Cefazolin Hypersensitivity: Toward Optimized Diagnosis.

BACKGROUND: Correct diagnosis of cefazolin hypersensitivity is not straightforward, mainly because of the absence of in vitro tests and uncertainties concerning the optimal cefazolin concentration for skin testing. Cross-reactivity studies suggest cefazolin hypersensitivity to be a selective hypersensitivity. OBJECTIVE: The first objective was to confirm that the application of a higher than 2 mg/mL test concentration could increase skin test sensitivity. A second part aimed at investigating the cross-reactivity between cefazolin and other ß-lactam antibiotics. METHODS: A total of 66 patients referred to our clinic after experiencing perioperative anaphylaxis, and exposed to cefazolin, underwent skin testing with cefazolin up to 20 mg/mL. Patients exhibiting a positive skin test with cefazolin had a panel of skin tests with other ß-lactams and, if indicated, graded drug challenges to study cross-reactivity. RESULTS: Increasing skin test concentration from the recommended 2 mg/mL to 20 mg/mL identified an additional 7 of 19 (27%) patients, who would otherwise have displayed negative skin testing. The concentration was proven nonirritating in 30 cefazolin-exposed control individuals in whom an alternative culprit for perioperative anaphylaxis was identified. Graded challenge testing, after negative skin testing, displayed that all patients tolerated alternative ß-lactam antibiotics (ie, amoxicillin, cephalosporins, monobactams, and carbapenems). Of them, 11 individuals also tolerated an alternative cephalosporin, suggesting that cefazolin hypersensitivity (generally) is a selective allergy. CONCLUSIONS: Increasing cefazolin concentration for skin tests up to 20 mg/mL benefits the sensitivity of diagnosis. Furthermore, our data confirm that cefazolin hypersensitivity seems to be a selective allergy with good tolerance to other ß-lactam antibiotics.

In vitro diagnosis of immediate IgE-mediated drug hypersensitivity: warnings and (unmet) needs.

Immediate drug hypersensitivity reactions (DHR) constitute an important health condition, with serious consequences of inadequate diagnosis. In this article, some of the most important issues related to in vitro diagnosis of IgE-mediated allergies are discussed. In vitro diagnostics will benefit from expanded and novel insights and understandings in drug chemical reactivity, protein binding, biotransformation, degradation, identification of (cross-reactive) drug antigenic determinants, and deeper understanding of sensitization routes. Collective efforts should be undertaken to activate fundamental and clinical investigations.

Basophil activation tests: time for a reconsideration.

Challenges in in vitro allergy diagnostics lie in the development of accessible and reliable assays allowing identification of all offending allergens and cross-reactive structures. Flow-assisted analysis and quantification of in vitro activated basophils serves as a diagnostic instrument with increasing applications developed over the years. From the earliest days it was clear that the test could constitute a diagnostic asset in basophil-mediated hypersensitivity. However, utility of the basophil activation test should be reassessed regarding difficulties with preparation, characterization and validation of allergen extracts; availability and the potential of more accessible diagnostics. Today, the added value mainly lies in diagnosis of immediate drug hypersensitivity. Other potential indications are monitoring venom-immunotherapy and follow-up of natural history of food allergies. However, results in these nondiagnostic applications are preliminary. We review the most relevant clinical applications of the basophil activation test. Some personal comments and views about perspectives and challenges about flow-assisted allergy diagnosis are made.