Background/Objectives: Severe allergic asthma is usually treated with omalizumab; however, this drug may not be effective for every patient. By its action, dupilumab could be an alternative in these patients. The objective of this study was to evaluate the efficacy of dupilumab in patients with severe allergic asthma, non-responsive to omalizumab, according to the maintenance of their oral corticosteroid (OCS) dose, an exacerbation rate decrease, or poor control of the disease, despite optimized treatment. Methods: A retrospective analysis of data from severe asthma clinics was performed, observing the efficacy of the switch to dupilumab in patients who experienced a failed treatment with omalizumab. Results: Forty-two patients were included. Dupilumab proved to be effective in patients who experienced a failed omalizumab treatment, with a significant reduction in the exacerbation number and OCS use. Furthermore, remission of the disease, according to the Severe Asthma Network of Italy (SANI) criteria, was achieved in 35 patients, with complete remission in 19 (45%) and partial remission in 16 (38%). The analysis of the predictors of the success of dupilumab therapy in achieving clinical remission, through univariate analysis of the data at baseline, showed that complete remission was more easily reached in patients with concomitant aspirin (ASA) intolerance or in those with nasal polyposis. Conclusions: Dupilumab is an effective drug for the treatment of patients with severe asthma with an allergic component, with better benefits in patients with an ASA intolerance or nasal polyposis.

Purpose: Immunoglobulin G4-related disease (IgG4-RD) is a complex systemic fibroinflammatory condition with different clinical manifestations affecting multiple organ systems. Despite its rarity, the disease presents diagnostic and therapeutic challenges due to its mimicry of malignancies and other immune-mediated disorders. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease is the current state of art to confirm the diagnosis of IgG4-RD even in the absence of histological analysis. However, this classification excludes atypical sites, focusing on the more typical ones, even in case of histological confirmation. In the ENT field, several localizations of this disease have been described. Methods: We report two clinical cases at the Otolaryngology Unit of IRCCS San Martino Hospital, Genoa affected by IgG4-RD arising in atypical sides of the head and neck region. Additionally, we perform a clinical review of the current literature. Discussion: The review provides an extensive overview of IgG4-RD, encompassing epidemiology, clinical manifestations, diagnostic approaches, and therapeutic strategies. We discuss the evolution of diagnostic criteria, emphasizing the necessity of interdisciplinary collaboration among clinicians, radiologists, and pathologists for accurate diagnosis. Diagnostic imaging plays a crucial role, with characteristic radiological patterns aiding in the identification of affected organs. However, definitive diagnosis often requires histopathological confirmation, highlighting the importance of biopsy in challenging cases. We also focus on the treatment of IgG4-RD which poses significant challenges, with glucocorticoids remaining the cornerstone of therapy. Emerging steroid-sparing agents such as rituximab and Dupilumab, show promising results in refractory or recurrent disease. Conclusions: IgG4-RD is a multisystemic fibroinflammatory disease that can potentially affect any part of the body. The 2019 ACR/EULAR 3-stage classification criteria for IgG4-RD considers only a few head and neck sites. Therefore, it is of paramount importance that neurosurgeons, head and neck surgeons, and oral and maxillofacial pathologists are familiar with the clinicopathological manifestations of IgG4-RD in these sites to avoid misdiagnosis and inappropriate treatment, which can lead to a decrease in patients’ quality of life. To our knowledge, there are no risk factors or genetic predispositions. Further studies are needed to elucidate the pathophysiology of IgG4-RD with the aim of providing a targeted therapy that could spare steroid-related effects and reduce relapses.

Background: The study aims to analyze the safety and efficacy of Mepolizumab and Dupilumab in the treatment of patients affected by severe chronic rhinosinusitis not controlled with nasal polyposis (CRSwNP) from a tertiary care regional referral center, with the aim of improving the concept of personalized medicine. Methods: A retrospective study was conducted on 72 adult patients selected for biologic therapy according to EPOS/EUFOREA criteria. The patients received either Mepolizumab or Dupilumab. Primary endpoints were reduction in nasal polyp size, improvement in disease-specific quality of life (sinonasal outcome test-22, visual analog scale), olfactory recovery, and asthma control. Secondary outcomes were the assessment of adverse events. Results: Both monoclonal antibodies significantly improved nasal polyps score (NPS), sinonasal outcome test-22 (SNOT-22), and asthma control test (ACT) over time, with no statistically significant differences between Mepolizumab and Dupilumab. In contrast, blood eosinophil counts showed significant differences: Dupilumab was associated with a transient increase in eosinophil levels (absolute Δ = 660.08% Δ = 9%; p < 0.001), while Mepolizumab produced a marked reduction (absolute Δ = 192.52% Δ = 2%; p < 0.001). Both treatments were well tolerated, with only mild adverse events reported. Conclusions: Mepolizumab and Dupilumab are both effective and safe in improving sinonasal symptoms and quality of life in severe uncontrolled CRSwNP. While improvements in NPS, SNOT-22, and ACT scores were comparable, Mepolizumab achieved a significant reduction in eosinophil counts, whereas Dupilumab was associated with faster clinical improvement but a transient eosinophilia. These findings suggest that biologic choice may be guided by individual patient profiles and inflammatory patterns.

Should computed tomography be used in the evaluation of biologic therapies for severe chronic rhinosinusitis with nasal polyps?

Objective(s): Radiological intratumoral calcifications in sinonasal adenocarcinoma have been scarcely investigated. This study aimed to assess their prevalence and evaluate their potential prognostic significance and to examine its association with surgical resectability. Materials and Methods: We conducted a retrospective single‐center study including patients treated with curative intent for sinonasal adenocarcinoma. Clinical, pathological, treatment, and computed tomography (CT) data were reviewed. Intratumoral diffuse calcifications were assessed on preoperative CT. Associations with tumor characteristics, surgical outcomes, and survival were analyzed using appropriate statistical methods, including Cox proportional hazards models. Results: Ninety‐six patients were included. Intratumoral calcifications were identified in 24 patients (25%). Compared with patients without calcifications, those with calcifications more frequently had locally advanced tumors (pT3–4: 79.2% vs. 47.2%, p = 0.013; pT4: 62.5% vs. 31.9%, p = 0.025), were more likely to receive induction chemotherapy (33.3% vs. 9.7%, p = 0.015), and had a higher rate of incomplete resection (R2: 20.0% vs. 1.5%, p = 0.007). Histological subtype and differentiation grade were similar between groups. The association with R2 resection persisted after adjustment for pT stage (penalized logistic regression: OR 7.74, 95% CI 1.26–82.61; p = 0.026). In univariable analysis, calcifications were associated with worse disease‐free survival (HR 2.36, 95% CI 1.23–4.54; p = 0.010), but this association did not persist after adjustment for pT stage (HR 1.47, 95% CI 0.76–2.88; p = 0.26) or in multivariable analysis (HR 1.41, 95% CI 0.70–2.85; p = 0.34). Calcifications were not associated with overall survival. Conclusion: Intratumoral radiological calcifications were present in 25% of sinonasal adenocarcinomas and were associated with more advanced local disease and a higher risk of incomplete resection. Although associated with poorer disease‐free survival in unadjusted analyses, this effect was attenuated after adjustment for tumor stage. These findings suggest that calcifications primarily reflect local tumor extent; although not an independent survival factor, their independent association with incomplete resection may make them a useful preoperative marker of surgical difficulty. Level of Evidence: 3.