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- Material and methods
Background: The objective was to investigate whether venom immunotherapy with bumblebee venom (BBV) is safe and effective.
Methods: Eleven patients with severe occupational anaphylaxis caused by stings of bumblebees were studied. Sensitization to bumblebee venom was confirmed by skin tests and RAST. Immunotherapy was started with bumblebee venom extract by the semirush procedure, because these patients showed a primary sensitization to Bombus venom, and a low or absent degree of cross-reactivity with honeybee venom. IgE titer and skin tests with bumblebee venom were performed yearly. Efficacy was evaluated by means of in-hospital sting challenge and/or occupational field stings from bumblebees.
Results: All patients reached maintenance dose in 6 weeks without severe side-effects. During the follow-up period (1.5–5 years), three systemic reactions in two patients were seen in 20 bumblebee stings. However, these reactions were milder than the index sting.
Conclusions: Immunotherapy with bumblebee venom is safe and effective, and is comparable with honeybee and yellow-jacket venom immunotherapy.
In contrast to honeybee venom (HBV) or yellow-jacket venom (YJV) allergy, immediate-type allergy to bumblebee (Bombus terrestis) venom is rare. However, the growing use of bumblebees for the pollination of vegetable flowers in The Netherlands accounts for the increasing number of anaphylactic reactions to their stings.
The efficacy of venom immunotherapy (VIT) for the treatment of patients with allergic systemic reactions to Hymenoptera stings has been established ( 1). It was our objective to investigate whether VIT with bumblebee venom (BBV) could be safe and effective as well.
Using a semirush protocol, we started immunotherapy with purified BBV extract in patients with anaphylactic reactions to BBV.
This paper describes the results of the follow-up study, regarding side-effects, skin tests, and RAST, in hospital sting challenge and field stings, on these 11 patients with BBV immunotherapy after reaching 1.5–5 years of the maintenance dose.
- Top of page
- Material and methods
Immunotherapy with insect venom is already known to be safe and effective ( 1, 5). In The Netherlands, we see an increasing number of patients with allergy to BBV as an occupational disease. As bumblebees and honeybees both belong to the Apidae family, strong cross-reactivity was supposed to exist, as has been proven by Hoffman & Jacobsen ( 6) and Jacobsen & Hoffman ( 7). As BBV was then not yet commercially available for diagnostic and therapeutic purposes, Kochuyt et al. ( 8) performed immunotherapy with HBV successfully in patients with BBV allergy. Nevertheless, earlier RAST-inhibition experiments showed in our patient group a low level of cross-reactivity, an observation which can be explained by the fact that these patients were primarily stung by and sensitized to bumblebees ( 9). This explains the results of Stern et al. ( 10). They reported two patients with occupational allergy to BBV who were hyposensitized with purified HBV. Both patients developed a severe anaphylactic reaction after an incidental sting. This suggests that immunotherapy with HBV is not effective in these BBV patients. Therefore, immunotherapy with purified BBV was started in our patient group, as the degree of systemic reaction and the risk of re-exposure were high. We did not have any data on the spontaneous prognosis of patients with BBV anaphylaxis; therefore, patients were advised to change their profession or start immunotherapy.
The side-effects of BBV immunotherapy can be compared to those of bee and wasp venom immunotherapy. There was no unacceptably high incidence of side-effects. Large local reactions were seen in 6.2% during the induction phase and 2.8% during the maintenance phase. During the induction phase, two systemic reactions occurred in a patient with unstable asthma. It must be stressed that more side-effects always occur with faster schedules ( 11). Therefore, we used a semirush procedure to lower the risk of reactions.
As far as efficacy is concerned, we had 18 field stings and two hospital challenges to evaluate. A provocation test with a sting from the responsible insect is without doubt the most reliable control of the effectiveness of immunotherapy, but, as some authors have mentioned ( 12), the low grade of a sting reaction does not ensure that the patient will remain free of a systemic reaction on any next sting. Nevertheless, we emphasize that our patients are still working among bumblebees and have tolerated several field stings without complications. As misidentification by the patient at work of the stinging insect is nearly impossible, more provocation tests seemed not to be necessary. The only three systemic reactions, which occurred in two patients, were less serious than the anaphylaxis before immunotherapy. In one patient, the systemic reaction took place before the maximum dose was reached. This confirms that the effectiveness of BBV immunotherapy (85%) is comparable with that of other VIT. Earlier studies in which patients on maintenance VIT were exposed to a provocation test showed that more than 90% of YJV-allergic and 75–80% of HBV-allergic patients were fully protected ( 5, 13).
In summary, we conclude that immunotherapy with BBV is safe and effective for patients with occupational BBV anaphylaxis.