This narrative review comprehensively elaborates the complicated interleukin (IL)-macrophage polarization axis as the core pathogenesis of allergic rhinitis (AR), focusing on layered molecular regulatory mechanisms covering inflammatory signaling, metabolic reprogramming and epigenetic modulation. Pro-inflammatory IL-1β, IL-6, IL-17 and TNF-α bind to TLR receptors to activate NF-κB, NLRP3 inflammasome and PI3K/Akt cascades, triggering M1 macrophage overactivation and acute nasal congestion, rhinorrhea via robust inflammatory mediator release. By contrast, anti-inflammatory IL-4 and IL-10 predominantly activate STAT6 signaling to drive abnormal M2 macrophage accumulation, sustaining persistent type 2 inflammation and irreversible nasal tissue remodeling; notably, IL-17 presents concentration-dependent bidirectional regulation on macrophage phenotypes. Metabolic reprogramming featured with glycolysis-oxidative phosphorylation switch, together with DNA methylation, histone modification and non-cRNA-mediated epigenetic regulation, serve as vital downstream executors linking IL signals to macrophage polarization imbalance. Conventional glucocorticoids, antihistamines and monoclonal antibodies including omalizumab and dupilumab (targeting IL-4Rα) exert therapeutic efficacy via intervening this axis, while multiple natural herbal constituents and classic TCM formulas also modulate relevant inflammatory pathways to alleviate AR symptoms. For translational application, the CD206/CD86 macrophage polarization ratio is highlighted as a representative candidate biomarker for disease severity assessment. Collectively, this review integrates multi-layered regulatory evidence and lays theoretical support for developing novel precision-targeted anti-allergic therapies.

BACKGROUND Allergic rhinitis (AR) is a common inflammatory disorder of the nasal mucosa triggered by allergens and characterized by sneezing, nasal congestion, and itching. This study aimed to identify and validate potential biomarkers associated with immune dysregulation in AR via bioinformatics analyses initiated with chemokine-related genes. MATERIAL AND METHODS AR-related datasets (GSE75011 and GSE50223) and 69 chemokine-related genes were analyzed via differential expression analysis and weighted gene co-expression network analysis to identify candidate genes. Random forest analysis was used to select optimal features. Expression analysis identified potential immunoregulatory biomarkers that were downregulated in AR samples. A nomogram incorporating these biomarkers was constructed as an exploratory tool to estimate individual AR probability and support future diagnostic model development. RESULTS Early growth response protein 2 (EGR2) and transforming growth factor-β1 (TGFB1) were identified as chemokine-related biomarkers in AR. Immune infiltration analysis showed significant correlations between TGFB1 and M2 macrophages, as well as activated memory CD4+ T cells. Drug prediction identified tretinoin as a potential therapeutic agent targeting both biomarkers; molecular docking confirmed stable binding of the 3 top-ranked predicted drugs with TGFB1. Pilot reverse transcription-quantitative polymerase chain reaction analysis demonstrated downregulation of EGR2 and TGFB1 in AR samples, providing preliminary supportive evidence. Gene set enrichment analysis indicated involvement in the MAPK and p53 signaling pathways, suggesting roles in cell proliferation, apoptosis, cell cycle regulation, and stress responses. CONCLUSIONS EGR2 and TGFB1 offer potential immunoregulatory biomarkers for AR diagnosis and may provide preliminary insights into AR pathogenesis and potential treatment strategies.

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease of the nasal and paranasal sinus mucosa, associated with significant impairment in quality of life, frequent postoperative recurrence, and repeated need for systemic glucocorticosteroid therapy. Despite the availability of biologics targeting IL-4/IL-13, IL-5, and IgE, a subset of patients shows incomplete or insufficient clinical response. In this context, upstream targeting of epithelial alarmins, particularly thymic stromal lymphopoietin (TSLP), has emerged as a potential therapeutic strategy. To critically review current evidence on the role of TSLP in CRSwNP and to evaluate available data on the mechanism of action, clinical efficacy, and therapeutic potential of tezepelumab in severe and recurrent disease. Materials and Methods: A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies published between 2016 and 2026 were included, comprising experimental research, phase II-III clinical trials, systematic reviews, and international guidelines. Results: TSLP functions as an epithelial alarmin that initiates and amplifies type 2 inflammation via dendritic cell activation, Th2 polarization, and activation of type 2 innate lymphoid cells (ILC2). Data suggests that tezepelumab, a monoclonal antibody targeting TSLP, may reduce inflammation and regulate the immune system. Evidence from asthma populations and relevant CRSwNP subgroups indicates potential improvements in nasal polyp score, congestion, olfactory function and quality of life. It is our understanding that the safety profile appears comparable to placebo, with no new safety concerns having been identified in long-term studies. Conclusions: Tezepelumab is a promising biologic that targets inflammation in CRSwNP. It may benefit severe, recurrent, treatment-resistant disease by modulating immune pathways. However, evidence is indirect and limited, and more trials are needed to define its efficacy, identify biomarkers, and clarify its role in treatment algorithms.

Allergic rhinitis (AR) is an underrecognized contributor to olfactory dysfunction (OD). Although smell loss in AR is commonly attributed to conductive obstruction, some patients exhibit persistent or disproportionate hyposmia despite improvement in nasal congestion, suggesting that additional sensorineural mechanisms may exist.

Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is a complex immune-mediated vasculitis characterized by the involvement of small blood vessels in various organ systems.  We describe the case of a 14-year-old girl who developed a non-typical manifestation of vasculitis with notable rhinological features. The patient presented with a vasculitis-type rash on the hands and lower extremities bilaterally and arthralgia, while she also complained about intense nasal congestion. The laboratory results were atypical for a specific disorder, and the skin and nasal mucosa biopsies were not diagnostic. Since the patient presented with microscopic hematuria, she underwent a kidney biopsy that confirmed the diagnosis of IgAV with nephritis. The patient was maintained on long-term therapy with corticosteroids, azathioprine, and hydroxychloroquine and showed improvement in symptoms. The aim of this case report is to highlight the atypical presentation of IgAV, particularly its rhinologic manifestations, which are infrequently reported in the literature. In addition, this report emphasizes the importance of long-term follow-up in such patients, as the diagnosis can be challenging.

Objective:This paper reports a case of a male patient who complained about nasal congestion and loss of smell for 20 years. Physical examination revealed polyp-like masses in bilateral olfactory clefts and middle meatus. The patient was diagnosed with chronic rhinosinusitis with nasal polyps（CRSwNP） and exhibited poor response to an adequate course of topical intranasal corticosteroids, then he enrolled in two clinical trials using anti IL4-Rα and anti-TSLP monoclonal antibodies consequently. The treatment duration for each trial was 16 weeks, respectively. The size of his nasal polyps did not change, which was the main endpoint result for both clinical trials. Then the patient underwent an endoscopic surgery and the pathology was respiratory epithelial adenomatoid hamartoma（REAH）, which was further confirmed by the single cell sequencing results of the operative specimen, which were different from normal nasal polyps. The diagnosis of REAH is dependent on pathology and preoperative examination has limited specificity, and REAH may share similarities with nasal polyps. Therefore, REAH should be considered for the differential diagnosis when patients with polyp-like masses exhibit poor response to sufficient treatment using biologics.

Objective:To evaluate the real-world efficacy and safety of stapokibart（CM310） in Chinese patients with moderate-to-severe seasonal allergic rhinitis（SAR）, and the impact of baseline blood eosinophil（EOS） levels on therapeutic outcomes. Methods:A prospective observational study was conducted, enrolling 31 SAR patients diagnosed at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from March to May 2025. Patients received subcutaneous injections of stapokibart: 2 initial doses（300 mg each）, followed by a booster dose（300 mg） 2 weeks later, with a 4-week follow-up. The primary endpoint was the mean change in Total Nasal Symptom Score（TNSS） from baseline to Week 4. Secondary endpoints included changes in Total Ocular Symptom Score（TOSS）, total nasal Visual Analogue Scale（VAS） score, concomitant medication use, and safety outcomes. Subgroup analysis was performed based on baseline blood EOS counts. Results:After 4 weeks of treatment, the mean TNSS decreased from（8.16±2.67） at baseline to （3.00±1.64）（P<0.001）, with the most significant improvements in nasal congestion and rhinorrhea. The mean TOSS reduced from（4.87±3.14） to （1.37±1.48）（P<0.001）, and the mean VAS score declined from（7.66±2.13） to （3.49±1.88）. Subgroup analysis showed that the high EOS subgroup（≥300/μL） had significantly better relief of nasal congestion（P<0.001） and nasal itching（P=0.002） compared with the low EOS subgroup. Regarding medication use, the proportion of patients not using any symptomatic medications increased from 12.0% to 43.3%, and the use of oral corticosteroids decreased to 0. No serious adverse events occurred during the study. Conclusion:Stapokibart is safe and effective in treating Chinese SAR patients, providing significant improvements in nasal and ocular symptoms and reducing medication dependence. A baseline blood EOS count of ≥300/μL is an important predictive factor for favorable nasal symptom outcomes.