Adverse events (Table 3)
The prevalence of cardiovascular diseases or hypertension was no risk
factor for systemic AE during VIT (p=0.11). Bee venom caused more
systemic AE during VIT: 13.0% of patients treated with bee venom had
systemic reactions, but only 4.3% of patients treated with vespid venom
(p<0.001). We did not detect a statistically significant
effect of elevated basal tryptase levels on the frequency of systemic AE
during VIT: 6.8% of patients with normal tryptase levels compared with
10.8% of patients with elevated tryptase levels had systemic AE
(p=0.16). Verified mastocytosis was also not a risk factor: Only 12.1%
of patients with verified mastocytosis had a systemic reaction compared
with 6.9% without mastocytosis (p=0.41). Neither high sIgE levels to
bee venom nor high sIgE levels to vespid venom correlated with a higher
frequency of systemic AE during VIT (p=0.99 and p=0.15, respectively).
The severity of the initial sting reaction had no influence on the
frequency of systemic AE during VIT: systemic AE occurred in 51 (6.7%)
patients with a previous Grade I or II reaction and in 42 (7.4%)
patients with a severe (Grade III or IV) initial sting reaction
(p=0.66). Premedication with oral non-sedative antihistamines was taken
by half of the patients during the up-dosing phase, but this had no
effect on the frequency of systemic AE (p=0.07); however, the frequency
of LLR was lower in patients taking premedication as compared with those
not taking antihistamines (23.5% vs. 29.3%; p<0.001).
Quicker up-dosing protocols (conventional vs. rush, cluster, and
ultrarush) did not cause more frequent systemic AE during VIT (p=0.50).
Nevertheless, large local reactions were seen more frequently when
quicker up-dosing protocols were used (OR: 8.72; 95% CI: 3.59–24.37;
p<0.001).
The parameters age, antihypertensive treatment, and bee venom were kept
for further analysis in a multivariable model: The risk of a systemic
adverse event during VIT was still 3.4 times (OR 3.35; 95% CI:
2.17–5.16) higher for patients treated with bee venom, compared with
patients treated with vespid venom (p<0.001).
During the first year of the maintenance phase, systemic AE occurred in
only 20 (1.7%) patients. Systemic adverse reactions were mild or
moderate in 17 patients; three bee-venom-allergic patients had a Grade
III reaction with loss of consciousness or bronchospasm. None of them
took β-blockers or ACEI, but one patient with loss of consciousness
suffered from systemic mastocytosis. Taking AHT drugs did not increase
the frequency of systemic AE (p=0.99). The intake of antihistamine
premedication decreased from about 50.0% during the up-dosing phase to
about 20.0% during the maintenance phase.