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.
Based on a comprehensive literature review, this paper evaluates the clinical effectiveness of house dust mite (HDM) avoidance measures. It aims to determine whether interventions actually lead to symptom relief or merely reduce allergen concentrations without significant clinical benefit. The reviewed data reveals a significant "clinical gap": while encasings and environmental cleaning effectively lower allergen loads, their impact on symptoms—especially in adults—is often statistically insignificant. In contrast, pediatric patients benefit more from aggressive, multimodal environmental control. The review concludes that isolated measures are rarely sufficient as a monotherapy. Complete allergen eradication is practically impossible, making avoidance a supportive effort rather than a standalone cure. Consequently, avoidance measures should be seen as a synergistic part of a broader treatment plan and must not be a prerequisite for Allergen Immunotherapy (AIT). AIT remains medically necessary precisely because environmental control alone cannot eliminate the triggers in modern daily life.
Storage mite allergy is a relevant differential diagnosis in perennial allergic disease and frequently causes occupational allergy in exposed individuals. However, storage mites are often underdiagnosed due to the similarity of reported symptoms to house dust mite allergy. The purpose of this review is to provide an overview of the latest developments with a focus on allergen-immunotherapy (AIT) for the underestimated epidemic of SM allergy. Storage mites continue to be a relevant factor for occupational allergy, for example in bakers and farmers. Reported sensitization frequencies vary widely depending on the geographical location. A shift from storage mite as an allergen relevant to rural areas only towards frequent urban sensitization is taking place. Lack of testing for storage mite allergy owes to missing test and therapeutic substances, as well as lack of consciousness. No recent advances in storage mite AIT can be reported, but recommendations on the standardized testing of storage mite allergy were made. The latest development lies in biologics as an alternative, non-disease-modifying therapy. Standardized testing for storage mite sensitization should be performed. AIT for storage mites has to be performed separately and independently of AIT for house dust mites. Lack of available test and therapy substances as well as limited number of patients in controlled trials needs to be addressed in the future.
The relationship between acute urticaria and chronic urticaria remains conceptually important yet poorly understood. We, in this review tried to examine if acute urticaria (AU) and chronic urticaria (CU) represent sequential phases of a single disease spectrum or biologically distinct entities that share a common clinical phenotype. In the review we synthesized current evidence on pathophysiology, trigger profiles, biomarkers, natural history, disease progression, and therapeutic responsiveness to understand the relationship between AU and CU. AU and CU converge on a common effector pathway mediated by mast cell and basophil and characterized by histamine release, increased vascular permeability, and wheal formation. This common downstream biology explains the overlapping clinical morphology and the broad efficacy of second-generation H1-antihistamines. However, recent evidence highlights important upstream differences. AU is predominantly trigger (e.g. infections, drugs, foods, vaccines. etc.) driven and usually resolves in days to weeks. In contrast, CU is driven by endogenous autoimmune or autoreactive pathways. Progression from AU to CU occurs in a subset of patients, particularly among patients with autoreactive biomarkers, low basophil counts, thyroid autoimmunity, NSAID or food hypersensitivity. Current evidence supports a hybrid spectrum model. The conventional six-week cutoff to differentiate between AU and CU remains practical for clinical classification but is insufficient to capture pathogenic diversity. Most AU requires minimal investigation and short-term symptomatic treatment, whereas CU warrants structured evaluation for autoimmune, inflammatory, and systemic associations. Biomarkers such as ASST, thyroid antibodies, basophil counts, CRP, and D-dimer may help identify patients at risk of chronicity and guide prognosis and treatment escalation. This framework supports a more nuanced approach to urticaria classification, integrating disease duration with endotype-informed assessment and personalized management.
Allergic rhinitis (AR) is an inflammatory condition that affects millions worldwide, causing significant healthcare costs and impairment in quality of life. While clinical guidelines recommend intranasal antihistamines as a first-line treatment for AR, current prescription azelastine hydrochloride 0.1
Anaphylaxis in infants presents a complex diagnostic and therapeutic challenge due to atypical presentations and communication barriers. This review aims to synthesize the current understanding of this condition, focusing mainly on the clinical phenotype of children under 2 years of age, the evolution of age-specific diagnostic criteria, and evidence-based recommendations for acute and long-term management, with the aim of improving outcomes in these patients. A recent international consensus, outlined in the GALEN 2024 report, has established a unified clinical framework and diagnostic decision support tool to standardize the recognition of anaphylaxis across all ages. This tool explicitly integrates baby-specific signs into a structured diagnostic algorithm. Recently proposed and validated diagnostic criteria for infants and toddlers, such as bowing, drooling, and itching, among others, expand the classic list of symptoms to mitigate the historically low sensitivity of traditional criteria in this population group. The diagnosis of anaphylaxis in infants is fraught with difficulties, often leading to underdiagnosis and a dangerous delay in the initiation of treatment. The central principle of management remains the rapid administration of intramuscular adrenaline. The recent development and dissemination of diagnostic tools adapted to the baby represents a fundamental advance for early recognition and intervention. Comprehensive long-term care requires identification of triggers, meticulous caregiver education, a written action plan for anaphylaxis, and follow-up with a childhood allergy specialist. The implementation and prospective validation of these new diagnostic frameworks in clinical practice are essential steps to reduce morbidity and mortality in this vulnerable age group.
Fish-mediated allergic diseases are characterized by high prevalence, clinical severity, sensitization potential, and lifelong persistence. Their growing threat to public health has made them a major public health challenge requiring urgent attention. Due to species diversity resulting from evolutionary processes and processing methods, fish consumption patterns vary appreciably across global diets. The molecular structural and physicochemical variations and conservation among different allergens can induce distinct or cross-reactive immunological responses and clinical phenotypes in vivo, posing appreciable challenges to precise clinical diagnosis and personalized treatment. Deepening our understanding of the underlying mechanisms linking these structural characteristics and immune responses will help overcome current clinical difficulties, providing theoretical support and practical guidance for developing more effective allergy prevention and control strategies for the majority of patients. Recent studies indicate that fish allergies involve diverse species, with the structural characteristics and conserved nature of antigenic epitopes serving as the core molecular basis for mediating allergies and cross-reactions. Bioinformatics technologies have advanced the identification, analysis, and prediction of fish allergens and antigenic epitopes, providing theoretical support for elucidating sensitization mechanisms and the nature of cross-reactions. Diagnostic techniques have appreciably enhanced specificity and clinical value. Building upon this foundation, hypoallergenic technologies leverage high-temperature processing, enzymatic hydrolysis, fermentation, and other methods to selectively disrupt antigenic epitope structures or reduce allergen content, effectively diminishing their allergenicity. This approach has led to notable progress in the production of hypoallergenic aquatic products. This review focuses on elucidating the key structural and molecular characteristics of fish allergens, emphasizing the immunological mechanisms underlying allergic reactions and the nature of cross-reactivity. It comprehensively reviews the current status and advances in diagnostic and therapeutic technologies, summarizes the developmental trends in the field, and outlines future research directions. By continuously deepening scientific understanding of the biological properties of fish allergens, this work provides additional theoretical foundations and conceptual insights for developing more efficient and precise strategies for allergy prevention, control, and intervention.
Chronic spontaneous urticaria (CSU) is a heterogeneous mast cell–driven disease with highly variable clinical course and treatment response. Traditional diagnostic approaches are insufficient to capture this complexity, highlighting the need for biomarker-based endotyping. This review aims to critically evaluate the current evidence on paraclinical biomarkers used in CSU, focusing on their role in defining disease endotypes, predicting treatment response, assessing disease severity, and estimating prognosis and remission potential. Recent advances have clarified the immunopathogenic distinction between Type I autoallergic and Type IIb autoimmune CSU, each characterized by distinct biomarker profiles. Elevated total IgE, IgE autoantibodies, and soluble FcεRI are increasingly linked to the autoallergic endotype and favorable response to omalizumab. In contrast, low total IgE, IgG autoantibodies to FcεRI or IgE, eosinopenia, basopenia, elevated CRP, D-dimer, and positivity in functional assays such as the basophil activation test (BAT) or basophil histamine release assay (BHRA) characterize Type IIb autoimmune CSU and predict treatment refractoriness to antihistamines and omalizumab, with better response to immunosuppressive therapies. Emerging functional platforms, including mast cell activation tests, further expand the diagnostic landscape. Paraclinical tests have evolved from ancillary investigations into essential tools for endotype-driven precision medicine in CSU. While no single biomarker is diagnostic in isolation, integrated interpretation of serological, cellular, and functional markers enables more accurate endotyping, improved treatment stratification, and realistic prognostic counseling. Future research should focus on assay standardization, validation of composite biomarkers, and development of practical diagnostic tools—particularly for Type I autoallergic CSU—to facilitate broader implementation of precision medicine approaches in routine clinical practice.
This review focuses on the current applications of AI in the management of patients with allergic diseases, aiming to provide insights for innovative applications of AI in this field. Several fields of artificial intelligence, including machine learning (ML), deep learning (DL), and natural language processing (NLP), have significant potential in treating allergic diseases, capable of enhancing diagnostic and therapeutic capabilities while improving the efficiency of clinicians and healthcare systems. With the advancement of information technology, artificial intelligence (AI) has increasingly demonstrated its advantages in the diagnosis, treatment, and management of allergic diseases. AI assists physicians in evaluating diagnostic and therapeutic outcomes, providing effective tools for assessing disease severity, monitoring allergies, and delivering health education to patients.
Anaphylaxis in older adults remains insufficiently studied despite a rising burden in an aging population. This review examines how comorbidities, polypharmacy, and atypical clinical presentations influence risk, diagnosis, and management in this group, and identifies major gaps in current evidence. Registry data show age-related differences in elicitors, with insect venom and drugs predominating in adults ≥ 65 years. Older patients more frequently present without skin symptoms and exhibit cardiovascular-dominant reactions, contributing to diagnostic delay. Cardiovascular and respiratory disease, beta-blockers, ACE inhibitors, and immunosenescence increase severity and complicate treatment. Real-world data suggest that epinephrine remains underused, and while intranasal adrenaline spray has emerged as an alternative, safety data in older patients are lacking. Long-term management is challenged by frailty, functional limitations, and reduced ability to use autoinjectors. Older adults experience more severe, atypical anaphylaxis driven by multimorbidity, medication effects, and age-related immune changes. Early recognition, prompt epinephrine use, and individualized prevention plans are essential. Targeted research is needed to refine diagnostic criteria, clarify medication-related risks, and guide age-adapted management strategies.
to describe the positive impact of timely diagnosis and treatment of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) on the symptoms of severe asthma in patients with both diseases in the context of Latin America based on available prevalence data in the region and to describe the diagnosis and treatment strategy currently employed. it is estimated that prevalence of CRSwNP in patients with severe asthma in Latin America is comparable to the data presented at global level. The impact on patients’ health is comparable to those patients with other chronic diseases with greater recognition (asthma, Typer 2 Diabetes, rheumatoid arthritis). Despite socioeconomic differences, the diagnosis and treatment strategies employed in these Latin American patients is comparable to those in Europe or the United States. In Latin America it is estimated that the prevalence of patients with severe asthma and CRSwNP is comparable to the data presented globally. Patients with severe asthma and CRSwNP present a more severe disease with lower chances of therapeutic success despite adequate medical and/or surgical treatment. The presence of CRSwNP in a patient with severe asthma should be considered as a treatable trait and as a predictor of therapeutic failure. Successful treatment of the symptoms inherent to CRSwNP will be reflected in the improvement of symptoms attributable to severe asthma. Despite less access, in Latin America biologics represent a therapeutic alternative reserved for those patients who are unable to control symptoms with standard treatment.
This review examines whether allergen immunotherapy (AIT) for grass pollen allergy should expand beyond the recent trend towards a mono-species approach based on Phleum pratense. It explores whether multi-species formulations better reflect natural exposure and could improve clinical outcomes. Research from aerobiology and immunology shows that grass pollen exposure involves diverse species with distinct flowering periods, influenced by climate and geography. Molecular analyses reveal species-specific allergen profiles, including unique peptides and variations in major allergens such as Group 1 and 5. Patient data confirm symptom variability across the season. In-vitro studies have observed limits to the cross-reactivity of T-cell epitopes, and comparative clinical studies suggest benefits for multi-species treatment options. Evidence indicates that mono-species extracts alone do not represent the full allergenic spectrum of grass pollen. Broad-spectrum AIT formulations incorporating multiple grass species provide a more comprehensive repertoire of allergens and epitopes, potentially enhancing immunogenicity and therapeutic benefit. This supports the hypothesis that diversity does not equate to dilution in broad-spectrum formulations. The approach aligns with patient symptom patterns and may improve efficacy and asthma prevention. Future research could further refine species selection and leverage molecular diversity to optimize treatment strategies.
To summarize current evidence on the immediate and long-term safety profile of the available monoclonal biological therapy (MBT) approved for the treatment of severe asthma. Clinical trials and real-world studies have shown that MBT are generally well tolerated, although certain adverse effects such as local reactions, anaphylaxis, parasitic or viral infections, malignancy, and cerebrovascular events are of special concern in these therapies or have already been reported. The frequency and severity of these effects vary depending on the specific agent and patient characteristics. MBT have significantly improved the management of severe asthma, yet continuous monitoring of their safety profile remains essential to optimize long-term outcomes and minimize risks.
Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly affects quality of life. Early identification of clinical or biomarkers capable of predicting response to topical therapies including topical corticosteroids, topical calcineurin inhibitors, and phosphodiesterase-4 inhibitors could reduce the time required to achieve disease control. The aim of this study was to explore the emerging literature on clinical or molecular biomarkers associated with the response to first-line topical treatment in AD. The review followed the PRISMA-ScR statement. Nine studies involving 345 patients were included. Different biomarkers have been explored as potential biomarkers of clinical responses to topical treatments in AD. TARC/CCL17 levels significantly decreased in both skin and blood, correlating with reduced SCORAD and pruritus. CCL27 and CXCL8 also showed reductions. While blood IL-31 was unrelated to treatment response, baseline skin levels of IFN-γ and IL-21 predicted improvements in SCORAD. Blood CCL22 strongly predicted clinical response to therapies. Elevated serum total IgE (≥ 10,000 IU/ml), high LDH levels, and contact allergies, were associated with poor clinical control with topical therapy. Although several biomarkers exhibit statistical associations with treatment response, none have yet been validated for predictive accuracy. Current evidence is exploratory, limited by small sample sizes, inconsistent methodologies, and lack of diagnostic performance metrics. More rigorous prognostic studies are needed to determine their clinical utility.
Occupational anaphylaxis is likely underdiagnosed but can affect worker’s health and careers. This review addresses reasons for underdiagnosis, the need to identify the causes of anaphylaxis, and approaches to prevention. While insect stings likely cause the majority of cases of occupational anaphylaxis, a wide variety of allergens can cause anaphylaxis. Prevention of sensitization is the most effective way to prevent anaphylaxis. Outdoor workers and those involved in food production and preparation, healthcare, and work with animals are at risk for sensitization to allergens and occupational anaphylaxis. Implementing measures to reduce exposure to allergens can prevent allergy and anaphylaxis. Prevention efforts should include, in order of decreasing effectivess, elimination, substitution, engineering controls, administrative controls (including work practices), and personal protective equipment. Occupational anaphylaxis is uncommon but likely also underdiagnosed, either because mild symptoms aren’t recognized as anaphylaxis or because the cause is not identified. Identifying the trigger for anaphylaxis is necessary to prevent recurrence and should be pursued when the cause is not evident. Workers with anaphylaxis should be removed from exposure. Venom immunotherapy is recommended for those with anaphylaxis to Hymenoptera stings.
This review aims to analyze the evidence regarding the role of the alpha-gal sensitization in other pathologies different from alpha-gal syndrome, mainly in the chronic spontaneous urticaria. The alpha-gal syndrome can present with a spectrum of clinical manifestations, with acute urticaria in the context of food ingestion in the previous hours being the most commonly reported by affected individuals. Autoimmune mechanisms have been described in the context of chronic spontaneous urticaria; nevertheless, its pathophysiology remains incompletely understood. Recently, different authors have hypothesized that alpha-gal sensitization might be one of the underlying causes of chronic spontaneous urticaria. Studies conducted to date, mostly by US and European groups, show contradictory results. Some of them report very high prevalence rates of sensitization to alpha-gal in patients with chronic urticaria, while others show even lower sensitization prevalences than in the general population. With the current evidence, alpha-gal sensitization cannot be associated with the onset of chronic spontaneous urticaria. Further studies with larger cohorts and proper control groups are needed to accurately assess the prevalence of alpha-gal sensitization in patients with chronic spontaneous urticaria.
Acute Generalized Exanthematous Pustulosis (AGEP) and its localized variant (ALEP) are severe T cell–mediated hypersensitivity reactions, most commonly triggered by β-lactam antibiotics. This review aims to update the allergological approach for identifying the culprit drug in AGEP/ALEP, contrasting it with immediate-type (IgE-mediated) hypersensitivity reactions. β-lactam antibiotics serve as a model to highlight the differing diagnostic pathways, including clinical assessment, histopathology, and immunological testing, to facilitate prompt recognition and safe management. The latest European consensus on AGEP diagnosis recommends delayed patch testing and intradermal testing (10–30
