Role of T cells in non-immediate drug allergy reactions.

PURPOSE OF REVIEW: Nonimmediate drug hypersensitivity reactions (NI-DHR) constitute the most complex group of drug allergy, with many drugs involved. Both parent drugs and their reactive metabolites can be implicated. Although with some drugs the number of metabolites is limited, with others it is quite extensive and many still remain to be identified. The diagnostic approaches are insufficient for the diagnosis and realistic approaches that reproduce the pathological response are lacking. RECENT FINDINGS: A wider view has now been considered, with the inclusion of several mechanisms that may contribute to drug hypersensitivity reactions (DHR): the classical hapten hypothesis, the danger signal and the pharmacological interaction. Monitoring the acute response provides relevant information about the mechanisms involved, with the identification of a large number of genes that can be over-expressed or under-expressed in the acute phase of the response. Assessment of risk of developing reactions can be verified by HLA associations. SUMMARY: Further knowledge of these NI-DHR, including molecular genetics and transcriptomic analysis, has enabled a better understanding and management of these reactions.

Selective immediate responders to amoxicillin and clavulanic acid tolerate penicillin derivative administration after confirming the diagnosis.

BACKGROUND: An increasing number of patients show immediate selective hypersensitivity reactions to clavulanic acid (CLV) and amoxicillin (AX), probably due to their increased prescription. The maintenance of this response should be established. OBJECTIVE: To assess that the immediate hypersensitivity selective response to AX or to CLV is maintained after repeated administration of penicillin G (PG)/penicillin V (PV) and AX. METHODS: Patients with proven immediate hypersensitivity to AX (Group A) or CLV (Group B) were included. Diagnosis was performed using skin tests with major and minor determinants of PG (PPL/MDM), AX and CLV and by drug provocation test (DPT) if required. Selectivity was established by confirming tolerance to PG/PV (Group A) and to PG/PV and AX (Group B). The maintenance of the selective response was verified by repeating DPT, 15 days after the initial investigation, with the same procedure. RESULTS: Of 51 patients, 78% belonged to Group A and 22% to Group B. Most had anaphylaxis. In Group A, 72% were skin test positive; 28% required DPT. In Group B, 63% were skin test positive; 37% required DPT. Only two AX-selective cases developed positive responses after re-provocation with PG/PV. No cases selective for CLV developed a positive response to PG, PV or AX. DISCUSSION: The selective response to AX appears consistent, and a response to penicillin determinants only develops in a minority of cases. For the case of CLV, the selective response appears not to be modified by exposure to penicillin determinants, meaning that patients with CLV allergy can take penicillin derivatives safely.