Chronic Invasive Fungal Rhinosinusitis Managed With Surgical Debridement and Topical Amphotericin B Without Systemic Antifungal Therapy: A Report of Two Cases

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J Rhinol. 2026;33(1):45-50

Publication date (electronic) : 2026 March 31

doi : https://doi.org/10.18787/jr.2025.00051

Do Hun Kim, MD, PhD¹, Yanggyun Lee, MD¹, Bomi Kim, MD, PhD², Seong Kook Park, MD, PhD¹

¹Department of Otorhinolaryngology-Head and Neck Surgery, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea

²Department of Pathology, College of Medicine, Inje University, Haeundae Paik Hospital, Busan, Republic of Korea

Address for correspondence: Seong Kook Park, MD, PhD, Department of Otorhinolaryngology-Head and Neck Surgery, Inje University Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan 47392, Republic of Korea, Tel: +82-51-890-6375, Fax: +82-51-892-3831, E-mail: sinus4@paik.ac.kr

Received 2025 October 20; Revised 2025 December 24; Accepted 2026 February 19.

Abstract

INTRODUCTION

Invasive fungal rhinosinusitis typically develops in immunocompromised hosts. Initial manifestations may include cough, fever, ulcerative or necrotic lesions of the nasal mucosa, epistaxis, and headache. Predisposing conditions include hematologic malignancies such as leukemia, various causes of neutropenia, diabetes mellitus, iron overload states such as hemochromatosis, and severe malnutrition [1].

Histologically, invasive fungal rhinosinusitis is classified into three categories: acute fulminant, granulomatous, and chronic invasive [2]. Chronic invasive fungal rhinosinusitis (CIFR) differs from the other types by its protracted clinical course and the presence of compact collections of fungal hyphae that resemble a mycetoma. CIFR is most commonly observed in patients with diabetes mellitus, a history of corticosteroid exposure, or orbital apex involvement. This contrasts with acute invasive fungal rhinosinusitis (AIFRS), in which most patients are severely immunocompromised due to underlying immunosuppression or immunodeficiency [3]. Clinical manifestations of CIFR are often nonspecific and substantially overlap with those of other invasive forms, including nasal obstruction, facial pain, rhinorrhea, headache, and epistaxis. Although CIFR generally follows a slower course than AIFRS, untreated disease may eventually progress in a manner similar to the acute fulminant form, resulting in serious complications such as seizures, proptosis, impaired consciousness, and intracranial extension [4,5].

Standard therapy for CIFR involves extensive surgical debridement combined with systemic antifungal treatment, most commonly amphotericin B or voriconazole [6]. Surgical intervention aims to remove necrotic tissue and reduce fungal burden, whereas systemic antifungal agents are administered to eradicate residual invasive disease. Strict control of underlying metabolic conditions, particularly diabetes mellitus, is also a critical component of management [7,8]. In contrast to AIFRS, which often requires aggressive systemic therapy because of rapid progression and profound immunosuppression, the treatment strategy for CIFR may be influenced by disease extent, host immune status, and comorbidities.

However, systemic antifungal therapy may not always be feasible because of drug-related toxicity, impaired renal function, or socioeconomic constraints. In such circumstances, alternative or adjunctive strategies may be considered, particularly when the disease is confined to the sinonasal cavity and complete surgical debridement is achievable. Previous reports have described the local application of topical amphotericin B to the sinonasal cavity as an adjunct to endoscopic debridement, typically in combination with systemic antifungal therapy [9]. However, data regarding outcomes without concomitant systemic antifungal agents remain extremely limited.

Herein, we report two patients with diabetes mellitus who had CIFR confined to the sinonasal cavity and were managed with endoscopic surgical debridement and adjunctive topical amphotericin B application, without systemic antifungal therapy because of patient-specific constraints. These cases highlight the potential role and limitations of a surgery-centered strategy in carefully selected patients and underscore the importance of meticulous postoperative care and strict glycemic control.

CASE REPORT

Case 1

A 76-year-old man with diabetes mellitus presented to the emergency department with a 4-day history of left orbital swelling, left facial swelling, left-sided ptosis, and facial tenderness (Fig. 1A and B). Diabetes mellitus had been diagnosed shortly before presentation, but had not yet been treated. Endoscopic examination revealed crust formation in the left nasal cavity.

Fig. 1

Clinical, radiologic, and histopathologic findings of left-sided invasive fungal sinusitis. A and B: Clinical photographs at presentation showing left-sided ptosis and facial swelling. C and D: Axial paranasal sinus computed tomography (CT) images demonstrating fat infiltration into the extraconal space and soft tissue swelling in the left periorbital region. E and F: Coronal CT images showing chronic ethmoidal and maxillary sinusitis on the left side. G: Fungal hyphae with irregular thickness, non-septation, and right-angle branching within necrotic material (hematoxylin and eosin stain, ×400).

Baseline laboratory studies demonstrated markedly uncontrolled diabetes and a severe inflammatory response: hemoglobin A1c (HbA1c) was 12.5%, white blood cell count was 25.32×10³/μL, and C-reactive protein was 11.35 mg/dL. Renal function was preserved, with a serum creatinine level of 0.62 mg/dL and an estimated glomerular filtration rate (eGFR) of 98.4 mL/min/1.73 m². The patient was not receiving dialysis.

Contrast-enhanced paranasal sinus computed tomography (CT) demonstrated fat extension into the extraconal space and left-sided periorbital soft tissue swelling (Fig. 1C and D), along with chronic ethmoidal and maxillary sinusitis (Fig. 1E and F). Based on these findings, fungal rhinosinusitis was suspected in an immunocompromised host. Magnetic resonance imaging (MRI) was not performed because of the urgent clinical presentation requiring immediate surgical intervention. Therefore, left middle meatal antrostomy, curettage of the maxillary sinus mucosa, ethmoidectomy, and partial middle turbinectomy were performed under general anesthesia. Hemostatic packing was placed intraoperatively and removed on postoperative day 2. Subsequently, 2×7 cm gauze soaked in amphotericin B solution was placed within the nasal cavity for 24 hours. After removal of the packing, crust and necrotic tissue were debrided. This process was repeated for 5 days. Ten days after surgery, pathology confirmed findings compatible with invasive mucormycosis (Fig. 1G). Based on clinical, radiologic, and intraoperative findings, the patient was diagnosed with invasive mucormycosis.

After surgery, systemic antifungal therapy was recommended. However, the patient declined systemic treatment primarily because of financial concerns rather than medical contraindications. Therefore, repeated local debridement and topical amphotericin B application were performed without systemic antifungal therapy. The patient was instructed to perform saline nasal irrigation twice daily. Glycemic control was optimized in consultation with endocrinology. At discharge, inflammatory markers had improved: white blood cell count 11.39×10³/μL and C-reactive protein 3.57 mg/dL. In the outpatient department (OPD), touch-up debridement was performed for 3 weeks postoperatively. After this period, no additional crust or debris was observed. During 5 years of follow-up, residual left-sided proptosis persisted without progression. The patient remained asymptomatic, with no abnormal findings on physical examination or nasal endoscopy; therefore, follow-up MRI was not performed. Five months after surgery, HbA1c had improved to 6.8%. In the absence of radiologic confirmation of complete resolution, the disease course was interpreted as persistent but stable rather than complete remission.

Case 2

A 53-year-old man with diabetes mellitus presented to the OPD with a 3-day history of left orbital swelling, left-sided proptosis, and left facial swelling. He had a 7-year history of diabetes mellitus and hypertension, both managed at a local clinic. Endoscopic examination revealed crusting in the left middle meatus (Fig. 2A).

Fig. 2

Endoscopic findings before and after treatment of left-sided invasive fungal rhinosinusitis. A: An endoscopic examination showed crust on the left middle meatus. B: Postoperative endoscopic findings showed no recurrence of invasive fungal rhinosinusitis after 2.5 years. SS, sphenoid sinus opening; PE, posterior ethmoid sinus.

Baseline laboratory evaluation demonstrated markedly uncontrolled diabetes and active systemic inflammation: HbA1c was 12.6%, white blood cell count was 15.68×10³/μL, and C-reactive protein was 13.31 mg/dL. Renal function was moderately impaired, with a serum creatinine level of 1.54 mg/dL and an eGFR of 50.8 mL/min/1.73 m². The patient was not receiving dialysis.

Contrast-enhanced paranasal sinus CT demonstrated chronic ethmoidal and maxillary sinusitis on the left side, accompanied by diffuse soft tissue edema of the left facial region. Importantly, no radiologic evidence of intracranial involvement was observed. MRI was not performed because the clinical presentation required urgent surgical intervention. Accordingly, left middle meatal antrostomy, ethmoidectomy, frontal sinusotomy, partial middle turbinectomy, and debridement of necrotic debris were performed under general anesthesia. Hemostatic packing was removed on postoperative day 2, after which 2×7 cm gauze soaked in amphotericin B solution was placed within the nasal cavity for 24 hours. Following removal of the packing, crust and necrotic tissue were debrided. This procedure was repeated for 6 consecutive days.

Four days after surgery, histopathologic examination confirmed findings compatible with invasive mucormycosis. Based on the clinical presentation, radiologic findings, and intraoperative evidence of tissue necrosis, the patient was diagnosed with invasive mucormycosis. Systemic antifungal therapy was not administered because of impaired renal function and financial constraints. The patient was instructed to perform twice-daily saline nasal irrigation. Glycemic control was optimized in consultation with endocrinology. At discharge, inflammatory markers had normalized: white blood cell count 8.59×10³/μL and C-reactive protein 1.84 mg/dL. In the OPD, touch-up debridement was performed for 4 weeks postoperatively. During follow-up, residual proptosis persisted but did not progress. The patient remained asymptomatic, with normal physical examination and endoscopic findings; therefore, follow-up MRI was not performed (Fig. 2B). Two months after surgery, HbA1c had improved to 6.1%. In the absence of radiologic confirmation, the disease course was interpreted as persistent but stable rather than complete remission.

DISCUSSION

The diagnostic criteria for invasive fungal rhinosinusitis include radiologic findings suggestive of sinusitis—such as air–fluid levels or mucosal thickening—together with histopathologic demonstration of fungal hyphae within the mucosa, submucosa, or bone, accompanied by granulomatous inflammation that may include multinucleated giant cells [2].

CIFR represents a chronic, slowly progressive fungal infection that typically evokes only mild inflammatory responses and most commonly occurs in patients with diabetes mellitus [3]. When the disease extends from the ethmoid sinus to the orbit, orbital apex syndrome may develop [10]. This complication results from fungal invasion of the orbital apex and may lead to vision loss, ophthalmoplegia, and proptosis [3]. In the present cases, both patients had diabetes mellitus and exhibited typical symptoms, including orbital swelling, proptosis, facial swelling, and necrotic debris within the nasal cavity.

CT or MRI findings are often nonspecific, which can delay the diagnosis of CIFR. In our cases, gradual symptom progression combined with destructive changes observed during endoscopic examination heightened clinical suspicion and facilitated timely surgical intervention [6]. Management generally includes correction of underlying immunosuppression, surgical debridement, and antifungal therapy [7].

In patients with diabetes mellitus, strict glycemic control is essential [8]. Careful regulation of blood glucose and stabilization of glycemic fluctuations are particularly important in cases of invasive fungal rhinosinusitis associated with diabetic ketoacidosis [7].

Surgical debridement remains the cornerstone of treatment for invasive fungal rhinosinusitis. All necrotic or devitalized tissue within the paranasal sinuses and nasal cavity should be removed, with resection continued until viable, bleeding tissue is encountered [7].

Selection of antifungal agents depends on infection severity and patient comorbidities [7]. Amphotericin B and voriconazole are the most commonly used agents [6]. However, amphotericin B is limited by potential toxicity, including acute infusion-related reactions (fever, chills, or anaphylaxis) and chronic nephrotoxicity manifested by rising creatinine levels. Voriconazole therapy may also be limited by cost.

In the present cases, systemic antifungal therapy was not administered because of patient-specific factors, including concerns regarding renal function and financial constraints. Additionally, disease was confined to the nasal cavity and adjacent ipsilateral maxillary and ethmoid sinuses, allowing extensive surgical debridement. Postoperatively, glycemic control was successfully achieved in both patients. The favorable clinical course was most likely attributable to early and thorough surgical debridement in the setting of localized disease and strict postoperative glycemic control; however, the independent contribution of topical amphotericin B remains uncertain [7,9]. Topical amphotericin B was applied to reduce local fungal burden, and repeated debridement facilitated removal of residual necrotic tissue during periods of improved glycemic control [9]. Previous reports have described topical amphotericin B administered using cottonoids or pledgets placed within the nasal cavity for short-duration, repeated applications over several consecutive days as an adjunct to surgical debridement [9]. After discharge, both patients performed twice-daily saline irrigation, and necrotic debris was periodically removed during OPD visits.

Persistent unilateral proptosis observed during follow-up in both patients warrants specific consideration. Orbital involvement is a recognized manifestation of CIFR, and several case series have reported frequent ocular symptoms and radiologic extension to the orbital apex or adjacent neurovascular structures in advanced disease [11]. Importantly, orbital deficits may persist despite appropriate treatment. Previous studies of CIFR have shown that visual dysfunction and other ocular manifestations often demonstrate limited recovery even after surgical debridement and antifungal therapy [11]. Similar findings have been described in AIFRS, in which visual loss, ophthalmoplegia, and orbital apex syndrome may be irreversible, particularly in advanced orbital disease [5,12]. Large reviews indicate that standard management of invasive fungal rhinosinusitis consists of extensive surgical debridement combined with systemic antifungal therapy, most commonly amphotericin B and/or voriconazole [13]. However, direct evidence that prolonged systemic antifungal therapy reliably prevents persistent proptosis after orbital involvement is lacking [13]. Accordingly, persistent but non-progressive proptosis in our patients, in the absence of worsening endoscopic findings or systemic deterioration, was interpreted as stable residual disease rather than treatment failure. Nevertheless, careful long-term surveillance with endoscopic examination—and consideration of radiologic follow-up—is essential. Systemic antifungal therapy should be reconsidered if clinical or endoscopic progression is observed.

Although histopathologic examination demonstrated fungal hyphae consistent with mucormycosis, definitive angioinvasion or fungal infiltration within viable tissue was not clearly identified in the available specimens. This limitation may reflect the nature of incisional biopsies obtained predominantly from necrotic tissue in routine clinical practice and should be considered when interpreting “invasiveness” in the present cases.

Systemic antifungal therapy remains necessary when infection extends beyond the sinonasal cavity, when complete surgical debridement is not feasible, or when postoperative glycemic control cannot be achieved. Therefore, when CIFR is managed without systemic antifungal agents, careful and prolonged follow-up is required until complete remucosalization is achieved, crusting has resolved, and bony sequestration has subsided [14].

Endoscopic surgical debridement combined with topical amphotericin B, without systemic antifungal therapy, may represent a reasonable management strategy for carefully selected patients with localized CIFR and well-controlled diabetes mellitus when complete surgical debridement is achievable. In previous reports, topical amphotericin B has been used as an adjunct to endoscopic debridement, typically in combination with systemic therapy rather than as a substitute [9]. In contrast, systemic therapy could not be administered in our cases because of patient-specific constraints; therefore, outcomes were interpreted as persistent but stable disease rather than complete remission in the absence of radiologic follow-up. Systemic antifungal therapy should be initiated promptly if glycemic control deteriorates or local findings suggest disease progression. Persistent proptosis in both patients may reflect residual fibrosis, chronic inflammatory changes, extraocular muscle involvement, or irreversible orbital remodeling rather than ongoing active infection, particularly in slowly progressive CIFR.

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