Background: Epidemiological studies of Hymenoptera stings, mainly bees (Apis mellifera), wasps (Vespula vulgaris) and hornets (Vespa crabro) living in colonies, in the general adult population show a sting prevalence of 56.6–94.5%, depending on the climate. Allergic patients to Hymenoptera stings can have varying levels of severity, which are assessed according to Mueller classification, from mild systemic reaction to anaphylaxis. The aim of the doctoral dissertation was to develope a model for factors that predict the degree of allergic reaction after subsequent Hymenoptera stings (wasps, bees and European hornet) in patients who have already had an allergic reaction
Methods: In the period between October 2019 and April 2021, we conducted a retrospective cohort epidemiological survey. In the research we included all patients who were admited at the Golnik University Clinic due to an allergic reaction after a wasp, bee or European hornet sting from 1997 to 2015. In the first round, we sent a written survey to the address of permanent residence. In the second round, we again sent a letter to non-respondents with instructions for completing the survey electronically. We used the hospital information system BIRPIS of the Golnik Clinic to obtain data on the patient's characteristics at the time of the first Hymenoptera sting. Using univariate and multivariate statistical models, we analyzed factors predicting the degree of allergic reaction after subsequent Hymenoptera stings in patients who had already had an allergic reaction.
Results: In the univariate analysis of the association between the degree of severity of the allergic reaction at the first sting and the second sting, we demonstrated a statistically significant correlation that those who reacted with a milder reaction the first time will also react with a milder reaction after the subsequent sting, for the wasp and for the bee as for the European hornet. For the wasp, we showed that those who reacted with a milder reaction at the first sting will in 92% react with a milder reaction after subsequent sting and in 7.8% with a severe reaction after subsequent sting (p<0.001). For the bee, we showed that those who reacted with a milder reaction at the first sting will in 94.2% react with a milder reaction after subsequent sting and in 5.8% with severe reaction after subsequent sting (p<0.001). For the hornet, we showed that those who reacted with a milder reaction at the first sting will in 92.8% react with a milder reaction after subsequent sting and in 7.2% with severe reaction after subsequent sting (p<0.001). Patients who reacted with a severe reaction to a European hornet sting, statistically significantly more often reacted with a severe reaction after subseqent wasp sting (p=0.022). In the univariate analysis of the association between the severity of the subsquent sting and age, we showed for wasp, tahat older patients have statistically significant more severe reactions after subsequent sting, but not for the bee. In the univariate analysis of the association between the severity of the subsequent sting and the levels of specific IgE antibody concentrations, we showed a statistically significant association for the wasp (p =0.021), but not for the bee. In the univariate analysis of the association between the severity of the subsequent stings and the number of stings, and the time between the first and the subsequent sting, we did not show any statistical characteristics for either the wasp or the bee. In multivariate analyses, we estimated that there is no correlation between the degree of severity of the allergic reaction after subsequent wasp stings for any of the observed characteristics and for the bee, the correlation between the degree of severity of the allergic reaction after subsequent bee stings and the allergic reaction to the bee sting in the family (p=0.003), and higher age (p=0,024) was significant. For protective medication, we estimated with univariate analysis that those re-stung by a wasp take medication equally often according to the severity of the re-reaction, whereas those re-stung by a bee take medication more often if the re-reaction is severe.
Discussion:. To the best of our knowledge, this is the first extended retrospective cohort study on the natural course of sensitization and severity of an allergic reaction to a Hymenoptera insect venom. In previous epidemiological studies, a provocation test was used to assess the severity of the allergic reaction after repeated stings by insects of the genus Hymenoptera. The research protocol introduced several new approaches that address the problem of identifying risk factors associated with the severity of systemic allergic reactions after Hymenoptera stings. Based on the population of respondents to the questionnaire, we found in the Slovenian area that most of those who experienced a mild reaction after the first insect sting will react with a mild reaction after subsequent sting. Still, 5% to 8% of patients will have a severe reaction after being re-spiked. We must be especially careful with the elderly, those with high sIgE levels and those with a history of bee allergy in the family. As a conclusion of the findings of our research, we state that the decision for immunotherapy must be based on an individual assessment, which takes into account the combination of all risk factors for a severe allergic reaction after subsequent Hymenoptera stings. In the case of a severe reaction after a European hornet sting, the introduction of immunotherapy with wasp venom makes sense.
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