Natural history of Hymenoptera venom sensitivity in adults

Background: Epidemiologic studies of Hymenoptera venom allergy in adults show a prevalence of positive venom skin test results. RASTs of 15% to 25%, or both, but most such individuals have had no systemic reactions to stings. The clinical significance and natural history of this apparently common sensitivity is uncertain. Objective: We sought to determine the natural history of venom sensitization by observing the rate of decrease or increase in sensitivity in normal adults over 5 to 10 years. The clinical significance of these findings is related to the frequency of systemic reactions to stings during the period of observation. Methods: Serial observations were planned in 520 volunteers and randomly selected subjects. Two follow-up visits were attempted, once after 2 to 3 years and again after 5 to 9 years, to perform repeat venom skin tests and RASTs and to review any history of interim stings and their outcomes. Results: Follow-up visits were conducted with 398 subjects (375 early visits and 205 late visits). Overall, in the 398 subjects with one or more visits after a mean of 4 years, skin test responses changed from positive to negative in 44 of 98 (45%) and from negative to positive in 27 of 309 (8.7%) of the subjects. Skin test responses changed from positive to negative in 29 of 87 (33%) subjects after 2.5 years and in 43 of 54 (80%) after 6.8 years. Even when the skin test response became negative, venom-specific IgE remained positive in 11 of 29 (38%) subjects after 2.5 years and in 13 of 43 (30%) after 6.8 years. The rate of loss of sensitivity was 12% per year, similar to retrospective estimates. Skin test sensitivity to venoms disappears more rapidly in these subjects without symptoms (half-life, 4 years) than in patients receiving venom immunotherapy (half-life, 7 years). Skin test responses changed from negative to positive in 23 of 288 (8%) subjects after 2.5 years and in 9 of 151 (6%) after 6.8 years. Insect stings caused no reaction in 120 subjects with a negative skin test response, but 17% (11 of 65) of subjects with a positive skin test response (but with a negative history had systemic reactions when stung. There was no difference between the early and late visits in the frequency of systemic reactions reported. The risk may be higher than 17% for the specific individuals (67% after 2.5 years and 20% after 6.8 years) whose positive skin test responses persist for years. This risk is lower than that of patients with a positive history (50%) but higher than that of "normal" adults or venom-treated patients (<2%). It is still not clear whether any subset of adults with a positive skin test response but a negative history can be identified, in whom the risk of systemic sting reaction would justify venom immunotherapy even before any reaction occurs. Conclusion: Asymptomatic venom sensitization in adults is common but transient, disappearing at the rate of 12% per year. However, the risk of a systemic reaction to a subsequent sting is significant in adults without symptoms but with positive venom skin test responses (17%) and may be higher when skin test sensitivity does persist for years.