Tests for evaluating non-immediate allergic drug reactions

Abstract

Non-immediate drug reactions (NIR) are induced by specific immunological mechanisms and involve the recognition of hapten molecules by the immune system, with the participation of dendritic cells and other antigen-presenting cells. This process is followed by an effector response that can induce several clinical entities, ranging from mild to severe. The type of immunological recognition can be used as the basis for the diagnostic approach. Both in vivo and in vitro tests are available for the diagnosis of NIR. In vivo tests consist of the reproduction of a diminished immune response with the culprit drug and in vitro tests are based on the stimulation of memory cells in culture. If both tests give negative results, a drug provocation test can be used.

Keywords::

• drug allergy
• drug provocation test
• in vitro test
• non-immediate reactions
• skin test
• T-cell mechanisms

Financial & competing interests disclosure

The study was funded by the FIS Thematic Networks and Co-operative Research Centres RIRAAF (ISCIII RD012/0013), Spanish Health Ministry (PI12/02529), Fundacion Salud 2000, Andalusia Health Ministry (PI-0352-2012) and Andalusia Innovation Ministry (CTS 06603). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• A precise diagnosis of hypersensitivity drug reactions is essential to identify the correct pathology and culprit drug, to allow us to select the best treatment and the most adequate alternative medication available.

• In vivo testing must not be performed in severe reactions due to the risk of eliciting the full response.

• Drug-provocation test (DPT) is recommended to exclude hypersensitivity in non-suggestive cases of drug hypersensitivity or to exclude cross-reactivity.

• DPT is usually required for the establishment of the diagnosis and is often used to search for alternatives, due in part to the comparatively low sensitivity of other methods.

• In vitro tests can help us to understand the ongoing pathological processes in these reactions and also improve the diagnosis, complementing in vivo tests.

• Efforts are needed to improve the sensitivity of in vitro tests in order to elevate them to ‘gold standard status’, since in some cases skin test and DPT are inappropriate, that is, for severe reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

• In vitro tests could be improved by determining which molecules and cell types might be missing from cell culture, in order to better mimic the reaction.

• In vitro tests can help to identify the drug involved once the reaction has resolved even years after the allergic response, meaning that patient samples should always be taken where possible.