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

Background Diagnostic 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. Objective To investigate real‐time histamine release from a positive intracutaneous test induced by penicillin in patients with positive and negative challenges to penicillin. Methods Skin 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. Results Only 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. Conclusion Histamine was only detected in the minority of positive intracutaneous tests with penicillin in penicillin‐allergic patients. Other mediators may be involved.