Figures & Tables

Table 1

Study patients as defined by the per-protocol analysis in Figure 1. Age was defined as the age at the 1st presentation in the allergy clinic.

Table 2

Overview of all test results in absolute and relative numbers: sIgE = specific IgE (positive/negative). Results of specific IgE (≥0.35 kU/l) is displayed in the first column. Prick and intradermal tests: 20 min / 24 hours / all tests. Patch tests 24 hours / all. The highest value of each category is in underline format. ( blue for immediate allergy, red for delayed allergy)

Figure 1

Flow diagram and definition of the patient populations.

Figure 2

Percentage of positive tests in relation to all tests: Positive tests for specific IgE (2a) and early readings in skin prick tests (2b) and intradermal tests (2c) were suggestive for immediate type I allergy ( blue). Late readings ( red) in skin prick tests (2b), intradermal tests (2c) and patch tests (2d) after 24 hours were suggestive for delayed type IV reactions.

Figure 3

As the primary endpoint of this study, it was possible to solve 37.1% of the cases (confirmed in green and disapproved in red) by exploiting all possibilities of the algorithm depicted in Figure 1. Penicillin and Cephalosporin differed as only 34% of the Penicillin but nearly half of the Cephalosporin cases could be solved.

Figure 4

Risk factor analysis for a confirmation ( red) of the drug hypersensitivity reaction (DHR) versus its’ disapproval ( green). Men and younger children had a significantly higher risk for a confirmed DHR than women and teenagers/adults. This analysis included only the 346 solved cases according to Figure 1 & 3. Significance was calculated using a Χ²-test.

Supplementary Figure 1

Cross-reactivity in penicillins and cephalosporins is caused by similarities in the chemical structure of the drugs, which share their common β-lactam ring structure ( light pink). That is why they are known as “β-lactam” antibiotics. The thiazolidine ring of penicillins ( light green) differentiates them from the dihydrothiazin ring of cephalosporins ( light grey). Cefaclor and ampicillin share their acyl side chain, and the one of amoxicillin is also rather similar ( light blue). Pictures were drawn according to Blumenthal et al. (42) and Zagursky and Pichichero (43).

Supplementary Figure 2

Algorithm for the workup of the study patients. Each individual physician could deviate from this procedure according to the patient’s individual needs. Drug provocation tests were not part of this study.

Supplementary Figure 3

The hypothetical lowering of the standard threshold for drug-specific IgE from ≥0.35 kU/l ( blue) to ≥0.1 kU/l ( purple) is recommended by some guidelines to increase the weak sensitivity in patients with low total IgE (16). Another hypothetical indirect measure in patients with a high total IgE is to determine the sIgE / total IgE ratio. Vultaggio et al. published a cut off of > 0.0022 for β-lactam antibiotics ( grey) (25).