Echoes of Silence: Diagnosing Granulomatosis with Polyangiitis via Progressive Hearing Loss: A Case Report

Echoes of Silence: Diagnosing Granulomatosis with Polyangiitis via Progressive Hearing Loss: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Echoes of Silence: Diagnosing Granulomatosis with Polyangiitis via Progressive Hearing Loss: A Case Report Nihal Ali This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6947405/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Granulomatosis with polyangiitis (GPA) may initially present with otologic manifestations that mimic common ear pathology, delaying diagnosis and treatment. We report a 33-year-old woman whose refractory bilateral hearing loss, despite standard ENT management, was subsequently accompanied by systemic features leading to the identification of PR3-ANCA positivity, pulmonary nodules on imaging, and granulomatous endobronchial inflammation consistent with GPA. Induction therapy per EULAR recommendations began with high-dose corticosteroids and cyclophosphamide but was escalated to rituximab due to clinical deterioration. Multidisciplinary management involving ENT, pulmonology, nephrology, audiology, and Rheumatology achieved stabilization of systemic disease, although hearing loss persisted, requiring rehabilitation. This case underscores the importance of early consideration of GPA in atypical otologic presentations to preserve hearing and control systemic involvement. Granulomatosis with Polyangitis ANCA vasculitis GPA hearing loss in GPA Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis characterized by necrotizing granulomatous inflammation affecting small-to-medium vessels, predominantly in respiratory tracts and kidneys [ 1 ]. ENT involvement occurs in > 90% of patients, with otologic manifestations-including sensorineural hearing loss (SNHL), serous otitis, and mastoiditis-reported in 30–60% of cases [ 2 , 3 ]. SNHL pathogenesis involves cochlear vasculitis, immune-complex deposition, or nerve compression [ 2 ]. Notably, rapidly progressive bilateral SNHL or refractory otitis unresponsive to conventional therapy, particularly with systemic features should prompt vasculitis evaluation [ 1 , 2 ]. Early immunosuppression may prevent permanent auditory damage, while delayed diagnosis risks irreversible deficits [ 2 ]. Case Presentation A 33-year-old woman with no significant past medical history presented in April 2021 with left ear pain and tinnitus, treated empirically as otitis media. Symptoms progressed to bilateral hearing loss despite antibiotics and corticosteroids. ENT evaluation revealed bilateral tympanic retraction with effusions and audiometry-confirmed mixed hearing loss. Temporal bone CT showed mastoid effusions. Bilateral grommet insertion provided transient relief. Over the next month, she developed systemic symptoms, including malaise, low-grade fevers, night sweats, and fatigue, followed by the onset of polyarthritis involving her shoulders, knees, and ankles. Concurrently, she noted the development of a persistent dry cough and occasional wheezing, but no hemoptysis, chest pain, or dyspnea at rest. She was then referred for further rheumatologic evaluation. Rheumatology Assessment and Laboratory Investigations Further assessments were undertaken, including a physical examination that showed evidence of middle ear fluid and bilateral conductive hearing loss. Systemic examination revealed no active synovitis or skin lesions. Her inflammatory markers were markedly elevated. Laboratory workup revealed positive PR3-ANCA, negative ANA/ENA/RF/CCP, preserved renal function with unremarkable urinalysis, and negative infectious screening (tuberculosis, HIV, hepatitis B and C, COVID-19) (Table 1 ). Table 1 Laboratory parameters Pre treatment and Post induction therapy parameter Reference Range Pre Treatment Post Treatment Hemoglobin 12–16 g/dL 11.1 g/dL 11.2 g/dL C-reactive protein (CRP) 90 mL/min/1.73 m² > 90 mL/min/1.73 m² >90 mL/min/1.73 m² PR3-ANCA Negative Positive Positive ANA, ENA, RF, anti-CCP Negative Negative Negative Urinalysis No proteinuria/hematuria Normal Normal Given the constellation of the upper airway, Systemic, and pulmonary symptoms, CT imaging of the thorax was performed. This revealed multiple pulmonary nodules, areas of ground-glass opacity, and irregular airway wall thickening, raising suspicion for vasculitis (Fig. 1 ). To evaluate her pulmonary findings further, she underwent bronchoscopy, which revealed endobronchial cobblestone mucosal nodularity, particularly affecting the right main bronchus (Fig. 2 ). Biopsies ruled out malignancy and infection but showed chronic inflammation with granulomatous changes consistent with granulomatosis with polyangiitis (GPA). Diagnosis With clinical, serological (PR3-ANCA positivity), radiological, and bronchoscopy evidence of systemic small-vessel vasculitis, a diagnosis of granulomatosis with polyangiitis was established. The disease predominantly involved the upper airways (otologic), lower respiratory tract, and systemic inflammatory features. A renal review was conducted due to GPA’s known risk of glomerulonephritis. At that time, her renal function was preserved, with no proteinuria or hematuria. A renal biopsy was not indicated, but nephrology established a baseline for surveillance and arranged ongoing monitoring with urinalysis and renal function every 1–2 months. Management and Clinical Course In view, of the patient’s aggressive presentation and multi-organ involvement, treatment was initiated per EULAR 2022 guidelines for organ-threatening GPA [ 1 ]. She received intravenous methylprednisolone (1 g/day for 3 days), followed by oral prednisolone (1 mg/kg/day), concomitant Pneumocystis jirovecii pneumonia prophylaxis was also commenced. Despite initial therapy, she reported ongoing malaise and worsening hearing, and inflammatory markers remained elevated. Repeat chest imaging showed progression of pulmonary nodules and persistent airway thickening (Fig. 3 ). Initial response Furthermore, her case was discussed with the respiratory team. A consensus was reached that she had an organ-threatening GPA with both ENT and lower respiratory involvement. And intravenous cyclophosphamide as induction therapy for organ-threatening GPA was stated and she received 6 cycles followed by Rituximab infusion. [ 2 , 4 ] . After switching to the induction therapy with cyclophosphamide and rituximab, the patient’s systemic symptoms improved, inflammatory markers normalized, and pulmonary findings stabilized (Fig. 4 ). Unfortunately, her hearing loss did not fully recover, and she was referred to audiology for a bilateral hearing aid fitting. She transitioned to maintenance rituximab therapy and entered a structured steroid taper plan, aiming to reach ≤ 5 mg/day by month 4–5 per protocol. ENT follow-up continued with serial audiometry, pulmonology monitored airway changes, and rheumatology arranged regular clinical assessments to monitor for relapse. Prognosis Modern immunosuppressive regimens have markedly improved survival in GPA, with two-year survival rates exceeding 80–90%. Relapse rates remain substantial, particularly in PR3-ANCA positive patients. Early recognition, especially when otologic symptoms herald systemic disease, can preserve vital functions such as hearing. Maintenance therapy and vigilant long-term follow-up are essential to sustain remission and minimize complications [ 1 , 5 ]. Discussion Otologic involvement in GPA often presents as serous otitis media, chronic otitis, mastoiditis, and SNHL [ 3 ]. Hearing-related symptoms occur in up to 90% of GPA patients, with SNHL in about one-third of cases [ 2 ]. SNHL mechanisms include cochlear vasculitis, immune-complex deposition, and granulomatous involvement. Rapidly progressive or refractory hearing loss-especially bilateral persistent effusions unresponsive to standard therapies should raise suspicion for vasculitis. Early recognition allows timely immunosuppression, which may reverse or halt the progression of hearing loss; delays risk permanent deficits [ 6 ]. In atypical otologic presentations, ANCA testing (PR3-ANCA for GPA) is essential alongside imaging (CT chest to assess pulmonary and airway involvement) and endoscopic evaluation (bronchoscopy for suspected airway lesions; ENT endoscopy for sinonasal assessment). Tissue biopsy confirming granulomatous vasculitis remains ideal when feasible. Exclusion of infectious and malignant etiologies prior to immunosuppression is critical. Multidisciplinary collaboration expedites diagnosis and management decisions [ 1 , 4 ]. Management per EULAR recommendations emphasizes severity stratification with remission induction using high-dose glucocorticoids plus rituximab or cyclophosphamide for organ-threatening disease, glucocorticoid tapering aiming for ~ 5 mg prednisolone equivalent/day by 4–5 months, choice of induction agent individualized by PR3-ANCA positivity, fertility concerns, comorbidities, and disease severity; maintenance therapy with rituximab preferred in PR3-ANCA positive GPA; and infection prophylaxis, vaccination updates, bone protection, and toxicity monitoring [ 1 ]. ENT interventions include audiometry-guided hearing rehabilitation, local procedures for effusions, airway surveillance, and integrated multidisciplinary care. Prompt initiation of induction therapy and ENT-specific interventions in patients with otologic involvement aligns with these recommendations and may improve outcomes by preserving hearing and controlling systemic disease [ 7 ]. Conclusion In a patient presenting with progressive bilateral hearing loss accompanied by systemic features, prompt recognition of GPA via ANCA testing and bronchoscopic evaluation enabled timely induction therapy consistent with EULAR recommendations for ANCA-associated vasculitis. High-dose corticosteroids combined with an appropriate induction agent (rituximab or cyclophosphamide) were administered alongside ENT-specific interventions and multidisciplinary collaboration. Transition to maintenance immunosuppression (favoring rituximab in PR3-ANCA positive disease), patient education, infection prophylaxis, and frequent monitoring are essential to preserve function and sustain remission. This case highlights the diagnostic significance of refractory otologic symptoms in GPA and the importance of adhering to current EULAR guidance to optimize patient outcomes. References Hellmich B, Sanchez-Alamo B, Schirmer JH: EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update . Annals of the Rheumatic Diseases. 2022, 83:30-47. Bakthavachalam S, Driver MS, Cox C: Hearing loss in Wegener’s granulomatosis. Otol Neurotol. 2004, 25:833-837. 10.1097/00129492-200409000-00030. Jones RB, Furuta S, Tervaert JW: Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomized trial. Annals of the Rheumatic Diseases. 2015, 74:1178-1182. 10.1136/annrheumdis-2014-206404. Kronbichler A, Bajema IM, Bruchfeld A: Diagnosis and management of ANCA-associated vasculitis. The lancet. 10.1016/S0140-6736(23)01736-1. Lyons PA, Rayner TF, Trived Holle : Genetically distinct subsets within ANCA-associated vasculitis. New England Journal of Medicine. 2012, 367:214-223. 10.1056/NEJMoa1108735 . Otolaryngologic Manifestations of Granulomatosis With Polyangiitis. http://emedicine.medscape.com/article/858001-overview. Carranza-Enríquez F, Meade-Aguilar JA, Hinojosa-Azaola A: Rituximab treatment in ANCA-associated vasculitis patients: outcomes of a real-life experience from an observational cohort. 10.1007/s10067-022-06192-1 Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6947405","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":474587207,"identity":"9f0bb3c0-cf0a-491a-84f0-b690e28b10f7","order_by":0,"name":"Nihal Ali","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYDACZh4GhgcMDDJszMwHH3yoAIkwNxDWksDAwMPGzpZsOOMMSISRgBYGqBYGfh4zad42kAgBLebsvAc/JDDY8fAx8xgbzpxXG83fDtTyo2IbTi2WzXzJEgkMyTxszGyFDz5uO5474zBjA2PPmds4tRgc5jEAamEGamHebDhz27HcBqAWZsY2vFqMfyQw1AO1MAD9MudY7nwitJgBbTkM1MIC1NJQk7uBGC0WCQbHQX4BBvKxA7kbgVoO4vXL+TPGNz5UVMvJ9x8GRmVNXe6880DGjwrcWqAa4azDYPIAAfUooI4UxaNgFIyCUTBCAADPfVJ8jdHBMgAAAABJRU5ErkJggg==","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Nihal","middleName":"","lastName":"Ali","suffix":""}],"badges":[],"createdAt":"2025-06-22 03:06:13","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6947405/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6947405/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85821721,"identity":"ef4da28f-fd03-4449-8b93-032bead0d865","added_by":"auto","created_at":"2025-07-02 06:39:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":458830,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCT thorax demonstrating bilateral pulmonary nodules and ground-glass changes\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6947405/v1/b0d6a053110c92826b1cb35d.png"},{"id":85822469,"identity":"43ecacf4-ef5b-46a7-a24c-4be4ce4cc904","added_by":"auto","created_at":"2025-07-02 06:47:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":716964,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBronchoscopic image showing endobronchial cobblestone mucosal nodularity\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6947405/v1/b10a4e106a15aae08e47610f.png"},{"id":85821727,"identity":"5747612b-cde1-4aa7-ac95-e29a54331d2d","added_by":"auto","created_at":"2025-07-02 06:39:20","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":692775,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eshowing progression of pulmonary nodules and persistent airway thickening\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6947405/v1/cb90fb22966a9dee0a4ed1e7.png"},{"id":85821724,"identity":"4b4b6ed8-597b-4c5c-8c79-00adf7b59efd","added_by":"auto","created_at":"2025-07-02 06:39:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":304590,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePlain film chest X-ray showing clear lung field\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6947405/v1/4587a7d513ef53a9ad43c0a2.png"},{"id":85822476,"identity":"0d7f701e-c7a1-4c1c-baf6-5320136590fb","added_by":"auto","created_at":"2025-07-02 06:47:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3292662,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6947405/v1/67651432-ba3c-4998-9864-2d3d0939cde7.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eEchoes of Silence: Diagnosing Granulomatosis with Polyangiitis via Progressive Hearing Loss: A Case Report\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGranulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis characterized by necrotizing granulomatous inflammation affecting small-to-medium vessels, predominantly in respiratory tracts and kidneys [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. ENT involvement occurs in \u0026gt;\u0026thinsp;90% of patients, with otologic manifestations-including sensorineural hearing loss (SNHL), serous otitis, and mastoiditis-reported in 30\u0026ndash;60% of cases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. SNHL pathogenesis involves cochlear vasculitis, immune-complex deposition, or nerve compression [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Notably, rapidly progressive bilateral SNHL or refractory otitis unresponsive to conventional therapy, particularly with systemic features should prompt vasculitis evaluation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Early immunosuppression may prevent permanent auditory damage, while delayed diagnosis risks irreversible deficits [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 33-year-old woman with no significant past medical history presented in April 2021 with left ear pain and tinnitus, treated empirically as otitis media. Symptoms progressed to bilateral hearing loss despite antibiotics and corticosteroids. ENT evaluation revealed bilateral tympanic retraction with effusions and audiometry-confirmed mixed hearing loss. Temporal bone CT showed mastoid effusions. Bilateral grommet insertion provided transient relief.\u003c/p\u003e\n\u003cp\u003eOver the next month, she developed systemic symptoms, including malaise, low-grade fevers, night sweats, and fatigue, followed by the onset of polyarthritis involving her shoulders, knees, and ankles. Concurrently, she noted the development of a persistent dry cough and occasional wheezing, but no hemoptysis, chest pain, or dyspnea at rest. She was then referred for further rheumatologic evaluation.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eRheumatology Assessment and Laboratory Investigations\u003c/h2\u003e\n \u003cp\u003eFurther assessments were undertaken, including a physical examination that showed evidence of middle ear fluid and bilateral conductive hearing loss. Systemic examination revealed no active synovitis or skin lesions. Her inflammatory markers were markedly elevated. Laboratory workup revealed positive PR3-ANCA, negative ANA/ENA/RF/CCP, preserved renal function with unremarkable urinalysis, and negative infectious screening (tuberculosis, HIV, hepatitis B and C, COVID-19) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eLaboratory parameters Pre treatment and Post induction therapy\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eparameter\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eReference Range\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePre Treatment\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePost Treatment\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHemoglobin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u0026ndash;16 g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1 g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.2 g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC-reactive protein (CRP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;5 mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e109 mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49 mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eErythrocyte sedimentation rate (ESR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;20 mm/hr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87 mm/hr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70 mm/hr\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eeGFR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;90 mL/min/1.73 m\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;90 mL/min/1.73 m\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;90 mL/min/1.73 m\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePR3-ANCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANA, ENA, RF, anti-CCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrinalysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo proteinuria/hematuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eGiven the constellation of the upper airway, Systemic, and pulmonary symptoms, CT imaging of the thorax was performed. This revealed multiple pulmonary nodules, areas of ground-glass opacity, and irregular airway wall thickening, raising suspicion for vasculitis (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eTo evaluate her pulmonary findings further, she underwent bronchoscopy, which revealed endobronchial cobblestone mucosal nodularity, particularly affecting the right main bronchus (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Biopsies ruled out malignancy and infection but showed chronic inflammation with granulomatous changes consistent with granulomatosis with polyangiitis (GPA).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eWith clinical, serological (PR3-ANCA positivity), radiological, and bronchoscopy evidence of systemic small-vessel vasculitis, a diagnosis of granulomatosis with polyangiitis was established. The disease predominantly involved the upper airways (otologic), lower respiratory tract, and systemic inflammatory features. A renal review was conducted due to GPA\u0026rsquo;s known risk of glomerulonephritis.\u003c/p\u003e\n \u003cp\u003eAt that time, her renal function was preserved, with no proteinuria or hematuria. A renal biopsy was not indicated, but nephrology established a baseline for surveillance and arranged ongoing monitoring with urinalysis and renal function every 1\u0026ndash;2 months.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eManagement and Clinical Course\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIn view, of the patient\u0026rsquo;s aggressive presentation and multi-organ involvement, treatment was initiated per EULAR 2022 guidelines for organ-threatening GPA [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]. She received intravenous methylprednisolone (1 g/day for 3 days), followed by oral prednisolone (1 mg/kg/day), concomitant Pneumocystis jirovecii pneumonia prophylaxis was also commenced.\u003c/p\u003e\n \u003cp\u003eDespite initial therapy, she reported ongoing malaise and worsening hearing, and inflammatory markers remained elevated. Repeat chest imaging showed progression of pulmonary nodules and persistent airway thickening (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eInitial response\u003c/h3\u003e\n\u003cp\u003eFurthermore, her case was discussed with the respiratory team. A consensus was reached that she had an organ-threatening GPA with both ENT and lower respiratory involvement. And intravenous cyclophosphamide as induction therapy for organ-threatening GPA was stated and she received 6 cycles followed by Rituximab infusion. [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e] .\u003c/p\u003e\n\u003cp\u003eAfter switching to the induction therapy with cyclophosphamide and rituximab, the patient\u0026rsquo;s systemic symptoms improved, inflammatory markers normalized, and pulmonary findings stabilized (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e ). Unfortunately, her hearing loss did not fully recover, and she was referred to audiology for a bilateral hearing aid fitting. She transitioned to maintenance rituximab therapy and entered a structured steroid taper plan, aiming to reach\u0026thinsp;\u0026le;\u0026thinsp;5 mg/day by month 4\u0026ndash;5 per protocol. ENT follow-up continued with serial audiometry, pulmonology monitored airway changes, and rheumatology arranged regular clinical assessments to monitor for relapse.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrognosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eModern immunosuppressive regimens have markedly improved survival in GPA, with two-year survival rates exceeding 80\u0026ndash;90%. Relapse rates remain substantial, particularly in PR3-ANCA positive patients. Early recognition, especially when otologic symptoms herald systemic disease, can preserve vital functions such as hearing.\u003c/p\u003e\n\u003cp\u003eMaintenance therapy and vigilant long-term follow-up are essential to sustain remission and minimize complications [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOtologic involvement in GPA often presents as serous otitis media, chronic otitis, mastoiditis, and SNHL [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Hearing-related symptoms occur in up to 90% of GPA patients, with SNHL in about one-third of cases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. SNHL mechanisms include cochlear vasculitis, immune-complex deposition, and granulomatous involvement. Rapidly progressive or refractory hearing loss-especially bilateral persistent effusions unresponsive to standard therapies should raise suspicion for vasculitis.\u003c/p\u003e \u003cp\u003eEarly recognition allows timely immunosuppression, which may reverse or halt the progression of hearing loss; delays risk permanent deficits [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In atypical otologic presentations, ANCA testing (PR3-ANCA for GPA) is essential alongside imaging (CT chest to assess pulmonary and airway involvement) and endoscopic evaluation (bronchoscopy for suspected airway lesions; ENT endoscopy for sinonasal assessment). Tissue biopsy confirming granulomatous vasculitis remains ideal when feasible.\u003c/p\u003e \u003cp\u003eExclusion of infectious and malignant etiologies prior to immunosuppression is critical. Multidisciplinary collaboration expedites diagnosis and management decisions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eManagement per EULAR recommendations emphasizes severity stratification with remission induction using high-dose glucocorticoids plus rituximab or cyclophosphamide for organ-threatening disease, glucocorticoid tapering aiming for ~\u0026thinsp;5 mg prednisolone equivalent/day by 4\u0026ndash;5 months, choice of induction agent individualized by PR3-ANCA positivity, fertility concerns, comorbidities, and disease severity; maintenance therapy with rituximab preferred in PR3-ANCA positive GPA; and infection prophylaxis, vaccination updates, bone protection, and toxicity monitoring [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eENT interventions include audiometry-guided hearing rehabilitation, local procedures for effusions, airway surveillance, and integrated multidisciplinary care.\u003c/p\u003e \u003cp\u003ePrompt initiation of induction therapy and ENT-specific interventions in patients with otologic involvement aligns with these recommendations and may improve outcomes by preserving hearing and controlling systemic disease [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn a patient presenting with progressive bilateral hearing loss accompanied by systemic features, prompt recognition of GPA via ANCA testing and bronchoscopic evaluation enabled timely induction therapy consistent with EULAR recommendations for ANCA-associated vasculitis. High-dose corticosteroids combined with an appropriate induction agent (rituximab or cyclophosphamide) were administered alongside ENT-specific interventions and multidisciplinary collaboration. Transition to maintenance immunosuppression (favoring rituximab in PR3-ANCA positive disease), patient education, infection prophylaxis, and frequent monitoring are essential to preserve function and sustain remission. This case highlights the diagnostic significance of refractory otologic symptoms in GPA and the importance of adhering to current EULAR guidance to optimize patient outcomes.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHellmich B, Sanchez-Alamo B, Schirmer JH: EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update . Annals of the Rheumatic Diseases. 2022, 83:30-47.\u003c/li\u003e\n \u003cli\u003eBakthavachalam S, Driver MS, Cox C: Hearing loss in Wegener\u0026rsquo;s granulomatosis. Otol Neurotol. 2004, 25:833-837. 10.1097/00129492-200409000-00030.\u003c/li\u003e\n \u003cli\u003eJones RB, Furuta S, Tervaert JW: Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomized trial. Annals of the Rheumatic Diseases. 2015, 74:1178-1182. 10.1136/annrheumdis-2014-206404.\u003c/li\u003e\n \u003cli\u003eKronbichler A, Bajema IM, Bruchfeld A: Diagnosis and management of ANCA-associated vasculitis. The lancet. 10.1016/S0140-6736(23)01736-1.\u003c/li\u003e\n \u003cli\u003eLyons PA, Rayner TF, Trived Holle : Genetically distinct subsets within ANCA-associated vasculitis. New England Journal of Medicine. 2012, 367:214-223. 10.1056/NEJMoa1108735 .\u003c/li\u003e\n \u003cli\u003eOtolaryngologic Manifestations of Granulomatosis With Polyangiitis. http://emedicine.medscape.com/article/858001-overview.\u003c/li\u003e\n \u003cli\u003eCarranza-Enr\u0026iacute;quez F, Meade-Aguilar JA, Hinojosa-Azaola A: Rituximab treatment in ANCA-associated vasculitis patients: outcomes of a real-life experience from an observational cohort. 10.1007/s10067-022-06192-1\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Beaumont Hospital","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Granulomatosis with Polyangitis,ANCA vasculitis,GPA, hearing loss in GPA","lastPublishedDoi":"10.21203/rs.3.rs-6947405/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6947405/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eGranulomatosis with polyangiitis (GPA) may initially present with otologic manifestations that mimic common ear pathology, delaying diagnosis and treatment. We report a 33-year-old woman whose refractory bilateral hearing loss, despite standard ENT management, was subsequently accompanied by systemic features leading to the identification of PR3-ANCA positivity, pulmonary nodules on imaging, and granulomatous endobronchial inflammation consistent with GPA. Induction therapy per EULAR recommendations began with high-dose corticosteroids and cyclophosphamide but was escalated to rituximab due to clinical deterioration. Multidisciplinary management involving ENT, pulmonology, nephrology, audiology, and Rheumatology achieved stabilization of systemic disease, although hearing loss persisted, requiring rehabilitation. This case underscores the importance of early consideration of GPA in atypical otologic presentations to preserve hearing and control systemic involvement.\u003c/p\u003e","manuscriptTitle":"Echoes of Silence: Diagnosing Granulomatosis with Polyangiitis via Progressive Hearing Loss: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-02 06:39:16","doi":"10.21203/rs.3.rs-6947405/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4e9a3f53-716d-4755-9eaa-276123a94b5f","owner":[],"postedDate":"July 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-02T06:39:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-02 06:39:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6947405","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6947405","identity":"rs-6947405","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}