recurrence. This is similar in principle to removing all cholesteatoma during a mastoidectomy. Functional endoscopic sinus surgery allows for visualization of pathology and anatomy, biopsy of lesions, flushing of the sinuses, and addressing any underlying anatomic issues. Polypectomy should always be performed as needed. Rarely, a craniotomy or external surgical approach may be preferred if complications arise before or during surgical debridement, eg, infections that spread or involve the cavernous sinus.[21] (B2)
Oral corticosteroids are beneficial in many cases of acute and chronic fungal sinusitis, improving symptoms by suppressing inflammation and lowering circulating IgE levels, although prolonged use is discouraged.[22][18] No specific regimen for corticosteroid use has been established; instead, the duration of treatment should be customized for each patient. Many surgeons prefer administering high-dose prednisone either before, during, or after surgery. Nasal topical steroids should not be used on their own; they are more effective when combined with systemic steroids and aggressive use of saline nasal rinses. One study indicated that this combined approach could help reduce the recurrence rate over a 2-year period.[42]
Immunotherapy may be beneficial as part of some patients' overall treatment.[43] Fungal immunotherapy may desensitize the body to fungal antibodies.[22][18] Although immunotherapy is a costly treatment modality, its short-term benefits outweigh the long-term drawbacks. This treatment may reduce the need for corticosteroids, thereby preventing the adverse effects associated with long-term corticosteroid use.[44](B3)
The FDA has approved dupilumab anti-IL-4/IL-13 for the treatment of adult and pediatric patients aged 6 years and older with AFRS who have a history of sino-nasal surgery.[Sanofi. Press Release: Sanofi and Regeneron’s Dupixent Approved in the US as the First and Only Medicine for Allergic Fungal Rhinosinusitis. 2026] The LIBERTY-AIMS (NCT04684524) was a phase 3 randomized, placebo-controlled study of patients with AFRS 6 years and older randomized to dupilumab (300 mg every 2 weeks for adults and children ≥60 kg or 200 mg every 2 weeks for children between 30 and 60 kg) or matched placebo for 52 weeks.[JACI. Dupilumab for Treatment of Allergic Fungal Rhinosinusitis in Adults and Children Aged 6 and Over: Results from LIBERTY-AIMS Study. 2026] Dupilumab improved AFRS clinical symptom measures, including NPS, in patients 6 years and older and was well-tolerated.
Systemic antifungals should be used only as adjunctive treatment for IFS.[45] Amphotericin B may be the first-line treatment for IFS because of its broad coverage against Mucor species and Aspergillus. Some azole antifungals may also be beneficial, but concurrent management by an infectious disease specialist is warranted.[22][18] Topical antifungals have shown limited success and are not recommended. Since most cases of IFS are secondary to an immunodeficiency, the underlying immunodeficiency must be managed to achieve optimal care.[45] Saprophytic fungal sinusitis typically does not require surgery, as it can be effectively managed with nasal douching, which involves saline cleansing of the nasal sinuses.[22][18]
Differential Diagnosis
The differential diagnosis is extensive, as symptoms may overlap with various nasal and sinus conditions, including:
- Acute and chronic rhinosinusitis (bacterial or viral)
- Allergic rhinosinusitis
- Nasal polyposis
- Sinus mucocele
- Odontogenic sinusitis
- Granulomatosis with polyangiitis
- Sarcoidosis
- Sinonasal tumor (benign or malignant)
- Foreign body
- Orbital cellulitis or abscess
- Cavernous sinus thrombosis
- Necrotizing soft tissue infection
- Skull base osteomyelitis [46][47]
Prognosis
The prognosis for noninvasive fungal sinusitis is generally favorable; however, the outlook for IFS is often grave, particularly if the underlying immune status is not restored. AFS usually responds well to surgical treatment, and its recurrence can be effectively managed either with office endoscopy and debridement or repeat endoscopic sinus surgery. Local debridement can be performed easily, provided no recurrence of nasal polyposis. If left untreated, the condition can rarely cause erosion into adjacent structures due to mass effect from longstanding disease.[22]
Many patients with allergic fungal sinusitis require both long- and short-term use of topical nasal steroids and systemic corticosteroids. With the potential benefit of biologic therapy with dupilumab (anti-IL-4/IL-13), the prognosis for many patients may improve.[Sanofi. Press Release: Sanofi and Regeneron’s Dupixent Approved in the US as the First and Only Medicine for Allergic Fungal Rhinosinusitis. 2026]
IFS is a potentially life-threatening condition that comes with a poor prognosis. The invasion can lead to complications, eg, cavernous sinus thrombosis and central nervous system infections, which have a mortality rate of around 50%. Therefore, urgent treatment is essential. Complications can develop rapidly, and disease recurrence is common, often necessitating repeated debridements. Survivors may face issues, eg, facial deformities, nerve damage, and chronic pain. The main prognostic factor is the patient's immune status. If the immune system can be normalized, the prognosis improves. Conversely, if the immune status cannot be restored, the outlook is very grim and often fatal.[48] GIFS may indicate systemic diseases, eg, Wegener's granulomatosis, and the prognosis depends on effective management of the underlying condition.[49]
Complications
Potential complications of noninvasive fungal sinusitis may include:
- Local bone and soft tissue erosion of adjacent structures
- Potential orbital and intracranial complications
- CSF leak
- Predispose the patient to recalcitrant chronic rhinosinusitis
Despite recent advances in research and analysis, IFS remains poorly understood and challenging to diagnose and treat.[16][50] IFS may lead to several severe potential complications, which include:
- Rapidly progressive locally destructive disease causing tissue necrosis
- Cavernous sinus thrombosis
- CNS invasion
- Orbital invasion and vision loss
- A rare but severe complication of IFS is aspergillosis affecting the cavernous sinus or orbital apex. When both areas are involved, the condition is referred to as cavernous sinus-orbital apex syndrome. Patients may experience symptoms, eg, headaches, sudden loss of vision in 1 eye, or ocular pain.[37] This condition usually results from cavernous sinus thrombosis or a carotid-cavernous fistula.
Deterrence and Patient Education
Most people are familiar with sinusitis, but they rarely consider fungus as a cause. Educating patients that sinusitis can have various causes is important. Deterrence of FRS focuses on minimizing environmental and host-related risk factors that promote fungal colonization and invasion. Patients should receive guidance on reducing exposure to damp, poorly ventilated environments and maintaining clean indoor air quality to limit fungal growth. Judicious use of antibiotics remains essential to prevent disruption of normal microbial flora and immune defenses. Immunocompromised individuals, including those with diabetes or receiving immunosuppressive therapy, require counseling on early symptom recognition and prompt medical evaluation due to the higher risk of IFS and associated complications. In people with uncontrolled diabetes, highlighting the significance of black nasal secretions and the risk of IFS is especially important.[51] Preventive strategies also include optimizing control of underlying conditions and adhering to follow-up care after sinus surgery to reduce recurrence.
Patient education should emphasize early recognition of symptoms, eg, persistent nasal congestion, facial pain, headache, visual changes, or the expulsion of discolored debris, which may indicate fungal involvement. Patients diagnosed with AFS or other forms of FRS benefit from education on the chronic and potentially recurrent nature of the disease, adherence to medical therapies, eg, corticosteroids and nasal irrigations, and the importance of routine monitoring. Clear communication regarding warning signs of invasive disease, including neurologic symptoms or facial swelling, supports timely intervention and reduces the risk of morbidity and mortality.
Enhancing Healthcare Team Outcomes
FRS comprises a spectrum of noninvasive and invasive disease processes with variable clinical severity, ranging from AFS and fungal ball to life-threatening invasive fungal sinusitis. Pathogenesis involves fungal colonization in susceptible environments, with invasive disease characterized by tissue and vascular invasion, particularly in immunocompromised hosts. Patients commonly present with chronic rhinosinusitis–like symptoms, though invasive forms may include neurologic deficits, facial pain, or orbital involvement. Diagnosis relies on clinical suspicion, nasal endoscopy, imaging, and histopathology, while management includes surgical debridement, corticosteroids or biologics for inflammatory disease, and systemic antifungal therapy for invasive forms. Early recognition remains critical to prevent complications such as intracranial spread and increased mortality.[52] Most researchers attribute the recent increase in the prevalence of FRS to immunodeficiency secondary to cancer therapy, diabetes mellitus, and posttransplant therapy, as well as the widespread use of antibiotics in modern societies.
Interprofessional collaboration strengthens patient-centered care by integrating expertise across disciplines to ensure timely diagnosis, individualized treatment, and coordinated follow-up. Otolaryngologists lead surgical and diagnostic management, while primary care clinicians and advanced practitioners facilitate early recognition, risk assessment, and referral. Nurses support patient education, symptom monitoring, and continuity of care, while pharmacists guide safe medication use, including antifungals and immunomodulators. Effective communication among team members promotes shared decision-making, addresses patient concerns and stigma, and ensures understanding of pathology results and treatment plans. Coordinated strategies, including timely referral, adherence monitoring, and risk factor modification, enhance safety, reduce complications, and optimize long-term outcomes.
References
Chakrabarti A, Denning DW, Ferguson BJ, Ponikau J, Buzina W, Kita H, Marple B, Panda N, Vlaminck S, Kauffmann-Lacroix C, Das A, Singh P, Taj-Aldeen SJ, Kantarcioglu AS, Handa KK, Gupta A, Thungabathra M, Shivaprakash MR, Bal A, Fothergill A, Radotra BD. Fungal rhinosinusitis: a categorization and definitional schema addressing current controversies. The Laryngoscope. 2009 Sep:119(9):1809-18. doi: 10.1002/lary.20520. Epub [PubMed PMID: 19544383]
Ebbens FA, Georgalas C, Rinia AB, van Drunen CM, Lund VJ, Fokkens WJ. The fungal debate: where do we stand today? Rhinology. 2007 Sep:45(3):178-89 [PubMed PMID: 17956015]
Montone KT. Pathology of Fungal Rhinosinusitis: A Review. Head and neck pathology. 2016 Mar:10(1):40-46. doi: 10.1007/s12105-016-0690-0. Epub 2016 Feb 1 [PubMed PMID: 26830404]
Franzese C. Fungal Sinusitis-Invasive Versus Noninvasive. The Medical clinics of North America. 2026 Jan:110(1):45-52. doi: 10.1016/j.mcna.2025.05.004. Epub 2025 Jun 14 [PubMed PMID: 41206202]
Chakrabarti A, Das A, Panda NK. Controversies surrounding the categorization of fungal sinusitis. Medical mycology. 2009:47 Suppl 1():S299-308. doi: 10.1080/13693780802213357. Epub 2008 Jul 28 [PubMed PMID: 18663658]
Granville L, Chirala M, Cernoch P, Ostrowski M, Truong LD. Fungal sinusitis: histologic spectrum and correlation with culture. Human pathology. 2004 Apr:35(4):474-81 [PubMed PMID: 15116329]
Taxy JB. Paranasal fungal sinusitis: contributions of histopathology to diagnosis: a report of 60 cases and literature review. The American journal of surgical pathology. 2006 Jun:30(6):713-20 [PubMed PMID: 16723848]
Level 3 (low-level) evidenceDas A, Bal A, Chakrabarti A, Panda N, Joshi K. Spectrum of fungal rhinosinusitis; histopathologist's perspective. Histopathology. 2009 Jun:54(7):854-9. doi: 10.1111/j.1365-2559.2009.03309.x. Epub [PubMed PMID: 19635105]
Level 3 (low-level) evidenceMontone KT, Livolsi VA, Feldman MD, Palmer J, Chiu AG, Lanza DC, Kennedy DW, Loevner LA, Nachamkin I. Fungal rhinosinusitis: a retrospective microbiologic and pathologic review of 400 patients at a single university medical center. International journal of otolaryngology. 2012:2012():684835. doi: 10.1155/2012/684835. Epub 2012 Feb 8 [PubMed PMID: 22518160]
Level 2 (mid-level) evidenceZinreich SJ, Kennedy DW, Malat J, Curtin HD, Epstein JI, Huff LC, Kumar AJ, Johns ME, Rosenbaum AE. Fungal sinusitis: diagnosis with CT and MR imaging. Radiology. 1988 Nov:169(2):439-44 [PubMed PMID: 3174990]
Mabry RL, Manning SC, Mabry CS. Immunotherapy in the treatment of allergic fungal sinusitis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 1997 Jan:116(1):31-5 [PubMed PMID: 9018254]
Glass D, Amedee RG. Allergic fungal rhinosinusitis: a review. Ochsner journal. 2011 Fall:11(3):271-5 [PubMed PMID: 21960761]
Marple BF. Allergic fungal rhinosinusitis: current theories and management strategies. The Laryngoscope. 2001 Jun:111(6):1006-19 [PubMed PMID: 11404613]
Mehta R, Panda NK, Mohindra S, Chakrabarti A, Singh P. Comparison of efficacy of amphotericin B and itraconazole in chronic invasive fungal sinusitis. Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2013 Aug:65(Suppl 2):288-94. doi: 10.1007/s12070-011-0444-y. Epub 2012 Jan 6 [PubMed PMID: 24427663]
Silveira MLC, Anselmo-Lima WT, Faria FM, Queiroz DLC, Nogueira RL, Leite MGJ, Lessa RM, Simões BP, Tamashiro E, Valera FCP. Impact of early detection of acute invasive fungal rhinosinusitis in immunocompromised patients. BMC infectious diseases. 2019 Apr 5:19(1):310. doi: 10.1186/s12879-019-3938-y. Epub 2019 Apr 5 [PubMed PMID: 30953465]
Sharif MS, Ali S, Nisar H. Frequency of Granulomatous Invasive Fungal Sinusitis in Patients with Clinical Suspicion of Chronic Fungal Rhinosinusitis. Cureus. 2019 May 25:11(5):e4757. doi: 10.7759/cureus.4757. Epub 2019 May 25 [PubMed PMID: 31363438]
Gao X, Li B, Ba M, Yao W, Sun C, Sun X. Headache Secondary to Isolated Sphenoid Sinus Fungus Ball: Retrospective Analysis of 6 Cases First Diagnosed in the Neurology Department. Frontiers in neurology. 2018:9():745. doi: 10.3389/fneur.2018.00745. Epub 2018 Sep 7 [PubMed PMID: 30245665]
Level 2 (mid-level) evidenceDeutsch PG, Whittaker J, Prasad S. Invasive and Non-Invasive Fungal Rhinosinusitis-A Review and Update of the Evidence. Medicina (Kaunas, Lithuania). 2019 Jun 28:55(7):. doi: 10.3390/medicina55070319. Epub 2019 Jun 28 [PubMed PMID: 31261788]
Galletti B, Gazia F, Galletti C, Perani F, Ciodaro F, Freni F, Galletti F. Rhinocerebral mucormycosis with dissemination to pontine area in a diabetic patient: Treatment and management. Clinical case reports. 2019 Jul:7(7):1382-1387. doi: 10.1002/ccr3.2255. Epub 2019 Jun 5 [PubMed PMID: 31360493]
Level 3 (low-level) evidenceLialiaris ST, Chaidas K, Fyrmpas G, Deftereou TE, Spyroulia D, Prokopakis EP, Katotomichelakis M. Inflammatory Factors and Chronic Rhinosinusitis: An Umbrella Review. Cureus. 2026 Jan:18(1):e101782. doi: 10.7759/cureus.101782. Epub 2026 Jan 18 [PubMed PMID: 41710830]
Level 1 (high-level) evidenceAl Otaibi FE. Fatal case of cerebral aspergilloma complicated by ventriculitis and bacteremia due to Salmonella species in a sickle cell disease patient. Saudi medical journal. 2018 Sep:39(9):935-939. doi: 10.15537/smj.2018.9.22821. Epub [PubMed PMID: 30251738]
Level 3 (low-level) evidenceSingh V. Fungal Rhinosinusitis: Unravelling the Disease Spectrum. Journal of maxillofacial and oral surgery. 2019 Jun:18(2):164-179. doi: 10.1007/s12663-018-01182-w. Epub 2019 Jan 28 [PubMed PMID: 30996535]
Crist H, Hennessy M, Hodos J, McGinn J, White B, Payne S, Warrick JI. Acute Invasive Fungal Rhinosinusitis: Frozen Section Histomorphology and Diagnosis with PAS Stain. Head and neck pathology. 2019 Sep:13(3):318-326. doi: 10.1007/s12105-018-0965-8. Epub 2018 Sep 12 [PubMed PMID: 30209746]
Gupta R, Gupta AK, Patro SK, Yadav J, Chakrabarti A, Das A, Chatterjee D. Allergic fungal rhino sinusitis with granulomas: A new entity? Medical mycology. 2015 Aug:53(6):569-75. doi: 10.1093/mmy/myv033. Epub 2015 May 30 [PubMed PMID: 26026173]
Kwiatkowska MA, Trębińska-Stryjewska A, Jurkiewicz D, Trafny EA. Microbiological PCR Characteristics of Odontogenic Sinusitis and Their Clinical Correlates: A Cross-Sectional Analysis. Journal of clinical medicine. 2026 Feb 27:15(5):. doi: 10.3390/jcm15051814. Epub 2026 Feb 27 [PubMed PMID: 41827230]
Level 2 (mid-level) evidenceLieberman SM, Jacobs JB, Lebowitz RA, Fitzgerald MB, Crawford J, Feigenbaum BA. Measurement of mycotoxins in patients with chronic rhinosinusitis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2011 Aug:145(2):327-9. doi: 10.1177/0194599811403891. Epub [PubMed PMID: 21493263]
Payne SJ, Mitzner R, Kunchala S, Roland L, McGinn JD. Acute Invasive Fungal Rhinosinusitis: A 15-Year Experience with 41 Patients. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2016 Apr:154(4):759-64. doi: 10.1177/0194599815627786. Epub 2016 Feb 16 [PubMed PMID: 26884367]
Melancon CC, Clinger JD. The Use of Frozen Section in the Early Diagnosis of Acute Invasive Fungal Sinusitis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2017 Aug:157(2):314-319. doi: 10.1177/0194599817697279. Epub 2017 Mar 28 [PubMed PMID: 28349786]
Tran GH, Luong KA, Ngo TP, Bui TM, Luong BA, Vu HA. Invasive Fungal Rhinosinusitis: The First Histopathological Study in Vietnam. Head and neck pathology. 2024 Oct 16:18(1):104. doi: 10.1007/s12105-024-01711-9. Epub 2024 Oct 16 [PubMed PMID: 39412604]
Phulwani RM, Mitra K, Phatak S, Onkar P, Rangari M. Dots, Circles, and Deception: Radiological Diagnosis of an Unusual Mycetoma. Cureus. 2026 Feb:18(2):e103249. doi: 10.7759/cureus.103249. Epub 2026 Feb 8 [PubMed PMID: 41822612]
Badiee P, Gandomi B, Sabz G, Khodami B, Choopanizadeh M, Jafarian H. Evaluation of nested PCR in diagnosis of fungal rhinosinusitis. Iranian journal of microbiology. 2015 Feb:7(1):62-6 [PubMed PMID: 26644876]
Melancon CC, Lindsey J, Russell GB, Clinger JD. The role of galactomannan Aspergillus antigen in diagnosing acute invasive fungal sinusitis. International forum of allergy & rhinology. 2019 Jan:9(1):60-66. doi: 10.1002/alr.22225. Epub 2018 Oct 25 [PubMed PMID: 30358938]
S S, Kant S, Verma S, Singh A, Singh V, Keshri A, Singh A, Marak RSK, Kumar S. Radiologic Characterization of Invasive Fungal Infections of the Paranasal Sinuses and Skull Base: A Prospective Analysis. Cureus. 2026 Feb:18(2):e104104. doi: 10.7759/cureus.104104. Epub 2026 Feb 23 [PubMed PMID: 41743147]
Li C, Li Y, Xu Y, Wei Y, Zhang H, Cai F, Duan Q, Seng D. [Clinical characteristics and therapeutic insights of pediatric allergic fungal rhinosinusitis]. Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery. 2026 Feb:40(2):182-187. doi: 10.13201/j.issn.2096-7993.2026.02.013. Epub [PubMed PMID: 41589374]
Im E, Donaldson L, Adelman A, Adappa ND, Chen YW, Chapurin N, Douglas JE, D'Souza GE, Eide J, Espinosa M, Fu CH, Fox MG, Garg R, Kuan EC, Kohanski MA, Kwiatkowska M, Li K, Liu DH, Locke TB, Lin CF, Makary C, Ottavi A, Papagiannopoulos P, Palmer JN, Tong CCL, Tajudeen BA, Venkatesh S, Wei K, Yoo F, Yu AJ, Jin J, Saibene AM, Craig JR. Clinical Features and Dental Pathologies in Maxillary Sinus Fungal Balls and Odontogenic Sinusitis. The Laryngoscope. 2026 Feb 7:():. doi: 10.1002/lary.70429. Epub 2026 Feb 7 [PubMed PMID: 41654324]
Hamashima R, Tashiro M, Nakano Y, Shirahige T, Namie H, Yano H, Ito Y, Yoshida M, Hirayama T, Takeda K, Iwanaga N, Kakiuchi S, Nishi K, Liu H, Takazono T, Tanaka T, Watanabe A, Komohara Y, Furumoto A, Yanagihara K, Mukae H, Filler SG, Takayama K, Izumikawa K. Non-viable Aspergillus fumigatus promotes chronic inflammation and angiogenesis in a murine fungus ball model. Microbiology spectrum. 2026 Mar 24:14(5):e0346725. doi: 10.1128/spectrum.03467-25. Epub 2026 Mar 24 [PubMed PMID: 41874171]
Huang Y, Gui L. Cavernous sinus-orbital apex aspergillus infection in a diabetic patient: A case report. Medicine. 2019 Mar:98(13):e15041. doi: 10.1097/MD.0000000000015041. Epub [PubMed PMID: 30921229]
Level 3 (low-level) evidenceGraison AA, Ansari A, Raverkar A. Correlation Between Endoscopic and Radiological Data in Rhino-Orbital-Cerebral Mucormycosis (ROCM). Cureus. 2026 Jan:18(1):e101461. doi: 10.7759/cureus.101461. Epub 2026 Jan 13 [PubMed PMID: 41694906]
Gorbunov S, Polev G. ANCA-Negative Granulomatosis With Polyangiitis Mimicking Sinusitis and Rhinoscleroma: A Case Report. Case reports in medicine. 2026:2026():4144957. doi: 10.1155/carm/4144957. Epub 2026 Feb 26 [PubMed PMID: 41768971]
Level 3 (low-level) evidenceAlsalem S, Almontashri A, Alsalem M, Altamimi F, Alyami N, Hajjaf S, Ahmed F. Value of MRI signal intensity in evaluation of allergic fungal rhinosinusitis compared with CT Hounsfield units: Retrospective study. Medicine. 2024 Jul 12:103(28):e38951. doi: 10.1097/MD.0000000000038951. Epub [PubMed PMID: 38996133]
Level 2 (mid-level) evidenceKim SC, Ryoo I, Shin JM, Suh S, Jung HN, Shin SU. MR Findings of Fungus Ball: Significance of High Signal Intensity on T1-Weighted Images. Journal of Korean medical science. 2020 Jan 20:35(3):e22. doi: 10.3346/jkms.2020.35.e22. Epub 2020 Jan 20 [PubMed PMID: 31950777]
Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012 Mar:50(1):1-12. doi: 10.4193/Rhino12.000. Epub [PubMed PMID: 22469599]
Bassichis BA, Marple BF, Mabry RL, Newcomer MT, Schwade ND. Use of immunotherapy in previously treated patients with allergic fungal sinusitis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2001 Nov:125(5):487-90 [PubMed PMID: 11700447]
Tyler MA, Luong AU. Current understanding of allergic fungal rhinosinusitis. World journal of otorhinolaryngology - head and neck surgery. 2018 Sep:4(3):179-185. doi: 10.1016/j.wjorl.2018.08.003. Epub 2018 Nov 9 [PubMed PMID: 30506049]
Level 3 (low-level) evidenceAkagawa Y, Egawa N, Shimizu T, Shinkai Y, Ono S, Koga S, Ishikawa K. Successful Long-Term Use of Isavuconazole in a Tacrolimus-Treated Japanese Kidney Transplant Recipient With Disseminated Cryptococcosis and Probable Invasive Aspergillosis. Cureus. 2026 Feb:18(2):e103470. doi: 10.7759/cureus.103470. Epub 2026 Feb 12 [PubMed PMID: 41841072]
Fernandez-Figares-Conde L, Isorna I, Torres-Carranza E, Garcia-Perla-Garcia A, Rollon-Mayordomo A, Infante-Cossio P. Rhinocerebral mucormycosis: A 15-year retrospective study in southern Spain. Medicina oral, patologia oral y cirugia bucal. 2026 Mar 7:():. pii: 27986. doi: 10.4317/medoral.27986. Epub 2026 Mar 7 [PubMed PMID: 41793736]
Level 2 (mid-level) evidenceSharifi I, Razzeto A, Sacco SB, Zamin M, Valencia V, Aoun ML, Varghese RT. Rhino-orbito-cerebral mucormycosis in new-onset type 1 diabetes mellitus: a case-based short review. The American journal of the medical sciences. 2026 Jun:371(6):576-581. doi: 10.1016/j.amjms.2026.03.003. Epub 2026 Mar 5 [PubMed PMID: 41794396]
Level 3 (low-level) evidenceSantos DW, Proença H, Medina-Pestana JO, Rangel ÉB. Fungal sinusitis in simultaneous pancreas-kidney transplant. Journal of clinical pathology. 2019 Oct:72(10):720. doi: 10.1136/jclinpath-2018-205258. Epub 2019 Jul 29 [PubMed PMID: 31358535]
Papo M, Martinot P, Sinico RA, Silvestre-Teixeira V, Venhoff N, Urban ML, Iudici M, Mahrhold J, Locatelli F, Cassone G, Schiavon F, Seeliger B, Neumann T, Feder C, Groh M, Marvisi C, Samson M, Barba T, Jayne D, Troilo A, Thiel J, Hellmich B, Monti S, Montecucco C, Salvarani C, Kahn JE, Bonnotte B, Durel CA, Puéchal X, Mouthon L, Guillevin L, Emmi G, Vaglio A, Porcher R, Terrier B, French Vasculitis Study Group and the Eosinophilic Granulomatosis with Polyangiitis European Study Group. Prediction of Relapse and Glucocorticoid Dependence in Eosinophilic Granulomatosis With Polyangiitis: Findings From a Large European Cohort. Arthritis & rheumatology (Hoboken, N.J.). 2026 Feb 8:():. doi: 10.1002/art.70072. Epub 2026 Feb 8 [PubMed PMID: 41656627]
Yan Y, Zhao Z, Wan H, Wu R, Fang J, Liu H. A novel fungus concentration-dependent rat model for acute invasive fungal rhinosinusitis: an experimental study. BMC infectious diseases. 2014 Dec 20:14():3856. doi: 10.1186/s12879-014-0713-y. Epub 2014 Dec 20 [PubMed PMID: 25526739]
Level 3 (low-level) evidenceRanganathan B, Natarajan K, Nandhan R, Abdlehamid A. Granulomatous disorders of the nose and paranasal sinuses: perspective from low- and middle-income countries. Current opinion in otolaryngology & head and neck surgery. 2025 Jun 1:33(3):170-175. doi: 10.1097/MOO.0000000000001048. Epub 2025 Apr 2 [PubMed PMID: 40177822]
Level 3 (low-level) evidenceChaker AM, Cantone E, Hellings PW, Heirman N, Verillaud B, Hox V, Jacomelli C, Mullol J. A patient-centric approach to chronic rhinosinusitis with nasal polyps (CRSwNP): developing tools to improve disease management and outcomes. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2026 Jan:283(1):249-261. doi: 10.1007/s00405-025-09763-5. Epub 2025 Dec 10 [PubMed PMID: 41372530]