Cross-reactivity in beta-lactams after a non-immediate cutaneous adverse reaction: experience of a reference centre for toxic bullous diseases and severe cutaneous adverse reactions

Background Cross-reactivity among beta-lactam antibiotics (BL) is essentially reported in immediate hypersensitivity. Objectives To evaluate cross-reactivity beyond BLs in patients with non-immediate cutaneous adverse drug reaction (non-immediate CADR) managed in a dermatology reference centre of toxic bullous and severe CADRs. Patients/Materials/Methods We conducted a retrospective single-centre study in consecutive patients consulting between 2010 and 2018 with an active BL-suspected non-immediate CADR and explored by cutaneous tests [patch tests (PT) and intradermal tests (P-IDR)] for at least three penicillin's subclasses and amino- and non-amino-cephalosporins (at least one aminocephalosporin). Cross-reactivity among subclasses was investigated for patients with positive tests. Results We included 56 patients, among whom 46 amoxicillin-suspected were and seven cephalosporin-suspected. Twenty-nine had severe CADR, and 27 had non-immediate maculopapular exanthema (MPE). Twenty-two had positive tests (18 for AS and four for CS). Among the 18 positive amoxicillin-suspected, 10 (55.6%) showed cross-reactivity with one or more other BL: 9 (50%) with another penicillin and 3 (16.5%) with a non-aminocephalosporin. No amoxicillin- or cephalosporin-suspected patient showed cross-reactivity with aztreonam or carbapenems. P-IDR showed cross-reactivity only once. Conclusion After a suspected BL-induced non-immediate CADR, a large allergologic exploration is needed to confirm the diagnosis and evaluate cross-reactivity. In our population including cases of severe CADRs and MPE with late delay of onset, cross-reactivity was frequent and PT was sufficient to this purpose. The frequent cross-reactivity among penicillins encourages stopping this whole family and to test cephalosporins, aztreonam and carbapenems for which cross-allergies are rarer.