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.