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Background: The safety profile of venom immunotherapy (VIT) is a relevant issue, and considerable differences have been reported in the safety and efficacy of this treatment modality. The primary aim of this study was to evaluate the safety of angiotensin-converting enzyme inhibitors and ß-blockers during VIT. In a second analysis, we evaluated data on premedication and venom preparations and their association with systemic adverse events (AEs) during the up-dosing phase and the first year of the maintenance phase, as well as the outcome of field stings and sting challenges., Methods: Ours was an open, prospective, observational, multicenter study that recruited 1425 patients, of whom 1342 underwent VIT., Results: Premedication with oral antihistamines was taken by 52.1% of patients during up-dosing and 19.7% of patients during the maintenance phase. Antihistamines had no effect on the frequency of systemic AEs (P=.11), although large local reactions (LLRs) were less frequent (OR, 0.74; 95%CI, 0.58-0.96; P=.02). Aqueous preparations were preferred for up-dosing (73.0%), and depot preparations were used for the maintenance phase (64.5%). The type of venom preparation had no influence on the frequency of systemic AEs or on the effectiveness of VIT (P=.26 and P=.80, respectively), while LLRs were less frequent with depot preparations (P<.001)., Conclusions: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLRs but not systemic AEs. All venom preparations were equally effective and did not differ in terms of the frequency of systemic AEs.

Background: There is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT)., Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment., Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI., Conclusions: This trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629)., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Currently available tests are unable to distinguish between asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A reliable serological marker to monitor venom immunotherapy (VIT) does also not exist. Our aim was to find reliable serological markers to predict tolerance to bee and vespid stings., Methods: We included 77 asymptomatically sensitized subjects, 85 allergic patients with acute systemic sting reactions, and 61 allergic patients currently treated with VIT. Levels of sIgE and sIgG 4 to bee and vespid venom, rApi m 1, and rVes v 5 were measured immediately after allergic sting reactions or before sting challenges and 4 weeks later. All sting challenges were tolerated. The inhibitory activity was determined using BAT inhibition and ELIFAB assay., Results: Median sIgG 4 levels were 96-fold higher in VIT patients (P < .001) while sIgE/sIgG 4 ratios were consistently lower (P < .001). The ELIFAB assay was paralleled by low sIgE/sIgG 4 ratios in VIT patients, showing markedly higher allergen-blocking capacity (P < .001). An almost complete inhibition of the basophil response was seen in all patients treated with vespid venom, but not in those treated with bee venom. Four weeks after the sting, sIgE and sIgG 4 levels were increased in allergic and asymptomatically sensitized patients, but not in VIT patients., Conclusion: Immunological responses after stings varied in bee and vespid venom-allergic patients. In patients under VIT, sIgE and sIgG 4 remained completely stable after sting challenges. Monitoring VIT efficacy was only possible in vespid venom allergy, and the sIgG 4 threshold for rVes v 5 had the highest sensitivity to confirm tolerance. The BAT inhibition test was the most reliable tool to confirm tolerance on an individual basis., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

For many years, only the major allergen rApi m 1 has been available on the ImmunoCAP system for routine diagnosis of bee venom (BV) allergy. Now, there are five components available, and we aimed to detect the sensitivity and specificity of rApi m 1, 2, 3, 5, and 10 in BV-allergic patients. We further evaluated the sensitivity of rApi m 1 and 2 of an alternative platform and investigated possible differences in the sensitization profile between monosensitization and clinically relevant double sensitization. Analysis of the whole panel of BV allergens of the CAP system still resulted in a lower sensitivity than analysis of the combination of rApi m 1 and 2 of the Immulite (71.6% vs 85.8%). Sensitization rate of rApi m 5 was more than doubled in double-sensitized patients, while there was no difference for rApi m 2. The benefit of the commercially available panel of BV components is questionable, due to the insufficient sensitivity and still unavailable important cross-reacting allergens., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Stings in the head region are considered to be a risk factor for severe systemic reactions to hymenoptera stings. We supposed that stings in skin areas, which are well supplied with blood, lead to more severe reactions and tested our hypothesis in 847 patients with confirmed hymenoptera venom allergy. However, symptom severity was independent from sting site: only 16.3% of patients with severe reactions were stung on the head (P = 0.017). But we confirmed age > 40 years (P < 0.001) as well as elevated basal tryptase levels (P = 0.001) as risk factors. Taking antihypertensive drugs seemed to have an influence: 41.7% of patients taking antihypertensive drugs experienced a severe reaction compared to 29.5% of patients, not taking such drugs (P = 0.019). However, considering patients' age in regression analysis, taking antihypertensive drugs had no effect on symptom severity (P = 0.342). Importantly, in most patients with severe reactions, cutaneous signs were absent (P < 0.001)., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)