In vitro testing to diagnose venom allergy and monitor immunotherapy: a placebo-controlled, crossover trial

Summary Background In people with a history of sting allergy, only prior reaction severity and older age are known to predict subsequent reaction risk. Furthermore, no diagnostic test other than a deliberate sting challenge has been found to identify people in whom venom immunotherapy (VIT) has been unsuccessful. Objective We aimed to assess the utility of a number of in vitro tests to diagnose venom allergy and to monitor immunotherapy. Methods During a double‐blind randomized placebo‐controlled crossover trial of Myrmecia pilosula ant VIT the following venom‐specific tests were performed at enrolment, and at completion of treatment prior to a diagnostic sting challenge; leucocyte stimulation index (SI), IL‐4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry. Results Only VST and HRT identified those at risk of sting anaphylaxis in the placebo group. Although IgE RAST, leucocyte SI and IL‐4 production, LRT and BAT all correlated well with intradermal VSTs, they did not predict sting challenge outcome. After successful VIT, venom‐induced leucocyte IL‐4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed. A confounding seasonal affect on laboratory results was suspected. Conclusion The HRT warrants further assessment for diagnosis of venom allergy. Uninformative performance of the commercially available LRT and BAT tests may be due to pre‐incubation with IL‐3. None of the tests evaluated appear to be reliable markers of successful VIT.