Controlled administration of penicillin to patients with a positive history but negative skin and specific serum IgE tests

Clin Exp Allergy. 2002 Feb;32(2):270-6. doi: 10.1046/j.1365-2222.2002.01296.x.


Background: Although subjects with a positive history of immediate allergy to penicillin and negative skin test are traditionally considered to tolerate penicillin, current evidence indicates that they may develop an immediate reaction despite negative skin and serum specific IgE tests. It is thought that 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 two evaluators from the same allergy unit using the following protocol: skin tests with major and minor determinants of benzylpenicillin (benzylpenicilloyl-poly l-lysine and minor determinant mixture), amoxicillin 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 then carried out.

Results: A total of 89 (27%) patients were skin test and CAP-FEIA-negative and therefore required controlled administration of the drug. Of these, 49 developed an immediate response and were therefore considered allergic, and the remainder had good tolerance after administration of both benzylpenicillin and amoxicillin. The clinical characteristics of this group were similar to the other allergic patients who were skin test or CAP-FEIA-positive, except that they were younger (P < 0.01). Twenty-two (45%) developed a response to benzylpenicillin and 27 (55%) had a selective response to amoxicillin. 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 benzylpenicillin and amoxicillin (P < 0.001).

Conclusion: These data indicate that an important number of subjects are not correctly identified if only skin tests and/or CAP-FEIA are used and that this is particularly relevant for side chain-specific reactions and younger subjects. This suggests that new diagnostic tests are required so as to limit the use of controlled administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amoxicillin / administration & dosage
  • Amoxicillin / immunology
  • Antibodies / blood
  • Drug Hypersensitivity / blood*
  • Drug Hypersensitivity / diagnosis
  • Drug Hypersensitivity / immunology*
  • Female
  • Humans
  • Immunoglobulin E / blood*
  • Male
  • Medical Records*
  • Middle Aged
  • Penicillin G / administration & dosage
  • Penicillin G / immunology
  • Penicillins / administration & dosage*
  • Penicillins / immunology*
  • Skin Tests*


  • Antibodies
  • Penicillins
  • Immunoglobulin E
  • Amoxicillin
  • Penicillin G