Diagnostic Value of Oral Challenge Testing in the Diagnosis of Macrolide Hypersensitivity

Abstract

Background: Hypersensitivity reactions (HRs) to macrolides are rare.

Objective: The aim of this study was to evaluate the diagnostic value of in vivo tests in the diagnosis of HRs to macrolides and also to assess cross-reactivity between 4 different macrolides (clarithromycin, dirithromycin, spiramycin, and azithromycin) belonging to 3 different groups.

Methods: Twenty-five patients with a history of immediate or delayed-type HRs to at least 1 macrolide and 20 healthy control subjects underwent skin testing for both the culprit and alternative macrolides. Then, all subjects underwent single-blind drug provocation tests (SBDPTs) with these drugs.

Results: Twenty-one patients (84%) described an early reaction, whereas the remaining 4 (16%) had delayed-type reactions. Skin prick test results with culprit macrolides were positive in only 2 patients who had experienced anaphylaxis. These 2 and another 4 patients with anaphylaxis history and 6 patients with negative skin test results who did not give consent were not challenged. A total of 13 patients with negative skin test results were challenged with the culprit drugs and all of them experienced HRs during the SBDPTs. Skin test results with alternative drugs were positive in only 2 patients with negative SBDPT results. Conversely, 5 patients with negative skin test results reacted to SBDPTs with alternative macrolides. In healthy control subjects, the skin test results were positive in 3 patients (1 positivity with clarithromycin, 2 positivity with spiramycin) whereas all DPT results were negative.

Conclusions: Our results suggested that DPT is the only reliable method to predict macrolide hypersensitivity as well as to detect cross-reactivity between macrolides.

Keywords: Anaphylaxis; Drug provocation tests; Drug skin tests; Hypersensitivity; Macrolides.