Isolated Sensorineural Hearing Loss as the Sole Manifestation of Granulomatosis with Polyangiitis

Introduction

Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a rare small-vessel systemic vasculitis associated with antibodies against the neutrophil cytoplasm [1]. Although its estimated prevalence is not known with certainty, in the United States, an approximate incidence of 21.8 cases per 100 000 inhabitants per year has been reported, with no significant difference between men and women [2].

Although the etiology of GPA has not been elucidated, genetic susceptibility, environmental agents, infectious episodes, and abnormalities in adaptive immunity are important factors in the development of ANCA-associated vasculitis. Genetic variants appear to be associated with specific antigens rather than a particular clinical phenotype. ANCAs directed against proteinase 3 (PR3-ANCA), present in 60–80% of GPA cases, are related to genetic variants of the human leukocyte antigen (HLA) DP1A and HLA-DP1B, which are responsible for encoding the major histocompatibility complex class II, SERPINA1, PRTN3, and the autoantigen proteinase 3 (PR3) [3].

Clinically, 70% of GPA cases present with involvement of the ears, nose, and throat (ENT), and up to 73–93% of cases present with involvement of the upper and lower respiratory tract [4]. Otological involvement specifically consists of recurrent otitis media, mastoiditis, and otalgia. On the other hand, isolated hearing loss preceding the onset of respiratory symptoms or renal involvement is quite rare and not well documented. In a case series of 85 patients, Fauci et al reported hearing loss as the only symptom in only 6% of patients [5]. We present the case of a 36-year-old patient with severe bilateral sensorineural hearing loss as the initial manifestation of GPA.

Case Report

A 36-year-old man with no significant medical history presented with sudden-onset orthostatic symptoms, without other associated complaints. Five days later, he arrived at the emergency department with acute unilateral hearing loss in the left ear. Empirical treatment with oral prednisone (40 mg/day) was initiated for presumed idiopathic sudden sensorineural hearing loss, resulting in partial improvement approximately 5 days after treatment onset. Four weeks later, the patient developed bilateral sensorineural hearing loss accompanied by non-disabling postural instability, tinnitus, and a sensation of fullness and pressure in both ears. Head MRI was unremarkable. Audiometry revealed moderate-to-profound bilateral sensorineural hearing loss (Figure 1), with word recognition scores of 83% in the right ear and 90% in the left ear. Intratympanic steroid injections were administered, followed by high-dose oral prednisone (60 mg/day), leading to partial improvement.

Comprehensive clinical examination revealed no ocular, nasal, or sinus involvement. The external and middle ear canals were patent, with intact tympanic membranes. Cardiopulmonary and neurological examinations were unremarkable. The patient denied recurrent respiratory infections, otitis, mastoiditis, asthma, and allergic conditions. He also reported no constitutional symptoms such as fever, weight loss, fatigue, arthralgias, skin changes, or mucosal ulcers. No sensory or motor deficits were observed in the extremities, and the patient did not report paresthesias or limb weakness. Given the absence of clinical signs suggestive of peripheral neuropathy, electromyography and nerve conduction studies were not performed.

Etiological investigations ruled out infectious and hematological causes. Serological testing for varicella-zoster virus and mumps was negative for acute infection. Antinuclear antibodies were negative, while ANCA testing by indirect immunofluorescence showed a perinuclear pattern at a titer of 1: 20. PR3-ANCA was positive by quantitative ELISA, with a value of 1.7. Inflammatory markers were mildly elevated, with an erythrocyte sedimentation rate of 31 mm/h and a CRP level of 9.6 mg/dL. Additional relevant laboratory findings are detailed in Table 1. Chest computed tomography revealed no evidence of pulmonary involvement. Cogan’s syndrome was initially considered; however, the absence of ocular findings – particularly interstitial keratitis – along with PR3-ANCA positivity, supported the diagnosis of GPA with isolated inner ear involvement.

Although the clinical presentation was not classified as organ-threatening, the involvement of a critical sensory organ in a young patient justified the initiation of rituximab therapy (1 g in 2 doses, 2 weeks apart), followed by maintenance therapy with 500 mg every 6 months and a gradual taper of prednisone. The patient had a favorable clinical course, with no recurrence of vasculitic symptoms during follow-up. Inflammatory markers normalized, and no new systemic involvement was detected. Repeat ANCA testing was not performed, as current guidelines do not recommend serial monitoring in the absence of clinical relapse.

Discussion

Sensorineural hearing loss was first described in 1944 by De Klein and refers to a loss of at least 30 decibels across 3 sequential frequencies in a standard pure-tone audiogram within 3 days or less [6]. The estimated incidence of acute sensorineural hearing loss is 5–20 cases per 100 000 individuals per year. Sensorineural hearing loss predominantly affects people between 50 and 60 years of age and typically presents unilaterally. Bilateral involvement occurs in less than 5% of the cases [7–9]. The exact etiology and pathophysiology remain unclear, although 3 main mechanisms have been proposed: viral theory (deafness due to cochleitis or cochlear neuritis), vascular occlusion, and immunological theory, which suggests organ damage in diseases such as systemic vasculitis, Sjögren’s syndrome, relapsing polychondritis, systemic lupus erythematosus, or Behçet’s disease [10–12]. For this reason, the initial approach to bilateral sensorineural hearing loss should include a complete blood count, C-reactive protein, the erythrocyte sedimentation rate, antiphospholipid antibodies, ANA, ANCAs, and exclusion of nonautoimmune differential diagnoses.

In systemic vasculitis, particularly ANCA-associated vasculitis (GPA and eosinophilic GPA), audiological involvement varies, with 5 recognized patterns of presentation: 1) serous otitis media (most common), 2) chronic otitis media with middle ear and mastoid cavity involvement, 3) vertigo due to immune complex deposition in the vestibular portion, 4) facial paralysis, and 5) sensorineural hearing loss [13,14]. The latter is attributed to vasculitic damage caused by immune complex deposition in the cochlea and its vascular structures, compression of the acoustic nerve by granulomatous lesions, and inflammatory or toxic effects on the vasa vasorum and endothelium of cochlear vessels [15]. Notably, serous otitis media with conductive hearing loss is the most frequently encountered middle ear disorder in GPA. In contrast, sensorineural hearing loss is a much rarer manifestation and has only occasionally been documented as an isolated otologic feature, without accompanying systemic signs such as recurrent or chronic otitis [5]. When GPA presents as localized disease involving only the middle or inner ear, it poses significant diagnostic and therapeutic challenges. This atypical presentation can easily lead to delays in diagnosis – especially in the absence of constitutional symptoms or vital organ involvement – which in turn may result in irreversible auditory damage and increased morbidity. Prompt recognition is therefore crucial. Differentiating GPA from other autoimmune, infectious, or idiopathic causes of hearing loss requires a high index of suspicion, along with comprehensive serological and imaging evaluation. Table 2 summarizes previously reported cases of GPA presenting with isolated sensorineural hearing loss.

Treatment of GPA involves high-dose corticosteroids – typically intravenous methylprednisolone pulses – followed by oral steroids and remission induction therapy tailored to disease severity and organ involvement [19]. Rituximab and cyclophosphamide are the agents of choice in severe cases. The Rituximab in ANCA-Associated Vasculitis (RAVE) trial reported remission rates of 67% for rituximab versus 42% for cyclophosphamide in systemic GPA [19–21]. However, evidence comparing treatment efficacy in isolated or ENT-limited manifestations remains scarce. Although rituximab has shown superior remission rates in systemic GPA, the RAVE trial did not specifically assess patients with localized otologic involvement [19–21]. As such, the optimal therapeutic strategy for this subset is still undefined. In our case, rituximab was selected for induction therapy despite the absence of classic organ-threatening disease, due to the functional impact of hearing loss in a young patient and the potential irreversibility of cochlear damage. A notable limitation of our report is the absence of post-treatment audiometric assessment, which precludes objective quantification of hearing recovery and limits a more precise characterization of treatment response in this manifestation of GPA. Nevertheless, the observed clinical improvement supports the presumed benefit of early immunosuppressive therapy. This finding emphasizes the importance of standardized follow-up protocols – including serial audiometry – to ensure adequate monitoring of auditory outcomes. It also reinforces the need for individualized treatment decisions in localized GPA, when preserving sensory function and overall quality of life may justify more intensive intervention. Further research is warranted to define the most effective management strategies for otologic GPA and to guide evidence-based care in these rare clinical scenarios.

Conclusions

Otorhinolaryngological manifestations in granulomatosis with polyangiitis are relatively common and clinically diverse; however, isolated audiological symptoms as the initial and sole presentation are exceedingly rare. In particular, progressive sensorineural hearing loss without systemic involvement poses a significant diagnostic challenge. Such atypical cases require urgent recognition, as delays in diagnosis may lead to irreversible auditory damage and increase the risk of systemic progression with potentially life-threatening consequences.

When isolated hearing loss is encountered, clinicians must pursue a broad differential diagnosis that includes infectious, vascular, and autoimmune causes. Among these, ANCA-associated vasculitides – despite their rarity - must be actively considered given their potentially severe outcomes. A high index of suspicion, thorough clinical assessment, and targeted laboratory workup are essential to ensure timely diagnosis and appropriate management.

Currently, no standardized treatment guidelines exist for GPA with isolated otologic involvement, and the scarcity of such presentations limits the feasibility of randomized controlled trials. Nevertheless, early therapeutic intervention is critical. We recommend initiating treatment promptly with intravenous methylprednisolone pulses, followed by oral prednisone (1 mg/kg/day, tapered gradually), combined with an induction agent such as rituximab or cyclophosphamide. Although comparative data between these agents in isolated otologic GPA are lacking, rituximab may offer a more favorable risk-benefit profile, particularly in younger patients.

Further research is needed to define evidence-based strategies for this rare and challenging clinical entity. Additionally, in patients who remain clinically stable without new symptoms, routine serial ANCA testing is not warranted, as current guidelines limit its use to diagnostic evaluation or suspected relapse.