Management of Rashes Associated With Beta-lactam Rx

Abstract

Source: Caubet JC, Kaiser L, Lemaitre B, et al. The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge. J Allergy Clin Immunol. 2011; 127(1): 218– 222; doi: 10.1016/j.jaci.2010.08.025Investigators from Switzerland assessed the role of infectious and allergic causes in delayed-onset urticarial and maculopapular rashes in children treated with beta-lactam antibiotics. This prospective observational study from 2006 to 2008 included children aged 0 to 16 years who presented to the pediatric emergency department (ED) with an urticarial or maculopapular rash during or within 72 hours of finishing beta-lactam therapy.Children presenting to the ED underwent a clinical evaluation which included history and physical examinations, pictures of skin lesions, antibody titers for viruses associated with childhood skin rashes, and throat swab polymerase chain reaction (PCR) screening for respiratory viruses. Subsequent follow-up two months later included a second set of viral serologies and work-up for beta-lactam allergy.Allergy work-up included intradermal skin tests (IST) performed with minor determinant mixture, penicilloyl-polylysine, amoxicillin, and cephalosporin as indicated. In vitro assays for beta-lactam antibiotic IgE were drawn. Patch testing was performed with incriminating drugs. Oral challenge testing (OCT) was performed in all children. Initiation dose depended on the results of beta-lactam testing. A final visit two days later included patch and late intradermal skin test reading.Eighty-eight children, with an average age of 3.5 years, completed the study. Of these, 48.9% were on amoxicillin, 38.6% on amoxicillin-clavulanic acid, and 12.5% on a cephalosporin at the time of the rash. ISTs were positive in 12.5% of patients. OCT produced six reactions: one with amoxicillin, three with amoxicillin-clavulanic acid, and two with cephalosporin. Only four of the six children who later had a positive OCT developed immediate positive ISTs. However, those with positive ISTs had a higher rate of positive OCTs than those without (P<.05, Fisher exact test). The overall sensitivity determined for IST was 66.7%, and the specificity was 91.5%. Patch testing and delayed intradermal testing were negative in all 88 patients.Viral screening was positive in 46 of 82 children with a negative OCT and 2 of 6 children with a positive OCT. The viruses most frequently identified were enteroviruses; three of the positive OCT patients had findings suggestive of acute Epstein-Barr virus infection.The authors conclude that children who present with a benign skin rash and no other symptoms of allergic reaction while treated with beta-lactam antibiotics rarely have beta-lactam allergy, and should receive a one-dose OCT under medical supervision followed by two days of antibiotic dosing at home to establish whether antibiotics are responsible for the rash.Dr Nimmagadda has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The development of urticarial and maculopapular rashes in the child with viral illness remains a diagnostic dilemma for pediatricians. Many children treated with beta-lactam antibiotics have an intercurrent viral illness as well. Oftentimes children with cutaneous urticarial or maculopapular rashes will get labeled as penicillin-allergic. These children are rarely re-challenged or tested.1 Studies have determined true antibiotic allergy prevalence to be under 10% in suspected drug-allergic pediatric populations.2Penicillin is degraded to major (95%) and minor determinants (5%). Immediate IgE-mediated reactions causing anaphylaxis are associated with minor determinants in 95% of the cases.3 Hypersensitivity to these two products can be assessed using cutaneous tests performed with major and minor determinants, thus avoiding serious anaphylactic reactions in beta-lactam-allergic individuals. Challenge and/or desensitization in patients with positive skin tests should only take place in well-controlled settings where emergency equipment and medications are available.3The current article highlights the infectious and allergic causes of benign skin rashes in relation to penicillin exposure. This understanding provides support for more accurate diagnosis and management in cases of suspected beta-lactam allergy. Caution should always be exercised in children with more than just cutaneous manifestations of drug allergy. OCT in these individuals is not recommended without further evaluation or consultation with an allergy specialist.This provocative study raises the question whether all children with benign skin rashes during beta-lactam treatment deserve carefully supervised OCTs.