This review evaluates the clinical, epidemiological, and mechanistic impacts of ambient air pollution on atopic dermatitis (AD) and urticaria. It specifically examines how anthropogenic airborne pollutants-including fine particulate matter (PM2.5 and PM10), gaseous oxidants (NO2, SO2, O3), and volatile organic compounds (VOCs)-interact with the skin barrier and immune signaling pathways to drive disease onset, exacerbations, and treatment resistance. Global meta-analyses and prospective birth cohorts confirm strong dose-response relationships between acute surges in PM2.5, NO2, and ground-level O3 and increased outpatient consultations for AD flares and acute/chronic urticaria. At the molecular level, xenobiotic ligands activate the Aryl Hydrocarbon Receptor (AhR), inducing reactive oxygen species (ROS) and triggering histone deacetylase (HDAC3/HDAC6)-mediated epigenetic silencing of filaggrin (FLG). In urticaria, ground-level O3 and aromatic VOCs induce lipid peroxidation and mast cell activation, displaying distinct lag structures up to 4 days post-exposure. Furthermore, pollution spikes can trigger breakthrough flares even in AD patients receiving biological therapy (e.g. dupilumab). Ambient air pollution is a major component of the cutaneous exposome. Clinical management must integrate environmental literacy, air quality index (AQI) tracking, indoor air purification, ceramide-dominant barrier rapair, and targeted antioxidant or AhR-modulating therapies.
Particulate matter (PM) exposure is increasingly associated with sinonasal disorders including allergic rhinitis (AR) and chronic rhinosinusitis (CRS), yet the mechanistic pathways linking PM to epithelial dysfunction remain incompletely defined. This review synthesizes experimental preclinical evidence to clarify the biologic mechanisms of PM-induced nasal epithelial injury and to propose an integrated model of PM-driven sinonasal pathology. We searched PubMed and Embase from inception to March 2025 for in vitro and in vivo studies examining PM effects on nasal tissue; 38 studies met prespecified inclusion criteria and were qualitatively synthesized. Across models, PM exposure consistently increased reactive oxygen species (ROS) and overwhelmed Nrf2-mediated antioxidant defenses, leading to mitochondrial dysfunction and autophagy associated cell death. Downstream ROS activation of NF-KB/MAPK signaling promoted proinflammatory cytokine release (including IL-6, IL-8, and TNF-a). In AR/CRS-relevant settings, PM amplified Th2-skewed inflammation, promoted eosinophilic recruitment, and disrupted epithelial tight junction proteins, impairing barrier integrity. PM also reduced mucociliary clearance through ciliary damage and IL-13-associated mucus hypersecretion. Collectively, current experimental evidence supports an ROS-initiated, Nrf2-modulated cascade as a central mechanism of PM-related sinonasal toxicity, linking pollutant exposure to inflammation, barrier breakdown, and impaired mucociliary function relevant to AR and CRS. Key priorities for future work include identifying the most harmful PM constituents, clarifying persistent regulatory effects (including epigenetic mechanisms), and testing targeted antioxidant or cytoprotective interventions to mitigate pollution-associated upper airway disease. Level of Evidence: Level 1 (Systematic Review).
Pollen sensitization is a major cause of asthma and allergic rhinitis worldwide, creating a serious public health issue. There is a significant gap in effective care because most diagnostic and allergen immunotherapy (AIT) products come from North America and Europe. This focus overlooks the unique allergenic profiles in Asia, Africa, and other areas. This article looks at current allergy products, highlighting these global differences and the urgent need for a Global-Local strategy. Our review shows a lack of clinically significant allergenic plants, which leads to poor management and missed sensitizations. We identify “diagnostic blind spots,” such as bottlebrush plants that have no commercial tools available, and we note a significant gap between diagnosis and treatment. A shift toward a Global-Local approach is necessary to create diagnostic panels and AIT products that reflect local plant life accurately. This change would meet the huge unmet needs of millions of patients globally and improve both treatment outcomes and diagnostic accuracy.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease that may be refractory to conventional medical and surgical therapies. Advances in the understanding of type 2 inflammatory mechanisms have led to the development of targeted biologic therapies. This review examines clinical trial evidence, and real-world data supporting biologic use in CRSwNP. Four biologics (dupilumab, omalizumab, mepolizumab, tezepelumab) are FDA approved in the United States for the management of refractory CRSwNP. Randomized controlled trials and multiple additional studies have demonstrated the efficacy of biologics in reducing nasal polyp burden and nasal congestion in patients who are refractory to traditional medical/surgical therapy or are poor surgical candidates. Guidelines for implementing these drugs into daily practice emphasize the importance of identifying appropriate patient subgroups, considering patient inflammatory profiles and comorbid conditions to select the best agent, and reassessing drug response to optimize resources and ensure patient safety. Biologics uniquely contribute to CRSwNP management by modulating the underlying type 2 inflammatory pathway cascade in patients who are otherwise refractory to conventional medical and surgical therapy. Ongoing and future trials will refine biomarker-guided therapy and define the role of biologics alongside surgery in comprehensive CRSwNP care.
In this review, we conducted a literature search seeking to better understand the relationship between chronic spontaneous urticaria (CSU) and nonsteroidal anti-inflammatory drugs hypersensitivity (NSAID-hypersensitivity) associated with NSAID exacerbated cutaneous diseases (NECD), its clinical course, and gain insight into the answers to clinical questions. The coexistence of CSU and NSAID-hypersensitivity specially NECD has been well documented. However, many questions remain unanswered: Why does this coexistence occur? Which condition appears first? If CSU is controlled, can the patient tolerate NSAIDs? If urticaria disappears, does NSAID-hypersensitivity remit as well? Although limited, current evidence shed light on potential immunological mechanisms and clinical course of these diseases and allow for the proposal of possible management algorithms that consider NSAID-hypersensitivity remission in urticaria.
