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Background: Identifying the drug(s) responsible for drug-induced chronic eczematous eruptions of aging individuals (CEEA) is a clinical challenge in patients on multiple medications. Reliable in vitro testing methods and biomarkers are needed to identify the causative agent and allow simultaneous assessment of T-cell responses to multiple drugs being taken concurrently. This study examined the feasibility of using in vitro , drug-specific T cell activation responses as a biomarker for drug-induced CEEA., Methods: This was a single center, proof-of-concept pilot study at the University of Utah Hospital, Salt Lake City, Utah. Eight aging study subjects having a history suggestive of chronic eczematous drug eruptions suspected to have resulted from calcium channel blocker (CCB) and/or hydrochlorothiazide (HCTZ) hypersensitivity plus three matched aging control subjects were identified. Drug patch testing for CCB and/or HCTZ, in vitro drug antigen-induced lymphocyte proliferation assays, and multianalyte-determined cytokine release assays were performed before and after HCTZ and/or CCB incubation., Results: All study and control subject blood samples tested failed to demonstrate detectable enhanced lymphocyte proliferation or cytokine release to in vitro CCBs or HCTZ challenge when tested with a fairly wide range of drug concentrations. Additionally, none of the enrolled patients developed a positive patch test to CCBs and/or HCTZ., Conclusions: This pilot study aimed to correlate in vitro drug-induced T lymphocyte transformation and cytokine production with the presence of drug-induced CEEA. Failure to identify T cell proliferative responses to CCB drug antigens in our in vitro studies could have, in part, resulted from a pharmacologic inhibiting effect of CCB on T cell activation., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.