Although subjects with a positive history of immediate allergy to penicillin and negative skin test are considered to tolerate penicillin, they may develop an immediate reaction despite negative skin and serum specific IgE tests. These patients require additional tests to confirm the diagnosis. Objective: To assess in a large group of patients with a history of immediate allergy to penicillins but with both skin test and CAP-FEIA-negative to classical and side chain penicillin determinants, the role of controlled administration of betalactams as a diagnostic test. Methods: A group of 330 patients with a history of immediate allergic reactions to penicillins was studied by 2 evaluators by means of skin tests with major and minor determinants of benzylpenicillin (BPO), amoxicillin (AX) and ampicillin, and determination of specific IgE antibodies to penicillins by CAP-FEIA, in serum. If both tests proved negative, a controlled administration of the drug was carried out. Results: A total of 89 (27%) patients were skin test and CAP-FEIA-negative and required controlled administration of the drug. Of these, 49 developed an immediate response and were considered allergic, and the remainder had good tolerance after administration of both BPO and AX. Patients in this group were younger that allergic patients who were skin test or CAP-FEIA-positive (P<0.01). Twenty-two (45%) developed a response to BPO and 27 (55%) had a selective response to AX. Although all reactions appeared within 1 h, a positive correlation was found between the dose inducing the response and the time elapsed from drug administration for both BPO and AX (P<0.001). Conclusion: An important number of subjects are not correctly identified if only skin tests and/or CAP-FEIA are used, being particularly relevant for side chain-specific reactions and younger subjects. This suggests that new diagnostic tests are required to limit the use of controlled administration.
