Studies assessing the prevalence of Hymenoptera venom allergy in the general adult population are relatively rare. Those studies that were performed in different European countries between 1992 and 2016 demonstrated a prevalence of self-reported systemic sting reactions ranging from 0.9 to 8.9% [14,15,16,17,18,19]. The observed divergent results regarding the prevalence might mirror differences in exposure depending on climate and activities , in the size of the study population or in the methodology using telephone interviews or different questionnaires. Many other studies were performed on selected patient populations such as factory workers or conscripts [20, 21]. However, in most of these studies the obtained prevalence is in a comparable range to the general population. In the past, one study assessed the prevalence of insect venom allergy in the German adult population (German Health Interview and Examination Survey for Adults; n = 8152) by addressing reported medical diagnoses of insect venom allergy . Here, a lifetime prevalence of 2.8% (3.6% for females and 2.0% for males) was identified for insect venom allergies. To our knowledge, only one study addressed the prevalence of Hymenoptera venom allergy in relation to venom sensitization in Germany so far . This study covered 232 adults and 45 children from a rural area population out of whom approximately 3.9% of the adults reported a history of a systemic sting reaction. Sensitization to HBV or YJV was present in 24.1% of the adults (16.5% only to HBV, 2.2% only to YJV, 5.4% to both venoms).
In order to address the prevalence of Hymenoptera venom allergy in relation to venom sensitization in a larger German adult cohort, we performed questionnaire-based analyses of the population-based Cooperative Health Research in the Region of Augsburg (KORA) S4 baseline study population (n = 4261) as well as of the follow-up F4 study population (n = 3074). The questionnaire of the F4 study was clearly more suitable to assess the prevalence of systemic reactions as the participants had the possibility to discriminate between “strong reactions at the site of the sting”, “mild to moderate general reactions”, “signs of shock” and “other reactions/don’t know”. Taking mild to moderate and shock reactions to HBV and/or YJV together, covering systemic reactions, their prevalence is 2.4% (2.1% in males and 2.6% in females) whereby reactions to YJV (1.6%) are slightly more common than to HBV (1.1%). Strong reactions at the site of sting were reported by 4.4% of the participants which is a very assimilable range compared to the prevalence of large local reactions of 4.6% found in an Austrian study .
In the S4 study the participants only had the possibility to discriminate between “reaction at the site of the sting”, “signs of shock” and “other reactions/don’t know”. This selection surely is less suitable to estimate the prevalence of systemic reactions as many participants suffering from mild to moderate systemic reactions most likely would have answered with “other reaction/don’t know”. This is also reflected by the fact that the percentage of participants giving this answer was much higher in the S4 than in the F4 study. However, estimating that many of the mild to moderate systemic reactions are represented in this group, the prevalence of systemic reactions in the S4 study is in a very comparable range to the F4 study. Local reactions were reported by 4.8% of the participants of the S4 study.
Taken together, the prevalence of self-reported systemic reactions to HBV and/or YJV in the German KORA cohort ranges between 2.3% (S4 study; shock and other reactions) and 2.6% (F4 study; mild to moderate, shock and other reactions). Reactions to YJV are slightly more common compared to HBV.
Applying the threshold level of 0.35 kUA/L, as done in most other studies, 23.1% and 31.7% of the S4 study population were sensitized to HBV and YJV, respectively; 41.6% were sensitized to HBV and/or YJV and 13.2% to both venoms. Although sIgE to cross-reactive carbohydrate determinants (CCDs) could not be measured in this study, their contribution to the obtained venom sensitization rate seems to be negligible as indicated by the low prevalence of double-positive test results to HBV and YJV (as well as to venoms and aeroallergens). Other studies reported a prevalence of sensitization to Hymenoptera venoms (indicated by positive skin test and/or the detection of sIgE) in the range between 9.3% and 28.7% in adults . A recent Danish study reported a prevalence of sIgE to HBV and YJV of 3.3% and 13%, respectively . Of note, in addition to a varying degree of exposure in different areas, differences in sensitization rates might also result from the use of different assay platforms for sIgE detection. In this study, the Immulite 2000® platform was used which reportedly leads to higher sIgE values compared to the ImmunoCAP® system, due to the different calibration approach that is used [24,25,26,27,28]. Another study that was conducted in Germany found a sensitization rate to Hymenoptera venoms of 27.1% . In this study, the sensitization to HBV (24.8%) was much more common than to YJV (8.5%). However, this fact might be explained by the rural origin of the patient population on the one hand and by the lower sensitivity of the RAST (radioallergosorbent test) that was used in this study for sIgE detection to YJV on the other hand .
In general, atopy is not regarded as risk factor for venom allergy [23, 29, 30]. Here, we found no association between asthma or atopic eczema with the presence of venom sIgE and only a weak association between hay fever and sIgE to HBV (OR = 1.264) but not to YJV. In contrast, as shown previously by others , the association between the presence of venom sIgE and sIgE to common aeroallergens as well as to the level of total IgE could be clearly demonstrated. Moreover, male sex represented a stronger risk factor for the presence of sIgE to HBV compared to YJV. This might be explained by the fact that more males are working in professions associated with outdoor work such as foresters or gardeners and, hence, with a higher degree of exposure to HB stings.
Intriguingly, only 2.8% of the HBV- and YJV-sensitized patients reported shock or other reactions following a sting. In the study mentioned before, 7.1% of the positively tested patients stated a history of a systemic sting reaction . However, it is not known if a certain fraction of the sensitized individuals would react to a future sting. Nevertheless, these results underline that venom sIgE-testing should not be a part of general health screenings . Although venom-sensitized individuals suffering from systemic reactions exhibit a significantly higher percentage of venom sIgE in relation to their tIgE level, this parameter is likely not suitable to discriminate between sensitized individuals and those with clinically relevant allergy due to high variability within the population.
Of note, 30.3% and 18.8% of the participants who had shock symptoms following a HB sting had sIgE to HBV of class 0 (≤0.1 kUA/L) and class 0/1 (>0.1–<0.35 kUA/L), respectively. Of the patient population reporting shock symptoms after YJ stings, 28.1% and 6.3% showed sIgE to YJV of class 0 and class 0/1, respectively. This is in concordance with a former study reporting that only 38% of individuals with abnormal sting symptoms to any insect had sIgE ≥0.35 kUA/L to HBV and/or YJV  and again illustrates the importance of a comprehensive approach for accurate diagnostics of Hymenoptera venom allergy including clinical history, sIgE measurement, skin tests and cellular tests. Moreover, future studies are needed to address the impact of the recently available component-resolved diagnostics [7, 31, 32] on this diagnostic gap on a population level.
In conclusion, the frequency of sensitization to Hymenoptera venoms in the general German population is high. However, a considerable gap exists between the presence of sIgE and a clinical history of venom allergy on the one hand and between systemic reactions and detectable sIgE on the other hand.