Occupational anaphylaxis-Data from the anaphylaxis registry.

BACKGROUND: Epidemiologic data on occupational anaphylaxis is scarce, and there is a need of more knowledge about work-related anaphylactic episodes. METHODS: Based on the data of the Anaphylaxis Registry, we identified cases related to occupational exposure and analyzed the elicitors, demographics, severity of clinical reaction and management. RESULTS: Since 2017, 5851 cases with an information about the occupational relation of the anaphylactic episode were registered whereby 225 (3.8%) were assigned to be caused by an occupational allergen. The vast majority of these occupational anaphylaxis cases were caused by insects (n = 186, 82.7%) followed by food (n = 27, 12.0%) and drugs (n = 8, 3.6%). Latex elicited occupational anaphylaxis in only two cases. Beekeepers, gardeners, farmers, and individuals working in professions associated with food handling, for example, employees in restaurants, bakery, pastry, and cooks were most frequently affected. The comparison of the occupational insect venom-induced anaphylaxis to a group of non-occupational insect anaphylaxis in adults (n = 1842) revealed a significant younger age in occupational anaphylaxis (46 vs. 53 years), a predominance of bee-induced cases (38% vs. 17%), and a higher rate of venom immunotherapy in a primary care setting (3.3% vs. 1.3%, p = .044). In the occupational- versus non-occupational adults with food-induced anaphylaxis atopic dermatitis as concomitant atopic disease was observed more frequently (n = 486; 20% vs. 10%), although this was not significant. CONCLUSION: Our data demonstrate the impact of venom allergy in work-related anaphylaxis. Foods and drugs are less frequently elicitors, and latex-induced occupational anaphylaxis was rare. More data are needed to determine risk factors associated with occupational anaphylaxis.

ANCA-negative EGPA: only eosinophils without vasculitis? Insights from anti-T2 biologics.

The pathogenic role of p-ANCA in eosinophilic granulomatosis with polyangiitis (EGPA) is a long-standing matter of debate. In this work, we report our real-life experience with EGPA patients, treated with biologics targeting type 2 (T2)-eosinophilic inflammation (Mepolizumab, Benralizumab, Dupilumab). Interestingly, we observed EGPA extrarespiratory relapses only in p-ANCA-positive patients (2/5 cutaneous vasculitis, 3/5 constitutional symptoms), with new rise of p-ANCA and normal eosinophil blood count. Notably, revising our cohort with the new ACR 2022 criteria, these five patients were the only ones to satisfy the entry criterion of vasculitis' defined diagnosis at disease onset. These observations may suggest that biologics, selectively turning off T2 inflammation, may have unmasked p-ANCA exclusive role in the pathogenesis of vasculitis in EGPA. Therefore, we raise the question whether EGPA vasculitis exists only in p-ANCA-positive patients, and whether p-ANCA-negative disease is "only eosinophils without vasculitis".

Allergy to stings and bites from rare or locally important arthropods: Worldwide distribution, available diagnostics and treatment.

Insect venom allergy is the most frequent cause of anaphylaxis in Europe and possibly worldwide. The majority of systemic allergic reactions after insect stings are caused by Hymenoptera, and among these, vespid genera induce most of the systemic sting reactions (SSR). Honey bees are the second leading cause of SSR. Depending on the global region, other Hymenoptera such as different ant genera are responsible for SSR. Widely distributed hornets and bumblebees or local vespid or bee genera rarely induce SSR. Hematophagous insects such as mosquitoes and horse flies usually cause (large) local reactions while SSR occasionally occur. This position paper aimed to identify either rare or locally important insects causing SSR as well as rarely occurring SSR after stings or bites of widely distributed insects. We summarized relevant venom or saliva allergens and intended to identify possible cross-reactivities between the insect allergens. Moreover, we aimed to locate diagnostic tests for research and routine diagnosis, which are sometimes only regionally available. Finally, we gathered information on available immunotherapies. Major allergens of most insects were identified, and cross-reactivity between insects was frequently observed. While some diagnostics and immunotherapies are locally available, standardized skin tests and immunotherapies are generally lacking in rare insect allergy.

EAACI Molecular Allergology User's Guide 2.0.

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

A narrative review on asthma and pest sensitization (cockroach, mouse and rat allergens): a social issue besides the medical problem.

OBJECTIVE: Among animals defined as "pests", cockroaches and rodents (mouse and rat) represent the most common cause of airway allergic sensitization and bronchial asthma worldwide. Their frequency of sensitization has been widely assessed in US and other countries but poorly in Western Europe. This narrative review aims to provide a synthesis of data resulting in MEDLINE concerning allergic sensitization/asthma to pests as well as their related environmental/social risk factors, specifically in the European area. DATA SOURCES: We performed a literature research in MEDLINE for clinical trials, randomized controlled trials, systematic reviews and meta-analyses. STUDY SELECTIONS: We selected studies to the following key words: allergic sensitization, allergic rhinitis, bronchial asthma, cockroach, hypersensitivity, integrated pest management, material hardship, medication compliance, mouse, pest, poverty, rat, rodents. RESULTS: Current evidence indicates that residence in poor and urban areas, exposure to outdoor/indoor pollutants and tobacco smoke, poverty, material hardship, poor-quality housing, differences in health care quality, medication compliance, health care access contribute to increased pest-related allergic sensitization and asthma morbidity. CONCLUSION: Further research should be done on many aspects of pest allergy such as a better characterization of allergens and epidemiological aspects. Relevant social actions should be carried out against poverty, healthcare disparities, psycho-social stress, poor compliance to therapy, with economic contributions to improve private and public living environments. Allergic sensitization to pests and pest-allergic respiratory diseases like asthma are "paradoxical" conditions, as they typically affect the poorest communities but can only be corrected by high-cost (diagnostic and preventive) interventions. We hope that progress can be made in this direction in the future.

Food-Induced Anaphylaxis: Data From the European Anaphylaxis Registry.

BACKGROUND: Food is one of the most common elicitors of anaphylaxis, with an increasing incidence over recent years. OBJECTIVES: To characterize elicitor-specific phenotypes and identify factors enhancing the risk or severity of food-induced anaphylaxis (FIA). METHODS: We analyzed data from the European Anaphylaxis Registry applying an age- and sex-matched analysis of associations (Cramer's V) for single food triggers and calculated odds ratios (ORs) for severe FIA. RESULTS: We identified 3,427 cases of confirmed FIA showing an age-dependent elicitor ranking (for children: peanut, cow's milk, cashew, and hen's egg; and for adults: wheat flour, shellfish, hazelnut, and soy). The age- and sex-matched analysis revealed defined symptom patterns for wheat and cashew. Wheat-induced anaphylaxis was more frequently associated with cardiovascular symptoms (75.7%; Cramer's V = 0.28) and cashew-induced anaphylaxis with gastrointestinal symptoms (73.9%; Cramer's V = 0.20). Furthermore, concomitant atopic dermatitis was slightly associated with anaphylaxis to hen's egg (Cramer's V = 0.19) and exercise was strongly associated with anaphylaxis to wheat (Cramer's V = 0.56). Additional factors influencing the severity were alcohol intake in wheat anaphylaxis (OR = 3.23; CI, 1.31-8.83) and exercise in peanut anaphylaxis (OR = 1.78; CI, 1.09-2.95). CONCLUSIONS: Our data show that FIA is age-dependent. In adults, the range of elicitors inducing FIA is broader. For some elicitors, the severity of FIA seems to be related to the elicitor. These data require confirmation in future studies considering a clear differentiation between augmentation and risk factors in FIA.

Health-Related Quality of Life and Mental Health in Drug Hypersensitivity Reactions and Drug-Induced Anaphylaxis: A Systematic Review and Meta-Analysis.

BACKGROUND: Drug hypersensitivity reactions (DHRs) are adverse drug reactions (ADRs) that are particularly impactful on health-related quality of life (HRQoL) and mental health. Although the role of HRQoL as an important patient-reported outcome has been recognized in past years, HRQoL and mental health in patients with ADRs are still poorly investigated. OBJECTIVE: To evaluate the prevalence, severity, and risk factors of HRQoL and mental health in DHRs, with a particular focus on drug-induced anaphylaxis. METHODS: We searched the MEDLINE, Scopus, and American Psychological Association PsycArticles databases to identify all studies up to December 31, 2022 that included subjects with at least one episode of DHR and assessments of mental health and/or quality of life. Results were reported as qualitative and quantitative analyses, with meta-analyses after assessment for risk of bias and heterogeneity. RESULTS: A total of 45 observational studies were included. Overall, a high prevalence of depression (up to 51.4%; odd ratio = 2.94; 95% CI, 1.42-6.10) and anxiety (up to 48%; odd ratio = 3.92; 95% CI, 1.91-8.05) were reported compared with healthy subjects. The HRQoL was significantly affected, especially in the case of drug-induced anaphylaxis (mean score, +5.88; 95% CI, 0.77-10.98). CONCLUSIONS: Despite the scarce and heterogeneous studies on this topic, the review shows that HRQoL and mental health are markedly affected after ADRs. A better assessment of HRQoL and characterization of patients' mental status may improve the efficacy of therapeutic strategies, which should include psychological support.

Relationship of long-term air pollution exposure with asthma and rhinitis in Italy: an innovative multipollutant approach.

BACKGROUND: air pollution is a complex mixture; novel multipollutant approaches could help understanding the health effects of multiple concomitant exposures to air pollutants. AIM: to assess the relationship of long-term air pollution exposure with the prevalence of respiratory/allergic symptoms and diseases in an Italian multicenter study using single and multipollutant approaches. METHODS: 14420 adults living in 6 Italian cities (Ancona, Pavia, Pisa, Sassari, Turin, Verona) were investigated in 2005-2011 within 11 different study cohorts. Questionnaire information about risk factors and health outcomes was collected. Machine learning derived mean annual concentrations of PM10, PM2.5, NO2 and mean summer concentrations of O3 (µg/m3) at residential level (1-km resolution) were used for the period 2013-2015. The associations between the four pollutants and respiratory/allergic symptoms/diseases were assessed using two approaches: a) logistic regression models (single-pollutant models), b) principal component logistic regression models (multipollutant models). All the models were adjusted for age, sex, education level, smoking habits, season of interview, climatic index and included a random intercept for cohorts. RESULTS: the three-year average (± standard deviation) pollutants concentrations at residential level were: 20.3 ± 6.8 µg/m3 for PM2.5, 29.2 ± 7.0 µg/m3 for PM10, 28.0 ± 11.2 µg/m3 for NO2, and 70.9 ± 4.3 µg/m3 for summer O3. Through the multipollutant models the following associations emerged: PM10 and PM2.5 were related to 14-25% increased odds of rhinitis, 23-34% of asthma and 30-33% of night awakening; NO2 was related to 6-9% increased odds of rhinitis, 7-8% of asthma and 12% of night awakening; O3 was associated with 37% increased odds of asthma attacks. Overall, the Odds Ratios estimated through the multipollutant models were attenuated when compared to those of the single-pollutant models. CONCLUSIONS: this study enabled to obtain new information about the health effects of air pollution on respiratory/allergic outcomes in adults, applying innovative methods for exposure assessment and multipollutant analyses.

Hymenoptera Venom Allergy and Anaphylaxis.

Hymenoptera stings can induce allergic and occasionally fatal reactions, and are responsible for significant morbidity and deterioration in health-related quality of life. The diagnostic work-up must consider the medical history of patients, in the context of venom allergy epidemiology and Hymenoptera taxonomy, and the clinical manifestations of the reactions, to channel the available in vivo and in vitro tests towards the most accurate diagnosis and the consequent appropriate management, also considering the risk profile of the patients on a precision-medicine approach. All these aspects are covered by this work that aims at providing an up-to-date review to increase the awareness of this topic among interested stakeholders, like healthcare professionals and political decision makers, who can contribute to the proper immediate and long-term management of venom allergy and anaphylaxis.

Health-related quality of life in food and venom induced anaphylaxis and role of influencing factors.

The impact on health-related quality of life (HRQL) plays a key role for patients suffering from allergies and anaphylaxis. In this narrative review we review the HRQL in allergic patients suffering from food and venom allergy, both being the most frequent elicitors of severe allergic, potential life-threatening reactions and provide an overview on the current knowledge and identified gaps. The data show that for food and venom allergy standardized assessment tools to measure HRQL are available and have been successfully applied. Our analysis shows that multiple factors can modulate HRQL in these patient groups. These include sociodemographic data like patients' age and sex, fear of accidental reactions but also external factors like the social environment and the appreciation of the seriousness of the condition by others. External factors may have a significant impact on HRQL and should be considered in patient-related outcome assessments to avoid biased measurements possibly affecting the results. The assessment of the quality of life in the context of specific immunotherapy should consider lifestyle factors and ideally, the individual change in HRQL should be measured. Although there are many data indicating a negative impact on HRQL in food allergic children and their caregivers, limited data are existing from adults with food allergy and venom allergic patients from all age groups. Also, the use of standardized questionnaires should be extended to allow for a better comparability of results between studies. Therefore, translation to additional languages is necessary. Taken together, the eliciting allergen, the severity of the allergic disease but moreover multiple external factors impact the outcome in HRQL and should be considered in HRQL assessment.

[The role of exposure to airborne pollutants in the workplace on the prevalence and severity of chronic respiratory disease in Italy]. / Il ruolo dell'esposizione a inquinanti aerodispersi nel luogo di lavoro sulla prevalenza e gravità della malattia respiratoria cronica in Italia.

OBJECTIVES: occupational exposure to vapours, gases, dusts and fumes (VGDF) plays an important role in the development and exacerbation of respiratory diseases. The aim of this study is to evaluate the possible association of occupational exposure to airborne pollutants and chronic respiratory diseases. DESIGN: multicase-control study. SETTING AND PARTICIPANTS: cases of chronic respiratory diseases and controls from the Italian multicentric study Gene Environment Interaction in Respiratory Diseases (GEIRD). MAIN OUTCOME MEASURES: the occurrence of rhinitis, asthma, chronic bronchitis/chronic obstructive pulmonary disease (COPD), asthma severity, spirometry data, exhaled nitric oxide (FeNO) were examined in relation to chronic and acute occupational exposures to airborne pollutants using multiple regression models. RESULTS: 2,943 subjects were enrolled in the study. Regularm exposure to VGDF was associated with a higher prevalence of chronic bronchitis/COPD (OR 1.40, 95%CI 0.98-1.99), especially in those also having asthma (OR 1.80, 95%CI 1.14-2.85), a lower prevalence of remittent asthma (OR 0.53, 95%CI 0.29-0.96) and, in those with asthma, an increased activity of the disease (severity score) (OR 1.77, 95%CI 1.20-2.60). No associations were observed between occupational exposure and prevalence of rhinitis, spirometry and FeNO data. Finally, an association was found between acute exposure to airborne pollutants (occupational and non-occupational) and the respiratory diseases investigated, in particular active asthma and asthma associated chronic bronchitis/BPCO. CONCLUSIONS: these data confirm a significant role of occupational exposure to airborne pollutants on respiratory health, underlying the importance of workplace exposure prevention, in particular for more susceptible subjects, as those with respiratory diseases.

Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement.

Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5-15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for patients with severe uncontrolled CRSwNP, but their positioning in the treatment algorithm is under discussion. Effective endotyping of CRSwNP patients who could benefit from biologics treatment is required, as suggested by international guidelines. Other issues affecting management include comorbidities, such as allergy, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and asthma. Therefore, the choice of treatment in CRSwNP patients depends on many factors. A multidisciplinary approach may improve CRSwNP management in patients with comorbidities, but currently there is no shared management model. We summarize the outcomes of a Delphi process involving a multidisciplinary panel of otolaryngologists, pulmonologists, and allergist-immunologists involved in the management of CRSwNP, who attempted to reach consensus on key statements relating to the diagnosis, endotyping, classification and management (including the place of biologics) of CRSwNP patients.

Allergen Content of Therapeutic Preparations for Allergen-Specific Immunotherapy of European Paper Wasp Venom Allergy.

Allergy to Polistes dominula (European paper wasp) venom is of particular relevance in Southern Europe, potentially becoming a threat in other regions in the near future, and can be effectively cured by venom immunotherapy (VIT). As allergen content in extracts may vary and have an impact on diagnostic and therapeutic approaches, the aim was to compare five therapeutic preparations for VIT of P. dominula venom allergy available in Spain. Products from five different suppliers were analyzed by SDS-PAGE and LC-MS/MS and compared with a reference venom sample. Three products with P. dominula venom and one product with a venom mixture of American Polistes species showed a comparable band pattern in SDS-PAGE as the reference sample and the bands of the major allergens phospholipase A1 and antigen 5 were assignable. The other product, which consists of a mixture of American Polistes species, exhibited the typical band pattern in one, but not in another sample from a second batch. All annotated P. dominula allergens were detected at comparable levels in LC-MS/MS analysis of products containing P. dominula venom. Due to a lack of genomic information on the American Polistes species, the remaining products were not analyzed by this method. The major Polistes allergens were present in comparable amounts in the majority, but not in all investigated samples of venom preparations for VIT of P. dominula venom allergy.

Common Variable Immunodeficiency in Elderly Patients: A Long-Term Clinical Experience.

Background: Common variable immunodeficiency (CVID) is a complex, predominantly antibody deficiency usually diagnosed between 20−40 years. Few data about elderly patients are reported in the literature. Our aim was to evaluate the clinical phenotypes of elderly patients with CVID. Method: A retrospective analysis of adult patients with CVID was performed in our Referral Centre, focusing on the main differences between "older" patients (≥65 years at the diagnosis) and "younger" patients (<65 years). Results: The data from 65 younger and 13 older patients followed up for a median period of 8.5 years were available. At diagnosis, recurrent infections represented the only clinical manifestation in 61% and 69% of younger and older patients, respectively. The incidence of autoimmune diseases was higher in elderly patients compared with younger ones (30 vs. 18%, respectively). During the follow-up, the incidence of autoimmune disorders and enteropathy increased in the younger patients whereas neoplasia became the most prevalent complication in the elderly (38%). All patients received a replacement therapy with immunoglobulin, with good compliance. Conclusion: CVID occurrence in elderly patients is rarely described; therefore, the clinical characteristics are not completely known. In our series, neoplasia became the most prevalent complication in the elderly during the follow-up. In elderly patients, 20% SCIg was as safe as in the younger ones, with good compliance. A genetic analysis is important to confirm the diagnosis, identify specific presentations in the different ages, clarify the prognosis and guide the treatment. Future clinical research in this field may potentially help to guide their care.

Use of face masks and allergic nasal symptoms: Why not mention pollen count and air pollution data?

The scientific quantification of symptoms in pollen-related allergic rhinitis cannot be separated from the aerobiological data of the geographical area in which the study was carried out.