Author:

Abstract:

Skin-related drug hypersensitivity reactions are, either by topical application or systemic administration a frequently encountered problem, despite their use in adequate doses and in the correct indications, They are associated with a significant morbidity and require an extensive diagnostic work-up to identify the culprit drug, potential cross-reacting drugs and/or chemicals and safe alternatives. Clinically, DHRs are classified as immediate, i.e. typically <1h, or non-immediate/delayed-type DHRs, i.e. >1h, until days following the start of a treatment with the culprit drug, respectively. This project focusses on delayed-type drug hypersensitivity reactions (DTHs). In the first part, the demographic characteristics of the patients, exposure, type and location of the lesions, frequency and causes of DTH will be analysed retrospectively. The electronic databases developed by Prof. A. Goossens at the Contact Allergy Unit since 1990 (n=14,911) will serve as a basis. Moreover, also the test results of patients observed at the Department of Allergy and Clinical Immunology (Prof. R. Schrijvers) will be included. Specific subgroup analysis will be performed for patients with a DTH following the use of topical drugs, topically used herbal medications, systemically administered drugs, and also following occupational exposure. Furthermore, interesting cross-reactivity patterns will be studied in detail. In a second part, data from patients will be collected prospectively from 2016 onwards. Analysis of test results over the years will enable the description of trends in sensitisation frequencies, allowing for increased pharmacovigilance. For those patients presenting with a remarkable or severe DTH, a blood sample will be collected for further in vitro analysis in the third part of this project. In this last part, the lymphocyte proliferation assay (LPA), used for the diagnostics of DTHs, will be modified using carboxyfluoresceine succinimidyl ester (CFSE) labelling of cells in order to enable a detailed characterisation of the proliferating cell population in the presence of a certain drug. Next, this assay will provide a generic model for the evaluation of subsets of immune cells and mediators in such reactions and can thus be used as a tool to study the pathophysiology of DTHs. Our goal is to obtain, in association with clinical data, a better understanding of the mechanisms involved and to guide patients and clinicians in such reactions, which often remain difficult to manage.