Allergy, Anaphylaxis, and Nonallergic Hypersensitivity: IgE, Mast Cells, and Beyond.

IgE-mediated type I hypersensitivity reactions have many reported beneficial functions in immune defense against parasites, venoms, toxins, etc. However, they are best known for their role in allergies, currently affecting almost one third of the population worldwide. IgE-mediated allergic diseases result from a maladaptive type 2 immune response that promotes the synthesis of IgE antibodies directed at a special class of antigens called allergens. IgE antibodies bind to type I high-affinity IgE receptors (FcεRI) on mast cells and basophils, sensitizing them to get triggered in a subsequent encounter with the cognate allergen. This promotes the release of a large variety of inflammatory mediators including histamine responsible for the symptoms of immediate hypersensitivity. The development of type 2-driven allergies is dependent on a complex interplay of genetic and environmental factors at barrier surfaces including the host microbiome that builds up during early life. While IgE-mediated immediate hypersensitivity reactions are undoubtedly at the origin of the majority of allergies, it has become clear that similar responses and symptoms can be triggered by other types of adaptive immune responses mediated via IgG or complement involving other immune cells and mediators. Likewise, various nonadaptive innate triggers via receptors expressed on mast cells have been found to either directly launch a hypersensitivity reaction and/or to amplify existing IgE-mediated responses. This review summarizes recent findings on both IgE-dependent and IgE-independent mechanisms in the development of allergic hypersensitivities and provides an update on the diagnosis of allergy.

Aspirin desensitization in nonsteroidal anti-inflammatory exacerbated respiratory disease: The first prospective cohort in Chile.

Background: Nonsteroidal anti-inflammatory exacerbated respiratory disease (N-ERD) is characterized by the Samter triad: chronic rhinosinusitis with nasal polyps, asthma, and nonallergic hypersensitivity to NSAIDs. Its diagnosis is based on a complete clinical history and an aspirin (ASA) challenge test. Medical treatments include biological drugs and ASA desensitization. Objective: This study aims to evaluate the clinical response of patients with N-ERD undergoing functional endoscopic surgery (FES), followed by ASA desensitization and maintenance treatment, being the first prospective cohort study carried out in Chile. Methods: We conducted 1-year follow-up of 12 patients with N-ERD treated with FES, desensitization, and maintenance with ASA. For each control, the medication score, sinonasal symptomatology (SNOT-22), PEF (peak expiratory flow), nasal polyposis (Lildholdt score), and the appearance of adverse effects were recorded. Computed tomography (CT) of the paranasal cavities was performed at baseline and at the 12-month follow-up to calculate the Lund-Mackay score. Results: Patients presented a reduction of SNOT-22 after the FES, which was maintained at 12 months (p = 0.002); the symptoms that showed the greatest reduction were feeling embarrassed and nasal obstruction. The Lildholdt score was also significantly reduced (p = 0.001); in only three patients, the nasal polyps recurred, and all were small. The PEF showed a slight nonsignificant increase of 3.3%. In total, 75% of patients had an adverse effect, the most frequent being abdominal pain (66.7%), but none of the 12 patients required discontinuation of aspirin treatment in 1-year follow-up. The Lund-Mackay score had a significant reduction of 6.6 points (p < 0.001). Conclusion: ASA desensitization is safe and effective in reducing upper and lower respiratory symptoms in patients with N-ERD and delays the reappearance of nasal polyps, although it is not exempt from adverse effects, with the vast majority being mild.