Diagnosis and management of chronic intractable otitis media as an initial manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV)

Diagnosis and management of chronic intractable otitis media as an initial manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) | 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 Article Diagnosis and management of chronic intractable otitis media as an initial manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) Ji Song Hong, Da Jung Jung, Myung Hoon Yoo, Eun hye Kwon, Seung woo Han, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4786009/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 Antineutrophil cytoplasmic antibody (ANCA)-mediated otitis media is rare, posing challenges for diagnosis and treatment. This study aimed to facilitate the diagnosis and understanding of the clinical features of intractable otitis media as the initial manifestation of ANCA-associated vasculitis (AAV) and provide a compelling basis for refining treatment guidelines specific to this rare condition. We retrospectively analyzed the medical records of patients exhibiting intractable chronic otitis media as their initial AAV. The most common initial symptoms were intractable chronic otitis media with effusion or otorrhea, unresponsive to standard treatments, leading to progressive hearing loss and facial palsy. Patients exhibited characteristic tympanic membrane findings, including typical vasodilated hypervascularity. Facial palsy was a common accompanying symptom, affecting 60% of the patients. Following a treatment regimen involving a combination of corticosteroids and immunosuppressants, otitis media subsided, restoring hearing. After initiating treatment with corticosteroids and immunosuppressants, all patients experienced significant improvement, with no reported relapses. Intractable chronic otitis media, as the initial presentation of AAV, originated from the middle ear before progressing to other organs, potentially causing severe otologic complications such as facial palsy and hearing loss. However, timely diagnosis of ANCA-associated otitis media and initiation of treatment should be considered to improve clinical outcomes. Biological sciences/Immunology/Autoimmunity Health sciences/Rheumatology Intractable chronic otitis media Antineutrophil cytoplasmic antibody Reversible sensorineural hearing loss Facial palsy tympanic membrane Figures Figure 1 Figure 2 INTRODUCTION Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic necrotizing vasculitis that affects small to medium-sized vessels 1 . AAV can be divided into three categories: granulomatosis with polyangiitis, microscopic poly angiitis, and eosinophilic granulomatosis polyangiitis 2 . Reports have shown that otitis media is an otologic manifestation of existing AAV 3,4 . Patients with AAV may suffer from only otologic symptoms, such as intractable otitis media, hearing loss, and facial palsy, without lung and kidney lesions 5 . Early diagnosis and treatment of AAV are crucial for patient survival, with delayed or missed diagnosis worsening the prognosis 6 . However, a favorable prognosis can be expected with appropriately diagnosis and treatment initiation at the early stages of AAV. Therefore, early diagnosis and treatment are important in preventing irreversible progression. However, early diagnosis of AAV localized to the middle ear is challenging 7 . Not only are such cases rare, they also do not exhibit other AAV-related organ lesions at the initial visit 5 . As such, they fail to fulfill the ordinary diagnostic criteria for AAV and cannot undergo intensive treatment, such as corticosteroids and/or immunosuppressants, at an early stage 8 . Thus we sought to investigate the clinical features and outcomes in patients presenting with intractable otitis media as the initial manifestation of AAV, aiming to facilitate the diagnosis and understanding of the disease, and to identify factors associated with early diagnosis and outcomes.. RESULTS Patient characteristics We retrospectively reviewed the medical records of patients with intractable otitis media as the initial manifestation of AAV who were treated at the tertiary medical hospital in Korea. Patients who were followed up for more than 12 months were included in this study. All patients who satisfied all of the following criteria were included in the study: ( 1 ) long-standing otitis media with effusion or otorrhea, unresponsive to standard treatments including antibiotics, steroid alone, and the insertion of tympanic ventilation tubes; ( 2 ) positive serum myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA; ( 3 ) absence of AAV lesions outside the ear upon initial diagnosis; ( 4 ) all other causes of intractable otitis media differentially diagnosed, such as cholesteatoma, cholesterol granuloma, eosinophilic otitis media, malignant otitis externa, skull-base osteomyelitis, neoplasm, and otitis media or inner ear inflammation caused by autoimmune disease and vasculitis other than AAV. A total of 10 patients with ANCA-mediated otitis media were enrolled in this study, and the detailed clinical characteristics of the patients are presented in Table 1 . The patient population predominantly consisted of females (80%, n = 8), with an older median age of 63 years. Among the 10 patients, 9 had bilateral otitis media, whereas 1 had right-sided otitis media. Eight patients tested positive for MPO antibodies, whereas two tested positive for PR3 antibodies. Upon the diagnosis of ANCA-mediated otitis media, no symptoms of the disease were observed in other organs aside from the ears. The follow-up period for the 10 patients ranged from 12 months to 16 years, with an average duration of 4 years and 11 months. Initial clinical course, otologic symptoms, and tympanic membrane findings The initial clinical course of the 10 patients, such as intractable otitis media with effusion or otorrhea, are listed in Table 1 . Otologic symptoms, which were resistant to antibiotics, steroids, and tympanostomy tube insertion, were observed in all patients. The patient visited the hospital primarily due to hearing loss and otorrhea. Among the 10 patients, 7 were referred to our hospital due to prolonged hearing loss and otorrhea, whereas 3 were transferred due to facial palsy accompanied by otitis media. Moreover, five had a history of tympanostomy tube insertion at a private clinic, whereas four underwent tympanostomy tube insertion during their initial hospital visit. Diagnosing intractable otitis media as the initial manifestation of AAV posed the most significant challenge. Based on our experience with the patients, we identified that precise microscopic or high definition otoendoscopic observation of the tympanic membranes could aid in distinguishing AAV from other forms of otitis media. As shown in Fig. 1 , dilated capillaries were observed from the external ear canal to the tympanic membrane in most patients, which did not respond to antibiotic or steroid treatment. Computed tomography in most patients revealed a soft tissue shadow in the middle ear and/or mastoid cavity without a bony erosion (Fig. 2 ). Audiometric findings After analyzing the results of the hearing tests conducted on 19 ears from 10 patients, we found conductive hearing loss in 7 ears, mixed hearing loss in 10 ears, and sensorineural hearing loss in 2 ears (Table 1 ). Before treatment, the average pure-tone audiometry (PTA) was 75.7 dB (range: 30 dB to 100 dB), which improved to 42.8 dB (range: 15 dB to 100 dB) after treatment. Following the diagnosis and treatment of ANCA-mediated otitis media, improved hearing was observed in all ears, except for one (Table 1 ). Facial palsy and other organ involvement Facial palsy occurred in 6 out of 10 patients (60%). Among them, three had facial paralysis at their first hospital visit, whereas three developed facial palsy during the diagnostic process. Facial palsy was predominantly observed in patients with bilateral otitis media. Out of the nine patients with bilateral otitis media, two had bilateral facial palsy, and four had left facial palsy. Notably, the side with facial palsy consistently correlated with the side exhibiting worse hearing levels in all patients with bilateral otitis media. The median time from the initial onset of otitis media to the occurrence of facial palsy was 3.7 months (range: 1–10 months). On average, facial palsy developed 3.7 months after the onset of otitis media and was primarily categorized as HB grade III–IV (Table 1 ). Importantly, none of the cases manifested facial palsy before the onset of symptoms associated with otitis media. The most severe grade of HB was IV in four patients and III in two patients. None of the cases demonstrated facial nerve palsy after treatments for vasculitis. All patients received a combination of corticosteroids and immunosuppressants as treatment. Following the initiation of this treatment regimen, all patients experienced significant improvement, with no reported relapses. No instances of facial palsy relapse were observed after treatment. The grade of HB at the last visit was I in five patients and II in one patient. On average, this evaluation occurred approximately 3 months after initiating immunosuppressants. Therefore, all patients were deemed to have experienced good recovery from facial palsy, resulting in a total recovery rate of 83.0%. Moreover, no relapses of palsy were observed in any patient during the follow-up period. Two patients underwent surgical intervention to reduce inflammation. However, no specific findings related to AAV were detected from the mucosa or granulation of the tympanic cavity or mastoid. Despite observing bone defects in the fallopian canal and swelling of the facial nerve during surgery, surgical treatments (e.g., mastoidectomy and tympanoplasty) aimed at reducing inflammation and facial nerve compression while improving hearing loss are not recommended in the early stages. This is because such procedures are deemed ineffective and may exacerbate the disease during the active phase of ANCA-mediated otitis media. The disease often involved the lungs (30%, n = 3) and kidneys (10%, n = 1) as additional lesions. Treatments Following serological diagnosis at the ENT department, the patient underwent further evaluation at the rheumatology department. After consultation, the patient commenced steroid and immunosuppressant treatment. For patients, prednisolone (0.3–1 mg/kg/day) and oral cyclophosphamide (25–75 mg/body/day) were prescribed for remission induction therapy. Cyclophosphamide was reduced by 5 mg every 4–8 weeks, after which it was maintained at 12.5–25 mg/day for a certain duration. Further dose reduction would require planning after local and hearing levels exhibit remission. Prednisolone dose reduction begins at 1–2 weeks after local and hearing levels exhibit remission, with the dose being tapered by 5–10 mg weekly up to 15–20 mg/day, which is maintained for at least 3 months. The dosages of steroids and immunosuppressants prescribed to the patients were based on consultation with the rheumatology department at our hospital. DISCUSSION The current study observed the outcomes of intractable chronic otitis media caused by AAV, a condition amenable to medical treatment. Although 10 patients with chronic otitis media attributed to AAV did not satisfy the typical diagnostic criteria, they received early diagnosis and appropriate treatment with a combination of immunosuppressants and steroids. These patients remained controlled without major complications for up to 192 months. The first patient, diagnosed in 2007, did not receive a diagnosis until after 2 months from their first visit. However, in subsequent cases, early diagnosis of AAV was achieved through serological tests prompted by facial nerve paralysis along with characteristic tympanic membrane findings. This allowed for the prompt initiation of appropriate combination immunosuppressant treatment, preventing further complications. The tympanic membrane findings in this disease (Fig. 1 ) are characterized by dilated capillaries appearing on the tympanic membranes. Among the 19 ears examined, 17 exhibited this finding, based on which AAV was diagnosed through serological testing. To diagnose this condition, characteristic tympanic membrane findings must be observed, which require serological tests for confirmation. In clinical practice, cases of chronic otitis media unresponsive to antibiotics are frequently prescribed steroids. However, the use of steroids alone is not a suitable treatment for this condition, and caution is advised due to the risk of delaying or failing to diagnose the disease 9,10 . If not diagnosed and treated early, this condition can involve various organs, which may lead to a poor prognosis 11 . Moreover, in the context of early diagnosis, performing tympanostomy tube insertion in cases with this condition may delay the diagnosis. In this group of patients, all four individuals had pre-existing ventilation tubes, making it challenging to observe accurate tympanic membrane findings. In such situations, the diagnosis was consequently delayed. Regarding treatment, immunosuppressants combined with steroids have been preferred over surgical intervention. Even in cases with severe facial paralysis or deafness, satisfactory results had been observed with medical treatment alone. Although several clinical practice guidelines have been available for the treatment of systemic AAV 12–15 , therapies for AAV localized in the upper respiratory tract and ANCA-mediated otitis media have yet to be standardized. Based on the results of previous studies 8,12–15 , combined administration of both prednisolone and immunosuppressants should initially considered as remission induction therapy for ANCA-mediated otitis media. As mentioned earlier, prednisolone and immunosuppressants, such as a cyclophosphamide or methotrexate, can be more effective at treating ANCA-mediated otitis media and preventing disease relapse and progression than would prednisolone treatment alone 8 . The dosage of steroids and immunosuppressants prescribed to the patients were based on consultations with the rheumatology department at our hospital and recent clinical guidelines 12,13 , as recommended by JMHLW for diseases limited to the upper respiratory tract 16 . Although hearing impairment was present due to chronic otitis media, significant improvements were achieved with a combination therapy of immunosuppressants and steroids. One patient, who had bilateral profound deafness upon initial assessment and did not show improvement even after treatment, underwent cochlear implantation. Among the 9 patients with a total of 17 ears, the mean pretreatment PTA threshold was 72.9 dB, which improved to 36.1 dB after treatment, indicating hearing improvement after treatment, with no subsequent hearing loss due to recurrence. Notably, hearing improvement, defined by a PTA threshold improvement of ≥ 40 dB, was observed in 11 ears (57%), whereas improvement of 20 dB or more was observed in 15 ears (79%), demonstrating favorable outcomes with medical treatment alone. This disease is frequently accompanied by facial paralysis, particularly in the absence of severe inflammation, a feature not commonly observed in general chronic otitis media. It is especially suspected in cases of bilateral facial paralysis. Whereas 1–3% of general chronic otitis media cases exhibit facial paralysis, 6 out of 10 patients with AAV demonstrated the same 17 . Notably, two patients experienced bilateral facial paralysis, a rarity in chronic otitis media. At a time when information about this disease was limited, two patients who visited the hospital underwent mastoidectomy due to facial nerve paralysis associated with otitis media. The surgical findings did not reveal characteristics commonly observed in facial paralysis caused by general chronic otitis media, such as dehiscence of the facial nerve canal, cholesteatoma, or severe granuloma. This indicated differences in the surgical findings between facial paralysis caused by AAV and that resulting from general chronic otitis media. Facial paralysis occurred in six patients, all of whom showed improvement after treatment. Although one patient exhibited incomplete recovery on one side of the face, all remaining patients exhibited complete recovery of facial paralysis. Among these patients, five showed abnormalities in the lungs, and one had renal abnormalities; however, functionally significant abnormalities were not present, and the conditions were under observation. One limitation of this study is the relatively small sample size of 10 patients. However, given the rarity of AAV-mediated otitis media, this study was designed not as an epidemiological study but to emphasize early diagnosis of this rare condition. Further analysis with a larger number of patients is necessary in the future. In conclusion, our study strengthens the call for heightened clinical awareness and astute diagnostic consideration when faced with chronic otitis media cases exhibiting specific clinical features. ANCA-associated otitis media, though infrequent, must remain a critical consideration for healthcare providers, particularly in the presence of intractable symptoms such as otorrhea, facial palsy, and bilateral tympanic membrane findings. Early recognition and expeditious serologic testing, followed by timely intervention, are pivotal in securing positive patient outcomes. By preventing disease progression and mitigating hearing loss and facial palsy, early diagnosis and treatment can significantly enhance patient well-being. Furthermore, our findings provide a compelling basis for refining treatment guidelines specific to ANCA-associated otitis media and underscore the centrality of immunosuppressive therapies, rather than surgical interventions, in the management of this distinctive clinical entity. Acknowledging this distinction can profoundly influence the care and outcomes of patients presenting with this rare yet curable condition. METHODS We retrospectively reviewed the medical records of patients with intractable otitis media as the initial manifestation of AAV who were treated at the Department of Otolaryngology, Head and Neck Surgery, Kyungpook National University Hospital between 2007 and 2023. Patients who were followed up for more than 12 months were included in this study. All patients who satisfied all of the following criteria were included in the study: ( 1 ) long-standing otitis media with effusion or otorrhea resistant to antibiotics, steroid alone, and the insertion of tympanic ventilation tubes; ( 2 ) positive serum myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA; ( 3 ) absence of AAV lesions outside the ear upon initial diagnosis; ( 4 ) all other causes of intractable otitis media differentially diagnosed, such as cholesteatoma, cholesterol granuloma, eosinophilic otitis media, malignant otitis externa, skull-base osteomyelitis, neoplasm, and otitis media or inner ear inflammation caused by autoimmune disease and vasculitis other than AAV. The study was approved by the Kyungpook National University Hospital Institutional Review Board (approval no. 2024-02-023). Informed consent was waived by the Kyungpook National University Hospital Institutional Review Board owing to the retrospective study design. This study was carried out in accordance with the approved guidelines and the Declaration of Helsinki. The patients’ hearing levels were assessed through pure-tone audiometry before and after treatment and expressed as a weighted four-frequency pure-tone average calculated according to the 1995 American Academy of Otolaryngology–Head and Neck Surgery, Committee on Hearing and Equilibrium consensus guidelines 18 . The average air and bone conduction pure-tone audiometry (PTA) thresholds were separated into four frequencies (0.5, 1, 2, and 3, kHz) within the speech range. Statistical analysis Differences in each parameter between the two groups were analyzed using the Wilcoxon signed-rank test. A p value of < 0.05 indicated statistical significance (SAS Institute, Inc., Cary, NC). Declarations Conflict of interest statement: No potential conflict of interest relevant to this article was reported. Author Contribution AUTHOR CONTRIBUTIONS Conceptualization: Kyu Yyp Lee, Ji Song Hong. Data curation: Ji Song Hong, Da Jung Jung, Myung Hoon Yoo, Eun Hye Kwon, Seung Woo Han, Kyu Yyp Lee. Formal analysis: Ji Song Hong. Funding acquisition: Kyu Yyp Lee. Investigation: Ji Song Hong. Methodology: Ji Song Hong. Supervision: Kyu Yyp Lee. Validation: Ji Song Hong. Visualization: Ji Song Hong. Writing–original draft: Ji Song Hong. Writing–review & editing: Ji Song Hong, Seung Woo Han, Kyu Yyp Lee. Acknowledgement: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HR22C1832) Data Availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. References Rowaiye, O. O., Kusztal, M. & Klinger, M. The kidneys and ANCA-associated vasculitis: from pathogenesis to diagnosis. Clin Kidney J 8, 343–350, doi: 10.1093/ckj/sfv020 (2015). Jennette, J. C. Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol 17, 603–606, doi: 10.1007/s10157-013-0869-6 (2013). Ferri, E., Armato, E., Capuzzo, P., Cavaleri, S. & Ianniello, F. Early diagnosis of Wegener's granulomatosis presenting with bilateral facial paralysis and bilateral serous otitis media. Auris Nasus Larynx 34, 379–382, doi: 10.1016/j.anl.2007.01.005 (2007). Mori, A. et al. Bilateral facial nerve palsy due to otitis media associated with myeloperoxidase-antineutrophil cytoplasmic antibody. Am J Med Sci 346, 240–243, doi: 10.1097/MAJ.0b013e318288371f (2013). Wojciechowska, J., Krajewski, W., Krajewski, P. & Krecicki, T. Granulomatosis With Polyangiitis in Otolaryngologist Practice: A Review of Current Knowledge. Clin Exp Otorhinolaryngol 9, 8–13, doi: 10.21053/ceo.2016.9.1.8 (2016). Fauci, A. S., Haynes, B. F., Katz, P. & Wolff, S. M. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 98, 76–85, doi: 10.7326/0003-4819-98-1-76 (1983). Wierzbicka, M., Szyfter, W., Puszczewicz, M., Borucki, L. & Bartochowska, A. Otologic symptoms as initial manifestation of wegener granulomatosis: diagnostic dilemma. Otol Neurotol 32, 996–1000, doi: 10.1097/MAO.0b013e31822558fd (2011). Harabuchi, Y. et al. Clinical features and treatment outcomes of otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV): A retrospective analysis of 235 patients from a nationwide survey in Japan. Mod Rheumatol 27, 87–94, doi: 10.1080/14397595.2016.1177926 (2017). Charles, S. J., Meyer, P. A. & Watson, P. G. Diagnosis and management of systemic Wegener's granulomatosis presenting with anterior ocular inflammatory disease. Br J Ophthalmol 75, 201–207, doi: 10.1136/bjo.75.4.201 (1991). de Groot, K. et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med 150, 670–680, doi: 10.7326/0003-4819-150-10-200905190-00004 (2009). Pearce, F. A. et al. Can granulomatosis with polyangiitis be diagnosed earlier in primary care? A case-control study. QJM 111, 39–45, doi: 10.1093/qjmed/hcx194 (2018). Nagasaka, K. et al. Systematic review and meta-analysis for 2017 clinical practice guidelines of the Japan research committee of the ministry of health, labour, and welfare for intractable vasculitis for the management of ANCA-associated vasculitis. Mod Rheumatol 29, 119–129, doi: 10.1080/14397595.2018.1500111 (2019). Harigai, M. et al. 2017 Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis. Mod Rheumatol 29, 20–30, doi: 10.1080/14397595.2018.1500437 (2019). Yates, M. et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 75, 1583–1594, doi: 10.1136/annrheumdis-2016-209133 (2016). Ntatsaki, E. et al. BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology (Oxford) 53, 2306–2309, doi: 10.1093/rheumatology/ ket445 (2014). Sada, K. E. et al. Different responses to treatment across classified diseases and severities in Japanese patients with microscopic polyangiitis and granulomatosis with polyangiitis: a nationwide prospective inception cohort study. Arthritis Res Ther 17, 305, doi: 10.1186/s13075-015-0815-y (2015). Choi, J. W. & Park, Y. H. Facial Nerve Paralysis in Patients With Chronic Ear Infections: Surgical Outcomes and Radiologic Analysis. Clin Exp Otorhinolaryngol 8, 218–223, doi: 10.3342/ceo.2015.8.3.218 (2015). Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy in Meniere's disease. American Academy of Otolaryngology-Head and Neck Foundation, Inc. Otolaryngol Head Neck Surg 113, 181–185, doi: 10.1016/S0194-5998(95)70102-8 (1995). Tables Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files table1.pdf 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-4786009","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":341000626,"identity":"6382b558-f6b6-467f-a322-108f01eb4e58","order_by":0,"name":"Ji Song Hong","email":"","orcid":"","institution":"Kyungpook National University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ji","middleName":"Song","lastName":"Hong","suffix":""},{"id":341000627,"identity":"6fddafa8-f3d6-4418-b0c0-8323ef4d3791","order_by":1,"name":"Da Jung Jung","email":"","orcid":"","institution":"Kyungpook National University 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06:10:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4786009/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4786009/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63420439,"identity":"02395e88-9a07-4141-8659-52d73d1f86d6","added_by":"auto","created_at":"2024-08-28 02:38:05","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":675376,"visible":true,"origin":"","legend":"\u003cp\u003eThe capillaries (arrow) were dilated from the external ear canal to the tympanic membrane, especially in the posterior quadrant.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4786009/v1/d3de0be3e5971c4d3b372d1e.jpeg"},{"id":63420438,"identity":"271e6882-f7d7-4ffe-8e83-d8ac5c352244","added_by":"auto","created_at":"2024-08-28 02:38:05","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":585094,"visible":true,"origin":"","legend":"\u003cp\u003eTemporal bone CT: Both sclerotic mastoid cavities were occupied by a soft shadow without an ossicle or bony erosion.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4786009/v1/c1c8a4dbd2ae9374a3a3457f.jpeg"},{"id":71503257,"identity":"661500c8-673e-4f51-b732-a889fb4cb6b9","added_by":"auto","created_at":"2024-12-16 09:24:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1595457,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4786009/v1/907ea731-f225-4bd7-bdc4-35ba36a32e3f.pdf"},{"id":63421334,"identity":"cee31733-29fc-4f47-8aa6-07b51f546621","added_by":"auto","created_at":"2024-08-28 02:46:05","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":116434,"visible":true,"origin":"","legend":"","description":"","filename":"table1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4786009/v1/42f047960b5bae1e82c59788.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnosis and management of chronic intractable otitis media as an initial manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV)","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic necrotizing vasculitis that affects small to medium-sized vessels \u003csup\u003e1\u003c/sup\u003e. AAV can be divided into three categories: granulomatosis with polyangiitis, microscopic poly angiitis, and eosinophilic granulomatosis polyangiitis \u003csup\u003e2\u003c/sup\u003e. Reports have shown that otitis media is an otologic manifestation of existing AAV \u003csup\u003e3,4\u003c/sup\u003e. Patients with AAV may suffer from only otologic symptoms, such as intractable otitis media, hearing loss, and facial palsy, without lung and kidney lesions \u003csup\u003e5\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eEarly diagnosis and treatment of AAV are crucial for patient survival, with delayed or missed diagnosis worsening the prognosis \u003csup\u003e6\u003c/sup\u003e. However, a favorable prognosis can be expected with appropriately diagnosis and treatment initiation at the early stages of AAV. Therefore, early diagnosis and treatment are important in preventing irreversible progression. However, early diagnosis of AAV localized to the middle ear is challenging \u003csup\u003e7\u003c/sup\u003e. Not only are such cases rare, they also do not exhibit other AAV-related organ lesions at the initial visit \u003csup\u003e5\u003c/sup\u003e. As such, they fail to fulfill the ordinary diagnostic criteria for AAV and cannot undergo intensive treatment, such as corticosteroids and/or immunosuppressants, at an early stage \u003csup\u003e8\u003c/sup\u003e. Thus we sought to investigate the clinical features and outcomes in patients presenting with intractable otitis media as the initial manifestation of AAV, aiming to facilitate the diagnosis and understanding of the disease, and to identify factors associated with early diagnosis and outcomes..\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003ePatient characteristics\u003c/h2\u003e\n\u003cp\u003eWe retrospectively reviewed the medical records of patients with intractable otitis media as the initial manifestation of AAV who were treated at the tertiary medical hospital in Korea. Patients who were followed up for more than 12 months were included in this study.\u003c/p\u003e\n\u003cp\u003eAll patients who satisfied all of the following criteria were included in the study: (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e) long-standing otitis media with effusion or otorrhea, unresponsive to standard treatments including antibiotics, steroid alone, and the insertion of tympanic ventilation tubes; (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e) positive serum myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA; (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e) absence of AAV lesions outside the ear upon initial diagnosis; (\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e) all other causes of intractable otitis media differentially diagnosed, such as cholesteatoma, cholesterol granuloma, eosinophilic otitis media, malignant otitis externa, skull-base osteomyelitis, neoplasm, and otitis media or inner ear inflammation caused by autoimmune disease and vasculitis other than AAV.\u003c/p\u003e\n\u003cp\u003eA total of 10 patients with ANCA-mediated otitis media were enrolled in this study, and the detailed clinical characteristics of the patients are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The patient population predominantly consisted of females (80%, n\u0026thinsp;=\u0026thinsp;8), with an older median age of 63 years. Among the 10 patients, 9 had bilateral otitis media, whereas 1 had right-sided otitis media. Eight patients tested positive for MPO antibodies, whereas two tested positive for PR3 antibodies. Upon the diagnosis of ANCA-mediated otitis media, no symptoms of the disease were observed in other organs aside from the ears.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eThe follow-up period for the 10 patients ranged from 12 months to 16 years, with an average duration of 4 years and 11 months.\u003c/p\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003eInitial clinical course, otologic symptoms, and tympanic membrane findings\u003c/h2\u003e\n\u003cp\u003eThe initial clinical course of the 10 patients, such as intractable otitis media with effusion or otorrhea, are listed in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Otologic symptoms, which were resistant to antibiotics, steroids, and tympanostomy tube insertion, were observed in all patients.\u003c/p\u003e\n\u003cp\u003eThe patient visited the hospital primarily due to hearing loss and otorrhea. Among the 10 patients, 7 were referred to our hospital due to prolonged hearing loss and otorrhea, whereas 3 were transferred due to facial palsy accompanied by otitis media. Moreover, five had a history of tympanostomy tube insertion at a private clinic, whereas four underwent tympanostomy tube insertion during their initial hospital visit.\u003c/p\u003e\n\u003cp\u003eDiagnosing intractable otitis media as the initial manifestation of AAV posed the most significant challenge. Based on our experience with the patients, we identified that precise microscopic or high definition otoendoscopic observation of the tympanic membranes could aid in distinguishing AAV from other forms of otitis media. As shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, dilated capillaries were observed from the external ear canal to the tympanic membrane in most patients, which did not respond to antibiotic or steroid treatment. Computed tomography in most patients revealed a soft tissue shadow in the middle ear and/or mastoid cavity without a bony erosion (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eAudiometric findings\u003c/h2\u003e\n\u003cp\u003eAfter analyzing the results of the hearing tests conducted on 19 ears from 10 patients, we found conductive hearing loss in 7 ears, mixed hearing loss in 10 ears, and sensorineural hearing loss in 2 ears (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Before treatment, the average pure-tone audiometry (PTA) was 75.7 dB (range: 30 dB to 100 dB), which improved to 42.8 dB (range: 15 dB to 100 dB) after treatment. Following the diagnosis and treatment of ANCA-mediated otitis media, improved hearing was observed in all ears, except for one (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003eFacial palsy and other organ involvement\u003c/h2\u003e\n\u003cp\u003eFacial palsy occurred in 6 out of 10 patients (60%). Among them, three had facial paralysis at their first hospital visit, whereas three developed facial palsy during the diagnostic process. Facial palsy was predominantly observed in patients with bilateral otitis media. Out of the nine patients with bilateral otitis media, two had bilateral facial palsy, and four had left facial palsy. Notably, the side with facial palsy consistently correlated with the side exhibiting worse hearing levels in all patients with bilateral otitis media. The median time from the initial onset of otitis media to the occurrence of facial palsy was 3.7 months (range: 1\u0026ndash;10 months). On average, facial palsy developed 3.7 months after the onset of otitis media and was primarily categorized as HB grade III\u0026ndash;IV (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Importantly, none of the cases manifested facial palsy before the onset of symptoms associated with otitis media. The most severe grade of HB was IV in four patients and III in two patients. None of the cases demonstrated facial nerve palsy after treatments for vasculitis. All patients received a combination of corticosteroids and immunosuppressants as treatment. Following the initiation of this treatment regimen, all patients experienced significant improvement, with no reported relapses. No instances of facial palsy relapse were observed after treatment. The grade of HB at the last visit was I in five patients and II in one patient. On average, this evaluation occurred approximately 3 months after initiating immunosuppressants. Therefore, all patients were deemed to have experienced good recovery from facial palsy, resulting in a total recovery rate of 83.0%. Moreover, no relapses of palsy were observed in any patient during the follow-up period. Two patients underwent surgical intervention to reduce inflammation. However, no specific findings related to AAV were detected from the mucosa or granulation of the tympanic cavity or mastoid. Despite observing bone defects in the fallopian canal and swelling of the facial nerve during surgery, surgical treatments (e.g., mastoidectomy and tympanoplasty) aimed at reducing inflammation and facial nerve compression while improving hearing loss are not recommended in the early stages. This is because such procedures are deemed ineffective and may exacerbate the disease during the active phase of ANCA-mediated otitis media. The disease often involved the lungs (30%, n\u0026thinsp;=\u0026thinsp;3) and kidneys (10%, n\u0026thinsp;=\u0026thinsp;1) as additional lesions.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003eTreatments\u003c/h2\u003e\n\u003cp\u003eFollowing serological diagnosis at the ENT department, the patient underwent further evaluation at the rheumatology department. After consultation, the patient commenced steroid and immunosuppressant treatment. For patients, prednisolone (0.3\u0026ndash;1 mg/kg/day) and oral cyclophosphamide (25\u0026ndash;75 mg/body/day) were prescribed for remission induction therapy. Cyclophosphamide was reduced by 5 mg every 4\u0026ndash;8 weeks, after which it was maintained at 12.5\u0026ndash;25 mg/day for a certain duration. Further dose reduction would require planning after local and hearing levels exhibit remission. Prednisolone dose reduction begins at 1\u0026ndash;2 weeks after local and hearing levels exhibit remission, with the dose being tapered by 5\u0026ndash;10 mg weekly up to 15\u0026ndash;20 mg/day, which is maintained for at least 3 months. The dosages of steroids and immunosuppressants prescribed to the patients were based on consultation with the rheumatology department at our hospital.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe current study observed the outcomes of intractable chronic otitis media caused by AAV, a condition amenable to medical treatment. Although 10 patients with chronic otitis media attributed to AAV did not satisfy the typical diagnostic criteria, they received early diagnosis and appropriate treatment with a combination of immunosuppressants and steroids. These patients remained controlled without major complications for up to 192 months. The first patient, diagnosed in 2007, did not receive a diagnosis until after 2 months from their first visit. However, in subsequent cases, early diagnosis of AAV was achieved through serological tests prompted by facial nerve paralysis along with characteristic tympanic membrane findings. This allowed for the prompt initiation of appropriate combination immunosuppressant treatment, preventing further complications. The tympanic membrane findings in this disease (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) are characterized by dilated capillaries appearing on the tympanic membranes. Among the 19 ears examined, 17 exhibited this finding, based on which AAV was diagnosed through serological testing.\u003c/p\u003e \u003cp\u003eTo diagnose this condition, characteristic tympanic membrane findings must be observed, which require serological tests for confirmation. In clinical practice, cases of chronic otitis media unresponsive to antibiotics are frequently prescribed steroids. However, the use of steroids alone is not a suitable treatment for this condition, and caution is advised due to the risk of delaying or failing to diagnose the disease \u003csup\u003e9,10\u003c/sup\u003e. If not diagnosed and treated early, this condition can involve various organs, which may lead to a poor prognosis \u003csup\u003e11\u003c/sup\u003e. Moreover, in the context of early diagnosis, performing tympanostomy tube insertion in cases with this condition may delay the diagnosis. In this group of patients, all four individuals had pre-existing ventilation tubes, making it challenging to observe accurate tympanic membrane findings. In such situations, the diagnosis was consequently delayed.\u003c/p\u003e \u003cp\u003eRegarding treatment, immunosuppressants combined with steroids have been preferred over surgical intervention. Even in cases with severe facial paralysis or deafness, satisfactory results had been observed with medical treatment alone. Although several clinical practice guidelines have been available for the treatment of systemic AAV \u003csup\u003e12\u0026ndash;15\u003c/sup\u003e, therapies for AAV localized in the upper respiratory tract and ANCA-mediated otitis media have yet to be standardized. Based on the results of previous studies \u003csup\u003e8,12\u0026ndash;15\u003c/sup\u003e, combined administration of both prednisolone and immunosuppressants should initially considered as remission induction therapy for ANCA-mediated otitis media. As mentioned earlier, prednisolone and immunosuppressants, such as a cyclophosphamide or methotrexate, can be more effective at treating ANCA-mediated otitis media and preventing disease relapse and progression than would prednisolone treatment alone \u003csup\u003e8\u003c/sup\u003e. The dosage of steroids and immunosuppressants prescribed to the patients were based on consultations with the rheumatology department at our hospital and recent clinical guidelines \u003csup\u003e12,13\u003c/sup\u003e, as recommended by JMHLW for diseases limited to the upper respiratory tract \u003csup\u003e16\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlthough hearing impairment was present due to chronic otitis media, significant improvements were achieved with a combination therapy of immunosuppressants and steroids. One patient, who had bilateral profound deafness upon initial assessment and did not show improvement even after treatment, underwent cochlear implantation. Among the 9 patients with a total of 17 ears, the mean pretreatment PTA threshold was 72.9 dB, which improved to 36.1 dB after treatment, indicating hearing improvement after treatment, with no subsequent hearing loss due to recurrence. Notably, hearing improvement, defined by a PTA threshold improvement of \u0026ge;\u0026thinsp;40 dB, was observed in 11 ears (57%), whereas improvement of 20 dB or more was observed in 15 ears (79%), demonstrating favorable outcomes with medical treatment alone.\u003c/p\u003e \u003cp\u003eThis disease is frequently accompanied by facial paralysis, particularly in the absence of severe inflammation, a feature not commonly observed in general chronic otitis media. It is especially suspected in cases of bilateral facial paralysis. Whereas 1\u0026ndash;3% of general chronic otitis media cases exhibit facial paralysis, 6 out of 10 patients with AAV demonstrated the same\u003csup\u003e17\u003c/sup\u003e. Notably, two patients experienced bilateral facial paralysis, a rarity in chronic otitis media. At a time when information about this disease was limited, two patients who visited the hospital underwent mastoidectomy due to facial nerve paralysis associated with otitis media. The surgical findings did not reveal characteristics commonly observed in facial paralysis caused by general chronic otitis media, such as dehiscence of the facial nerve canal, cholesteatoma, or severe granuloma. This indicated differences in the surgical findings between facial paralysis caused by AAV and that resulting from general chronic otitis media. Facial paralysis occurred in six patients, all of whom showed improvement after treatment. Although one patient exhibited incomplete recovery on one side of the face, all remaining patients exhibited complete recovery of facial paralysis.\u003c/p\u003e \u003cp\u003eAmong these patients, five showed abnormalities in the lungs, and one had renal abnormalities; however, functionally significant abnormalities were not present, and the conditions were under observation.\u003c/p\u003e \u003cp\u003eOne limitation of this study is the relatively small sample size of 10 patients. However, given the rarity of AAV-mediated otitis media, this study was designed not as an epidemiological study but to emphasize early diagnosis of this rare condition. Further analysis with a larger number of patients is necessary in the future.\u003c/p\u003e \u003cp\u003eIn conclusion, our study strengthens the call for heightened clinical awareness and astute diagnostic consideration when faced with chronic otitis media cases exhibiting specific clinical features. ANCA-associated otitis media, though infrequent, must remain a critical consideration for healthcare providers, particularly in the presence of intractable symptoms such as otorrhea, facial palsy, and bilateral tympanic membrane findings. Early recognition and expeditious serologic testing, followed by timely intervention, are pivotal in securing positive patient outcomes. By preventing disease progression and mitigating hearing loss and facial palsy, early diagnosis and treatment can significantly enhance patient well-being.\u003c/p\u003e \u003cp\u003e Furthermore, our findings provide a compelling basis for refining treatment guidelines specific to ANCA-associated otitis media and underscore the centrality of immunosuppressive therapies, rather than surgical interventions, in the management of this distinctive clinical entity. Acknowledging this distinction can profoundly influence the care and outcomes of patients presenting with this rare yet curable condition.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e We retrospectively reviewed the medical records of patients with intractable otitis media as the initial manifestation of AAV who were treated at the Department of Otolaryngology, Head and Neck Surgery, Kyungpook National University Hospital between 2007 and 2023. Patients who were followed up for more than 12 months were included in this study.\u003c/p\u003e \u003cp\u003eAll patients who satisfied all of the following criteria were included in the study: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) long-standing otitis media with effusion or otorrhea resistant to antibiotics, steroid alone, and the insertion of tympanic ventilation tubes; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) positive serum myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) absence of AAV lesions outside the ear upon initial diagnosis; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) all other causes of intractable otitis media differentially diagnosed, such as cholesteatoma, cholesterol granuloma, eosinophilic otitis media, malignant otitis externa, skull-base osteomyelitis, neoplasm, and otitis media or inner ear inflammation caused by autoimmune disease and vasculitis other than AAV. The study was approved by the Kyungpook National University Hospital Institutional Review Board (approval no. 2024-02-023). Informed consent was waived by the Kyungpook National University Hospital Institutional Review Board owing to the retrospective study design. This study was carried out in accordance with the approved guidelines and the Declaration of Helsinki.\u003c/p\u003e \u003cp\u003eThe patients\u0026rsquo; hearing levels were assessed through pure-tone audiometry before and after treatment and expressed as a weighted four-frequency pure-tone average calculated according to the 1995 American Academy of Otolaryngology\u0026ndash;Head and Neck Surgery, Committee on Hearing and Equilibrium consensus guidelines \u003csup\u003e18\u003c/sup\u003e. The average air and bone conduction pure-tone audiometry (PTA) thresholds were separated into four frequencies (0.5, 1, 2, and 3, kHz) within the speech range.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDifferences in each parameter between the two groups were analyzed using the Wilcoxon signed-rank test. A p value of \u0026lt;\u0026thinsp;0.05 indicated statistical significance (SAS Institute, Inc., Cary, NC).\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest statement:\u003c/h2\u003e \u003cp\u003eNo potential conflict of interest relevant to this article was reported.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAUTHOR CONTRIBUTIONS Conceptualization: Kyu Yyp Lee, Ji Song Hong. Data curation: Ji Song Hong, Da Jung Jung, Myung Hoon Yoo, Eun Hye Kwon, Seung Woo Han, Kyu Yyp Lee. Formal analysis: Ji Song Hong. Funding acquisition: Kyu Yyp Lee. Investigation: Ji Song Hong. Methodology: Ji Song Hong. Supervision: Kyu Yyp Lee. Validation: Ji Song Hong. Visualization: Ji Song Hong. Writing\u0026ndash;original draft: Ji Song Hong. Writing\u0026ndash;review \u0026amp; editing: Ji Song Hong, Seung Woo Han, Kyu Yyp Lee.\u003c/p\u003e\u003ch2\u003eAcknowledgement:\u003c/h2\u003e \u003cp\u003eThis research was supported by a grant of the Korea Health Technology R\u0026amp;D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health \u0026amp; Welfare, Republic of Korea (grant number: HR22C1832)\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRowaiye, O. 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This study aimed to facilitate the diagnosis and understanding of the clinical features of intractable otitis media as the initial manifestation of ANCA-associated vasculitis (AAV) and provide a compelling basis for refining treatment guidelines specific to this rare condition. We retrospectively analyzed the medical records of patients exhibiting intractable chronic otitis media as their initial AAV. The most common initial symptoms were intractable chronic otitis media with effusion or otorrhea, unresponsive to standard treatments, leading to progressive hearing loss and facial palsy. Patients exhibited characteristic tympanic membrane findings, including typical vasodilated hypervascularity. Facial palsy was a common accompanying symptom, affecting 60% of the patients. Following a treatment regimen involving a combination of corticosteroids and immunosuppressants, otitis media subsided, restoring hearing. After initiating treatment with corticosteroids and immunosuppressants, all patients experienced significant improvement, with no reported relapses. Intractable chronic otitis media, as the initial presentation of AAV, originated from the middle ear before progressing to other organs, potentially causing severe otologic complications such as facial palsy and hearing loss. However, timely diagnosis of ANCA-associated otitis media and initiation of treatment should be considered to improve clinical outcomes.\u003c/p\u003e","manuscriptTitle":"Diagnosis and management of chronic intractable otitis media as an initial manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-28 02:38:00","doi":"10.21203/rs.3.rs-4786009/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":"31dc3f7f-ec71-4624-8e17-6dfa212f55bf","owner":[],"postedDate":"August 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":36129802,"name":"Biological sciences/Immunology/Autoimmunity"},{"id":36129803,"name":"Health sciences/Rheumatology"}],"tags":[],"updatedAt":"2024-12-16T09:24:16+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-28 02:38:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4786009","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4786009","identity":"rs-4786009","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}