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Abstract: Hymenoptera venom allergy is a potentially life‐threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic‐allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life‐threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1‐antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence‐based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta‐analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom‐allergic children and adults to prevent further moderate‐to‐severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence‐based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence. [ABSTRACT FROM AUTHOR]

Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells ( MC) in different tissues, with a preferential localization in skin and bone marrow ( BM). The excess of MC in mastocytosis as well as the increased releasability of MC may lead to a higher frequency and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti-inflammatory drugs, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC disorders using MEDLINE, EMBASE, and Cochrane Library, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. [ABSTRACT FROM AUTHOR]

Summary: Airways hyperresponsiveness (AHR) is a pathognomonic event of asthma in which the airways are reactive to various bronchoconstrictor stimuli at 'doses' that normally have no bronchoconstrictor effect in non-asthmatics. AHR is an objective measure of clinical efficacy, and the introduction of biologics revived interest as a marker of disease and its pathophysiologic mechanism. This article aims to discuss the mechanisms of AHR, focusing on the role of epithelial damage and TSLP production, and promote its correct assessment for the evaluation of patients with severe asthma, to predict the risk of exacerbations and outcomes, and the eligibility for treatment with an anti-TSLP agent. AHR is a complex trait of asthma, induced by the concurrence of many pathophysiological factors and related to different clinical manifestations. Recent evidence demonstrates the important role of airway epithelial damage and TSLP production in many of these events. A therapeutic response based on AHR control could be considered as a condition of disease remission and seems a promising new goal for the management of patients with severe asthma.

Summary: The aim of this contribution was to highlight the "favorable" and "unfavorable" roles of domestic and non-domestic animals on airway sensitization processes and on the type/severity of the clinical symptoms induced by their exposure. We performed a literature research in MEDLINE for allergic manifestations and animals. Pets can be "allergy friends" through mechanisms related to hygiene hypothesis and translational aspects, the dual role of IgG4 antibodies for pets, and their promising role as healthcare service animals (dogs). On the contrary, animals can be "allergy enemies" when inducing allergic sensitization and  respiratory symptoms (sometimes leading to severe reactions), and also due to cross reactivity with other pets allergens, indirect exposure and ubiquity of their allergens, cross reactivity between Can f 5 and human prostate-specific antigen (PSA). Moreover, in some cases they can trigger anaphylaxis, induce occupational asthma, and act as pests. Finally, we must outline the modest efficacy of allergen immunotherapy (AIT) for their allergens. From a strictly allergological perspective, it is evident that the "negative" aspects resulting from exposure to domestic / non-domestic animals outweigh the "positive" aspects. As a consequence, it is up to humans to seek new ways to balance the pros and cons by exploring research areas that can allow the best possible coexistence with subjects at risk of allergy with domestic and non-domestic animals.

Summary: Eosinophil-associated diseases (EADs) refer to heterogeneous conditions in which eosinophils are believed to play critical pathological roles. They encompass common respiratory conditions, such as asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), less common primary eosinophilic disorders of gastrointestinal tract, and rare conditions including eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). A literature search was carried out in January 2024 in the MEDLINE and Scopus databases using the PubMed search engine (PubMed, National Library of Medicine, Bethesda, MD). We focused on blood eosinophilia and hypereosinophilia. A diagnostic workup is proposed. From allergist's point of view, we focused the review on 4 groups of eosinophilic disorders of specific interest. Our increased understanding of type 2 inflammation and biology has recently led to development of highly effective precision targeted therapies that are now approved for a growing number of eosinophilic disorders. Novel targeted biologics have a major impact on treatment strategies and have resulted in major advances in our understanding of the pathogenesis of these disorders. In the context of EADs, according to the heterogeneity of eosinophilic disorders a multidisciplinary approach should be adopted. Allergists and Clinical Immunologists play an important role as they have a clear understanding of the eosinophilic inflammation and the role of cytokines and are trained to recognize and characterize type 2 (T2) inflammation and its associated pathologies.

Summary: Dogs and cats are the most common pets worldwide. In Italy, the prevalence of allergic sensitization to cats and dogs is 16% and 9% respectively. The limited standardization of allergenic extracts, especially for dogs, emphasizes the importance of Component Resolved Diagnosis (CRD) for accurate diagnosis and subsequent prescription of allergen immunotherapy (AIT). However, this low standardization is the main factor contributing to the unsatisfactory clinical efficacy of traditional AIT, AIT with modified allergens, and intralymphatic allergen-specific immunotherapy (ILAIT). Emerging immunological approaches, particularly for controlling the primary cat allergen, show promise but are hindered by high costs (e.g., use of anti-Fel d 1 monoclonal antibodies in humans) or by exclusively targeting Fel d 1 produced by one's own animal (e.g., immunizing cats to induce neutralizing antibodies against Fel d 1 or including an egg product with anti Fel d 1 IgY antibodies in feline diet). Further studies are imperative for standardizing pet allergens, enhancing the efficacy of various AIT modalities, and exploring other immunological approaches, to optimize the relationship between pets and their owners and prevent distressing "forced removals".

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Summary: Background. Asthma affects millions of people worldwide, with a subgroup suffering from severe asthma (SA). Biologics have revolutionized SA treatment, but challenges remain in managing different patient traits. This study analyzed data from the Italian Registry on Severe Asthma (IRSA) to investigate changes in SA characteristics and effectiveness of treatments after one year of follow-up, and to identify factors associated with response to treatments in a real-world setting. Methods. Data on SA patients with one year of follow-up were extracted from IRSA. Asthma control, exacerbations, lung function, and treatments, were assessed at follow-up and analyzed against baseline characteristics. Results. After one year of follow-up, notable improvements were observed in all the outcomes of SA of the included patients (n = 570). The effectiveness of biologic therapies was particularly evident, as they contributed significantly to these positive outcomes. Additionally, certain factors were found to be associated with improvement, namely T2 phenotype, baseline eosinophil count (BEC), and area of residence. On the other hand, comorbidities (obesity, gastro-esophageal reflux disease) and poor lung function were risk factors. Notably, poor-responders to biologics exhibited lower level of education, BEC, and exacerbations, and higher frequency of atopy and ACT score ≥ 20. Conclusions. The findings demonstrate the effectiveness of biologics in asthma management, when implemented as part of a planned follow-up strategy aimed at optimizing and fine-tuning the therapy. Moreover, the study highlights the importance of considering key traits such as the T2 phenotype, BEC, education, and comorbidities when tailoring SA treatment. Overall, this study contributes to enhancing our understanding of SA management and guiding the development of personalized treatment approaches for patients with SA.

Summary: At the beginning of SARS-CoV 2 pandemic, in the absence of "targeted" therapies, the national health authorities have introduced some measures aimed at reducing the spread of infection in the community (lockdown, social distancing, personal protective equipment (PPE), personal hygiene and disinfection of living environments). All the containment measures have led to both positive and negative effects in patients with allergic diseases. We believe that further studies should be undertaken to investigate the possible correlations between SARS-CoV-2 infection and allergy, from a broader perspective. In particular, the risk factors for the development of undesirable effects should be investigated, especially in healthcare professionals forced to use PPE and sanitizing agents for a long time. However, since the COVID-19 pandemic probably will not be short-lived, the use of such protective aids will necessarily be widespread even in the general population. Therefore, further studies on the materials used for the production of PPE and sanitizing agents would be necessary to reduce their sensitizing and, in some cases, toxic potential.

Summary: It is currently recognized that the airway epithelium plays a pivotal role in orchestrating inflammatory, immune, and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. The impact of pollen on respiratory epithelium is multifaceted and goes beyond the direct barrier damage driven by the best-known Type-2 response. After pollen-driven activation, airway epithelial cells play an active role in triggering several pathways. In particular, the release of epithelial cytokines (or alarmins) activates both innate and adaptive immunity, with downstream effects implicated to the pathogenesis of asthma. Pollutants also have a pleiotropic effect on respiratory epithelium. Diesel exhaust particles can directly damage the respiratory epithelium with consequent barrier dysfunction, increased permeability, and local inflammation, but they can also activate Th2 responses. Innate immune responses also are triggered by pollutants through release of epithelial cytokines and redox-sensitive pathways that generate mechanical and immunologic changes in the respiratory epithelium. In addition to the typical Type-1 immune response, respiratory virus infections stimulate type-2 innate lymphoid cells in the airway epithelium to release epithelial cytokines. Finally, the action of epithelial triggers on airway smooth muscle is the central element in the induction of remodeling and hyperreactivity of the airways in asthma. This article reviews the pathophysiology and functions of the airway epithelium and the role of epithelial damage by different triggers in the development, persistence, and exacerbations of asthma.

Summary: Anaphylaxis is the most severe systemic hypersensitivity reaction, it can be caused by a number of well identified triggers such as foods, drugs, stinging insects and facilitated by predisposing clinical conditions. However, sometimes anaphylaxis shows up with uncommon or peculiar characteristics which could delay diagnosis and therapeutic treatment. In this report we aimed to describe less accounted / difficult-to-approach shapes of anaphylaxis to facilitate clinicians to suspect these severe reactions even in uncommon conditions. We choose to present data on anaphylaxis regarding simulation, mode of exposure to sensitizing agents, pregnancy, exposure to animals, intimate behaviour, psychological stress and other situations.

Summary: Objective. The purpose of the study was to describe the characteristics of patients experiencing hypersensitivity reactions (HRs) to iodinated contrast media (ICM) in a large Italian population and to investigate potential risks factors in order to obtain a risk stratification, helpful in the management of these patients. Methods. Data of 407 patients investigated in 9 Italian Allergy Centers for suspected HRs to ICM were analyzed and compared with a control group of 152 subjects that tolerated one or more ICM-enhanced examinations. The univariate and multivariate logistic regression model was used to evaluate associated factors. Results. The mean age of reactive patients was 61 years and 60% were female; 67% of patients reported immediate reactions and 35% experienced the reaction, more frequently with immediate onset, at the first examination in life. Iomeprol, iopromide and iodixanol were the most frequent culprit agents and 20% of patients showed a positive skin test result. Previous adverse reactions to ICM were reported by 15.6% of patients, whereas 35% of subjects experienced the reaction, more frequently immediate, after the first ICM-enhanced examination in their life. The multivariate analysis showed that male gender and age > 65 were associated with ICM reactions as protective factors [OR adja = 0.51; 95% CI: 0.33-0.77 and OR adja = 0.60; 95% CI: 0.39-0.92 respectively]. Cardio-vascular disease [OR adja = 2.06; 95% CI: 1.22-3.50)], respiratory allergy [OR adja = 2.30; 95% CI: 1.09-4.83)] and adverse drug reactions [OR adja = 1.99; 95% CI: 1.05-3.77)] were identified as risk factors for ICM reactions. Food allergy was not significantly associated with reactions [OR adja = 1.51; 5% CI: 0.41-5.56]. Conclusions. This is the largest study on Italian patients experiencing hypersensitivity reactions to ICM. Most results are in line with other studies, showing some association with factors that could influence the incidence of hypersensitivity reactions but not allowing an easy risk stratification.

Summary: Background. The Italian Registry on Severe Asthma (IRSA) is the most recent and largestregistry in Italy. Objective. To improve the knowledge on the clinical and biological features of severe asthma (SA), and to monitor its treatments. Methods. To analyze clinical,functional, inflammatory, and treatment characteristics of severe asthmatics from the IRSA registry. Results. 851 subjects were enrolled. 31.8% and 64.5% of patients were submitted to oral corticosteroids (OCS), and monoclonal antibodies (MABs), respectively. At least tw ocomorbidities affected 77.4% patients. Asthma was uncontrolled in 62.2% patients. Uncontrolled patients had a higher frequency of exacerbations, and hospitalization, showing a highere osinophilic phenotype, a greater use of OCS, and being treated with MAB less frequently. However, uncontrolled patients treated with MAB had a lower use of OCS and a lower rateof hospitalization. Comparing SA patients with atopy and without atopy, the latter showeda greater use of OCS, and more frequent nasal polyposis and osteoporosis. Among SA patients with atopy treated with MAB, 36% were on a treatment targeting the IL-5 pathway. Conclusions and clinical relevance. This study shows the features of the greatest Italian registryof SA patients, revealing at the time of enrollment a poor disease control, and the use of OCSand MABs in about one third and two thirds of patients, respectively. SA is a complex diseasethat requires a more precise phenotyping and a greater disease control.

Background and Objectives: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients., Material and Methods: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7., Results: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP., Conclusion: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Summary: Anaphylaxis is the most severe systemic hypersensitivity reaction, and it can be life-threatening or even fatal. It involves the activation of multiple immune and non immune pathways beyond IgE, thus exhibiting different phenotypes. New symptoms of hypersensitivity caused by chemotherapy drugs, monoclonal antibodies, and biological agents have been suggested to be recognized as anaphylaxis phenotypes. No biomarker has been described that allows an unequivocal diagnosis of anaphylaxis. Moreover, more biomarkers for specific endotypes are needed to stratify severity, to predict risk, and to optimaze tretament choice in the individual patient. Food, drugs and stinging insects represent the most commly identified triggers. Idiopathic anaphylaxis is a diagnosis of exclusion and it can hide a clonal mast cell disorder. Individual risk factors and co-factors may influence the severity of anaphylaxis or its onset, and they should be identified to implement the appropriate measures to prevent recurrence. Prompt recognition and treatment are critical in anaphylaxis, adrenaline being the first-line saving therapy. Individualized anaphylaxis action plan should include avoidance measures, prescription of an adrenaline autoinjector, education, optimal management of relevant comorbidities, venom specific immunotherapy, food oral immunotherapy, and drug desensitization, when appropriate. However, the quality of acute and long-term anaphylaxis management is variable influencing the poor outcomes experienced by many patients. Clinical practice guidelines have the potential to improve outcomes, but they often prove challenging to implement in routine clinical care.

Summary: Tryptase is a serin-protease produced and released by mast cells after IgE-mediated or non-IgE mediated stimuli. We here review the various aspects related to the molecular characteristics of the enzyme and its biological effects, the genetic basis of its production and the release kinetics. Recommendations for the clinical use of tryptase measurement developed by a task force of Società Italiana di Patologia Clinica e Medicina di Laboratorio and Associazione Allergologi Immunologi Italiani Territoriali e Ospedalieri are given on the best procedure for a correct definition of the reference values in relation to the inter-individual variability and to the correct determination of tryptase in blood and other biological liquids, in the diagnosis of anaphylaxis (from drugs, food, insect sting, or idiophatic), death from anaphylaxis (post mortem assessment) and cutaneous or clonal mastcell disorders.

Summary: Hymenoptera venom allergy (HVA) is the most frequent cause of anaphylaxis in Europe, accounting for most of the severe reactions occurring in adults, and being the second cause of anaphylaxis in children. Prevention of further episodes in patients who developed a systemic reaction (SR) is based on the correct management of the allergic emergency, the referral to an allergist for a correct diagnosis, prescription of adrenaline auto-injectors (AAI) and specific venom immunotherapy (VIT), if recommended. Diagnosis is based on the classification of the type of reaction, confirmation of an IgE-mediated pathogenesis and the identification of the offending insect. The use of component resolved diagnostics may be helpful in case of poly-sensitization or negative allergy tests with a proven history of previous SRs. When a severe SR occurs, baseline serum tryptase levels should always be assessed. The prescription of AAI is recommended or suggested for untreated patients, patients undergoing VIT and after discontinuation of treatment, according to multiple evidence. VIT is the most effective treatment available for HVA patients, as confirmed by recent European guidelines. VIT has an early, sustained and persistent protective effect and modifies the natural course of the disease. Moreover, VIT proved to be safe and well tolerated. According to a recent systematic review, no treatment-related fatalities were recorded to date. Compared to AAI, VIT significantly improves the quality of life of HVA patients by reducing the anxiety and limitations in daily activities caused by the fear of stinging insects. The memory of a life-threatening experience is the most likely reason why adherence to VIT is higher compared to immunotherapy with inhalant allergens. Several risk factors in HVA have been identified that can influence not only the severity of sting reactions in untreated patents, but also the occurrence of side effects, treatment effectiveness and the risk of relapse after discontinuation of VIT. Patient and treatment-related risk factors must be considered while selecting the best candidates for VIT, the type and duration of treatment. In this paper we address the most important issues related to HVA and VIT that may have an impact on daily clinical practice.

Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care.

Summary: The number of patients with uncontrolled asthma is growing especially in young people. Although current therapies improve the disease management, the heterogeneity of clinical outcomes results in patients whose asthma is refractory to standard therapies. To understand not responsive phenotypes, we instituted a web-registry aimed to collect real life data of adolescent and adult patients. One-hundred and five Italian medical Centers are part of the network. Participants above 14 years and affected by severe asthma will be included in the study. Demographic and clinical data will be collected for 5 years on a dedicated electronic database. For the first time in Italy, our study will provide information on epidemiological, clinical and therapeutic aspects related to the natural course of the disease, filling the gap between adolescents and adults.

Near-fatal asthma (NFA) is described as acute asthma associated with a respiratory arrest or arterial carbon dioxide tension greater than 50 mmHg, with or without altered consciousness, requiring mechanical ventilation. Risk factors for near fatal asthma have not been fully elucidated. In 80-85% of all fatal events, a phenotype, characterized by eosinophilic inflammation associated with gradual deterioration occurring in patients with severe and poorly controlled asthma, has been identified. Regarding to the management, acute severe asthma remains a significant clinical problem, which needs to be identified to facilitate early and appropriate therapeutic interventions. The assessment relies on clinical signs, but additional information might be obtained from chest radiography or blood gas analysis. No investigation should delay the initiation of appropriate therapy. The goals of therapy are the maintenance of oxygenation, relief of airflow obstruction, reduction of airways edema and mucus plugging (with Increased use of medications such as beta-agonists via metered dose inhalers and nebulizers, oral and/or intravenous (other than by inhalation) corticosteroids and oral or intravenous theophylline) whereas supporting ventilation as clinically indicated. Of course, the emergency physician needs to consider the wide range of potential complications, as attention to these problems when managing severe acute asthma might significantly improve outcome. An understanding of the available agents and potential pitfalls in the management of NFA is mandatory for the emergency physician.