Adding a second skin prick test reading and modifying the cut-off for beta-lactam-specific IgE enhances the sensitivity in the routine diagnostic workup for immediate beta-lactam hypersensitivity

BACKGROUND: Beta-lactam (BL)–antibiotics are the most frequent reason for drug-induced hypersensitivity reactions. Because they are more efficient, less toxic, and less costly than other antibiotics, confirmation or exclusion of BL allergy is worthwhile. However, allergy tests for drug allergies are often false-negative. OBJECTIVES: To evaluate the components of a stepwise diagnostic algorithm for immediate BL hypersensitivity with regard to sensitivity (SENS). METHODS: Consecutive patients with suspected allergy to BL antibiotics were retrospectively analyzed with regard to increasing sensitivity (plausible history of immediate BL hypersensitivity serving as external criterion) of (i) skin prick test (SPT) by adding a second reading (n = 746), (ii) BL-specific IgE-determination in vitro at two cut-offs (n = 539), and (iii) adding in vivo testing of minor and major BL determinants (n = 288). RESULTS: In the history-based population indicative of immediate BL hypersensitivity (n = 457), SPT with a sole 20-minute reading identified 99 (SENS: 0.21) and SPT with 20- and 40-minute-reading identified 133 cases (SENS: 0.29). in vitro specific IgE-examination identified 31 positives at a cut-off ≥0.35 kUA/L (5.8% of tested) and 99 at cut-off ≥0.11 kUA/L (18.4% of tested). In 203 SPT-negative individuals, immediate BL hypersensitivity was identified by additional tests: in 79 by specific IgE (cut-off ≥0.11 kUA/L) (thereof 53 identified solely by this test) and in 150 by in vivo testing of BL determinants in combination with Penicillin and Ampicillin intradermally (thereof 124 solely by this test); in 26 individuals both additional tests were positive. The combination of the three outpatient-based test modalities—(i) optimized SPT, (ii) specific IgE at optimized cut-off, and (iii) in vivo testing of BL determinants/Penicillin/Ampicillin—identified altogether 336/457 individuals with immediate BL-hypersensitivity (SENS: 0.73), whereas the combination of the two (i) + (ii) identified 212/457 (SENS: 0.46); (i) + (iii) 283/457 (SENS: 0.61). CONCLUSIONS: To overcome the low sensitivity of allergological tests, optimized reading times of the SPT of BL, a lower cut-off for in vitro detection of BL-specific IgE, and intradermal testing of Penicillin, Ampicillin, and BL-determinants contribute to overall sensitivity under real life conditions to diagnose immediate BL-hypersensitivity