Ampicillin and amoxicillin delayed hypersensitivity: Side-chain-specific allergic reactions in a child

Background: Maculopapular rashes are common cutaneous adverse reactions to ampicillin and amoxicillin. Usually they are not due to a known allergic mechanism. However, type I (IgE mediated) and type TV (T cell mediated, delayed hypersensitivity) cutaneous reactions to beta-lactams in general, and especially to ampicillin and amoxicillin, can be side-chain-specific. Case Report: A 30-month-old boy developed a generalized maculopapular rash which progressed to desquamation while the child was being treated intravenously for 7 days with ampicillin. Results: When the child was 40 months old, the maculopapular rash was reproduced (onset, 5-8 hours) by a diagnostic oral challenge with amoxicillin (one dose, 62.5 mg). Three days after onset of the rash, he was treated with methylprednisolone, and the rash resolved without desquamation. Penicillin V (phenoxymethyl penicillin) challenge (62.5 mg orally) and trial (125 mg orally three times a day for 10 days) were negative. Radioallergosorbent tests to penicilloyl G and penicilloyl V were negative. Immediate (15 minutes) and delayed (48 hours) skin tests to penicillin G, its major and minor determinants, and cefazolin were negative before and after the challenges with amoxicillin and penicillin V. Immediate intradermal skin tests (0.02 mt) to ampicillin (0.25 and 2.5 mg/mL) were negative. However, induration and erythema (7 x 8 mm and 10 x 10 mm) began 5 to 8 hours and reached a maximum at 48 hours after the tests were applied. Biopsies were not done. Conclusions: These observations emphasize that (1) ampicillin/amoxicillin maculopapular desquamative rashes in children can be due to delayed hypersensitivity mechanisms, (2) betalactam ampicillin/amoxicillin delayed reactions can be side-chain-specific (amino-benzyl group), (3) ampicillin should be included in skin testing protocols, (4) skin test sites should be examined not only at 15 minutes but also at 48 hours after the tests are applied, and (5) other beta-lactam (not amino-benzyl) antibiotics may be tolerated.