Original article Skin testing and drug provocation in the diagnosis of nonimmediate reactions to aminopenicillins in children Nonimmediate (NIR) reactions to betalactams occur more than 1 h after drug administration, and most are T-cell mediated (1). Although considerable interest has been evinced on immediate reactions (IR), the same cannot be stated for NIR (2). The entities involved are greater than that for IR and includes maculopapular exanthema, urticaria-like exanthema, serum-sickness-like syndrome, the Steven Johnson-Toxic epidermal necroly- sis syndrome complex, acute exanthematic pustulosis and drug hypersensitivity syndrome, in addition to organ- specific reactions (3). Exanthematic reactions were initially reported with ampicillin therapy and usually associated with viral infections, with the subsequent replacement by other aminopenicillins, such as amoxicil- lin and amoxicillin-clavulanic acid, which are the most frequently involved (4). Although a high proportion of subjects with exanthematic reactions to aminopenicillins show good tolerance (5–7), a few develop further reactions after re-exposure, and are therefore considered as allergic (4, 7). Although reports suggest that the incidence of IR in children appears to be lower than in adults (1, 8, 9) no information is available for NIR. We studied a group of children aged 1.5–12 years referred to the allergy unit of Gregorio Maran˜on childrenÕs hospital to rule out allergy to aminopenicillins. After the allergological study, we found that intradermal/ patch testing to different penicillin determinants seemed to be of limited value to diagnose children with NIR, and a drug-provocation tests (DPT) was necessary. Material and methods Patient selection Children referred for evaluation of a NIR to aminopenicillin were included. Reactions were maculopapular or urticaria-like exan- Background: Nonimmediate allergic reactions (NIR) to aminopenicillin include several entities, the most common of which are urticaria-like and maculopapular exanthemas. Aims of the study: To evaluate a group of children who developed one or more episodes of skin reactions suggestive of NIR after aminopenicillin administra- tion. Methods: The inclusion criteria required negative immediate skin tests and absence of specific IgE antibodies to different penicillins. Intradermal and patch tests were carried out with delayed readings and, if negative, a drug-provocation test including a full therapeutic course of the drug was given. Two different groups were compared: A) children with positive skin testing or a positive drug- provocation test and B) children with negative skin testing and good tolerance after a drug-provocation test. Results: Group A was composed of 20 patients. Positive intradermal/patch tests were found in one patient and in the remaining 19, a positive response to a drug- provocation test confirmed the diagnosis. Group B (the control group) consisted of 19 patients with similar symptoms after aminopenicillin intake but good tolerance. No differences in age, dose or number of previous treatments were observed between the groups. The clinical entities were also similar in both groups. Conclusions: Reproducible nonimmediate skin reactions to aminopenicillins may occur in children in spite of negative skin testing. The value of this diagnostic procedure seems to be limited in this type of reaction, with drug-provocation tests (DPT) being a reasonable and safe alternative if the diagnosis has to be confirmed. N. Blanca-López 1 , L. Zapatero 2 , E. Alonso 2 , M. J. Torres 3 , V. Fuentes 2 , M. I. Martínez-Molero 2 , M. Blanca 3 1 Allergy Service, 12 de Octubre Hospital, Madrid; 2 Pediatric Allergy Unit, Gregorio MaraÇon Hospital, Madrid; 3 Allergy Service, Carlos Haya Hospital, Mµlaga, Spain Key words: aminopenicillins; children; drug-provocation tests; nonimmediate reactions; skin testing. Maria Jose Torres JaØn Allergy Service, Carlos Haya Hospital Pl. Hospital Civil, 29009 Malaga, Spain Accepted for publication 25 August 2008 Abbreviations: NIR, nonimmediate reactions; IR, immediate reactions; BPO, benzylpenicilloyl determinant; MDM, minor determinant mixture; DPT, drug-provocation tests; PPL, penicil- loyl-polylisine; ENDA, European Network for Drug Allergy. Allergy 2009: 64: 229–233 Ó 2009 The Authors Journal compilation Ó 2009 Blackwell Munksgaard DOI: 10.1111/j.1398-9995.2008.01903.x 229