Allergy to beta-lactam antibiotics in children

Background. Skin tests with soluble beta-lactams can be used to diagnose im mediate and delayed hypersensitivity (HS) reactions to beta-lactam antibiot ics. Very few studies have been performed with children with suspected beta -lactam allergy. In these studies, immediate HS to beta-lactams was diagnos ed 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 chil dren with negative skin test results have positive oral challenge (OC) test results. Delayed responses in skin tests (intradermal and patch tests) hav e been reported in adult patients and children suffering with urticaria, an gioedema, and maculopapular rashes during treatments with beta-lactam antib iotics. However, the diagnostic and predictive values of late responses are unknown. Semi-late responses in skin tests with beta-lactams have never be en studied in adults or children. Objectives. The aims of this study were to confirm or rule out the diagnosi s of allergy to beta-lactams in children with histories of adverse reaction s to these antibiotics, to determine whether allergic children were sensiti zed to one or several classes of beta-lactams, and to evaluate the frequenc y and diagnostic value of immediate, accelerated, and delayed responses in skin tests with beta-lactam antibiotics in children. Methods. We studied 325 children with suspected beta-lactam allergy. Skin t ests (prick and intradermal) were performed with soluble forms of the suspe cted (or very similar) beta-lactams and with one or several beta-lactams fr om other classes. The reaction was assessed after 20 minutes (immediate), 8 hours (accelerated), and 48 to 72 hours (delayed). OCs with the suspected beta-lactams were performed in patients with negative skin test results, ex cept those with severe serum sickness-like reactions and potentially harmfu l toxidermias. Results. Skin tests and OCs led to the diagnosis of beta-lactam allergy in 24 (7.4%) and 15 (4.6%) of the children, respectively. Thus, only 12% of th e children were diagnosed as allergic to beta-lactams by means of skin test s and OC. HS to beta-lactams was suspected from clinical history in 30 (9.2 %) children reporting serum sickness-like 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 a nd of semi-late or delayed sensitizations to beta-lactam assessed were simi lar (6.8% vs 5.2%, respectively). Most immunoglobulin E-dependent sensitiza tions were diagnosed by means of skin tests (86.4%). In contrast, most semi -late and delayed sensitizations were diagnosed by OC (70.6%). The likeliho od of beta-lactam allergy was significantly higher for anaphylaxis (42.9% v s 8.3% in other reactions) and immediate reactions (25% vs 10% in accelerat ed and delayed reactions). Of the children diagnosed as allergic to beta-lactam by means of skin tests , OC, and clinical history, 11.7% were sensitized to several classes of bet a-lactams. The risk was significantly higher in children with anaphylaxis ( 26.7% vs 7.5% of the children with other reactions) and in children reporti ng 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 beta-l actams, and number of reactions to other drugs were not significant risk fa ctors for beta-lactam allergy. Conclusion. The skin tests were safe, and the immediate reaction to skin te sts successfully diagnosed allergy to beta-lactam antibiotics in children r eporting reactions suggestive of immediate HS. In contrast, most accelerate d and delayed reactions were diagnosed by OC. Thus, our results suggest tha t the diagnostic and predictive values of skin tests for nonimmediate HS to beta-lactams in children are low. They also strongly suggest that most rea ctions reported in children are attributable to infectious diseases or inte ractions between drugs and infectious agents rather than to beta-lactam HS.