Basic aspects related to penicillin-allergy skin testing: on the variability of the hapten-paratope interaction.

Ampicillin and benzylpenicillin conjugated to human serum albumin were used as immunogens in order to obtain antihaptenic IgG responses in outbred guinea pigs according to different schedules, all involving complete Freund's adjuvant. The individual responses were characterized by ELISA and by ELISA inhibition using ampicillin, benzylpenicillin, and carbenicillin peptidic conjugates for coating and for inhibition. In several instances, drastically reduced cross-reactivity and even its absence were observed, although the penicillin antigens differ only in the side-chain. The notion that the invariantly present thiazolidine ring will always provide significant binding to antibodies against all penicillins differing only in the side-chain has to be dropped. The experiments were performed in relation to newer findings of clinical penicillin-allergy skin testing which suggest that benzylpenicillin-based reagents alone are not able to detect or predict all reactions against semisynthetic penicillins. The experimental evidence here obtained corroborates this conclusion.

Desensitization of anaphylactic hypersensitivity specific for the penicilloate minor determinant of penicillin and carbenicillin.

A 68-yr-old man with a history of a morbilliform rash caused by intravenous penicillin required carbenicillin (CB) therapy for refractory Serratia marcescens septicemia. Skin testing showed a positive immediate skin test to the penicilloate minor determinant in the presence of negative tests to benzylpenicilloylpolylysine (BPL) and penicillin G (PG), as well as cross-reactivity between the penicilloate derivatives of PG and CB. True densensitization was accomplished by gradual administration of CB intravenously and was accompanied by a diffuse flush reaction. There was specific loss of wheal-and-flare reactivity as well as of specific serum reaginic antibody activity during the procedure, and there was no evidence of activation of serum complement. This case illustrates the usefulness of skin tests in the prediction and management of penicillin allergy and presents data pertaining to immunologic mechanisms involved in true desensitization.