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.
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.
Entities:
Keywords:
Chronic eczematous eruptions in aging individuals; T cell proliferative response; calcium channel blockers (CCBs); cytokine release assay; delayed hypersensitivity reactions (DHR); drug reaction; eczematous drug eruptions; hydrochlorothiazide (HCTZ); lymphocyte proliferation assay
Authors: Thomas B Martins; Jeffrey L Anderson; Joseph B Muhlestein; Benjamin D Horne; John F Carlquist; William L Roberts; John F Carlquist Journal: Am J Clin Pathol Date: 2006-06 Impact factor: 2.493
Authors: Michael Girardi; Karynne O Duncan; Robert E Tigelaar; Suguru Imaeda; Kalman L Watsky; Jennifer M McNiff Journal: Am J Dermatopathol Date: 2005-08 Impact factor: 1.533
Authors: Pascal Joly; Cloe Benoit-Corven; Sophie Baricault; Audrey Lambert; Marie F Hellot; Véronique Josset; Annick Barbaud; Philippe Courville; Emmanuel Delaporte; Evelyne Collet; Priscille Carvalho; Anne B Modeste-Duval; Jean P Lacour; Marie H L'Anthoën-Arditi; Christian Thuillez; Jacques Benichou Journal: J Invest Dermatol Date: 2007-08-23 Impact factor: 8.551