Hymenoptera venoms

Bee and wasp venoms

The toxins in bee venom include apamin, which inhibits small-conductance calcium-dependent potassium channels, and melittin, which activates phospholipase A2 and causes pain; histamine and other biogenic amines also contribute to pain and itching [ ]. Wasp venom contains kinins, hydrophobic peptides, mastoparans, and chemotactic peptides; the mastoparans cause degranulation of mast cells, releasing histamine, and act on adrenal chromaffin cells, releasing catecholamines and adenylic acids; some cause hemolysis and release of serotonin from platelets [ ].

The intensity of a reaction can be classified by the method described by Mueller [ ] or by the system of the National Cancer Institute for grading allergic reactions in general [ ] ( Table 1 ).

When bees or wasps sting they inject on average 174 and 17 micrograms of venom respectively. This results in intense burning pain followed by erythema and edema at the site of the sting. Although this usually resolves within a few hours, systemic adverse reactions can occur, of which the most serious is IgE-mediated anaphylaxis.

The prevalence rate of large local reactions in the general population is 2.4–26%, but up to 38% in beekeepers, and 3% of adults and 1% of children have severe reactions. Large local reactions predict systemic reactions in 5–15%. There is a 60–79% chance of recurrence after one episode of anaphylaxis, although the risk may fall with time. In the UK stings cause 2–9 deaths per year.

Diagnosis of allergy to bee and wasp venoms involves skin prick tests using Hymenoptera venom protein extracts 0.001–1.0 μg/ml, testing for both bees and wasps [ ]. If skin prick tests are negative, intradermal skin tests, which are 90% more sensitive, should be performed. If they are negative the tests should be repeated 1–2 months later and serum-specific IgE should be measured.

In people who have had systemic allergic reactions to these venoms, desensitization can be attempted, using subcutaneous injections of increasing amounts of venom [ ]. The evidence suggests that wasp venom is effective in 95% of cases and bee venom in 80% of cases [ ].

The following protocols have been used:

• In the initial phase, the initial dose is increased stepwise until a maximum dose of 0.01 microgram of venom is reached:

  • -

    conventional dosage schedule: one injection every 3–7 days;

  • -

    modified rush schedule: two to four injections per week at intervals of 30 minutes;

  • -

    rush schedule: one injection every 120 minutes, with a maximum of four injections per day.

• In the maintenance phase, a dose of 100 micrograms/ml is given during weeks 0, 2, 5, and 9, then every 4 weeks for at least 3 years. If allergic reactions persist, the dose can be increased to a maximum of 200 micrograms.

Immunotherapy is normally discontinued after 3–5 years.

Ant venoms

The venom of fire ants (family Myrmicinae) consists mainly of alkaloids in aqueous suspension with only trace amounts of protein. In skin tests there is cross-reactivity or shared antigens between fire ant venom, whole body extracts of fire ants, and whole body extracts of Hymenoptera [ ].and with venom from the common striped scorpion, Centruroides vittatus [ ]. The toxins in jack jumper ant venom are pilosulins [ ].

The highest population prevalence of allergy to ant stings (3.0%) is in South-eastern Australia, due mainly to jack jumper ants ( Myrmecia pilosula ) [ ]. In an Australian survey of 376 individuals who reported 735 systemic reactions to ant stings, the cause was determined in 299, of whom 265 (89%) reacted to Myrmecia species and 34 (11%) to green-head ants ( Rhytidoponera metallica ) [ ]. Of those with reactions to Myrmecia species, 176 reacted to jack jumper ant ( Myrmecia pilosula species complex), 18 to other jumper ants (15 to Myrmecia nigrocincta and three to Myrmecia ludlowi ), and 56 to a variety of bulldog ants.

Observational studies

Of 387 patients who completed venom immunotherapy, 130 who had been sensitized to Apis and 68 to Vespula suffered spontaneous re-stings during treatment [ ]. Of these, 123 (95%) did not have any reaction and 64 (94%) had only a local reaction; 62 patients sensitized to Apis and 14 sensitized to Vespula had spontaneous re-stings after stopping treatment and only three had a systemic reaction. At the end of treatment, skin tests and specific IgE to whole extract had improved significantly and the beneficial effects persisted for at least 1 year.

In 42 patients with confirmed hypersensitivity to honey bees or yellow jacket wasps, who were treated with the respective venoms (7 with honey bee venom, 5 with yellow jacket venom, and 30 with both), there were large local reactions in eight, slight systemic reactions in 12, and moderate to severe systemic reactions in four [ ]. Of 24 re-exposed patients, 17 had no reactions at all, six had a markedly reduced reaction, and one had an unchanged reaction.

In 36 patients with a history of systemic reactions (grade III or IV according to Mueller) after exposure to a wasp sting, who were given immunotherapy with aluminium hydroxide-adsorbed wasp venom extract in an open retrospective study, a maintenance monthly depot of 50 micrograms of venom was used [ ]. After the first year, the dose was injected every other month. Desensitization therapy was well tolerated. There were few mild local adverse events. Thirteen patients were exposed to stings during maintenance immunotherapy and four after withdrawal at the end of the 5-year treatment period. Field stings only provoked local skin reactions.

In a follow-up study of adults for 5 years after stopping venom immunotherapy the residual risk of a systemic reaction to a sting was 5–10% [ ]. There were no severe or life-threatening reactions after 270 challenge stings in 74 patients after 1–5 years without venom immunotherapy. The authors extended these observations to 5–10 years and attempted to identify patients at greater risk of reactions. The patients were surveyed for 3 consecutive years to determine the frequency of systemic reactions to field stings and the course of venom sensitivity. They included the original 74 (group 1) and 51 other patients followed after stopping venom immunotherapy (group 2). Eleven of the 74 patients in group 1 had field stings again after 3–7 years without venom immunotherapy. One systemic reaction (dyspnea) was reported. Of the 51 patients in group 2, 15 were stung, of whom 4 (26%) had systemic reactions, including respiratory symptoms necessitating the use of adrenaline. Six of the 13 patients (groups 1 and 2) with a systemic reaction to a sting after stopping venom immunotherapy had had a systemic reaction to an injection or a sting during venom immunotherapy. Only six of 76 patients who had no reaction during venom immunotherapy had a systemic reaction when stung after cessation of venom immunotherapy. Other susceptibility factors were persistent strongly positive skin test sensitivity and the severity of the pretreatment reaction.