Allergic fungal sinusitis (AFS) is a representative noninvasive subtype of chronic rhinosinusitis associated with nasal polyps. In 1994, Bent and Kuhn [1] proposed diagnostic criteria for AFS requiring the presence of five features: 1) type I hypersensitivity to fungi, 2) multiple nasal polyps, 3) characteristic computed tomography (CT) findings, 4) allergic mucin, and 5) fungal hyphae within the mucin.

However, in clinical practice, a subset of patients presents with typical clinical and radiological features of AFS but does not meet all diagnostic criteria. Cody et al. [2] described these cases as AFS-like syndrome. This category includes patients with evidence of type I hypersensitivity without detectable fungal hyphae, as well as those with confirmed fungal hyphae in the absence of demonstrable type I hypersensitivity.

AFS accounts for approximately 6%–9% of patients undergoing surgery for chronic rhinosinusitis [3]. Although the Bent and Kuhn [1] criteria have long been regarded as the diagnostic standard, atypical presentations continue to be reported. In this report, we present a case of AFS-like syndrome and examine its clinical and immunological characteristics within the framework of the “united airway disease” concept, which considers the upper and lower airways as a continuous system.

A 33-year-old woman presented to the otorhinolaryngology clinic with a 1-year history of persistent left-sided nasal obstruction. She had no history of bronchial asthma, relevant occupational exposure, or notable family history. To evaluate potential lower airway involvement, she was referred to the Department of Allergy, where no clinical evidence of asthma was identified. Nasal endoscopy revealed a deviated nasal septum and multiple polyps within the left nasal cavity (Fig. 1).

Paranasal sinus (PNS) CT demonstrated heterogeneous opacification involving the left nasal cavity, ethmoid sinus, and sphenoid sinus, with indistinct bony margins of the middle turbinate. High-density lesions were observed extending from the ethmoid to the sphenoid sinus (Fig. 2).

PNS magnetic resonance imaging (MRI) revealed low signal intensity within the lesion on T1-weighted images without enhancement, whereas the surrounding mucosa demonstrated contrast enhancement (Fig. 3A). T2-weighted images showed predominantly low signal intensity corresponding to the high-density regions observed on CT (Fig. 3B). Proton density sampling perfection with application-optimized contrasts using different flip angle evolutions coronal MRI similarly demonstrated low signal intensity within the ethmoid sinus, consistent with the T2-weighted findings (Fig. 3C).

Serological evaluation demonstrated an elevated total immunoglobulin E (IgE) level of 1,142 IU/mL. Skin prick testing showed positive reactions (2+ to 3+) to several tree pollen allergens and dust mites; however, reactions to six fungal species (Alternaria, Aspergillus fumigatus, Cladosporium, Candida albicans, Mucor, and Aspergillus niger) were negative.

Based on a presumptive diagnosis of AFS-like syndrome, the patient underwent functional endoscopic sinus surgery. Intraoperatively, multiple polyps and partial bony defects were identified, along with a crystalloid mass containing thick, brown “peanut butter–like” mucin and suspected fungal ball–like material within the ethmoid and sphenoid sinuses. These materials were removed via suction for histopathological examination, and the procedure was completed following thorough irrigation (Fig. 4).

Histopathological examination demonstrated eosinophilic infiltration accompanied by lymphocytes and plasma cells. Grocott methenamine silver staining confirmed the presence of sparse fungal hyphae without evidence of tissue or vascular invasion (Fig. 5).

Postoperatively, the patient received a 2-week tapering course of oral prednisolone (40 mg/day for 4 days, 30 mg/day for 3 days, 20 mg/day for 4 days, and 10 mg/day for 3 days). At 1-, 2-, and 4-month follow-up visits, the surgical site had healed appropriately, with no evidence of recurrence (Fig. 6).

This patient was diagnosed with AFS-like syndrome because she fulfilled four of the Bent and Kuhn [1] criteria—nasal polyps, characteristic CT findings, allergic mucin, and the presence of fungal hyphae—but did not demonstrate type I hypersensitivity to fungal antigens based on the available allergy testing panel. Specifically, the skin prick test included only six common fungal species, and additional diagnostic modalities, such as serum-specific IgE assays (e.g., multiple allergosorbent test or ImmunoCAP), were not performed. A limitation of this case report is that sensitization to a broader range of fungal antigens cannot be definitively excluded.

AFS-like syndrome, first described by Cody et al. [2] in 1994, encompasses cases that closely resemble AFS clinically but either lack demonstrable fungal hypersensitivity or, conversely, exhibit hypersensitivity in the absence of detectable fungal hyphae within the mucin.

Accurate diagnosis requires differentiation from other noninvasive fungal conditions. This case can be distinguished from a fungal ball, which typically represents a localized fungal accumulation without a significant host inflammatory response, by the presence of characteristic allergic mucin and marked eosinophilic infiltration. It is also distinct from eosinophilic mucin rhinosinusitis, which shares a similar mucin profile but, by definition, lacks fungal hyphae; the histological identification of fungal hyphae in this case supports classification within the AFS spectrum [4,5].

This case underscores the limitations of current diagnostic frameworks. The negative skin prick test despite histological evidence of fungal hyphae suggests that the antigen panel may have been insufficiently broad or that immunological mechanisms beyond type I hypersensitivity may contribute to disease pathogenesis.

In patients with atypical features, clinicians should consider whether upper airway lesions represent a localized process or part of a systemic immune response. Because fungal hypersensitivity can involve both the upper and lower airways, the possible coexistence of allergic bronchopulmonary aspergillosis (ABPA) was considered from the outset. The patient had no history of asthma and reported no lower respiratory symptoms, such as cough or dyspnea. Chest radiography showed no bronchiectasis or pulmonary lesions suggestive of ABPA. She was also referred to the Department of Allergy to further exclude underlying asthma. Based on these clinical and radiological findings, ABPA was excluded.

Both AFS and ABPA are IgE-mediated allergic responses to fungal antigens,[3,6] and both are characterized by eosinophilic mucin and Charcot-Leyden crystals without tissue invasion [7]. Immunopathologically, both conditions involve a T helper 2 (Th2)-driven hypersensitivity response in which fungal antigens induce cytokines such as interleukin (IL)-4, IL-5, and IL-13. This pathway promotes systemic and local eosinophilia; activated eosinophils then release toxic granules and inflammatory mediators that contribute to mucosal injury and airway remodeling. When this hypersensitivity reaction predominates in the PNSs, it manifests as AFS, whereas predominant bronchopulmonary involvement results in ABPA. This shared inflammatory pathway supports the concept of “united airway disease,” in which upper and lower airway disorders are regarded as manifestations of a continuous inflammatory process [8–10].

Reported rates of coexistence between these conditions vary substantially. In a large evaluation of 67 patients with AFS, only approximately 3% (2 cases) had concomitant allergic bronchopulmonary mycosis. In contrast, studies that enrolled patients with ABPA have reported higher rates of sinus involvement: one study found that 7.4% of patients with ABPA had AFS, whereas a more recent prospective study reported sinus involvement in up to 80% of patients. The apparent rarity of dual diagnoses, sometimes termed sinobronchial allergic mycosis, may partly reflect fragmentation between medical specialties [8,10,11].

When patients present with chronic rhinosinusitis, clinicians should assess for lower respiratory symptoms suggestive of ABPA and for characteristic chest CT findings, such as central bronchiectasis or pulmonary infiltrates. This distinction is important because it directly influences treatment strategy [8].

The standard treatment for AFS combines surgical and medical therapy. Functional endoscopic sinus surgery is the cornerstone of treatment because it physically removes the thick allergic mucin that serves as an antigen reservoir and perpetuates eosinophilic inflammation. Surgery also restores sinus aeration and creates a wide pathway for topical medication delivery. Because AFS and its variants are characterized by substantial mucosal edema and high recurrence rates of up to 60%, aggressive anti-inflammatory therapy is often required. In this case, a 14-day tapering course of oral prednisolone, starting at 40 mg/day, was used to suppress the systemic Th2 response and prevent early recurrence. Short courses of oral corticosteroids for 2–3 weeks have been reported to improve quality-of-life and health scores in the immediate postoperative period by reducing sinonasal mucosal edema. In addition, clinical evidence suggests that combined oral and nasal steroid therapy reduces recurrence compared with local therapy alone (15.2% vs. 50.0%). Long-term control is then maintained with topical steroid rinses [12,13].

In contrast, ABPA is treated using a stepwise pharmacological approach. Oral corticosteroids are first-line therapy for acute exacerbations and for suppressing severe eosinophilic inflammation. Recommended protocols generally begin with an intermediate dose of prednisolone (0.5 mg/kg/day), followed by gradual tapering over 3–5 months. Azole antifungals, primarily itraconazole or voriconazole, are administered for 4–6 months as steroid-sparing agents. By reducing fungal burden and antigenic stimulation within the airways, these agents facilitate inflammatory control at lower steroid doses [14].

Although AFS and ABPA share similar pathophysiological features within the framework of united airway disease, they differ in clinical presentation and treatment strategy. The key clinical, diagnostic, and therapeutic differences between the two conditions are summarized in Table 1.

The divergent evolution of diagnostic criteria for AFS and ABPA is also noteworthy. The diagnostic criteria for ABPA have been repeatedly revised by the International Society for Human and Animal Mycology. Recent updates have incorporated real-world clinical scenarios to improve diagnostic sensitivity, including lowering the total IgE threshold from 1,000 IU/mL to 500 IU/mL and recognizing predisposing conditions such as chronic obstructive pulmonary disease and bronchiectasis [14,15]. In contrast, the Bent and Kuhn [1] criteria for AFS have remained largely unchanged since 1994, creating challenges in classifying atypical cases such as the present case. In ABPA, serum total IgE is used as a core biomarker for monitoring treatment response and recurrence [6], whereas its role in AFS has been less emphasized. However, emerging evidence suggests that postoperative total IgE monitoring in patients with AFS may provide a noninvasive means of assessing disease activity and predicting early recurrence, warranting further clinical investigation [3,11,16].

This case of AFS-like syndrome, characterized by the absence of demonstrable fungal type I hypersensitivity, is consistent with the hypothesis that AFS and ABPA may exist along a continuous immunopathological spectrum rather than as entirely independent clinical entities. This perspective may help identify atypical patients who fall outside conventional diagnostic criteria and supports an integrated approach across clinical specialties. Clinicians should remain vigilant for lower airway involvement in patients with chronic rhinosinusitis and, conversely, for sinus disease in patients with refractory asthma. A multidisciplinary strategy may improve diagnostic precision and guide individualized management. Further research is needed to modernize AFS diagnostic criteria and establish unified management guidelines for these related conditions [17].