Introduction
Insect stings by Hymenoptera species are very common with data indicating that 56.6–94.5% of the general population has been stung at least once in their lifetime.1 Systemic sting reactions (SSR) have been reported in 2.3–5.4% of adults in European and US epidemiological studies.2-4 Hymenoptera venom allergy is a potentially life-threatening disease, and venom immunotherapy (VIT) is the only treatment that can potentially prevent further SSR.5 It is effective in 77–84% of patients treated with honeybee venom6,7, and in 91–96% of patients receiving vespid venom.6,7 There are two well-established risk factors for severe SSR: higher age8-10 and elevated tryptase levels >11.4 mg/L indicating clonal mast cell disorders.8,9,11 The major risk factor for systemic adverse events (AE) during VIT is treatment with bee venom.12,13 There has been an ongoing debate over decades whether antihypertensive (AHT) treatment with β-blockers and/or ACE-inhibitors (ACEI) is a risk factor for the development of more severe SSR and whether it increases the number of (more severe) AE during VIT. The global prevalence of arterial hypertension in the adult population ranges from 26.4–27.7%, and 40.7% of patients older than 35 years suffer from hypertension.14,15 Overall, ACEI or angiotensin receptor blockers are the most commonly used blood pressure-lowering agents followed by diuretics and β-blockers in high-income countries.14 Given that higher age is a major risk factor for severe SSR, it is very likely that these patients also take antihypertensive medication. Replacing or discontinuing antihypertensive medication is cumbersome, time-consuming, and may even be harmful. This could prevent patients from receiving potentially life-saving VIT. Available data are controversial and invariably originate from case reports or studies with underpowered designs to evaluate the effect of antihypertensive drugs.8,16,17 We hypothesized that the risk of β-blockers and/or ACEI for AE during VIT could have been overestimated, and the alleged higher risk for more severe sting reactions could have been biased by patients’ age. We therefore initiated an open, prospective, observational, multicenter study, recruiting 1,425 patients in 26 centers from eight European countries.