Abstract
Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic noninvasive sinusitis accounting for 7.8% (0.2%-26.7%) of all chronic rhinosinusitis cases. A definitive diagnosis is usually made after sinus surgery. Successful treatment requires a combination of surgical and medical management. Although orbital involvement is relatively common, reports on optic neuropathy and acute vision loss are limited. Herein, we present a series of 3 patients with AFRS who presented with acute visual loss as the chief complaint. All 3 patients were otherwise healthy adults in their early 20s with extensive nasal polyps on endoscopic nasal examination and bone erosion in the bilateral orbits and lateral wall of the sphenoid sinus on the affected side on imaging. One of the 3 patients had bilateral cranial nerve IV defects in addition to cranial nerve III defects. All patients underwent endoscopic sinus surgery with orbital decompression and were followed up postoperatively by both otolaryngology and ophthalmology services with endoscopic and radiologic evaluation. Unfortunately, no meaningful improvement in vision was observed in any patient despite successful nerve decompression. Prompt diagnosis and early medical and surgical intervention are warranted to prevent complications in patients with AFRS with orbital extension.
Introduction
Allergic fungal rhinosinusitis (AFRS) is a distinctive subtype of noninvasive chronic sinusitis that results from a localized allergic response to noninvasive fungal growth.1,2 The pathophysiology of AFRS is consistent with chronic, intense T-helper type 2 allergic inflammation due to fungal colonization. The sinuses are filled with thick, inspissated mucus with numerous degranulating eosinophils. 3 T-helper type 2-derived cytokines, interleukin-5 and interleukin-13, are involved in local eosinophilic accumulation and attack the fungal hyphae in the mucus. 4 The most common fungi reported to cause AFRS are Bipolaris, Curvularia, Aspergillus, Exserohilum, and Drechslera species, with a wide variety of other fungi reported in the literature.5,6
A global examination of 35 cities distributed across 5 continents was conducted. The resultant average global prevalence of AFRS in chronic rhinosinusitis (CRS) cases was found to be 7.8%, with a range of 0.2% to 26.7%. Of these cities, 57% displayed a low prevalence of AFRS, while the remainder exhibited intermediate (11%) and high (32%) prevalence. 7 This disease primarily affects young immunocompetent atopic patients. 8
The symptoms of AFRS are comparable to those of CRS with nasal polyposis, since all patients with AFRS have nasal polyposis. Patients with early disease may present with nasal congestion or obstruction, anosmia, and/or postnasal drip. Further, patients may report semisolid nasal crusts or rubbery, dark-colored mucus that are periodically expelled from the nose. 9 Microscopically, clusters of eosinophils, Charcot-Leyden crystals, and rare fungal hyphae are observed. Some patients present with myriad symptoms, including anosmia, rhinorrhea, and/or cough. However, none of these are specific to AFRS. Occasionally, AFRS presents with complete nasal obstruction, gross facial asymmetry, and/or visual changes.10,11
Moderate and severe AFRS can lead to bony expansion and erosion, with extension to extra-sinus regions, such as the orbit, skin, and brain. This occurs more frequently in patients with AFRS than in those with other forms of CRS. The following signs and symptoms may develop because of bony expansion or erosion: double or impaired vision, proptosis, periorbital edema, ophthalmoplegia, facial dysmorphia, focal neurological signs, severe headache, meningeal signs, and significant or recurrent epistaxis.5,12,13 Urgent referral to an otolaryngologist or head and neck surgeon is indicated even if these signs and symptoms develop gradually.
The evaluation of AFRS is similar to that of CRS. Diagnosis involves clinical history, allergy evaluation, imaging studies such as computed tomography (CT) and magnetic resonance imaging (MRI), and consideration of immune suppression and infectious complications that warrant further investigation. Histological evidence of eosinophilic mucin is generally obtained at the time of surgery and is required for diagnosis.
Diagnosing AFRS is complex due to symptom similarities with other conditions. Differential diagnoses for AFRS can include Allergic Rhinitis, CRS, Fungus ball, Acute or Chronic invasive fungal sinusitis, and Eosinophilic mucin rhinosinusitis, presenting a significant challenge for accurate identification. In the pursuit of diagnostic precision, Bent and Kuhn
14
put forth a diagnostic schema for AFRS in 1993, derived from an exhaustive analysis of 15 patient cases. The diagnostic quintet they proposed encapsulates:
The exhibition of Type I hypersensitivity responses to fungal constituents. The identification of distinct hyperattenuation regions in CT scans. The detection of eosinophilic mucin, a salient clinical attribute. The emergence of nasal polyps, a frequent symptomatic manifestation in AFRS patients. The discovery of noninvasive fungal organisms within the sinus mucin.
This set of criteria has been profoundly consequential in the clinical detection and comprehension of AFRS since its inception.
The orbit can be involved in sinonasal diseases owing to its close proximity. 15 However, in AFRS, the sinus cavities uniquely expand because of pressure build-up; particularly, the ethmoid air cells tend to expand in all directions until they come into contact with compact bone. The posterior ethmoid and sphenoid cells are of utmost importance because of their proximity to the optic nerve. The optic canal wall separating the optic nerve from the sinus cavity measures about 1 mm. 16 Expansion of these cells may cause nerve injury because of direct pressure. 15
Rarely, AFRS may extend beyond the sinuses and compress the optic and abducens nerves. The process is extradural via bony erosion, inducing damage by compression but not invasion, leading to proptosis, diplopia, visual disturbances, and hypertelorism. 17
Treatment of AFRS also comes with its own set of challenges. While most patients with AFRS have favorable outcomes without the use of antifungal medications if corticosteroids and surgical debridement of the affected sinuses are promptly initiated,18–21 there are cases where these measures may not be sufficient. Invasive fungal rhinosinusitis differs from AFRS in that the fungi invade blood vessels through the paranasal sinus mucosa, bone, and dura, leading to thrombosis and infarction.8,22,23 Invasive fungal rhinosinusitis typically affects immunocompromised patients and requires aggressive surgery to remove the affected tissue and parenteral antifungal medication. However, aggressive treatments may be insufficient to prevent blindness, stroke, or death. Herein, we present a series of 3 patients with AFRS with persistent visual loss despite adequate surgical intervention and medical treatment.
Case Series
Case 1
A 21-year-old woman with no relevant medical history presented to the otolaryngology clinic at King Faisal Specialist Hospital with nasal obstruction, nasal discharge, and hyposmia. Endoscopy revealed bilateral nasal polyps, and nonenhanced CT revealed extensive sinonasal polyposis with expansion of the sphenoid and ethmoid sinuses with bone thinning (Figure 1). The patient did not report for a scheduled endoscopic sinus surgery (ESS) and was lost to follow-up. Two months later, she experienced sudden right-sided vision loss and severe right ocular pain. Her vision deteriorated over the course of 3 days, and she took aspirin for the severe pain. Endoscopic evaluation revealed disease progression, and the patient was referred to the neuro-ophthalmology department.
Preoperative coronal computed tomography images showing characteristic expansile changes in the paranasal sinuses with extensive bone remodeling and erosion of the bone of the lamina papyracea, fovea ethmoidalis, and lateral wall of the sphenoid sinus.
Upon assessment, the right eye showed a nonreactive pupil and loss of light perception. All laboratory investigations were normal except for leukocytosis. Further, nonenhanced CT revealed enlarged and inflamed ethmoid and sphenoid sinuses compressing the optic nerve, mainly in the region of the optic canal (Figure 1).
Systemic steroids were started preoperatively and continued for a short period after surgery (40 mg of oral prednisone tapered over the course of 2 weeks). The patient underwent urgent ESS with orbital decompression. Dehiscence of the bone overlying the right optic nerve within the sphenoid sinus was observed, likely due to pressure caused by the nasal polyps. The acute vision loss could be related to nerve infarction due to compression of the blood supply. The surgical intervention was terminated after completing the right ESS and orbital decompression. Histopathological findings revealed allergic fungal sinusitis caused by Aspergillus species. However, the biopsy samples did not demonstrate any evidence of fungal invasion within the examined areas.
Postoperatively, a nonenhanced CT scan was done (Figure 2). No improvement in vision was observed throughout the follow-up period of >12 months.
Coronal computed tomography images after right-sided endoscopic sinus surgery.
Case 2
A 20-year-old man with no known medical history, presented to the emergency room at King Abdulaziz University Hospital with a 3-day history of progressively worsening left-sided blurry vision. There was an associated headache that started a week prior but increased in severity over 3 days.
Clinical examination revealed visually perceptible hand motion in the left eye, and the visual acuity in the right eye was 20/20. A relative afferent pupillary defect was observed on the left side with reduced color vision. Intraocular pressure and extraocular movement were within normal limits bilaterally. Neuroophthalmic assessment revealed left optic neuropathy with unremarkable bilateral lids, conjunctivae, sclerae, cornea, iris, lens, and retina. Other cranial nerves were unaffected.
All laboratory analyses yielded within-normal-range results, with the sole exception of an elevated leukocyte count. A nonenhanced CT (Figure 3A) revealed an expansile heterogeneous sphenoid opacity with bowing of the lateral wall of the sphenoid sinus. The lesion mainly involved the left posterior ethmoid air cells and the posterior part of the nasal cavity. Associated erosion of the left lateral wall of the sphenoid sinus extending to the ipsilateral anterior clinoid process was observed with mucosal thickening of the left maxillary and frontal sinuses and an intact lamina papyracea.
(A), Coronal computed tomography image. (B) Coronal gadolinium-enhanced magnetic resonance image.
Gadolinium-enhanced MRI of the orbit (Figure 3B) demonstrated findings suggestive of sphenoethmoidal allergic fungal sinusitis causing compression of the anterior intracranial and posterior canalicular segments of the left optic nerve, with no evidence of demyelinating disease or optic neuritis.
Clinical and radiological findings suggested that allergic fungal ethmoid sinusitis was the most likely diagnosis. Thus, emergency image-guided left ESS was performed. Intraoperatively, the left internal carotid artery and left optic nerve were exposed after removal of large amounts of fungal mucin.
Postoperatively, the patient was administered a brief course of systemic antibiotics, comprising of clindamycin 300 mg orally 4 times daily for 14 days, in addition to ciprofloxacin 500 mg orally twice daily for the same duration. Furthermore, the patient was prescribed prednisolone orally in a dose-tapering regimen of 40 mg, 20 mg, and 10 mg for the initial 7 days, subsequent 7 days, and final 7 days, respectively. Additionally, the patient was advised to use budesonide 0.5/2 mL via inhalation twice daily for 12 weeks, mixed with 250 mL of normal saline 0.9%, in conjunction with sodium chloride irrigation (60 mL thrice daily for 30 days). The patient's postoperative course was uneventful, and his headache subsided; however, no improvement in visual acuity in the left eye was observed. Postoperative nonenhanced CT was performed (Figure 4).
Postoperative coronal computed tomography image showing expansion of sphenoid sinus with destruction in the superior wall extending into the optic canal.
At the one-week follow-up, all culture results were negative. The histopathologic evaluation of the biopsy samples did not demonstrate any signs of fungal invasion within the affected regions.
Furthermore, a nonenhanced CT scan demonstrated mild mucosal thickening at the surgical bed with no evidence of residual disease or other abnormalities. The patient was subsequently lost to follow-up, and after one year had elapsed, the patient presented to the clinic with no discernible improvement in visual acuity.
Case 3
A 23-year-old woman presented to the otolaryngology clinic at King Faisal Specialist Hospital with a history of AFRS involving the right ethmoid and maxillary sinuses with intracranial and orbital extension, and right-sided vision loss at the age of 6 years underwent surgical debridement via a right lateral rhinotomy approach, with right lateral canthotomy followed by prolonged systemic antifungal therapy. Although histopathological examination results were not available, there was no indication of invasive fungal sinusitis, as the patient had always been immunocompetent.
The patient reported no sinonasal symptoms until one-week prior to her presentation to the Emergency Department, when she had left-sided visual loss, proptosis, and rhinorrhea. Clinical examination revealed bilateral grade IV nasal polyps and proptosis with only light perception in the left eye.
Ophthalmic assessment revealed a clear conjunctiva and cornea, with a deep and quiet anterior chamber and a clear lens, iris, and fundus. However, bilateral optic nerve atrophy was observed.
With the exception of leukocytosis, all laboratory tests returned normal results. The nonenhanced CT of the paranasal sinuses (Figures 5 and 6) revealed multiple areas of bony remodeling, thinning, and dehiscence along the sinonasal bony wall, including the posterior table of the frontal sinus and the roof and lateral wall of the ethmoid sinus. The patient underwent urgent ESS with optic nerve decompression. Intraoperatively, bilateral grade IV polyps with left medial canthal destruction, left lamina papyracea dehiscence, and an intact periorbit were observed. In addition, skull base dehiscence with an intact underlying dura, left inferior turbinate fracture and dislocation, and thinning of the medial maxillary wall were observed. The patient underwent medial maxillectomy, inferior turbinectomy, and total ethmoidectomy and received systemic steroid therapy postoperatively for 2 weeks (40 mg of oral prednisone tapered over 2 weeks). Histopathological findings revealed allergic fungal sinusitis, and fungal culture confirmed the presence of Aspergillus niger. However, the histopathological evaluation of the biopsy samples did not provide any indications of fungal invasion within the examined areas.
Preoperative nonenhanced coronal computed tomography images showing extensive remolding of the bony walls of the sphenoid sinus along with the lamina papyracea and the roof of the ethmoid sinus.
Axial computed tomography images.
Two weeks postoperatively, clinical examination revealed minimal visual improvement to counting fingers. Ophthalmological evaluation revealed bilateral optic nerve atrophy, with light perception only on the left side. No further improvement was observed during the 4-month follow-up.
Discussion
This study involved 3 patients with AFRS, a condition often muddled with similar disorders, our study navigated the diagnostic path etched by Bent and Kuhn. 14 Their quintessential criteria for AFRS identification encompass Type I hypersensitivity to fungal components, identifying specific CT scan hyperattenuation, detecting the presence of eosinophilic mucin, observing the formation of nasal polyp, and noninvasive fungal detection in sinus mucin. Despite the diagnostic criteria. The findings were sobering, with devastating outcomes such as irreversible optic neuropathy in 2 cases and limited improvement in the third. The optic nerve contains retinal ganglion cell axons that extend from the globe and move posteriorly through the orbit and optic canal until they reach the optic chiasm. Compressive optic neuropathy occurs when an extrinsic lesion develops along this pathway. The optic nerve is most vulnerable to injuries involving the adjacent bones or confined spaces, such as the orbital apex or optic canal. In all 3 cases, the mechanism is believed to be compression by the sphenoid and ethmoid air cells, which has been well documented in previous studies.13,18,19,24–27 This leads to ganglion cell axonal atrophy through either ischemia or mechanical disruption of axonal transport. 28 The clinical hallmark of compressive optic neuropathy is progressive vision loss. In our patients, visual loss was acute, which could be explained by acute infarction of the optic nerve, possibly due to compression of its blood supply. A delay in diagnosis is not uncommon because vision loss is insidious in onset, and clinical findings may be missed. Early diagnosis can be difficult, and difficulties in accessing specialized healthcare can further delay diagnosis and management. 8
Neuroimaging studies are warranted in patients with clinically suspected compressive optic neuropathy or ophthalmoplegia. Because of the sensitivity and specificity of modern neuroimaging, a negative scan essentially rules out compression as the cause of vision loss, and cavernous sinus thrombosis or a cavernous sinus fistula is considered based on the findings. Magnetic resonance imaging is the imaging modality of choice because it provides excellent soft-tissue resolution for the anterior visual pathway and parasellar region. For sinus abnormalities, enhanced CT is considered more appropriate. 13 However, histopathological examination is the most reliable method of diagnosis. 29
Management of compressive optic neuropathy is somewhat difficult given the proximity of compressive lesions to critical neurovascular structures in the orbit and intracranial space. However, managing AFRS is important to relieve pressure on vital structures, including the optic nerve. Extensive debridement with ESS is the first-line treatment and was performed in our cases followed by a course of high-dose corticosteroids and follow-up ophthalmic assessments. Notably, we didn’t administer antifungal treatments in these cases.
Patients diagnosed with AFRS tend to have a history of allergic rhinitis and/or atopy. Thick tenacious and viscous fungal debris and mucin are characteristic features of this condition, with allergic mucin being a pathognomonic finding. Often, the mucin color ranges from brown to dark green. 30
Visual improvement has been reported when surgery was performed within 30 days of vision loss. 19 The duration of visual impairment before intervention is a significant determinant of favorable visual outcomes, with delayed response decreasing the likelihood of vision restoration. This assertion aligns with a study showing a notable difference (P value = .038) among patients with full, partial, and no visual recovery based on the mean duration between the onset of visual impairment and the intervention. 31 Unfortunately, in our case series, no meaningful improvement in visual acuity was observed in all 3 patients, although surgery was performed less than one month after diagnosing vision loss.18,24–26 Moreover, the COVID-19 pandemic has complicated timely AFRS diagnosis and management, exacerbating disease progression and resultant complications at presentation. 32
In this context, it's noteworthy that our case series consisted solely of adult patients. Interestingly, the literature suggests that orbital involvement, is less common among adults compared to children. This accentuates the presence of age-dependent differences in AFRS presentations, despite the limited number of comparative studies. A specific study reported higher orbital involvement in children (68%) than adults (33%), greater intracranial disease extension in the pediatric population, slightly more bone erosion in children (25%) compared to adults (23%), and a higher proptosis incidence in the pediatric group (22% vs 9%). 33 This could be attributed to the enhanced flexibility of children's facial skeletons, predisposing them to disease expansion. This observation underlines the necessity of further research to decipher the underlying mechanisms and potential implications for treatment strategies across different age groups.
This AFRS case series underscores the critical role of established diagnostic criteria and neuroimaging in identifying cases, especially with vision loss. It reaffirms the importance of comprehensive surgical and medical intervention, despite the complexities presented by lesion locations. The series also highlights the potential severity of AFRS outcomes, emphasizing the need for early intervention to increase chances of visual recovery. Overall, it stresses the necessity for continued research to enhance our understanding and treatment strategies for AFRS, particularly in severe manifestations.
Conclusion
Allergic fungal rhinosinusitis is a serious disease with devastating consequences. Considering that the orbit is frequently involved due to its close proximity to the sinuses, patients may present with visual changes or even blindness. Thus, urgent multidisciplinary management is required, as any diagnostic delay may result in irreversible damage. Therefore, prompt surgical intervention is recommended to improve the prognosis and visual outcomes.
