Golden DB, Kagey-Sobotka A, Norman PS, Hamilton RG, Lichtenstein LM. N Engl J Med. 2004;351:668–674
Purpose of the Study.
To determine if children outgrow their allergy to insect stings and to determine the long-term efficacy of venom immunotherapy.
Subjects included were patients who had a reaction after an insect sting as a child. Reactions varied in severity and included large local reaction, mild (cutaneous) systemic reaction, and moderate-to-severe systemic reactions. Patients in the study either received venom immunotherapy or did not receive venom immunotherapy after their initial reaction.
Between 1978 and 1985, allergic reactions to insect stings were diagnosed in 1033 children, of whom 356 received venom immunotherapy. A survey of these patients was conducted by telephone and mail between January 1997 and January 2000 to determine the outcome of stings that occurred in the period from 1987 to 1999.
Of the 1033 patients, 512 (50%) responded, with a mean follow-up period of 18 years, a mean duration of venom immunotherapy of 3.5 years in treated patients, and a sting incidence of 43%. Systemic reactions occurred less frequently in patients who had received venom immunotherapy (2 of 64 patients [3%]) than in untreated patients (19 of 111 patients [17%]; P = .007). Patients with a history of moderate-to-severe reactions had a higher rate of reaction if they had not been treated (7 of 22 patients [32%]) than if they had received venom immunotherapy (2 of 43 patients [5%]; P = .007). In patients who had been treated and had a history of mild (cutaneous) systemic reaction, none of the 21 subjects who received stings had a systemic reaction; however, there was not statistical significance between the rates of reaction when comparing the treated versus the untreated groups. Among the patients who had not received venom immunotherapy, there were no severe systemic reactions after a subsequent sting. Twenty-seven percent of patients who had moderate-to-severe initial reactions sustained subsequent reactions of similar severity (otherwise, the reactions were less severe), and 6.7% of patients with initial mild (cutaneous) systemic reactions developed moderate systemic reactions on subsequent stings (otherwise, the reactions were less severe than the original [87% had no subsequent systemic allergic reaction]).
A clinically important number of children do not outgrow allergic reactions to insect stings. Venom immunotherapy in children leads to a significantly lower risk of systemic reaction to stings even 10 to 20 years after treatment is stopped, and this prolonged benefit is greater than the benefit seen in adults.
This study demonstrates that a significant number of children do not outgrow their insect allergy and that venom immunotherapy can have long-lasting protective effects. Venom immunotherapy should be offered to children with systemic reactions who test positive for venom-specific IgE (performed by skin testing and serum tests only if skin tests are negative); however, it is not usually recommended for children ≤16 years old who have generalized cutaneous reactions without other symptoms. Venom immunotherapy is also generally not recommended for persons with large local reactions. The study emphasizes the important role of allergen immunotherapy in the treatment of a potentially fatal allergic disorder.