Skin tests have greater sensitivity and specificity than in vitro tests measuring serum venom-specific IgE (SSIgE) [39]. Levels of SSIgE and skin test responses do not correlate with clinical reactivity. Venom-specific IgE can also be measured Opaganib concentration by a basophil activation test

(BAT), but the latter is currently a research tool and does not have significant advantages over routinely employed enzyme immunoassays. In patients with a history of moderate–severe SR reaction, plasma baseline tryptase should also be measured to screen for underlying disorders of mast cell overload, such as telangectasia macularis eruptiva perstans (TMEP) and other forms of cutaneous (urticaria pigmentosa) and systemic mastocytosis which may warrant further investigation, including bone marrow studies, tissue biopsy and appropriate management [45–50]. Elevated baseline tryptase is an important risk factor for anaphylaxis [45–50] and will have implications for VIT, as discussed in the following sections. Choice of venom for VIT.  This is dictated by clinical history and demonstration of venom-specific IgE. There is no significant cross-reactivity between clinically significant antigens of Apidae and Vespidae (honey bee and wasp/hornet) venoms [51–53]. Within the Vespidae family, there is significant overlap between wasps and hornet venoms [54–56]. However, there is little cross-reactivity

between wasps/hornet and paper wasps (not

encountered in the United Kingdom) [56]. These facts, as well as Dichloromethane dehalogenase knowledge of local entomology of hymenoptera insects, have to be taken into consideration carefully to make a correct MLN2238 order choice of the venom for immunotherapy. For example, in a British patient with a history of hornet sting anaphylaxis during a visit to mainland Europe, the ideal choice for immunotherapy would be wasp venom, as the prevalence of wasps is greater in the United Kingdom and wasp venom immunotherapy will protect the patient from either insect sting. VIT protocols.  Different protocols (Example 1), including conventional, clustered, rush and ultra-rush, have been described in the literature. A conventional protocol involves weekly up-dosing, reaching the maintenance dose in 12 weeks [57–60]. Maintenance dose is reached in 4–7 days in a rush up-dosing [61–63] protocol and 1–2 days in an ultra-rush schedule [61,64,65]. A recent national audit in the United Kingdom has shown that more than 90% of allergy specialists employ the conventional protocol, as services in this country are primarily out-patient-based [66]. Accelerated protocols are popular in North America and Europe, and have been shown to be safe as well as efficacious [61,63,64,67–69]. The target maintenance dosage is 100 µg and this is administered at 4-, 6- and 8-weekly intervals during the maintenance phases of years 1, 2 and 3 respectively [37].