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Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one-quarter of sting-induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long-term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline-directed antihypertensive treatment. The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom-allergic patients. Measurement of platelet-activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use., (© 2020 EAACI and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The prevalence and predisposing factors of asymptomatic sensitization to Hymenoptera venom marker allergens are largely unknown., Objective: To evaluate sensitization profiles in a group of 490 dermatologic patients without a history of sting-induced anaphylaxis., Methods: Clinical data were collected using a structured questionnaire; sera were tested for total IgE and specific IgE to venom preparations, recombinant venom marker allergens, inhalative allergens, and cross-reactive carbohydrate determinants., Results: The lifetime prevalence of Hymenoptera stings was 85.3%. IgE rates exceeding cut-off values of 0.35 kU A /L were 17.3% for rVes v 1, 18.0% for rVes v 5, and 3.5% for rApi m 1. Median specific/total IgE ratios for the above mentioned marker allergens were 0.05%, 0.02%, and 0.00%, respectively. Marker allergen-directed sensitization was detectable in 85.5% of 138 Vespula venom-reactive sera. Of 68 bee venom-reactive participants, 23.5% were sensitized to rApi m 1 and 64.7% to any one or several of five commercially available bee venom allergens. Although double reactivity to bee and Vespula venom was clearly associated with sensitization to cross-reactive carbohydrate determinants (P < 0.001), sensitization to marker allergens of both species was detectable in most double-reactive sera (56.5%). Vespula venom marker allergen-directed sensitization was associated with recent stings (P = 0.010), large local reactions (P = 0.009), total IgE elevation (P < 0.001), and sensitization to cross-reactive carbohydrate determinants (P = 0.008)., Conclusions and Clinical Relevance: The high sensitization rates observed in individuals without a history of sting-induced anaphylaxis as well as total IgE levels and cross-reactive carbohydrate determinant-directed reactivity as potential confounders need to be considered in any interpretation of positive test results for Hymenoptera venom marker allergens., (© 2018 John Wiley & Sons Ltd.)

Background: The hypothetical risks of cardiovascular medication during Hymenoptera venom immunotherapy (VIT) are still a matter of controversy., Objective: To assess the potential influence of β-blockers (BBs) and/or angiotensin-converting enzyme inhibitors (ACEIs) on the long-term safety and outcome of VIT., Methods: Data on the course of VIT maintenance phase, Hymenoptera re-stings, and concurrent medication were retrospectively derived from standardized questionnaires in a cohort of patients with significant cardiovascular comorbidity., Results: Of 225 patients, 125 (55.6%) were taking cardiovascular medication at the time of data collection: 71 (31.6%) took an ACEI, and 40 (17.8%) took a BB. A total of 3,397 months of maintenance VIT during intake of an ACEI and 1,418 months during BB therapy were evaluated. Cumulative VIT-related reaction rates, including subjective symptoms, were 9.1% per treatment cycle and 0.31% per injection, with objective reaction rates of 1.7% and 0.06%, respectively. The incidence of adverse events was significantly higher in patients with a previous history of systemic reactions at VIT buildup (P = .004). Surprisingly, reaction rates were lower in patients taking any kind of cardiovascular medication (P = .04) or an ACEI (P = .03). The overall reexposure rate to Hymenoptera stings was 42.7%, and the field sting-induced objective reaction rate was 7.3%. There was no evidence of an increase of field sting-related relapse or hospitalization rates by concurrent cardiovascular medication., Conclusion: Cardiovascular medication does not impair the safety and/or the efficacy of Hymenoptera VIT., (Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: There is an ongoing debate on whether angiotensin-converting enzyme inhibitors (ACEI) should be substituted prior to initiation of venom immunotherapy (VIT) for safety reasons., Objective: We aimed to assess the influence of ACEI medication on the incidence of systemic reactions (SR) during the build-up phase of VIT in a large and homogeneous cohort of patients., Methods: The frequency of SR during 775 consecutive cycles of VIT initiation was analyzed in relation to cardiovascular medication, age, sex, venom, reactivity in diagnostic tests, severity of preceding sting-induced anaphylaxis, comorbidities, latency before the initiation of VIT, and treatment protocols. ACEI were routinely maintained throughout VIT, beta-blockers replaced if appropriate., Results: During VIT-initiation, 190 (24.5%) patients were on some kind of cardiovascular treatment, 90 (11.6%) on ACEI, 23 (3.0%) on beta-blockers. VIT-related SR rates were 11.7% (any documented reactions including subjective symptoms) and 3.0% (reactions fulfilling objective diagnostic criteria of anaphylaxis). Medication with ACEI (P = 0.097) or beta-blockers (P = 1.0) was not significantly related to the incidence of SR. A reduced rate of SR in patients taking cardiovascular drugs was not statistically significant in the final multivariate regression model. A prolonged latency before the initiation of VIT (P = 0.018, odds ratio = 1.010), and use of 5-day compared to 3-day rush protocols (P = 0.008, odds ratio = 3.522) increased the frequency of SR., Conclusions and Clinical Relevance: Study data do not provide evidence of an ACEI-mediated increase of VIT-related SR, supporting the continued use of these valuable and hard-to-replace substances throughout VIT., (© 2014 John Wiley & Sons Ltd.)

Background: Severe anaphylaxis in Hymenoptera venom allergy has been associated with a number of risk factors including elevation of baseline serum tryptase (BST), older age, concomitant diseases, and concurrent medication., Objective: The aim of this study was to evaluate indicators and risk factors for severe anaphylaxis due to Hymenoptera field stings with an emphasis on details related to the sting reaction and concurrent medication., Methods: In this single-center observational cohort study, we included 657 consecutive patients fulfilling the criteria for venom immunotherapy. Severity of sting-induced anaphylaxis was analyzed in relation to patient-specific risk factors (age and sex, preexisting cardiopulmonary conditions, cardiovascular medication) and details related to the sting reaction (culprit insect, localization of the sting, time interval to onset of symptoms, and presence or absence of cutaneous involvement). BST was determined in a subgroup of patients with moderate to severe anaphylaxis., Results: Four significant indicators and risk factors of severe anaphylaxis were identified (P < .001): (1) elevation of BST, (2) absence of urticaria or angioedema during anaphylaxis, (3) time interval of less than 5 minutes from sting to onset of symptoms, and (4) senior age. The absence of urticaria/angioedema is significantly related to BST elevation (P = .02). No relationship could be established between the severity of anaphylaxis and comorbidities or concurrent cardiovascular medication., Conclusions: Absence of urticaria/angioedema is an indicator of severe anaphylaxis and possibly mastocytosis, requiring determination of BST. Study data do not provide evidence for an aggravation of sting-induced anaphylaxis by concurrent beta-blockade or angiotensin-converting enzyme inhibition., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)