Eosinophilic Otitis Media Research Articles

Intractable otitis media-Pathogenesis and treatment of Eosinophilic otitis media (EOM) and otitis media with Antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (OMAAV)

Intractable otitis media-Pathogenesis and treatment of Eosinophilic otitis media (EOM) and otitis media with Antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (OMAAV)

Biologics for eosinophilic otitis media: a retrospective case study in a multidisciplinary center.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is refractory to conventional treatments and is strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The diagnostic criteria for EOM were established by IINO in 2011. With the recognition of type 2 inflammatory diseases, the gold standard of treatment is the systemic and topical administration of corticosteroids. Recently, several retrospective studies have demonstrated the efficacy of biologic treatments in EOM. We aimed to share our experience regarding the response of EOM after the use of biologics. This is a retrospective observational analysis including patients with refractory EOM treated with different biologics (benralizumab, omalizumab, mepolizumab, dupilumab) for concomitant severe asthma, urticaria and/or severe uncontrolled CRSwNP from 2011 to 2023. Treatment effectiveness in terms of EOM severity was measured using medical Global Evaluation of Treatment Effectiveness (GETE). We illustrated 4 clinical cases of uncontrolled comorbid EOM and demonstrated the complexity of multidisciplinary medical pathway with good response to biologics. We also observed that response to EOM and CRSwNP does not always follow that of asthma. The results of our small sample were consistent with those found in the literature and showed control of EOM with biologics. We need a larger multicentric sample and methodology to confirm these results and to compare the efficacy of different biologics.

Efficacy of biologics for eosinophilic otitis media

Background Eosinophilic otitis media (EOM) is an intractable condition primarily treated with steroids. Recently, biologics targeting IgE or IL-5 have been introduced. Objectives This study aimed to evaluate the efficacy of biologics for EOM. Materials and Methods We retrospectively collected data on EOM patients treated from January 2008 to December 2020 from electronic medical records. Patients were classified into the steroid group, treated with systemic or local steroids, and the biologics group, treated with biologics with or without steroids. Results The otorrhea remission rate was 63.33% in the steroid group, comparable to 58.82% in the biologics group (p = 0.760). Before treatment, the steroid group showed better bone-conduction (BC) thresholds at 0.5 kHz and 1 kHz than the biologics group. Post-treatment, the steroid group improved in air-conduction (AC) threshold and air-bone gap (ABG) at 1 kHz and 2 kHz. The biologics group exhibited stable audiological results. No significant differences were observed post-treatment between the groups, except for the BC threshold at 0.5 kHz, which remained as pre-treatment. Conclusions and Significance Biologics demonstrated similar efficacy in otorrhea remission as steroids and might help maintain hearing levels. Biologics can be considered for controlling EOM with active otorrhea and reducing systemic steroid use.

Bezold Abscess in a Case of Eosinophilic Otitis Media.

A 57-year-old man with a history of bronchial asthma and eosinophilic sinusitis presented to the emergency department with an exacerbation of otitis media. His primary complaints were otopyorrhea, headache, and neck pain with redness. Contrast-enhanced computed tomography revealed a posterior neck abscess contiguous with the mastoid process. The patient underwent mastoidectomy and received antimicrobial therapy. Eosinophilic granulation tissue in the middle ear obstructed the middle ear aditus and directed the inflammatory process toward the mastoid tip. Bezold abscess is a rare extracranial complication of acute mastoiditis. Therefore, clinicians should consider neck pain with redness as an important physical sign that suggests Bezold abscess in patients with otitis media.

Dupilumab in the Treatment of Eosinophilic Otitis Media: A Case Report

Eosinophilic otitis media (EOM) differs from classic chronic otitis media as it is a refractory disease with the accumulation of eosinophils in thick mucinous middle ear effusion and mucosa. A 66-year-old male with a history of asthma, chronic sinusitis with polyposis, nasal polyposis, and multiple sets of ventilation tubes was presented to our center for the management of hearing loss and otorrhea. He had a history of consistent otorrhea and hearing loss even with the ventilation tube insertions and medical treatment. Both systemic and intratympanic steroid was administered, but the effect was insignificant and other systemic adverse effects occurred. Finally, the otologic symptoms including hearing loss and otorrhea improved after being given a Dupilumab injection. This case report discusses Dupilumab treatment resulting in remission in a patient suffering from refractory EOM.

Efficacy of dupilumab and risk factors for dupilumab-induced hypereosinophilia in severe asthma: a preliminary study from China

Objective Dupilumab has been approved for the treatment of severe asthma with type 2 inflammation by inhibiting interleukin (IL)-4 and IL-13 signaling. However, dupilumab-induced hypereosinophilia (HE) has been reported and should not be ignored. The aim of this study was to investigate the efficacy of dupilumab in Chinese patients with severe asthma, whether HE affects its efficacy, and the possible risk factors for HE. Methods 20 patients with severe asthma who received dupilumab treatment for at least 12 months in the First Affiliated Hospital of Guangzhou Medical University from 2019 to 2022 were included. We compared clinical data and laboratory tests results before dupilumab treatment and at 4 and 12 months after treatment. Based on whether dupilumab treatment triggers HE defined as blood eosinophil count (BEC) ≥ 1.5 × 109 cells/L, the patients were allocated into non-HE and HE groups. Results The patients showed a significant increase in asthma control test (ACT) scores, a decrease in the number of exacerbations, a decrease in the proportion of patients taking an oral corticosteroid (OCS) and in the dose, and a significant improvement in the pulmonary function parameters FEV1/FVC (%) and FEV1 (% predicted) after 4 and 12 months of treatment with dupilumab. For type 2 inflammatory biomarkers, the levels of fractional concentration of exhaled nitric oxide (FeNO), sputum eosinophil count percentage (SEC%) and total immunoglobulin E (TIgE) decreased significantly, whereas BEC were higher after 4 months of treatment, but returned to baseline levels after 12 months. 8 patients (40%) developed asymptomatic HE after dupilumab, and the efficacy was not significantly different between the HE and non-HE groups. The earliest BEC elevation appeared at 1 month after treatment, but most of them declined after 6 months, and basically returned to the baseline level around 12 months of treatment. In addition, we further found that when patients had FeNO ≥ 60 ppb, food allergens positive and combined eosinophilic otitis media (EOM), their BEC increased significantly more than that of the control group after 4 months as well as 12 months of treatment. Conclusions This study demonstrated that dupilumab was efficacious in Chinese patients with severe asthma, and some patients developed asymptomatic, self-limited HE, which did not affect its efficacy. Additionally, FeNO ≥60 ppb, food allergens positive, and co-morbidities with EOM may be the risk factors for developing HE.

A Case of Eosinophilic Otitis Media Who Developed Temporal Muscle Abscess and Facial Nerve Palsy due to MRSA Infection

A Case of Eosinophilic Otitis Media Who Developed Temporal Muscle Abscess and Facial Nerve Palsy due to MRSA Infection

Clinical observation of the course of eosinophilic otitis media against the background of biological therapy of chronic polypous rhinosinusitis

Clinical observation of the course of eosinophilic otitis media against the background of biological therapy of chronic polypous rhinosinusitis

Diagnosis of Eosinophilic Otitis Media Using Blood Eosinophil Levels

Eosinophilic otitis media (EOM) is a rare middle ear disease with unfavorable outcomes. Under the current diagnostic criteria of EOM, it is challenging to suspect EOM before tympanostomy. Therefore, this study attempted to use blood eosinophil levels for the differential diagnosis of EOM from other conditions. Three disease groups with features of recurrent otorrhea were categorized, which included the following: EOM (n = 9), granulomatosis with polyangiitis (GPA, n = 12), and primary ciliary dyskinesia (PCD, n = 6). Clinical and radiological characteristics were analyzed in the three groups. Patients who underwent ventilation tube insertion due to serous otitis media were enrolled as the control group (n = 225) to evaluate the diagnostic validity of blood eosinophilia. The EOM group showed a significantly higher blood eosinophil concentration (p < 0.001) and blood eosinophil count (p < 0.001) compared to the GPA and PCD groups. The estimated sensitivity and specificity for diagnosing EOM from OME patients who underwent ventilation tube insertion were 100% and 95.6%, respectively. In addition, EOM tended to have protympanic space soft tissue density and a relatively clear retrotympanic space in temporal bone computerized tomography. Blood eosinophil evaluation is a significant clinical indicator of EOM. Furthermore, the assessment of exclusive protympanic soft tissue density can provide an additional diagnostic clue.

Higher Prevalence and Severity of Eosinophilic Otitis Media in Patients with Asthma-COPD Overlap Compared with Asthma Alone

Introduction: Eosinophilic otitis media (EOM) is well-known to frequently co-exist with adult-onset asthma. Both diseases are similar type 2 inflammation and are considered to have a “one airway, one disease” relationship. Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO), characterized by airway obstruction caused by airway wall thickening (AWT), is a severe condition with a higher incidence of mortality compared to asthma alone or COPD alone. Based on the “one airway, one disease” concept, we hypothesized that the inflammatory pathophysiology of EOM differs depending on its comorbidity with ACO or with asthma alone. Methods: A total of 77 chronic rhinosinusitis (CRS) patients with asthma were enrolled in this study. The subjects were divided into 2 groups: a group with comorbid asthma alone (asthma group; 46 patients), and a group with comorbid ACO (ACO group; 31 patients). The 2 groups were compared and assessed with regard to various factors, including the patients’ clinical characteristics, prevalence rate of EOM, EOM severity, EOMs relationships with smoking and AWT, and the eosinophil and neutrophil cell counts in the middle ear effusion (MEE). Results: The ACO group included significantly more males (p < 0.05), was significantly older (p < 0.05), and showed significantly lower lung function values (FEV1 [L], FEV1 [%pred]) (p < 0.01) compared with the asthma group. The ACO group also had a significant history of smoking as shown by the Brinkman index (p < 0.01) and greater AWT as assessed by high-resolution computed tomography (p < 0.05). The EOM prevalence rate was significantly higher in the ACO group (p < 0.05), especially with increased ACO severity (p < 0.05). The EOM severity was also significantly higher in the ACO group (p < 0.05) and also correlated with the ACO severity (p < 0.05). The pretreatment ear clinical characteristics score and the average air conduction hearing level were significantly higher in the ACO group (p < 0.05). The eosinophil percentage in the MEE/otorrhea was significantly lower in the ACO group (25.3%) than in the asthma group (54.7%) (p < 0.05). Conversely, the neutrophil percentage was significantly higher in the ACO group (75.7% vs. 41.9%) (p < 0.05). Conclusions: Our findings suggest that, in CRS patients with asthma, comorbidity with ACO may be a clinical factor leading to increased EOM prevalence and severity, as well as a higher neutrophil infiltration percentage in the middle ear. Cessation of smoking and early therapeutic intervention for ACO may mitigate progression of bronchial remodeling (i.e., reduce AWT) and help reduce the prevalence and severity of EOM.

Pathophysiological Link Between Chronic Rhinosinusitis and Ear Disease.

In the clinical practice, patients affected by chronic rhinosinusitis (CRS) commonly complain of otologic symptoms. This review aims to describe the available literature evidence assessing the relationship between CRS and ear illnesses published in the last 5years. Available evidence suggests a higher prevalence of otologic symptoms in patients suffering from CRS, affecting up to 87% of patients. These symptoms may be related to Eustachian tube dysfunction, which improves after treatment for CRS. A few studies suggested a potential but not confirmed role of CRS in cholesteatoma, chronic otitis media, and sensorineural hypoacusis. A special type of otitis media with effusion (OME) may occur in patients with CRS, which seems to respond well to new biologic therapy. Ear symptoms appear to be highly prevalent in patients with CRS. So far, the available evidence is robust only for Eustachian tube dysfunction, which has been shown to be particularly impaired in CRS patients. Additionally, the Eustachian tube function appears to improve after treatment for CRS. Finally, interesting preliminary data were described for eosinophilic otitis media, as it appears to respond well to the treatment with biologics.

Myringoplasty for Eosinophilic Otitis Media.

Surgical intervention of eosinophilic otitis media (EOM) has been considered contraindicated because middle ear surgery is associated with a risk of deafness. Myringoplasty is believed to be less invasive. Therefore, we analyzed the surgical results of myringoplasty for perforated eardrums in patients with EOM treated by biological drugs (biologics). Retrospective chart review. Tertiary referral center. Nine ears of seven patients with EOM with eardrum perforation associated with bronchial asthma were treated with add-on biologics; myringoplasty was then performed. The controls comprised 17 ears of 11 patients with EOM treated by myringoplasty without biologics. The EOM status of each patient of both groups was assessed using severity scores, hearing acuity, and temporal bone computed tomography scores. Preoperative and postoperative changes in severity scores and hearing acuity, postoperative closure of the perforation, and relapse of EOM. Severity scores significantly decreased after the use of biologics but did not change after myringoplasty. One patient developed postoperative relapse of middle ear effusion (MEE); in the control group, however, 10 ears developed recurrence of MEE. Significant improvement of the air conduction hearing level was obtained in the biologics group. No patients showed deterioration of the bone conduction hearing level. This is the first report to describe successful surgical interventions with add-on biologics for patients with EOM. In the era of biologics, surgical interventions such as myringoplasty will be indicated to improve hearing and to avoid recurrence of MEE in patients with EOM with perforated eardrums, with the use of biologics.

Eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma: a case report

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis, and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis (ECRS) in cases when there are no findings that suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as refractory asthma and chronic rhinosinusitis (CRS). Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with refractory asthma and CRS associated with dupilumab, few studies have examined the development of EGPA.Case presentationWe report a case of a 61-year-old woman treated with dupilumab for refractory ECRS and eosinophilic otitis media (EOM) complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis before the initiation of dupilumab. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. A blood test showed an eosoinophilia and re-elevation of MPO-ANCA levels after the administration of dupilumab. Therefore, dupilumab was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy.ConclusionTo the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, measuring MPO-ANCA in patients with multiple eosinophilic disorders before the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with a previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.

Dupilumab improves eosinophilic otitis media associated with eosinophilic chronic rhinosinusitis

BackgroundEosinophilic otitis media (EOM) is a refractory condition associated with eosinophilic chronic rhinosinusitis and bronchial asthma. EOM is characterized by type-2 inflammation and is refractory to various treatments. We investigated the efficacy of dupilumab, interleukin-4 receptor alpha antagonist, for patients with EOM complicated by eosinophilic chronic rhinosinusitis (ECRS). MethodsBetween April 2017 and April 2022, we treated 124 patients with dupilumab for refractory CRS or bronchial asthma. Of these, 14 had EOM concurrently, and 10 of them who had been treated for >6 months were included in our study. We retrospectively evaluated the efficacy of dupilumab by the amount of systemic corticosteroid used, the frequency of exacerbations, severity score of EOM, computed tomography (CT) score of temporal bones, and pure tone audiometry. We also enrolled 8 EOM patients without dupilumab treatment as a control group. ResultsDupilumab significantly improved the amount of systemic corticosteroid used and the frequency of exacerbation and compared with before dupilumab was used (p = 0.01 and <0.01, respectively). All patients could be weaned from systemic-corticosteroid therapy by 54 weeks of dupilumab use. The severity score of EOM and CT score for temporal bones were significantly lower than before the treatment (p = 0.01 and 0.01, respectively). Compared to the control group, the systemic corticosteroid used and severity scores were improved in the dupilumab group (p = 0.02 and < 0.01, respectively). ConclusionsDupilumab could be used to wean patients from systemic corticosteroids with the improvement of severity score in EOM associated with ECRS and bronchial asthma.

Improvement of Suspected Eosinophilic Otitis Media with Targeted Biologic Therapy.

To compare the responses of suspected eosinophilic otitis media to treatment with or without a targeted biologic therapy against interleukin-4 (IL-4), IL-5, or IL-13 signaling. Retrospective review. Tertiary referral center. Subjects with type 2 chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and otitis media who underwent treatment between 2005 and 2021. Treatment with targeted biologic therapy. Pre- and posttreatment nasal endoscopy, ear examination, and audiologic evaluation. Four hundred seventy-seven subjects with type 2 CRSwNP were treated between 2005 and 2021. Sixty-two had otitis media with pre- and posttreatment evaluation. Retrospective chart review assessed pre- and posttreatment exam findings, nasal endoscopy, audiometry, and tympanometry. Nineteen subjects received a biologic therapy, whereas 43 did not. Exam, endoscopy, and tympanometry were graded for severity and compared pre- and posttreatment. Subjective ear exam and tympanometry were significantly improved with biologic therapy (control = 0.05, biologic = 0.84, p = 9.3 × 10 -5 ; control = -0.1, biologic = 0.62, p = 0.0002). Conductive hearing loss as assessed by air-bone gaps did not change between groups (control = 1.2 dB better, biologic = 1.2 dB worse, p = 0.32). Nasal endoscopy findings improved with biologic therapy relative to the control group, although not statistically significant (control = 1.04, biologic = 1.36, p = 0.22). Biologic therapies targeting interleukin-4 (IL-4), IL-5, and IL-13 signaling are potential new treatments for eosinophilic otitis media. This is the largest study demonstrating improvement in subjects with suspected eosinophilic otitis media in response to biologic therapy, and immune modulation represents a novel treatment strategy for this challenging condition. Current treatment strategies for otologic symptoms in eosinophilic disease are not tremendously effective or durable, resulting in a need for improved treatment options. To determine if targeted biologic therapy, often used for eosinophilic asthma and type 2 chronic rhinosinusitis with nasal polyposis, improves coexistent suspected eosinophilic otitis media. Treatment of suspected eosinophilic otitis media with targeted biologic therapy will result in improvement of otologic symptoms with a durable response compared with current treatment options. Level IV. Exempt. HUM00182703.

A Case of Eosinophilic Otitis Media Implanted with Bone-Anchored Hearing Aid

Eosinophilic otitis media (EOM) is characterized by the presence of highly viscous middle ear effusion containing eosinophils, and is usually associated with bronchial asthma. Intratympanic corticosteroid administration and/or systemic steroid administration are effective treatments. However, the middle ear effusion and progressive hearing loss are difficult to control, significantly affecting the patient’s quality of life. Therefore, appropriate care is important not only for controlling the middle ear effusion and otorrhea, but also for preventing the progression of hearing loss.A 46-year-old woman was referred to our hospital with suspected eosinophilic otitis media. She had a history of asthma and aspirin sensitivity. In addition, she had recurrent nasal polyps despite having undergone nasal polypectomy on two occasions. She was diagnosed as having bilateral EOM according to the diagnostic criteria. She was started on steroid treatment, but after showing initial response, the middle ear effusion recurred immediately after withdrawal of steroid treatment. Although the patient also had difficulty in communication because of bilateral hearing loss, she could not wear hearing aids because of the middle ear effusion. Hearing aids sometimes aggravate middle ear infection by blocking aeration, increasing the risk of sensorineural hearing loss. Therefore, we implanted a bone-anchored hearing aid (Baha®) in her right ear. Average hearing threshold of 500, 1000 and 2000 was 35 dB using Baha®. Although audiometry revealed deterioration of the bone-conduction threshold in the right ear at five years after the Baha® implantation, she still had sufficient bone conduction hearing using Baha® because of the preserved bone-conduction in the contralateral ear. The Baha® hearing system is a clinically effective and good hearing rehabilitative device for patients with EOM.

A Case of Eosinophilic Otitis Media Treated by Dupilumab and Regenerative Medicine with Trafermin

A Case of Eosinophilic Otitis Media Treated by Dupilumab and Regenerative Medicine with Trafermin

Risk factors for bacterial infection in eosinophilic otitis media

Risk factors for bacterial infection in eosinophilic otitis media

Is Omalizumab Related to Ear and Labyrinth Disorders? A Disproportionality Analysis Based on a Global Pharmacovigilance Database.

Introduction: Asthma is a chronic disease, characterized by reversible airway obstruction, hypersensitivity reactions, and inflammation. Oral corticosteroids are an important treatment option for patients with severe or steroid-resistant asthma. Biologics for asthma are recommended in patients with severe asthma, owing to their steroid-sparing effect as well as their ability to reduce the severity and aggravation of uncontrolled asthma. Most clinical trials of omalizumab in patients with asthma have suggested its tolerability and safety. However, some studies reported eosinophilic comorbidities in the ear, nose, and throat during omalizumab treatment, particularly eosinophilic otitis media. This study examined the relationship between ear disorders and omalizumab compared with that of other biologics for asthma using a large real-world database. Materials and Methods: Individual case safety reports from the Uppsala Monitoring Centre Vigibase of biologics for asthma (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) up to 29 December 2019, were used. A disproportionality analysis was performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information components (IC). A hierarchy analysis used the Medical Dictionary for Regulatory Activities Terminology. A tree map was generated using R studio version 4.2. Results: In 32,618 omalizumab reports, 714 adverse events (AEs) were detected as signals. Among the 714 signals, seventeen AEs were detected as signals of omalizumab-related ear and labyrinth disorders in 394 reports. Only three AEs (ear pain, ear disorder, and ear discomfort) were detected from mepolizumab. No signal was detected from reslizumab, benralizumab, and dupilumab. Conclusions: Careful monitoring of ear disorders is recommended when omalizumab treatment is started, with decreased oral corticosteroid use in patients with severe asthma. Further studies are necessary to confirm the omalizumab-related signals.

Effectiveness of Dupilumab in the Treatment of Patients with Severe Uncontrolled CRSwNP: A "Real-Life" Observational Study in the First Year of Treatment.

The aim of this study was to evaluate the efficacy of dupilumab in the treatment of severe uncontrolled Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), with or without asthma as add-on therapy with intra-nasal corticosteroids in a real-life setting over the first year of treatment. Our data demonstrated that subcutaneous 300 mg dupilumab administered at home via a pre-filled auto-injector every two weeks, based on indications set by the Italian Medicines Agency, was rapidly effective in reducing the size of polyps, decreasing symptoms of disease, improving quality of life, and recovering olfaction. Significant improvement was observed after only 15 days of treatment, and it progressively increased at 6 and 12 months. Dupilumab was also effective in reducing the local nasal eosinophilic infiltrate, in decreasing the need for surgery and/or oral corticosteroids, and in improving control of associated comorbidities such as chronic eosinophilic otitis media and bronchial asthma. After 12 months of treatment, 96.5% of patients had a moderate/excellent response. From our data, it was evident that there was a group of patients that showed a very early response within one month of therapy, another group with early response within six months from baseline, and a last group that improved later within 12 months. The results of this study support the use of dupilumab as an effective option in the current standard of care for patients affected by severe uncontrolled CRSwNP.