Diagnosis of nonimmediate reactions to β‐lactam antibiotics

Abstract

Nonimmediate manifestations (i.e. occurring more than 1 h after drug administration), particularly maculopapular and urticarial eruptions, are common during β‐lactam treatment. The mechanisms involved in most nonimmediate reactions seem to be heterogeneous and are not yet completely understood. However, clinical and immunohistological studies, as well as analysis of drug‐specific T‐cell clones obtained from the circulating blood and the skin, suggest that a type‐IV (cell‐mediated) pathogenic mechanism may be involved in some nonimmediate reactions such as maculopapular or bullous rashes and acute generalized exanthematous pustulosis. In the diagnostic work‐up, the patient's history is fundamental; patch testing is useful, together with delayed‐reading intradermal testing. The latter appears to be somewhat more sensitive than patch testing, but also less specific. In case of negative allergologic tests, consideration should be given to provocation tests, and the careful administration of the suspect agents. With regard to in vitro tests, the lymphocyte transformation test may contribute to the identification of the responsible drug.Under the aegis of the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity and the European Network for Drug Allergy (ENDA), in this review we describe the general guidelines for evaluating subjects with nonimmediate reactions to β‐lactams.

Drug provocation tests to betalactam antibiotics: experience in a paediatric setting

“…A diagnostic protocol which includes skin testing to betalactams is considered useful in clarifying the nature of the reaction. 14 In the present study we have studied 161 consecutive children seen at our outpatient clinic referred for a suspected betalactam antibiotic allergy. A drug allergy diagnosis was established in only 13% of the patients nonskin tested and in 19% of the skin tested to betalactams (nine children: eight by skin tests and in one trough DPT).…”

Management of allergy to penicillins and other beta‐lactams

“…Patch tests are necessary when the drug is only available in tablet or topical formulation. For beta-lactam patch tests, a concentration of 5-10% in petrolatum is generally considered suitable [134]. Although recent consensus recommends that the drug is diluted in petrolatum [117] Appendix table A1, if saline is used to dilute the beta-lactam for patch testing, then a 10% concentration is necessary to increase sensitivity [136].…”

“…Negative skin tests with delayed reactions may occur if the reaction was not immune-mediated, or because of poor penetration of the drug into the skin or because of the absence of cofactors present at the time of the reaction. Both patch tests and delayed reading of intradermal tests can be used to diagnose T-cell-dependent reactions to beta-lactams [134][135][136][137][138]. The addition of penicillin determinants in evaluating non-immediate reactions is of only very limited diagnostic value [139].…”

Allergic hypersensitivity to topical and systemic corticosteroids: a review

“…The in vivo tests are mainly Ôskin prickÕ test and/or an early-reading intradermal reaction (IDR) test in cases of IAHS and Ôpatch testÕ and/or a latereading IDR test in cases of DAHS. In vitro diagnosis may include the identification of basophil activation/ degranulation and IgEs specific to the drug for IAHS (10,11) and lymphocyte transformation test (LTT) and IFN-gamma enzyme-linked immunospot assay (ELISPOT) for DAHS (12)(13)(14). Biological diagnosis of a DAHS reaction has made significant progress in recent years thanks to the work of Rozie`res et al (12) and Pichler et al (14).…”