Histamine intolerance (HIT) is a clinical condition caused by decreased intestinal degradation of ingested histamine, primarily due to reduced enzyme diamine oxidase (DAO) activity, leading to ...histamine accumulation and causing various clinical manifestations. The measurement of serum DAO is commonly used as the main diagnostic test for HIT, although its diagnostic use is still uncertain. In this retrospective study, we aimed to assess the validity of DAO determination in patients with clinically suspected HIT. We measured DAO levels in 249 patients with suspected HIT and 50 healthy adult controls without HIT-related problems. Based on five clinical criteria, we divided patients into two groups: high (all five inclusion criteria; 41 patients) and low probability of HIT (≤4 inclusion criteria; 208 patients). Patients with a “high probability of HIT” had the lowest DAO (median: 8 U/mL, IQR: 6–10) in comparison to patients with a “low probability of HIT (median: 10 U/mL, IQR: 7–16, p = 0.0006) and healthy controls (median: 18 U/mL, IQR: 14–22, p < 0.0001). The specificity and sensitivity for DAO levels < 3/< 10 U/mL (manufacturer’s set cut-off) to discriminate between patients with ‘‘high probability of HIT’’ and healthy controls were 100%/92% and 2%/71%. On the other hand, the specificity and sensitivity to discriminate between patients with ‘‘high probability of HIT’’ and ‘‘low probability of HIT’’ were 97%/61% and 2%/71%, respectively. Serum DAO determination represents an additional asset to the diagnosis of HIT based on clinical evaluation and assessment, but the diagnosis should not solely rely on DAO measurements.
IntroductionSystemic allergic reaction (SAR) to a Hymenoptera venom is a potentially life-threatening disorder. The rate of SAR between beekeepers in comparison with a healthy individual is ...different. The risk for an SAR is particularly high in beekeepers due to their persistent or seasonal exposure to the stinging Hymenoptera. We aim to provide a critical appraisal and a synthesis of evidence-based data from epidemiological observational studies, focusing on SARs to a Hymenoptera venom and the associated risk factors for SARs in beekeepers worldwide.Methods and analysisSearching will include seven electronic databases for published studies without language restrictions, from inception up to 3 August 2021, and it will be rerun for all electronic databases prior publication. Only epidemiological observational studies in beekeepers will be included. The risk of bias in the included studies will be appraised by using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies and the Newcastle-Ottawa Scale, adapted for cross-sectional studies. For the certainty of evidence, the Grading of Recommendations Assessment, Development and Evaluation approach will be used. Qualitative synthesis will be presented in a tabulated format with the selected characteristics across primary studies and the main outcome of interest. A meta-analysis is planned to be performed if there will be a sufficient number of homogeneous studies with complete data. The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement will guide the reporting of this systematic literature review.Ethics and disseminationNo ethics approval is needed to conduct the systematic literature review since it will be solely based on the published literature. Findings will be disseminated through the relevant conferences, peer-review and open-access journals.PROSPERO registration numberCRD42021260922.
Abstract Background Beekeepers represent a high-allergic risk population group due to their unavoidable seasonal or persistent exposure to the elicitors of Hymenoptera venom allergy, bees in ...particular. A systematic literature review and meta-analysis aimed to estimate the prevalence of self-reported systemic allergic reaction to Hymenoptera venom among beekeepers worldwide. Methods We rigorously reviewed and conducted meta-analysis on observational studies retrieved from seven electronic databases (MEDLINE via PubMed, Web of Science Core Collection, Scopus, Academic Search Complete, ScienceDirect, Cumulative Index to Nursing and Allied Health Literature, Zoological Record), spanning data from inception to August 1, 2023. The Joanna Briggs Institute Prevalence Critical Appraisal Tool was employed to assess the risk of bias. A meta-analysis was conducted to synthesize evidence. Results Out of 468 studies, eight original articles met the inclusion criteria. The estimated overall lifetime and one-year prevalence of self-reported systemic allergic reaction to bee venom were 23.7% (95% CI: 7.7–53.4) and 7.3% (95% CI: 5.8–9.2), respectively. The estimated lifetime prevalence of self-reported systemic allergic reaction to bee venom for grades III–IV (severe systemic allergic reaction) was 6.0% (95% CI: 3.0–11.7). In general, substantial heterogeneity and a high risk of bias were observed across the majority of studies. The impact of geographical location and climate differences on the estimated lifetime prevalence is suggestive for severe systemic allergic reaction. Conclusions Future observational cross-sectional studies should employ rigorous study designs, using validated questionnaires, and thoroughly report the observed health outcomes, verified by physicians.
Allergic reactions to Hymenoptera stings can have varying levels of severity, according to the Müller grading system.
By an epidemiological concept, this is a retrospective cohort study. The observed ...cohort was represented by patients referred to the University Clinic Golnik due to Hymenoptera allergic reaction in the period from 1997 to 2015. From the immunological database of the University Clinic Golnik, we obtained laboratory data (sIgE, skin tests and basophil activation test). The clinical characteristics of patients were obtained from BIRPIS. With the help of a questionnaire, which was sent to each patient in the period from May 2019 to April 2021, we obtained epidemiological data. For the assessment of the association between the severity of allergic reaction for the observed outcome, the severity of the first allergic reaction after Hymenoptera sting was used. Other variables were grouped according to risk factors.
We will identify the risk factors that could play an important role in a severe systemic reaction: the aetiology of the Hymenoptera sting, sex, age, history and severity of previous systemic reactions, being re-stung in an interval of two months, the frequency of re-stings, atopy, genetic predisposition, preventive medication use, other medication use, beekeeping or living next to beehives and why immunotherapy was not taken. Laboratory data will also be analysed to determine if there is any association with laboratory tests and the severity of the allergic reactions after Hymenoptera stings.
Several new approaches are introduced in the study design. The most important is that the protocol covers epidemiological data gained from the questionnaire, as well as clinical data gained from the Immunological database and BIRPIS database. We expect to obtain significant results that will explain the risk factors for the natural history of Hymenoptera sting allergic reactions and will help allergologists, as well as general doctors, when facing those patients allergic to Hymenoptera venom without immunotherapy.
•Variants in VEGFA gene are associated with asthma treatment response to ICS.•Carriers of C allele in variant rs2146323 appear to respond better to ICS treatment.•Atopic status influences response to ...ICS treatment.
Clonal mast cell disorders and elevated basal serum tryptase (BST) levels with unknown cause(s) are associated with severe Hymenoptera venom–triggered anaphylaxis (HVA). However, some individuals ...with clonal disease have a normal BST level (<11.4 ng/mL).
Our aim was to evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy.
We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis who were referred to our center during the years 2018 and 2019. KIT p.D816V was determined in their peripheral blood by quantitative PCR, and tryptase genotyping was performed by droplet digital PCR.
In all, 351 patients (93.9%) had normal levels of BST, and KIT p.D816V was detected in 8% of patients (28 of 351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2% 24 of 132 vs 1.8% in patients with lower grades 4 of 88 with grade III and 0 of 131 with other grades; P < .001). In grade IV patients with a normal BST level, KIT p.D816V was associated with more severe symptoms, including a significantly higher frequency of loss of consciousness (58.3% 14 of 24 vs 34.3% 37 of 108; P = .03) and absence of skin symptoms (41.7% 10 of 24 vs 15.7% 17 of 108; P = .004). Among patients with a normal BST level, KIT p.D816V (OR = 10.25 95% CI = 3.75-36.14; P < .0001) was the major risk factor associated with severe HVA. Hereditary α-tryptasemia (HαT) due to increased germline copies of TPSAB1 encoding α-tryptase was the most common cause (65.2% 15 of 23) of elevated BST level in patients with HVA, and together with KIT p.D816V, it accounted for 90% of BST level elevations (20 of 23) in patients with HVA.
These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk patients with HVA who are regularly missed when BST level is used alone.
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Anaphylaxis is an acute life-threatening allergic reaction and a concern at a global level; therefore, further progress in understanding the underlying mechanisms and more effective strategies for ...diagnosis, prevention and management are needed.
We sought to identify the global architecture of blood transcriptomic features of anaphylaxis by integrating expression data from human patients and mouse model of anaphylaxis.
Bulk RNA-sequencings of peripheral whole blood were performed in: i) 14 emergency department (ED) patients with acute anaphylaxis, predominantly to
venom, ii) 11 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge (DBPCFC) to peanut, iii) murine model of IgE-mediated anaphylaxis. Integrative characterisation of differential gene expression, immune cell-type-specific gene expression profiles, and functional and pathway analysis was undertaken.
1023 genes were commonly and significantly dysregulated during anaphylaxis in ED and DBPCFC patients; of those genes, 29 were also dysregulated in the mouse model. Cell-type-specific gene expression profiles showed a rapid downregulation of blood basophil and upregulation of neutrophil signature in ED and DBPCFC patients and the mouse model, but no consistent and/or significant differences were found for other blood cells. Functional and pathway analysis demonstrated that human and mouse blood transcriptomic signatures of anaphylaxis follow trajectories of upregulation of cell movement, migration and neuroinflammatory signalling, and downregulation of lipid activating nuclear receptors signalling.
Our study highlights the matched and extensive blood transcriptomic changes and suggests the involvement of discrete cellular components and upregulation of migration and neuroinflammatory pathways during anaphylaxis.
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