Search Results (12)

Background and Clinical Significance: Otitis media with effusion (OME) is characterized by persistent middle ear effusion without acute infection. Type 2 inflammation, mediated by IL-4 and IL-13 signaling via the IL-4Rα receptor, has been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and possibly OME. Refractory OME in adults remains a therapeutic challenge, as conventional treatments often fail to achieve long-term resolution. Targeted biologic therapies that modulate type 2 inflammation may offer a novel treatment option. Case Presentation: We report the case of a 60-year-old man with a 15-year history of allergic rhinitis and CRSwNP, complicated by recurrent asthma exacerbations, who presented with bilateral aural fullness, hearing loss, and tinnitus. His symptoms persisted despite repeated tympanic punctures, Eustachian tube insufflation, and corticosteroid therapy. Otoscopy revealed dull tympanic membranes with effusion, and audiometry showed conductive hearing loss with a B-type tympanogram on the left. Laboratory findings demonstrated mild peripheral eosinophilia. The patient was diagnosed with OME, likely secondary to type 2 inflammation. After nine biweekly injections of Stapokibart (CM310)—a humanized monoclonal antibody targeting IL-4Rα—aural fullness completely resolved. Otoscopic findings and tympanograms normalized, and hearing thresholds improved significantly. Retrospective evaluation using Iino’s diagnostic framework suggested that the patient did not meet the full criteria for eosinophilic otitis media (EOM); nevertheless, marked symptomatic and functional improvement was achieved. No recurrence or adverse effects were observed during follow-up. Conclusions: This case suggests that IL-4Rα blockade with Stapokibart may be effective in treating refractory OME associated with type 2 inflammation, even in patients who do not fulfill the diagnostic criteria for EOM. These findings highlight the potential of anti-IL-4Rα biologics as a novel therapeutic option for middle ear diseases driven by type 2 inflammation. Full article

Background and Objectives: Otitis media with effusion (OME), frequently associated with obstructive adenoid hypertrophy (OAH), is a leading cause of paediatric hearing loss. Clinically distinguishing effusion types (serous vs. mucoid) and predicting postoperative hearing recovery are unresolved challenges. This study evaluated the utility of preoperative blood inflammatory markers in predicting effusion characteristics and short-term hearing outcomes following adenoidectomy with tympanostomy tube (TT) insertion. Materials and Methods: In this retrospective cohort study, 232 children under 12 years old in 2024 and undergoing adenoidectomy (with or without TT insertion) were categorised into serous OME (n = 42), mucoid OME (n = 78), and non-effusion (n = 112) groups. Preoperative blood sample analyses assessed neutrophil, lymphocyte, eosinophil, basophil, and platelet counts, along with derived indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-basophil ratio (EBR), mean platelet volume (MPV), and systemic immune–inflammation index (SII). Hearing was evaluated at 2 weeks and 1 month postoperatively. Statistical analyses used SPSS v.28, with significance set at p < 0.05. Result: Mucoid OME patients exhibited significantly elevated neutrophil counts, platelet counts, eosinophils, NLR, and SII compared to those in serous OME and non-effusion groups (p < 0.05). All serous OME children achieved normal hearing by the first follow-up, whereas 15.4% of mucoid OME cases had transient mild hearing loss persisting after 2 weeks (p = 0.008; OR=15.97) but resolving by 1 month. Preoperative neutrophil count independently predicted delayed hearing recovery (p = 0.021). Conclusions: Systemic inflammatory markers, particularly neutrophil count, NLR, and SII, effectively differentiate mucoid OME from other effusion types and correlate with short-term hearing recovery. Neutrophil count may serve as a prognostic tool for surgical planning and patient counselling. Prospective studies are warranted to validate these findings in broader paediatric populations. Full article

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic otitis media (EOM) are frequently co-existing eosinophilic disorders related to type 2 inflammation, which significantly impair the quality of life of patients. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha and anti-IL-13, has demonstrated a promising profile of efficacy and safety in the treatment of CRSwNP; however, evidence on its role in concomitant EOM and CRSwNP remains limited in the literature. This study aims to evaluate the clinical efficacy of dupilumab in patients with concomitant CRSwNP and EOM over a six-month observational period. Materials and Methods: A retrospective observational cohort study was conducted on twenty-two patients (aged 18–75 years) over six months with severe uncontrolled CRSwNP and confirmed refractory EOM who were treated with dupilumab (300 mg every two weeks). Demographic data are collected, and outcome measures included Nasal Polyp Score (NPS), Sino-Nasal Outcome Test (SNOT-22), Visual Analog Scale for nasal congestion (VAS), tympanogram classification, and Chronic Otitis Media Outcome Test (COMOT-15), evaluated at baseline and 6 months. Results: Over the six-month treatment period, patients with coexisting CRSwNP and eosinophilic otitis media experienced significant improvements across the multiple validated clinical and patient-reported outcome measures. The Nasal Polyp Score (NPS) significantly decreased from a median of 5.7 (IQR: 1.2) at baseline to 1.5 (IQR: 1.3) at six months (p < 0.0001). The SNOT-22 showed a substantial decline from a median of 77.6 (IQR: 19.0) to 21.5 (IQR: 13.4), p < 0.0001. Visual Analog Scale (VAS) scores for nasal congestion improved significantly from 8.4 (IQR: 1.1) to 1.7 (IQR: 1.2), p < 0.0001. Tympanogram scores improved from Tympanogram type “B” to Tympanogram type “A” (p = 0.018). COMOT-15 scale decreased from a median of 51.3 (IQR: 8.4) to 19.2 (IQR: 5.0) (p < 0.0001). Peripheral eosinophil counts remained unchanged or increased (baseline 0.80 vs. 0.84 cells/μL at six months, (p = 0.834)). Conclusions: Dupilumab treatment in patients with CRSwNP and EOM led to significant clinical improvements in sinonasal symptoms, middle ear function, and quality of life over six months, with no significant change in peripheral eosinophilia. Full article

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitis sharing a common pathophysiology, which affects small and medium blood vessels. There are three categories of AAV: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). As a systemic disease, AAV can affect basically every organ. The goal of this publication is to sum up and underline the problem of the aural manifestation of AAV; it details the definition of Otitis Media with Antineutrophil Cytoplasmic Antibody Associated Vasculitis (OMAAV) and allows for a better understanding of the specific tasks of medical professionals taking part in the diagnostic and therapeutic process. Among others, this publication is directed to otolaryngologists who may encounter patients with AAV and often are the first specialists who see patients with early symptoms of AAV. This publication presents brief characteristics of AAV, descriptions of aural manifestations and symptoms, differential diagnosis, and both pharmacological and surgical treatment options, based on current recommendations and information found in the literature and clinical databases. Full article

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. Full article

Reports of eosinophilic pneumonia (EP) as a side effect of dupilumab administration are limited in previous studies. Herein, we report two cases in which EP developed subsequent to the administration of dupilumab for eosinophilic chronic rhinosinusitis (ECRS). Case 1: A 55-year-old woman presented with ECRS, eosinophilic otitis media, and bronchial asthma, and was treated with dupilumab for ECRS. Five weeks later, fever and dyspnea developed, and infiltration shadows were observed in her lungs. The peripheral blood eosinophil count (PBEC) was 3848/μL (26%), bronchoalveolar lavage fluid showed eosinophilic infiltration, and EP was subsequently diagnosed. Her condition improved following prednisolone treatment. Case 2: A 59-year-old man presented with fatigue and dyspnea after receiving dupilumab for ECRS. He had infiltrative shadows throughout his left lung field, and his PBEC was 4850/μL (26.5%). Prednisolone was initiated, and his condition improved. EP developed in both patients during the period of elevated PBEC after dupilumab administration, and dupilumab was suspected to be the causative agent in their EP. Hence, EP should be considered as a differential diagnosis when fever and dyspnea appear following dupilumab administration. Full article

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. Full article

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. Full article

Type 2 (T2) inflammation plays an important role in the pathogenesis of allergic diseases such as asthma, eosinophilic chronic rhinosinusitis (ECRS), or eosinophilic otitis media (EOM). Currently, in severe asthma with the T2 phenotype, biologics targeting mediators of T2 inflammation dramatically improve the management of severe asthma. While treatment with a single biologic is common, little is known about cases of the sequential use of two biologics. Here, we report a case of severe asthma with refractory ECRS and EOM in which total control of these allergic diseases could not be achieved with a single biologic but could be achieved via the sequential use of the anti-IL-5 receptor antibody and human anti-IL-4/13 receptor monoclonal antibody. It is suggested that it is necessary to control multiple T2 inflammatory pathways to achieve total control of severe allergic diseases. Sequential biotherapy may help solve the clinical challenges associated with single-agent molecular-targeted therapies. Full article

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is resistant to conventional treatments and strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of our study is to evaluate the effectiveness of biologics drugs in the control of EOM. This is a retrospective no-profit real-life observational study, involving patients affected by refractory EOM and in treatment with different biologics for concomitant severe eosinophilic asthma or severe uncontrolled CRSwNP (Dupilumab: n = 5; Omalizumab: n = 1; Mepolizumab: n = 1; Benralizumab: n = 1). We analyzed data at baseline and at the 6-month follow-up, including specific nasal and otological parameters. We observed an improvement of all nasal outcomes, including NPS, SNOT-22, VAS, and smell function. Regarding specific otological parameters, we observed a significant reduction in the mean value of COMOT-15 score and of Otitis Severity Score at 6-month follow-up compared to baseline (p < 0.05). Finally, we observed an improvement in terms of air conduction hearing levels during the treatment. Our results demonstrated that anti type-2 inflammatory pathway biologics can be effective in improving symptoms control and in reducing the severity of eosinophilic otitis media when treating coexisting type-2 diseases, such as asthma and or CRSwNP. Full article

A woman in her 50s was a super responder to benralizumab administered for the treatment of severe bronchial asthma (BA) with eosinophilic chronic rhinosinusitis with nasal polyp (ECRS) and eosinophilic otitis media (EOM). She exhibited the gradual exacerbation of ECRS/EOM despite good control of BA approximately 1 year after benralizumab initiation. Therefore, the treatment was switched to dupilumab, and the condition of the paranasal sinuses and middle ear greatly improved with the best control of her asthma. The patient reported that her physical condition was the best of her life. However, she developed a pulmonary opacity on chest computed tomography after 6 months. Histological examination of the lung parenchyma and cell differentiation of the bronchoalveolar lavage fluid indicated atypical chronic eosinophilic pneumonia, and treatment was switched to mepolizumab. Similarly to the period of benralizumab treatment, exacerbation of ECRS/EOM reduced her quality of life approximately 10 months after the administration of mepolizumab. Dupilumab was again introduced as a replacement for mepolizumab. The clinical course and consideration of the interaction between inflammatory cells led us to speculate that interleukin-13 could play a key role in the development of ECRS/EOM with severe BA. Full article

Aims: Langerhans Cell Histiocytosis is a rare hematologic disorder usually affecting children and most commonly involving the head and neck region. Primary oro-facial manifestations are rare, and their diagnosis is often challenging as they are numerous and often resemble common pathologies, refractory to conventional medical and/or instrumental treatments. For such reasons, the diagnosis is frequently delayed, as is the following staging and therapy onset. We retrospectively studied 45 pediatric patients affected by Langerhans Cell Histiocytosis with onset in the head and neck, to examine their clinical and radiological features at the early stage. Materials and Methods: The study was a retrospective bi-institutional analysis (Department of Pediatric Dentistry and Pediatric Oncology of “Sapienza” University of Rome, Department of Interdisciplinary Medicine of the University of Bari “Aldo Moro”), which enrolled 45 patients (age range 0–18 year-old) affected by Langerhans Cell Histiocytosis with oro-facial onset. Data regarding clinical appearance, number, site, synchronous or metachronous occurrence, involved tissues/organs, radiographic features and clinical outcomes were collected, listed and overall differentiated by two age ranges (0–10-year-olds and 10–18-year-olds). Results: Patients were 26 males and 19 females, with an average age at the time of diagnosis of 4.8 ± 3.8 years (median = 3.9 years). The most common findings were inflamed, hyperplastic, painful and often ulcerated gingival lesions (22 cases), associated with deciduous tooth mobility and/or dislocation with bone loss in 18 cases, followed by nine single eosinophilic granulomas of the mandible and two of the maxilla. Lesions of the palatal mucosa were observed in six patients; nine patients showed on radiograms the characteristic “floating teeth” appearance in the mandible with synchronous lesions of the maxilla in six. Paresthesia was relatively un-frequent (three cases) and the pathological fracture of the mandible occurred in six. Head/neck lymph nodes involvement was associated with oral lesions in 12 cases and skull lesions in 14. Otitis (media or externa) was detected in four instances, exophthalmia in two, cutaneous rush in nine, contextual presence or subsequent onset of insipidus diabetes in eight. As for therapy, single or multiple small jaw lesions were all surgically removed; chemotherapy with vinblastine alone or associated with corticosteroids was the principal treatment in almost the 80% of cases; more than 50% of patients received corticosteroids, while only three patients received adjunctive radiotherapy. The overall mortality account for less than 9% (four of 45 cases) and recurrence observed in eight patients after therapy. Conclusions: Langerhans Cell Histiocytosis may mimic several oro-facial inflammatory and neoplastic diseases. Considering the potential disabling sequela following head and neck localization of Langerhans Cell Histiocytosis in children, especially at the periodontal tissues with teeth and alveolar bone loss, lesion recognition along with the histological examination of suspicious tissues is mandatory to achieve an early diagnosis and to prevent further organ involvement. Full article