Vaccines constitute the most effective medications in public health as they control and prevent the spread of infectious diseases and reduce mortality. Similar to other medications, allergic reactions can occur during vaccination. While most reactions are neither frequent nor serious, anaphylactic reactions are potentially life-threatening allergic reactions that are encountered rarely, but can cause serious complications. The allergic responses caused by vaccines can stem from activation of mast cells via Fcε receptor-1 type I reaction, mediated by the interaction between immunoglobulin E (IgE) antibodies against a particular vaccine, and occur within minutes or up to four hours. The type IV allergic reactions initiate 48 h after vaccination and demonstrate their peak between 72 and 96 h. Non-IgE-mediated mast cell degranulation via activation of the complement system and via activation of the Mas-related G protein-coupled receptor X2 can also induce allergic reactions. Reactions are more often caused by inert substances, called excipients, which are added to vaccines to improve stability and absorption, increase solubility, influence palatability, or create a distinctive appearance, and not by the active vaccine itself. Polyethylene glycol, also known as macrogol, in the currently available Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines, and polysorbate 80, also known as Tween 80, in AstraZeneca and Johnson & Johnson COVID-19 vaccines, are excipients mostly incriminated for allergic reactions. This review will summarize the current state of knowledge of immediate and delayed allergic reactions in the currently available vaccines against COVID-19, together with the general and specific therapeutic considerations. These considerations include: The incidence of allergic reactions and deaths under investigation with the available vaccines, application of vaccination in patients with mast cell disease, patients who developed an allergy during the first dose, vasovagal symptoms masquerading as allergic reactions, the COVID-19 vaccination in pregnancy, deaths associated with COVID-19 vaccination, and questions arising in managing of this current ordeal. Careful vaccine-safety surveillance over time, in conjunction with the elucidation of mechanisms of adverse events across different COVID-19 vaccine platforms, will contribute to the development of a safe vaccine strategy. Allergists’ expertise in proper diagnosis and treatment of allergic reactions is vital for the screening of high-risk individuals.

Chronic rhinosinusitis (CRS) with (CRSwNP) or without (CRSsNP) nasal polyps is a prevalent and heterogeneous disorder existing as a spectrum of clinical conditions with complex underlying pathomechanisms. CRS comprises a broad syndrome characterized by multiple immunological features involving complex interactions between the genes, the microbiome, host- and microbiota-derived exosomes, the epithelial barrier, and environmental and micromilieu exposures. The main pathophysiological feature is an epithelial barrier disruption, accompanied by microbiome alterations and unpredictable and multifactorial immunologic overreactions. Extrinsic pathogens and irritants interact with multiple epithelial receptors, which show distinct expression patterns, activate numerous signaling pathways, and lead to diverse antipathogen responses. CRSsNP is mainly characterized by fibrosis and mild inflammation and is often associated with Th1 or Th17 immunological profiles. CRSwNP appears to be associated with moderate or severe type 2 (T2) or Th2 eosinophilic inflammation. The diagnosis is based on clinical, endoscopic, and imaging findings. Possible CRS biomarkers from the peripheral blood, nasal secretions, tissue biopsies, and nasally exhaled air are studied to subgroup different CRS endotypes. The primary goal of CRS management is to maintain clinical control by nasal douching with isotonic or hypertonic saline solutions, administration of nasal and systemic steroids, antibiotics, biologic agents, or, in persistent and more severe cases, appropriate surgical procedures.

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease of the nasal and paranasal sinus mucosa with substantial impact on quality of life. Although atopy and/or allergic rhinitis frequently coexist with CRS, often alongside type 2-skewed inflammation, the extent to which allergic mechanisms define a discrete CRS entity remains debated, in part due to inconsistent operational definitions and overlapping clinical phenotypes. In parallel, culture-independent sequencing studies have reframed CRS as a disorder of host–microbe interactions, with many cohorts reporting reduced sinonasal microbial diversity, enrichment of potentially pathogen taxa (including Staphylococcus aureus), and biofilm-associated community states. However, causality and directionality remain uncertain. In this narrative review, we synthesize evidence at the interface of epithelial barrier dysfunction, type 2 cytokine networks (IL-4/IL-13/IL-5), and microbiome dysbiosis, highlighting where data are consistent across studies versus where findings are heterogeneous or predominantly associative. We discuss representative allergy-associated CRS prototypes such as allergic fungal rhinosinusitis and central compartment atopic disease as clinical models to interrogate these interactions, while distinguishing them from non–IgE-mediated type 2 entities such as aspirin-exacerbated respiratory disease. We also summarize current data linking atopy to sinonasal microbial signatures and discuss emerging microbiome-directed interventions (topical probiotics, bacteriophages, and microbiota transfer concepts) alongside biologics and precision anti-inflammatory therapies. Finally, we highlight key knowledge gaps, including the limited endotype-resolved and longitudinal studies, variable allergic phenotyping in microbiome research, and the need for standardized definitions and biomarker-driven stratification to clarify clinical utility and to guide mechanism-informed therapeutic trials.

Allergen Immunotherapy (AIT) is a well-established, efficient, and safe way to treat respiratory and insect-venom allergies. After determining the diagnosis of the clinically relevant culprit allergen, AIT can be prescribed. However, not all patients are eligible for AIT, since some diseases/conditions represent contraindications to AIT use, as described in several guidelines. Allergists are often preoccupied on whether an extensive workup should be ordered in apparently healthy AIT candidates in order to detect contra-indicated diseases and conditions. These preoccupations often arise from clinical, ethical and legal issues. The aim of this article is to suggest an approach to the workup and assessment of the presence of any underlying diseases/conditions in patients with no case history before the start of AIT. Notably, there is a lack of published studies on the appropriate evaluation of AIT candidates, with no globally accepted guidelines. It appears that Allergists are mostly deciding based on their AIT training, as well as their clinical experience. Guidance is based mainly on experts’ opinions; the suggested preliminary workup can be divided into mandatory and optional testing. The evaluation for possible underlying neoplastic, autoimmune, and cardiovascular diseases, primary and acquired immunodeficiencies and pregnancy, might be helpful but only in subjects for whom the history and clinical examination raise suspicion of these conditions. A workup without any reasonable correlation with potential contraindications is useless. In conclusion, the evaluation of each individual candidate for possible medical conditions should be determined on a case-by-case basis.

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory syndrome of the sinonasal mucosa that is imperfectly captured by phenotypes with or without nasal polyps. Since allergic rhinitis (AR) and atopy often occur alongside CRS, the term “allergic CRS” is commonly used. However, it is uncertain whether this term indicates a specific allergen-related, IgE-mediated endotype or merely represents a clinical overlap. We synthesize epidemiologic data, mucosal immunobiology, epithelial barrier dysfunction, and host–microbe interactions that can generate IgE-rich type 2 inflammation in CRS. We propose an operational entity test (objective CRS; clinically relevant allergy; evidence of IgE relevance in target tissue; exposure–response patterns; and differential response to allergy-directed interventions) to guide hypothesis testing rather than diagnosis. Using this framework, allergic fungal rhinosinusitis and central compartment atopic disease emerge as the clearest clinical prototypes where allergen contact patterns and IgE relevance plausibly contribute to disease expression. In contrast, microbial superantigens and other non-allergen stimuli can drive local IgE amplification, limiting the specificity of systemic sensitization as a causal marker. We discuss therapeutic implications, including biologics targeting type 2 pathways and epithelial alarmin blockade, and outline research priorities for endotype-resolved cohorts and mechanism-informed trials to test whether allergic CRS should evolve from a heuristic descriptor into a validated endotype.