A pilot study evaluating biomarker development for drug-induced chronic eczematous eruptions of aging individuals.

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.