Purpose of the Study. To increase awareness about the patient with a negative skin test response and insect sting allergy and to determine the frequency and significance of negative skin test responses in patients with a history of systemic reactions to insect stings.
Study Population. Subjects were recruited for insect sting challenge study using advertisements. Subjects with a history consistent with a systemic immunoglobulin E (IgE)-mediated allergy to insects were evaluated.
Methods. Venom skin testing, serologic IgE venom testing, and insect sting challenges were conducted. Intradermal skin testing to venom extracts (ALK-Abello Labs, Copenhagen, Denmark) was conducted in a range from 0.001 μg/mL to 1.0 μg/mL. Venom-specific serum IgE was detected using radioallergosorbent testing (RAST) (on-site assay using precommercial venom preparations). Sting challenge was performed using standards reported by this group with stings classified as mild, moderate, or severe based on defined criteria.
Results. After 4 years of recruitment, 307 subjects were enrolled. Skin testing was positive in 208 (68%) of patients. Skin testing was negative in 99 (32%) of whom 56 (57%) also had a negative RAST and 43 (43%) had a positive RAST. Of those with negative skin testing and positive RAST, 36 had a low-level RAST (1–3 ng/mL) and 7 had a high-level RAST (4–243 ng/mL). Sting challenge was conducted in 51 of the 99 patients with negative skin tests. Systemic reactions occurred in 11 of these 51 patients: 9 had low-level RAST and 2 had no specific IgE. Positive sting challenge was mild in 7 patients and moderate in 4, with no patient demonstrating a severe reaction. All systemic reactions occurred with yellow jacket stings, the focus of this group’s research. The systemic reaction rate to sting challenge in skin test negative patients (22%) was not different from the systemic reaction rate (21%) in skin test positive patients. The reaction rate was higher in patients with negative skin tests and positive RAST results (24%) than in those with negative RAST results (14%). Additionally, there was no significant difference in the severity of the reported past systemic reactions by patients with positive or negative skin tests, with both groups reporting 25% mild, 55% moderate, and 20% severe reactions.
Conclusions. The authors conclude that negative venom test results do not exclude the possibility of a systemic reaction. Authors also note their low recruitment of patients with negative skin tests and RAST for sting challenge make it possible that the overall frequency of reaction is as low as 11%; however, this does not diminish the potential risk of reaction in patients with a convincing history and negative testing. These results likely reflect limited diagnostic sensitivity of current testing methods. Authors recommend that patients with a convincing history of systemic reaction and negative skin testing to insects should be evaluated by means of RAST analysis and repeat skin testing after 3 to 6 months. If all results are negative, the authors suggest that patients be counseled to the limitations of testing and the possibility of systemic reaction, as well as appropriate avoidance and treatment recommendations.
Reviewer’s Comments. This study provides a practical assessment of an important aspect of insect sting allergy. Current practice guidelines state that patients with negative skin tests are not candidates for immunotherapy, but they provide no guidance for the management of these patients. The authors of this study have thus provided insight into the clinical risks for these patients and have provided practical diagnostic and management suggestions to more fully evaluate and care for these patients. In addition, this study highlights the need for improved diagnostic testing for insect sting allergy.
- Copyright © 2002 by the American Academy of Pediatrics