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

Abstract

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.

Cross With Caution: Antibiotic Cross-Reactivity and Co-Reactivity Patterns in Severe Cutaneous Adverse Reactions

“…in which patch testing was performed against a panel of penicillin and cephalosporin antibiotics and IDT was only performed if the patch test was negative. As a result this study did not find IDT with delayed readings to be of added diagnostic value ( 20 ).…”

“…The majority of non-SJS/TEN SCAR patients with cross-reactivity in the Berot et al. study had initially reacted to amoxicillin and then had positive penicillin M and Penicillin G/V patch tests ( 20 ). In the Romano et al.…”

“…described 56 patients with delayed beta-lactam allergies including 26 patients with non-SJS/TEN SCAR’s. Of these patients, 30% (1/3 DRESS cases; 8/23 AGEP cases) had evidence of cross reactivity on patch testing ( 20 ).…”

“…Our study included patients with SCAR’s to a range of beta-lactam antibiotics which is in contrast to Romano’s and Berot’s studies in which 97% and 82.1% of the patients included had previously reacted to an aminopenicillin ( 13 , 20 ). Finally, in these previous cohort studies they were comprised predominantly of benign delayed drug reactions with a small number of SCAR patients included, making it difficult to assess results on the SCAR patients separately.…”

Practice Parameters for Diagnosing and Managing Iodinated Contrast Media Hypersensitivity

“…Non-ionic dimeric ICM induce significantly more often cutaneous NIHRs than non-ionic monomeric ICM [69]. In fact, more than 50% of MPE are induced by the non-ionic dimeric ICM iodixanol [70].…”