Hymenoptera Venom Immunotherapy

Beatrice M Bilò; Floriano Bonifazi


Immunotherapy. 2011;3(2):229-246. 

In This Article

VIT Monitoring

The current options for monitoring VIT include skin tests, in vitro tests and sting challenge tests. The level of venom-specific IgE level and skin-test sensitivity usually increase in the first months of therapy, return to baseline after 12 months and then decline steadily during maintenance VIT.[31] This decline continues even after cessation of therapy or a sting.[105] Less than 20% of patients are skin-test negative after 5 years of VIT, but 50–60% become negative after 7–10 years.[106] The reduction of skin reactivity may be attributable to a factor present in the patient's serum, since serum of VIT-treated patients is able to neutralize skin reactions to yellow jacket extracts in vivo[107] and this ability correlates with VIT duration as well as with the concentration of venom-specific IgG and IgG4.[107] However, the protective role of VIT at a re-sting, which may correlate with this lower skin test reactivity, was not evaluated by sting challenge test.

Specific IgG antibodies increase and remain elevated at least as long as VIT is continued.[107,108] Initially, these are IgG1 antibodies, and later on IgG4 antibodies. The ratio of venom-specific IgE:IgG4 first increases, then later decreases during VIT,[107] although no difference in the pattern of venom-specific IgE and IgG4 was observed in patients who tolerated a field sting compared with those who continued to experience SRs to stings despite VIT.[109]

In one study by Ebo et al., no effect of VIT on BAT was observed after a 5-day incremental phase, but a significant decrease in CD63 expression after 6 months of VIT was.[41] Following 3 years of VIT, 60% of the patients had a negative BAT, whereas only 17.9% of them had a reduction of wasp IgE.[41] Moreover, BAT showed a higher reactivity in patients who still reacted to bee or wasp stings compared with those who tolerated field stings.[109] By contrast, there was no change in basophil CD63 expression compared with pretreatment values in 20 vespid-venom allergic patients who received VIT and had already tolerated a sting challenge.[110]

Recently, a small but continuous decrease in baseline tryptase concentration over time was reported, which correlated with VIT duration, suggesting a dampened mast-cell function or decline in mast-cell burden.[111] However, despite the availability of new laboratory techniques, it is not yet possible to measure clinical efficacy based on laboratory parameters,[110] even though the concentration of specific IgG antibodies is used by some specialists to confirm protective levels after starting VIT and then to verify that the IgG level is adequately maintained at the longer intervals used for maintenance treatment.[5]

A sting challenge with a single, live insect can be used in treated patients to identify those who are not protected.[112] This should be performed in an emergency care setting approximately 6–18 months after the maintenance dose has been reached and also immediately after the dose-increase phase in patients at greater risk of exposure.[45] A tolerated sting challenge has a higher predictive value in terms of the results of a single later sting, even though some patients may still experience a reaction to a subsequent sting.

Whether protected patients also tolerate several stings is unknown. In the case of incomplete VIT protection, revealed by sting challenge or in-field stings, increasing the maintenance dose to 200 µg almost invariably bestows complete protection.[113]

Annual appointments with the allergist serve to review the treatment plan, ensure that the patient has not been prescribed any new medication or has a medical condition that could influence VIT or has not tolerated an in-field sting. According to some authors, there is no need for annual skin or blood tests, although repeating the skin tests every 2–3 years is recommended so that patients who can be taken off VIT can be identified.[31] Other specialists believe tests should be performed annually and after any accidental hymenoptera sting.[45]


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