A convincing clinical history and proven Vespula venom sensitization are required for the diagnosis of Vespula venom allergy (2, 9). As venom sensitization is identified in approximately 10–30% of history-negative persons, only those with a history of a previous systemic reaction are usually eligible for diagnostic testing (2, 9).
In vitro tests to whole venom extracts are negative in approximately 20% of patients with positive skin tests, and positive in an estimated 10% of patients with negative skin tests, therefore the European guidelines recommend sequential skin and venom specific IgE testing as a standard protocol in all patients with a history of systemic reactions, ensuring a high diagnostic sensitivity of 94% (2, 9, 15). Recent data confirmed that in vitro and skin tests with Vespid venom extracts yielded complementary rather than overlapping results, and suggested that in vitro diagnosis might suffice, or might be performed as the first-line test (19, 22).
As Hymenoptera venom IgE persist for extended periods, in vitro and skin testing can be done even a long time after the reported clinical reaction, however, it is recommended to observe a 2-week interval after the reaction before performing skin tests (2, 19). If, based on clinical history, the index of suspicion for anaphylactic reaction is high, but in vitro and skin tests are negative, testing should be repeated after one to six months (5, 9).
In vitro diagnostics
In vitro testing is devoid of clinical risk of adverse reactions to applied venom and is less labor-intensive than skin testing (22).
In a prospective diagnostic study, the positive predictive value of ImmunoCAP in vitro testing of Hymenoptera extracts was 77% and the negative predictive value 59%, while intradermal skin tests yielded 87% and 55% respectively (19). The diagnostic sensitivity of the whole allergen extract of Vespula spp venom is 83-91%, with improved performance since its spiking with Ves v 5 (2, 23)
Besides allergen-extract specific IgE, in vitro investigation of Hymenoptera sting-induced reactions comprises allergen component IgE and CCD IgE determination to assess genuine versus cross-reactive sensitization, as double positivity to bee and wasp venom extracts during in vitro testing occurs in up to 50% of venom-allergic patients (2, 24, 25).
A combination of the Vespula spp recombinant allergen components rVes v 1 and rVes v 5 has been reported to yield a sensitivity as high as 92–98% for the identification of genuine sensitization to Vespula spp venom (2). Conversely, a patient who tests negative for specific IgE to both rVes v 1 and rVes v 5 is unlikely to have genuine wasp venom sensitization, regardless of IgE to other wasp components (26).
Total IgE could be useful, particularly in cases with low levels of specific IgE, for calculating the specific-to-total IgE ratio, a proposed indicator for clinically relevant sensitization (2).
Diagnostic investigation of Hymenoptera sting-induced systemic reactions also requires determination of baseline tryptase in search for a mast cell disorder, with levels at 8 µg/L or higher suggesting hereditary α-tryptasemia (2, 13). Further investigations such as testing for the D816V c-kit mutation in peripheral blood may be considered (12).
In the approximately 5% of Hymenoptera venom-allergic patients with elevated baseline tryptase levels and/or mastocytosis, diagnostic sensitivity is enhanced by using molecular components and a cut-off level of 0.1 kUA/L for specific IgE positivity (27).
Skin tests
Skin tests with Vespid venom extracts can be performed as skin prick tests or intradermal tests (9). Their diagnostic sensitivity is estimated at 64% (2).
The skin test reaction to venom extracts is not correlated to the severity of past or recurrent reactions to a future sting (2, 9). The sensitivity of the skin prick test is lower than that of the intradermal test, which is used to confirm a negative result (9). Diagnostic intradermal testing is usually carried out using venom extracts of concentrations of between 0.001 µg/mL and 1.0 µg/mL. The accuracy of the test is subject to proportionate representation of the relevant allergens in the extract, as false-negatives may be the result of underrepresented components and, conversely, irritant compounds may lead to false-positives (1).
Challenge tests
Live sting challenges are not a standard procedure in clinical practice (1, 2, 15).
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