In vitrotests for drug hypersensitivity reactions: anENDA/EAACIDrug Allergy Interest Group position paper

Abstract

Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis.

Basophil Activation in Immediate Drug Hypersensitivity Reactions and Basophil Activation Test (BAT)

“…In the cases in whom respiratory symptoms (NSAIDs exacerbated respiratory disease; NERD) occur due to NSAID-induced hypersensitivity, BAT susceptibility was found as 30% to 78%, and it was found as 37% to 100% in the cases with skin symptomatic/urticariaangioedema (NECD and NIUA). BAT specificity was found to be 40% to 83% for NERD and 31% to 90% for those having skin symptoms (NECD and NIUA) (8).…”

“…One third of the allergic patients with negative skin test can also be detected through BAT. Although it is not superior to the skin tests, BAT is considered to be superior in detecting DHR to the drug-specific IgE immunoassay tests (8,11). BAT also detects the cases in which drug-specific IgE cannot be demonstrated (as in the reactions of clavulanic acid which is a b-lactamase inhibitor).…”

“…BAT also detects the cases in which drug-specific IgE cannot be demonstrated (as in the reactions of clavulanic acid which is a b-lactamase inhibitor). For these reasons, BAT is now accepted as a complementary test to skin tests (8,11,19).…”

“…The photodegradation that occurs in these drugs also leads to falsenegative results. For example, when BAT, which is performed to detect fluoroquinolone moxifloxacin reactions, is performed in the dark, positive results are doubled (8,11). In a small number of studies reported in the literature, the BAT sensitivity in quinolone allergies is still very variable, and the average of the studies was found as 43% (0-100) and the specificity as 95% (90-100).…”

“…As it is reported in the 2016 ENDA/ EAACI (European Network of Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology) position article, if IgE-mediated/early DHR is suspected in the person, if the person is in the high-risk group, if an anaphylactic reaction has developed or in vivo skin tests cannot be performed, then in vitro tests (tests such as IgE or BAT specific to the medication) can be prioritized in this person together with the in vitro tests which have developed over time (8). In this compilation, we will dwell on the BAT method, its importance, its potential for the use in drug allergies, and its limits.…”