Allergy to b-Lactam Antibiotics in Children

Background. Skin tests with soluble b-lactams can be used to diagnose immediate and delayed hypersensitivity (HS) reactions to b-lactam antibiotics. Very few studies have been performed with children with suspected b-lactam allergy. In these studies, immediate HS to b-lactams was diagnosed by skin tests in 4.9% to 40% of children. The diagnostic and predictive values of immediate responses in skin tests are good, because very few children with negative skin test results have positive oral challenge (OC) test results. Delayed responses in skin tests (intradermal and patch tests) have been reported in adult patients and children suffering with urticaria, angioedema, and maculopapular rashes during treatments with b-lactam antibiotics. However, the diagnostic and predictive values of late responses are unknown. Semi-late responses in skin tests with b-lactams have never been studied in adults or children. Objectives. The aims of this study were to confirm or rule out the diagnosis of allergy to b-lactams in children with histories of adverse reactions to these antibiotics, to determine whether allergic children were sensitized to one or several classes of b-lactams, and to evaluate the frequency and diagnostic value of immediate, accelerated, and delayed responses in skin tests with b-lactam antibiotics in children. Methods. We studied 325 children with suspected b-lactam allergy. Skin tests (prick and intradermal) were performed with soluble forms of the suspected (or very similar) b-lactams and with one or several b-lactams from other classes. The reaction was assessed after 20 minutes (immediate), 8 hours (accelerated), and 48 to 72 hours (delayed). OCs with the suspected b-lactams were performed in patients with negative skin test results, except those with severe serum sickness-like reactions and potentially harmful toxidermias. Results. Skin tests and OCs led to the diagnosis of b-lactam allergy in 24 (7.4%) and 15 (4.6%) of the children, respectively. Thus, only 12% of the children were diagnosed as allergic to b-lactams by means of skin tests and OC. HS to b-lactams was suspected from clinical history in 30 (9.2%) children reporting serum sicknesslike reactions and potentially harmful toxidermias. In a few children, we diagnosed food allergy and intolerance to excipients or nonsteroidal antiinflammatory drugs. No cause was found in the other children. Based on skin tests and OC, the prevalences of immunoglobulin E-dependent and of semi-late or delayed sensitizations to b-lactam assessed were similar (6.8% vs 5.2%, respectively). Most immunoglobulin E-dependent sensitizations were diagnosed by means of skin tests (86.4%). In contrast, most semi-late and delayed sensitizations were diagnosed by OC (70.6%). The likelihood of b-lactam allergy was significantly higher for anaphylaxis (42.9% vs 8.3% in other reactions) and immediate reactions (25% vs 10% in accelerated and delayed reactions). Of the children diagnosed as allergic to b-lactam by means of skin tests, OC, and clinical history, 11.7% were sensitized to several classes of b-lactams. The risk was significantly higher in children with anaphylaxis (26.7% vs 7.5% of the children with other reactions) and in children reporting immediate reactions (33.3% vs 8.5% of the children with accelerated and delayed reactions). Finally, age, sex, personal history of atopy, number of reactions to b-lactams, and number of reactions to other drugs were not significant risk factors for b-lactam allergy. Conclusion. The skin tests were safe, and the immediate reaction to skin tests successfully diagnosed allergy to b-lactam antibiotics in children reporting reactions suggestive of immediate HS. In contrast, most accelerated and delayed reactions were diagnosed by OC. Thus, our results suggest that the diagnostic and predictive values of skin tests for nonimmediate HS to b-lactams in children are low. They also strongly suggest that most reactions reported in children are attributable to infectious diseases or interactions between drugs and infectious agents rather than to b-lactam HS. Pediatrics 1999; 104(4). URL: http://www.pediatrics.org/cgi/content/full/ 104/4/e45; b-lactams, allergy, skin tests, oral challenge, child. ABBREVIATIONS. ID, intradermal; PPL, benzyl-penicilloyl polylysine; MDM, minor determinant mixture; HS, hypersensitivity; MPR, maculopapular rash; OC, oral challenge; SSLR, serum sickness-like reaction; EM, erythema multiforme; SJS, Stevens– Johnson syndrome; GEP, generalized exanthematous pustulosis; DTH, delayed-type hypersensitivity. Between 1% and 10% of patients treated with b-lactam antibiotics report reactions suggestive of allergy to these drugs.1–4 Immediate responses to prick tests and intradermal (ID) tests with benzyl-penicilloyl polylysine (PPL) and minor determinant mixture (MDM) have good diagnostic and predictive values in patients with reactions suggestive of immediate hypersensitivity (HS) to penicillins.2,5–7 However, skin tests with PPL and MDM may fail to detect specific sensitization to individual blactams.8–12 In contrast, skin tests using soluble blactams diagnose a significant number of immediate sensitizations to penicillins and b-lactams.5,12–18 Delayed responses to individual b-lactams in skin tests (ID and patch tests) have been reported in adult From the Departments of Pediatric Pulmonology and Allergology, Sick Children Hospital, Paris V University, Paris, France Received for publication Sep 14, 1998; accepted Mar 9, 1999. Reprint requests to (C.P.) Service de Pneumologie & Allergologie Pédiatriques, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015, Paris, France. E-mail: [email protected] PEDIATRICS (ISSN 0031 4005). Copyright © 1999 by the American Acad-