Orbital complications in allergic fungal rhinosinusitis: a case series from a tertiary center hospital experience

Introduction

Background

Contrary to some popular beliefs, fungal rhinosinusitis is not a rare entity and can reach up to 42.6% among all cases of chronic rhinosinusitis (1). Depending on the degree of sinus invasion, fungal rhinosinusitis is classified into two categories: non-invasive fungal rhinosinusitis, which includes saprophytic fungal rhinosinusitis, fungal ball, and allergic fungal rhinosinusitis (AFRS), and invasive fungal rhinosinusitis, which includes granulomatous invasive rhinosinusitis, acute invasive rhinosinusitis, and chronic invasive rhinosinusitis. Among those different types, AFRS is considered to be the most common type of fungal rhinosinusitis and has an average rate of 7.8 across all cases of chronic rhinosinusitis (2,3). Geographical variations in the reported incidence of AFRS are explained by greater atmospheric humidity, temperature, and fungal spore load, all of which promote sensitivity to fungus like Aspergillus and Curvularia. As a result, AFRS is more common in our region, whereas fungal rhinosinusitis subtypes (such as fungal ball or chronic invasive fungal rhinosinusitis) are more prevalent in temperate climates.

AFRS is a non-invasive form of sinus inflammation characterized by immunoglobulin E (IgE)-mediated eosinophilic-rich type 1 hypersensitivity reaction initiated in response to the exposure of sinonasal mucosa to fungal antigens which occur primarily in immunocompetent patients with atopy. The paranasal cavities get filled by eosinophilic mucin, fungal hyphae, and Charcot-Leyden crystals in response to complex humoral and cellular immune reactions (4). Fungi organisms like Aspergillus, Bipolaris, Exserohilum, and Curvularia are the most commonly associated with AFRS (5).

AFRS symptoms are usually not specific and are similar to chronic rhinosinusitis. Those symptoms include nasal polyposis, which is present in all patients with AFRS, in addition to nasal congestion, postnasal drip, anosmia, nasal discharge, and facial pain. Furthermore, some patients may present with complications as the first symptoms like facial asymmetry, headache, and visual changes (6-8).

Rationale and knowledge gap

The diagnosis of AFRS is challenging as it has many differential diagnoses with similar symptoms such as chronic rhinosinusitis, allergic rhinitis, and fungal ball. Bent and Kuhn are diagnostic criteria that are widely accepted and aided in the detection of AFRS. It includes five major criteria that need to be met for the diagnosis to be made, which are: confirmed type I hypersensitivity to fungi either by history, in vitro testing, or skin tests, nasal polyposis, eosinophilic mucus without invasion, signs that are in characteristic computed tomography (CT), and positive biopsy with fungal stain from the removed content of sinus during surgery (9). The management of AFRS is mainly focused on topical corticosteroids as well as surgery. While fungal-specific immunotherapy, short courses of systemic corticosteroids, and systemic antifungals can be used in case of recalcitrant disease (9).

However, many complications may develop in the case of moderate or severe AFRS. It can result in bone erosion, expansion, and extension to areas like the brain, skin, and orbit. This can lead to headaches, focal neurological signs, meningeal signs, epistaxis, and facial dysmorphia. In addition, many ophthalmic complications, such as ophthalmoplegia, proptosis, periorbital edema, double vision, and even visual loss may develop (6,10).

Objective

The primary objective of this study was to provide a detailed account of four distinct cases of AFRS that manifested with orbital complications. In addition to presenting these cases, the study aimed to conduct an in-depth analysis of the clinical presentations and radiological characteristics associated with each case. By exploring the diagnostic findings, the study sought to highlight the typical and atypical features of AFRS with orbital involvement. Furthermore, the study aimed to review the management strategies implemented for these patients and to evaluate the clinical outcomes following treatment. We present this article in accordance with the AME Case Series reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-195/rc).

Case presentation

Out of 40 patients with AFRS identified retrospectively from the medical records in one tertiary hospital center, four patients experienced orbital complications as a consequence of AFRS. All four individuals met at least four of the five Bent and Kuhn main criteria for AFRS diagnosis. Each case had immunologic (total/specific IgE increase or a positive skin test), radiologic (heterogeneous sinus opacification, hyperattenuation, bone remodeling), and pathologic (allergic mucin with fungal elements) confirmation. Table 1 shows the details of the included patients in the study.

Case 1: mixed AFRS with superimposed mucormycosis and cavernous sinus thrombosis

A 44-year-old female, with no significant past medical or surgical history, referred from another tertiary hospital as a case of post-turbinoplasty with suspicion of cavernous sinus thrombosis. The patient was doing well after turbinoplasty until 10 days later when she started complaining of progressive left facial swelling. It was associated with left eye redness, ptosis, and proptosis. The patient also complained of dysphagia and slurred speech. Afterward, the patient started to deteriorate and developed left-sided loss of vision and restricted ocular movement. Upon examination, mild left-sided facial edema was noted without skin change or facial asymmetry. Eye examination showed left-sided proptosis, lid edema, red conjunctiva, whitish discharge, and restricted ocular movement. Pupils were fixed and non-reactive. Otolaryngological examination showed right nasal discharge with crustations and left nasal dry crustations. Serum total IgE was increased (1,240 IU/mL), whereas Aspergillus fumigatus-specific IgE was positive (class 3). The peripheral eosinophilia rate was 1.2×10⁹/L (13%). CT scan and magnetic resonance imaging (MRI) of paranasal sinuses (Figure 1A,1B) revealed acute pansinusitis with left orbital extension. An emergency endoscopic sinus surgery (ESS) and bilateral debridement were performed (Figure 1C). Histopathology showed thick eosinophilic mucin with Charcot-Leyden crystals and a large number of eosinophils [>200 per high-power field (HPF)] surrounding necrotic mucosa with non-septate hyphae typical of Mucor species. These results were more consistent with mixed fungal rhinosinusitis (AFRS with mucormycosis) than acute invasive fungal rhinosinusitis alone. The patient was treated empirically with amphotericin B, posaconazole, vancomycin, and meropenem. The patient improved significantly and was doing well at 6 months follow-up postoperative, and CT scan revealed clear sinuses with no signs of recurrence.

Figure 1 Imaging and intraoperative views of invasive fungal rhinosinusitis with orbital extension. Preoperative (A) coronal view and (B) axial view MRI of the paranasal sinuses showing acute pansinusitis with left orbital extension (white arrow). (C) Intraoperative endoscopic view showing debridement of invasive fungal rhinosinusitis within the sphenoid sinus, with extension towards the sellar region. MRI, magnetic resonance imaging.

Case 2: unilateral abducens nerve palsy secondary to AFRS

A 40-year-old woman, known case of AFRS and bronchial asthma with a history of multiple sinus surgeries, the last one was 10 years ago, presenting to the emergency department with a severe headache that started two weeks prior to her presentation, associated with nasal discharge and on-off nasal blockage and left eye diplopia, with limited left-eye movement. Ophthalmologic examination revealed left abducens nerve palsy, but visual acuity was intact. Other neurologic examinations were within normal. Otolaryngological examination revealed bilateral grade 3 nasal polyps with discharge. Laboratory test showed a total IgE was 970 IU/mL, and specific IgE to Aspergillus flavus was positive (class 3). Peripheral eosinophilia was 9.4%. A CT scan of the paranasal sinuses (Figure 2A,2B) revealed extensive sinus opacification consistent with AFRS, along with resorption and thinning of the lamina papyracea and cribriform plate, all of which are radiologic markers of AFRS. A subsequent sphenoethmoidal mucocele caused by previous surgical intervention was further suspected to contribute to the abducens nerve palsy. The patient was diagnosed with AFRS and underwent ESS (Figure 3). Histopathology confirmed allergic mucin without invasion. Postoperatively, she showed dramatic improvement in eye movement after a few hours. The next day the patient was discharged on nasal wash and steroids. Six months later, she came to the outpatient clinic, and a follow-up nasal endoscope showed a normal sinus cavity.

Figure 2 Imaging findings of AFRS. CT scan (A) coronal, and (B) axial showing fungal rhinosinusitis causing bony resorption out of the lamina papyracea and cribriform plates. AFRS, allergic fungal rhinosinusitis; CT, computed tomography; L, left; R, right.

Figure 3 Intraoperative views of a patient with AFRS. Intraoperative views: (A) sphenoid fungal disease of mixed mud and mucin, (B) sphenoid fungal mucin, (C) sphenoid fungal mud (D), wide sphenoidotomy post cleaning. AFRS, allergic fungal rhinosinusitis.

Case 3: proptosis and left optic atrophy: atypical presentation of AFRS

A 33-year-old female, presented to the otolaryngology clinic with no significant medical history, complaining of chronic nasal obstruction, greenish nasal discharge, and loss of smell over the past four years. It was associated with facial pain, severe headache and chronic blurry vision, which had progressively worsened over the last month. Otolaryngological examination and nasal endoscopy revealed bilateral grade 4 nasal polyps. This presentation was clinically suggestive of AFRS. Ophthalmological examination revealed visual acuity of 0.8 in the right eye and counting fingers at 3 meters in the left. Her serum total IgE was elevated at 980 IU/mL, and specific IgE to Aspergillus fumigatus was positive and peripheral eosinophilia was 7.6%. A CT scan indicated complete opacification of the right frontal, maxillary, and sphenoid sinuses, along with extensive involvement of ethmoid air cells, suggestive of chronic sinonasal polyposis and AFRS (Figure 4A,4B). MRI revealed sinus contour bulging and mass effect upon the intra-orbital extraconal compartment bilaterally and superior displacement of the pituitary gland associated with thinning and superior displacement of the optic chiasm without intracranial or intra-orbital invasion (Figure 4C,4D), resulting in mild to moderate proptosis of the right eye and partial optic atrophy of the left. The case was managed by an image guided ESS. Intraoperatively, thick eosinophilic mucin with fungal debris was identified and completely removed (Figure 5A-5D). A biopsy from the posterior ethmoid tissue was taken for histopathological analysis showing chronic mixed inflammatory cells approximately 200 eosinophils/HPF. Fungal culture revealed Aspergillus species, with specific IgE positive for Aspergillus fumigatus, supporting the diagnosis of AFRS. Postoperatively, the patient was discharged with no complications. One year later, she came to the outpatient clinic, and a follow-up nasal endoscope showed a normal sinus cavity.

Figure 4 Imaging findings are suggestive of sinonasal polyposis with AFRS. CT scan (A) coronal view, (B) axial view showing thinning and remodelling of the walls of ethmoid air cells and bilateral sphenoid sinuses associated with multifocal osseous severe thinning/dehiscence (white arrow). MRI (C) coronal view, (D) axial view, showing intra-orbital extraconal compartment compression bilaterally and superior displacement of the pituitary gland associated with thinning and superior displacement of the optic chiasm without intracranial or intra-orbital invasion (white arrow). AFRS, allergic fungal rhinosinusitis; CT, computed tomography; MRI, magnetic resonance imaging.

Figure 5 Intraoperative views of AFRS before and after removal of fungal mucin. Intraoperative endoscopic view of sphenoid sinus showing fungal mucin and mud (A) and (B), image guided intraoperative view of clean sphenoid sinus (C). Clean sphenoid sinus after complete removal of fungal mud and mucin (D). AFRS, allergic fungal rhinosinusitis.

Case 4: a severe presentation of AFRS with rare unilateral blindness and intracranial extension

A 24-year-old female known case of skin eczema, referred from a secondary hospital to the otolaryngology clinic with a diagnosis of AFRS of the sphenoid and ethmoid sinuses, with intra-orbital and intracranial extension. The patient initially complained of a three-month history of thick nasal discharge with postnasal drip, on and off nasal obstruction, and progressive loss of vision in her right eye over the past 2 months. It was associated with headaches and facial heaviness that worsened with leaning forward, but denied any bleeding, anosmia, or hyposmia. Otolaryngological examination using flexible nasal scope revealed bilateral grade 2 nasal polyps with mucinous content, consistent with AFRS. She was referred to ophthalmology, as her eye examination revealed a loss of light perception in the right eye, and extraocular muscle movement remained unrestricted. Her serum total IgE was 1,350 IU/mL, and skin prick test was positive for Aspergillus flavus and Curvularia lunata. Peripheral eosinophilia was 10.1%. MRI showed aggressive sinus disease in the ethmoid and sphenoid sinuses, with extensive mucosal thickening, erosion of the skull base, and extension into intra-orbital and intracranial regions, resulting in optic nerve compression (Figure 6). The patient underwent bilateral ESS to relieve optic nerve compression and clear the sinuses. Intraoperative findings revealed mud-like material within the sphenoid sinus, along with mucin mixed with mud-like material (Figure 7A,7B). A biopsy was obtained intraoperatively, microbiological analysis confirmed Aspergillus flavus, and histopathology of sinus tissue indicated severe acute and chronic rhinosinusitis and allergic inflammatory polyps with eosinophilic mucin-containing septate fungal hyphae and no signs of tissue invasion. These results were consistent with the typical radiologic picture of expansile sinus disease and bone remodeling reported on MRI. Given these findings, the diagnosis was confirmed as AFRS with right optic nerve compression. The patient was discharged with no complications. Six months after the procedure, the patient was presented to the clinic and was free of symptoms. All patients received topical intranasal mometasone furoate nasal spray (200 µg/day) twice a day and a short course of oral prednisolone (starting at 0.5 mg/kg/day, tapered over 4–6 weeks) with saline irrigation.

Figure 6 Preoperative MRI showing aggressive sinus disease in the ethmoid and sphenoid sinuses. ILA, inferior-left-anterior; LAS, left-anterior-uperior; MRI, magnetic resonance imaging; RPI, right-posterior-inferior; SRP, superior-right-posterior.

Figure 7 Intraoperative view of the sphenoid sinus in patient with AFRS. Intraoperative endonasal ESS showing (A) mud in sphenoid sinus and (B) mud mixed with mucin. AFRS, allergic fungal rhinosinusitis; ESS, endoscopic sinus surgery.

Ethical consideration

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Compared to chronic rhinosinusitis with nasal polyposis (CRSwNP), AFRS has a significantly higher likelihood of ocular manifestations due to the accumulation of eosinophilic mucin, sinus expansion, and localized bone remodeling (6,8,10,11). In AFRS, the severe eosinophilic inflammatory response and pressure effects from allergic mucin frequently cause thinning or erosion of the lamina papyracea, resulting in proptosis, diplopia, or vision loss (6,8,10). On the other hand, because mucosal inflammation frequently limited to the sinus cavity without significant bony remodeling or enlargement, CRSwNP have not often results in such orbital complications (12,13). Radiographically, AFRS is distinguished by heterogeneous sinus opacification, CT hyperattenuation, and sinus wall expansion, whereas CRSwNP is characterized by homogeneous soft tissue density and no bone erosion (11-13). Despite being non-invasive, our results demonstrate the more aggressive sinonasal behavior of AFRS and the necessity of early detection to avoid visual morbidity.

Ophthalmic manifestation in AFRS is considered to be uncommon with a prevalence that ranges from 18.3% and 34%. Ophthalmic presentations such as proptosis, epiphora, dystopia, ptosis, diplopia, and even visual loss in rare cases have all been reported to occur in AFRS patients (14,15). This study presents a diverse range of orbital complications secondary to AFRS, including several uncommon presentations, such as cavernous sinus thrombosis. By highlighting these varied clinical manifestations, the study aims to broaden the understanding of the potential severity and complexity of AFRS-related orbital involvement. Among the four cases that have been presented, three had reduced visual acuity, two had proptosis, ptosis in one case, and diplopia in another.

The mechanism behind those manifestations is the direct optic chiasm or optic nerve compression due to the bony remodelling and expansion of the sinus. It can lead to retrograde or anterograde degeneration, demyelination, ischemic injury, and blockage of the conduction which can result in nerve damage that can be permanent. Furthermore, another mechanism could be the fungal allergen immunological reaction which can lead to optic nerve inflammation and irritation (16). Other cranial neuropathies such as abducens neuropathy can also be seen due to its sphenoid sinus proximity and its medial location in the cavernous sinus (17). In our case series, chronic visual impairment in two of the cases is most likely attributed to the mass effect and optic nerve or optic chiasm compression. On the other hand, the diplopia of another case was attributed to the 6th nerve palsy.

Although it is very rare, there have been few documented reports, which are similar to one of our cases, of cavernous sinus thrombosis secondary to AFRS. It is hypothesized that secondary super bacterial infection or adjacent inflammation could be the cause of the involvement of the cavernous sinus. Restricted ocular movement, periorbital swelling, proptosis, and blurry vision can all be seen in such cases. Early recognition and surgical department and intravenous antibiotics are extremely important to prevent and decrease mortality and morbidity (18,19).

If a patient is suspected to have ophthalmoplegia or optic nerve compression, neuroimaging is indicated. Visual loss due to compressive optic neuropathy can be ruled out due to neuroimaging studies’ high specificity and sensitivity. In addition, depending on the findings of these imaging studies, cavernous sinus thrombosis or fistula can be considered. MRI can provide great resolution of visual pathology soft tissue; it is considered the modality of choice in such cases (14). Common MRI and CT scan findings are asymmetrical sinus opacification with bony expansion in addition to erosion which is frequently noted in patients with ophthalmic presentations. These findings were consistent with our four cases.

However, histopathological examination of the sinus content is the most reliable method to confirm the AFRS diagnosis. Hypertrophic mucosa with typical inflammatory infiltrates that contain lymphocytes, plasma cells, and eosinophils are consistent with AFRS, which were positive in our cases. Fungal cultures are crucial to confirm the diagnosis as it can yield variable organisms (20). Three of our cases were positive for Aspergillus species, which is the most common organism. On the other hand, the patient who had cavernous sinus thrombosis showed elements suggestive of mucormycosis in the pathology report.

Invasive fungal rhinosinusitis was significantly more associated with orbital involvement compared to non-invasive fungal rhinosinusitis (73.5% vs. 12.1%). Moreover, the most common type of fungal rhinosinusitis associated with orbital involvement was chronic granulomatous fungal rhinosinusitis, which was observed in 88.9% of these patients (21). This highlights the importance of differentiating between invasive and non-invasive fungal rhinosinusitis, as these two entities can both present with orbital involvement, but with different clinical implications. Recently, Rupa et al. [2013] identified a new entity known as mixed fungal rhinosinusitis, characterized by the concurrent occurrence of AFRS with invasive fungal rhinosinusitis (22). Notably, one of the reported cases in their study demonstrated orbital involvement, which is consistent with the presentation of the first case we reported, where the patient was diagnosed with mixed fungal rhinosinusitis.

The management of AFRS is focused on sinus decompression and relieving the pressure that occurs over the brain, orbit, or optic nerve. ESS debridement is considered to be the first line of management in addition to corticosteroids which also can help in reducing recurrence (15). All the cases underwent ESS. In addition, systemic antifungal should be considered in patients with positive mucor species (19).

The most essential factor that is related to better visual outcomes is visual impairment duration before any intervention. A study reported by Alhussien et al. found that the mean number of days of visual impairment to have complete recovery after surgical management is 33.1 days. In addition, sudden and partial visual loss was associated with better outcomes while progressive courses and complete visual loss were related to less favorable outcomes (16). Fortunately, all the patients in our case series have shown improvement after management. However, it is important to acknowledge the limitations in this study, such as the limited follow-up period and the retrospective nature of the study, which highlights the need for future long-term prospective studies in the future.

Although bone remodeling and thinning in AFRS have been extensively studied, this series adds value by reporting unusual orbital sequelae such as cavernous sinus thrombosis, isolated abducens nerve palsy, and a mixed fungal rhinosinusitis presentation. This emphasizes the clinical variability and diagnostic difficulty of AFRS, as well as the significance of integrating immunological, radiologic, and histopathologic confirmation for proper distinction from invasive fungal illness.

Conclusions

Preventing vision loss and other serious complications from AFRS requires early diagnosis, timely surgical intervention, and effective medical management. This case series highlights the importance of a multidisciplinary approach to AFRS management, demonstrating that successful outcomes are best achieved when multiple specialties collaborate. Moreover, maintaining a high index of suspicion for AFRS in patients presenting with sinonasal symptoms and ocular manifestations is crucial for ensuring early detection and appropriate treatment. However, larger future prospective studies with longer follow-up periods are needed to highlight the characteristics of these complications and their predispose factors.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-195/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-195/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-195/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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