Is a positive intracutaneous test induced by penicillin mediated by histamine? A cutaneous microdialysis study in penicillin-allergic patients

Abstract

BackgroundDiagnostic workup of penicillin allergy comprises skin testing with penicillins, and patients are deemed allergic if skin test is positive. However, the literature suggests that skin test-positive patients may be challenge-negative, indicating that the skin test may be falsely positive.ObjectiveTo investigate real-time histamine release from a positive intracutaneous test induced by penicillin in patients with positive and negative challenges to penicillin.MethodsSkin microdialysis was performed in 21 penicillin-allergic patients with positive skin test, 13 non-allergic volunteers serving as negative controls, and 7 grass pollen-allergic patients serving as positive controls. Histamine was measured by microdialysis after skin test with penicillin/grass/NaCl. Penicillin challenge was subsequently performed in 12 of the patients.ResultsOnly 10/21 patients (47.6%) were skin test positive at microdialysis. During microdialysis 13 single intracutaneous tests were positive and histamine was detected in 4/13 occurring in four challenge positive patients. Thirteen/21 patients (61.9%) were deemed allergic to penicillin; eight had positive skin test. Two patients with positive skin test were challenge negative. In grass pollen allergic patients, 7/7 had a positive intracutaneous test to grass and all released histamine in the wheals. All 13 negative controls had negative intracutaneous test to penicillin and no histamine release.ConclusionHistamine was only detected in the minority of positive intracutaneous tests with penicillin in penicillin-allergic patients. Other mediators may be involved.

Accuracy of penicillin allergy diagnostic tests: A systematic review and meta-analysis

“…Among patients reporting nonimmediate reactions (largely maculopapular exanthema or urticaria/angioedema), 26,28,32,40,42,46 Eleven studies were included in the meta-analysis assessing the accuracy of specific IgE. 24,28,30,33,[36][37][38][39]42,47,48 The studies had been mostly performed in Europe (n 5 10), 24,28,30,33,36,38,39,42,47,48 and among outpatients (n 5 9). 24,28,33,[36][37][38][39]42,47,48 Four studies assessed adults, 28,37,38,47 whereas 3 assessed children 36,42,48 and other 4 studies patients of all age groups.…”

Who needs penicillin allergy testing?

“…Penicillins can directly activate the RhoA/Rock signaling pathway, which affects endothelial hyperpermeability. 39 Tannert and coworkers 40 recently reported that histamine was only detected in a few positive intracutaneous penicillin skin test results by microdialysis.…”

Skin microdialysis: methods, applications and future opportunities—an EAACI position paper

“…So far, SMD has been used to a limited extent in the investigation of drug hypersensitivity. In one study, SMD in penicillin allergic patients demonstrated that histamine was only released in the minority of positive intracutaneous tests with penicillin [38 ].…”