Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is defined by necrotizing granulomatous inflammation involving the upper and lower respiratory tracts, along with necrotizing vasculitis primarily affecting small to medium-sized vessels, often accompanied by necrotizing glomerulonephritis [1]. GPA was historically considered a severe and life-threatening disease, with untreated cases demonstrating a mean survival of only 5 months due to the risk of renal or pulmonary failure. However, advancements in immunosuppressive therapies have significantly improved patient outcomes, with the median survival now estimated at 21.7 years after diagnosis. Early recognition and intervention are critical to improving long-term prognosis [2].

Unfortunately, 94% of patients are initially misdiagnosed with a simple inflammatory disease by the otolaryngology department [3]. This underscores the important role of otolaryngologists in the management of GPA patients. The most common nasal symptoms include foul-smelling rhinorrhea, epistaxis, erythematous mucosa, crusting, and granulation tissue formation. The nasal septum is most frequently involved, with extension to the sinuses occurring in some cases [4,5]. During the active phase, GPA typically affects the nasal cavity and septum, leading to crust formation and nasal obstruction, and can also result in septal perforation [6]. In this report, we present a case of GPA mimicking chronic sinusitis with polyp and review the updated diagnostic criteria.

A 64-year-old man presented to a local clinic with a three-month history of nasal congestion and olfactory disturbance. Nasal endoscopy revealed polyp-like masses in both nasal cavities, and he was subsequently referred to our hospital. The patient had a history of multiple treatments for sinusitis, and more recently had experienced nasal congestion, intermittent rhinorrhea, and headache. Polyp-like masses were noted in the middle meatus (Fig. 1A), and paranasal computed tomography (CT) demonstrated soft tissue density throughout the bilateral sinuses (Fig. 1B). As the endoscopic and CT findings suggested pansinusitis with nasal polyps, endoscopic sinus surgery was scheduled, and a punch biopsy was performed on a mass in the left nasal cavity to rule out tumors such as inverted papilloma. There were no abnormalities in the nasal septum or turbinate mucosa.

While awaiting surgery, histopathological analysis of the punch biopsy revealed chronic inflammation with poorly formed granulomas and focal necrosis, along with infiltration by mixed inflammatory cells including plasma cells, neutrophils, and a few eosinophils. However, there were no granulomas within an artery or in the perivascular area of an artery or arteriole. GPA was suspected, and further laboratory and radiological examinations were conducted. Laboratory testing showed a positive cytoplasmic-antineutrophil cytoplasmic antibody (C-ANCA) result, confirmed by positive proteinase-3 (PR-3) antibody (Fig. 2). Although C-ANCA demonstrates 90%–95% sensitivity in acute generalized GPA and 60% sensitivity in early or localized disease [7], GPA could not be diagnosed definitively at that time, as C-ANCA was not included in the diagnostic criteria. During evaluation for GPA, the patient presented to the emergency room with subacute dyspnea. Chest CT revealed a newly developed left hilar mass (Fig. 3A), and both main bronchi were narrowed by multiple cavitary lesions (Fig. 3B). Ultimately, the patient was diagnosed with GPA prior to undergoing endoscopic sinus surgery and was admitted to the rheumatology department, where he is receiving combination therapy with cyclophosphamide and prednisolone. During hospitalization, the patient reported nasal pain, and non-endoscopic examination revealed severe crusting around the middle turbinate (Fig. 4A). After conservative treatment, the middle turbinate and uncinate process were absent, but endoscopic and CT findings of the nasal mucosa and sinuses showed improvement (Fig. 4B and C). The patient is currently under medical management in the rheumatology department.

The diagnosis of GPA begins with clinical suspicion based on symptoms and physical findings. Sinonasal involvement is the most common manifestation of GPA in the head and neck region, affecting approximately 85% of patients. Notably, more than 25% of patients present solely with sinonasal symptoms [2,8]. While nasal obstruction and discharge are the most common symptoms, clinical manifestations can range from mild nasal obstruction to significant structural damage involving the external nose, paranasal sinuses, and skull base. Hyposmia or anosmia frequently occurs when the nasal mucosa is extensively involved, resulting in mucosal swelling. Additionally, cacosmia may develop due to purulent discharge and bacterial colonization, such as infections with Pseudomonas aeruginosa or Staphylococcus aureus [6]. Sinonasal involvement typically begins in the anterior septum area, which is supplied by the Kiesselbach plexus, and then extends to the paranasal sinuses [5,9]. Involvement of the nasal septum can cause perforation, which may be identified by a whistling sound, and in advanced cases can progress to saddle nose deformity [10]. Mucosal abnormalities in the nasopharynx and paranasal sinuses are well characterized and range from granulomatous lesions to diffuse mucosal thickening [7]. Although these clinical symptoms and signs are commonly observed in GPA, they are not highly specific for the differential diagnosis and may vary depending on the disease activity at the time of examination [4]. In the present case, the nasal septum exhibited normal mucosa and no abnormal findings at the time of initial diagnosis.

According to the 1990 American College of Rheumatology (ACR) criteria [11], GPA is diagnosed if two or more of the following four criteria are met: 1) inflammation of the sinus or oral cavity, 2) abnormal findings on lung X-ray, such as nodules, a fixed pulmonary infiltrate, or cavitary lesion, 3) hematuria or red cell casts in the urinary sediment, and 4) presence of histological granulomas within an artery or in the perivascular area of an artery or arteriole. The sensitivity and specificity of the 1990 ACR criteria are 88% and 92%, respectively. The 1990 ACR criteria have been effective and widely accepted in the medical community, playing a significant role in standardizing the diagnosis of GPA and promoting consistency in research and clinical practice [12]. However, these criteria lack detailed histopathological descriptions and do not include ANCA testing, making diagnosis difficult in certain cases. In disease flares, C-ANCA testing demonstrates a sensitivity of 65%–91% and a specificity of 96%–99% [13]. In March 2022, a revised classification for GPA was introduced following consensus that the ANCA test, widely used since 1985 and known for its high sensitivity and specificity, should be included in the criteria [14].

In the revised classification for GPA, nasal involvement and C-ANCA positivity carry the highest weights, with scores of 3 and 5 points, respectively. As a total of 5 or more points is sufficient for diagnosis, C-ANCA positivity alone is adequate for diagnosing GPA in patients presenting to otolaryngology with sinusitis or rhinitis when suspicion is high. Although tissue biopsy of an affected organ remains necessary for differentiating GPA from neoplastic or infectious diseases, only 16% of GPA patients have all three classic histological features of vasculitis, necrotizing inflammation, and chronic granulomatous inflammation [6]. Furthermore, up to 50% of biopsy specimens may be non-diagnostic, so repeat biopsies may be required in some patients [15]. Serologic tests and chest radiographs may facilitate more rapid diagnosis than biopsy, as results are typically available within a few days. In the present case, the 2022 ACR criteria had not yet been published at the time of diagnosis, so a diagnosis could not be established based on sinonasal symptoms and C-ANCA positivity alone, and surgery was planned for both diagnostic and therapeutic reasons. However, applying the 2022 ACR criteria would have allowed for an earlier diagnosis, prior to the onset of pulmonary symptoms.

Because otolaryngologists are often the first to encounter patients with GPA, it is essential to remain up-to-date with newly revised diagnostic criteria and to facilitate rapid diagnosis and treatment through a thorough diagnostic workup. Diagnosing GPA in patients presenting only with sinusitis and polyps can be challenging. Nevertheless, ENT physicians should always consider the possibility of GPA in patients with sinusitis and pursue appropriate testing to avoid unnecessary surgical interventions.