Hymenoptera Venom Immunotherapy

Beatrice M Bilò; Floriano Bonifazi


Immunotherapy. 2011;3(2):229-246. 

In This Article

Selection of Venoms

Selection is based on the identification of the hymenoptera species that is involved, on the results of the diagnostic tests and on venom cross-reactivity.[1,4,10,63] It is often difficult to distinguish between vespids and bees, even though vespids do not usually sting in spring and, unlike the honeybee, do not usually leave the stinger embedded in the skin, though exceptionally in the USA, in 30–50% of cases[31] Vespula maculifronts does just that.

In North America, allergists and immunologists believe it prudent to prescribe VIT with any venom, which gives a positive skin test, or sIgE result, since there have been cases where VIT was tailored towards the primary culprit insect but the patients subsequently reacted to an insect to which they had previously been sensitized.[47] Other investigators recommend treatment only with the venom of the suspected culprit insect.[63] When vespids are involved, the common practice is to treat with Vespula venom alone or, in North America, with a mixed vespid venom preparation, the latter containing equal parts (in general 100 µg) of each venom of yellow jacket (Vespula species), yellow hornet (Dolichovespula arenaria) and white-faced hornet (Dolichovespula maculata),[64] and that are unavailable in Europe.

In Europe, the geographical distribution of each species and the ample cross-reactivity among venoms of Vespula, Dolichovespula and Vespa, usually makes treatment with Vespula venom alone sufficient in the temperate European climate.[2,10] The extracts are typically a mix of five or six species of Vespula (vulgaris, germanica, maculifrons, flavopilosa, pensylvanica and squamosa).

Double diagnostic positivities to wasp (Polistes) and yellow jacket (Vespula species) venoms have been observed in more than 50% of vespid allergic patients. Owing to the incomplete cross-reactivity between vespinae and paper wasps (Polistes) in the Mediterranean area, patients who test positive to both venoms should be treated with both, unless RAST-inhibition reveals cross-reactivity.[10] The same approach is used in the Gulf states of the USA, where Polistes is common as a species.[31]

A weaker cross-reactivity between European and American paper wasps was recently demonstrated.[27] The species P. dominulus and Polistes gallicus are European paper wasps; P. dominulus has spread to northeastern USA and has also been reported in Australia. The species Polistes exclamans, Polistes annularis and Polistes fuscatus are indigenous to North America and are not present in Europe. All these findings raise the need to introduce, at least in Europe, the P. gallicus or P. dominulus extract (the latter only recently being available in some European countries) into clinical practice for diagnostic and therapeutic purposes to replace the American Polistes species mixture presently being used.[27,37,65]

Allergic reactions to the European hornet (V. crabro) are rare, except in Mediterranean countries where its sting is a risk factor for severe SRs.[55]V. crabro venom has some antigens in common with Vespula venom; however, a third of V. crabro-allergic individuals have positive skin and sIgE tests restricted to only V. crabro venom.[66,67] As a consequence, in Italy, it is a common practice to use V. crabro extract for both diagnostic and therapeutic purposes.

Dual positivity of diagnostic tests with Vespula and honeybee is also frequent, especially in some European countries where bee venom allergy is more frequent than vespid venom allergy.[2] In the case of an uncertain culprit insect, both venoms should be used for VIT,[4,10] unless complete cross-reactivity can be demonstrated by RAST inhibition with whole venoms and CCDS, such as horseradish peroxidase or bromelain.[33]

Honeybee and bumblebee venoms show high cross-reactivity.[1] Immunotherapy with honeybee venom alone may be sufficient in nonprofessionally exposed bumblebee-allergic patients with bee venom primary sensitization, whose reaction is most likely due to cross-reactivity. In occupationally exposed patients, who are frequently stung by bumblebees, purified bumblebee venom for immunotherapy, when available, is recommended owing to the low or absent cross-reactivity with honeybee venom.[68] In the USA, no approved diagnostic or therapeutic extracts for the bumblebee or Mediterranean wasp (P. dominulus) are commercially available.[47]

In the USA, whole-body fire ant extract immunotherapy, which contain sufficient venom allergens to provide reasonable clinical protection is used; fire ant venoms are available in Australia (Jack Jumper) where a very successful controlled trial was performed.[69] By contrast, allergic reactions to ants are rare in Europe,[70] and a venom extract is not commercially available.


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