Hymenoptera Venom Immunotherapy

Beatrice M Bilò; Floriano Bonifazi


Immunotherapy. 2011;3(2):229-246. 

In This Article

Duration of VIT

The question of how long VIT should last so that long-term protection can be achieved after discontinuation is a long-standing one.[10,114,115]

On the premise that the duration of VIT should be decided following a thorough patient–physician discussion of the issues involved, the present recommendations for discontinuing VIT take into account all these findings, which are very similar in Europe[10] and America.[4] Although not a common occurrence, conversion to a negative venom skin test is an unequivocal indication that VIT should be stopped immediately. If the patient has had a very severe initial allergic reaction, an in vitro test should be carried out to confirm disappearance of venom specific IgE,[10] as only the combination of negative intradermal skin testing at 1 µg/ml with the absence of venom-specific serum IgE antibodies is associated with a strongly diminished risk of relapse.[10,115]

Most patients with mild-to-moderate anaphylactic symptoms and positive skin tests remain protected even years after a 3–5-year course of VIT has been discontinued.[10] In fact, a number of studies have investigated the reliability of short- and long-term VIT despite the persistence of positive venom skin tests, as a criterion for discontinuing VIT. To sum up, the studies where long-term protection, up to 7 years after discontinuing VIT of at least a 3-year duration, were evaluated on the basis of field stings or sting challenges revealed more frequent relapses than those with a shorter follow-up (protection rate of ~80 vs 83–100%), with a more favorable outcome in Vespula than in bee venom allergic patients and in children than in adults.[10,31] There are no data on the outcome after more than 15 years of VIT.

It is likely that short- and long-term results are more favorable with the much higher total dose administered in the USA than that with the 100 µg applied elsewhere. More European data on the discontinuation of VIT in allergic vespid patients with 100 µg maintenance dose are needed.[28]

Owing to the small but relevant risk of a reaction from a re-sting, self-administering emergency kits, including epinephrine autoinjectors, should be discussed with every patient when discontinuing VIT.[116]

A number of risk factors for the recurrence of SRs following hymenoptera stings after discontinuing VIT have since been identified and are summarized in Box 4.[10,31,48,115,117–119] They include insect type, old age, severity of pretreatment reactions, generalized allergic side effects to VIT injections, incomplete protection upon re-sting during VIT, mast-cell diseases and an elevated baseline tryptase level.[10,31]

In a recent paper on the discontinuation of VIT, the reaction rate to stings in the subgroup that prematurely stopped VIT was greater, but not statistically significantly different, from that of the group of patients treated for more than 3 years. The risk of SR increases with subsequent stings after discontinuing VIT and all patients reported that symptoms experienced with stings after stopping VIT were milder than those before VIT.[120] However, the study was mostly carried out via email and telephone interviews, patients were not stratified by the severity of their initial reaction, by the venom they were allergic to or by the occurrence of reaction during VIT, but in relation to the duration of VIT alone.

According to EU guidelines, longer-term treatment (or life-long treatment) should be considered in patients with:

  • A higher risk of very severe sting reactions (e.g., older age, history of very severe previous sting reactions, elevated basal serum tryptase, mastocytosis or use of β-blockers);

  • Generalized allergic reactions to stings or to immunotherapy injections or during VIT;

  • Highly exposed patients, such as beekeepers and their immediate family members.[10]

However, some patients at a low risk of relapse prefer to perform long-term VIT out of a sense of personal safety and improved quality of life. At present, we do not know if an improvement in HRQL remains even after discontinuing VIT.

According to some authors,[45] the tests recommended as treatment monitoring should continue to be performed regularly, even after discontinuing VIT, while sting challenge tests are not recommended for routine testing of protection studies as they may have a booster effect.[112]

After ending VIT, patients should continue to avoid being stung. Some authors agree that patients should still carry an emergency kit.[91] If SR occurs after stopping VIT, further allergy tests are required; there is no contraindication to resuming VIT.


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