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Background Large local reaction to Hymenoptera stings is usually defined as a swelling >10 cm which lasts longer than 24 hours, sometimes associated with erythema, pruritus and blisters. Currently, the risk of subsequent systemic reactions after re-stings is considered low (2%-15%). Therefore, a diagnostic workup in case of large local reaction is often judged unnecessary, as well as adrenaline auto-injector and venom immunotherapy prescription. The aim of this study was to prospectively evaluate the outcome of re-stings in a real-world setting, in patients with a history of one previous large local reaction. Methods We consecutively enrolled patients who experienced their first large local reaction (as per EAACI definition), treated with antihistamine and steroids. They were followed for field re-stings and assessed for risk of subsequent systemic reactions. Results We enrolled 662 patients. Out of the 225 re-stung subjects, 24% did not experience reactions, 52% reported a second large local reaction and 24% had systemic reactions. The risk of subsequent systemic reactions was higher in case of skin test reactivity to Apis mellifera or Vespula species (OR 2.1 and 3.8, respectively), in particular if positive at 0.001 µg/mL concentration (OR 13.4 and 16.5, respectively). Conclusions Systemic reactions, after a previous large local reaction, occur more frequently than that reported by literature. After analysing the predictive role of large local reactions for systemic reactions, we demonstrated that an accurate diagnostic workup may be considered, particularly skin tests. Further studies in different countries are needed to confirm these results and large local reaction management.

International audience; Background: In ascertained allergic sensitization to Vespa crabro (VC) venom, the European guidelines still consider venom immunotherapy (VIT) with Vespula (VE) venom sufficient to achieve an adequate protection against VC. However, antigen 5 immunoblotting studies showed that a genuine sensitization to VC venom may exist. In such cases, a specific VC venom would be preferable for VIT treatment. Since in the last few years, VC venom extracts became available for diagnosis and desensitization, we assessed the efficacy and safety of VIT with a VC-VIT, compared to VE extract. Methods: Patients stung by VC, and carefully diagnosed for specific sensitization and indication to VIT underwent a 5-year course of immunotherapy with either VE or VC extracts. The severity of reactions at the first sting (pre-VIT) and after field re-stings (during VIT) were compared. Results: Eighty-three patients, treated with VE extract and 130 patients treated with VC extract completed the 5-year course of VIT. Only a fraction of those patients (43,8%) were field-re-stung by VC: 64 patients on VC VIT and 69 on VE VIT. In the VC VIT group, reactions at re-sting were: 50 negative, 12 large local reactions, 4 systemic reactions (Muller grade I). In this group the VC VIT efficacy was 93,8%. In the VE VIT treated group the reactions at VC re-sting were: 51 negative, 10 large local reactions and 9 systemic reactions (5 Muller I, 3 Mueller III, 1 Muller IV). In this group the overall efficacy of VIT was 87,0%. The difference in efficacy between the two groups was not statistically significant, as previously reported in literature. Nonetheless, field sting systemic reactions Muller III and IV were recorded only in those patients receiving VE VIT. Conclusion: This observation suggests that in patients with ascertained VC-induced allergic reactions a specific VC VIT, where available, would be more adequate, at least concerning the safety profile.