BACKGROUND: In the non-immediate type of drug eruptions, the populations of circulating T cells may be altered as a consequence of T cell responses to a culprit drug. OBJECTIVE: The aim of this study was to investigate differences among the types of drug eruptions in propagating T cell populations of the patients' peripheral blood. METHODS: The type of eruptions were divided into three categories: (1) generalized maculopapular eruption (MPE), (2) erythema multiforme (EM)/Stevens-Johnson syndrome (SJS), and (3) drug-induced hypersensitivity syndrome (DIHS) or drug rash with eosinophilia and systemic symptoms (DRESS). T cell populations were phenotypically analyzed by flow cytometry in the percentage of T helper (Th) 1 (CXCR3+CD4+), Th2 (CCR4+CD4+), Tc1 (CXCR3+CD8+), and Tc2 (CCR4+CD8+) subsets and their activation states as assessed by CD69, CD25 or HLA-DR positivity. RESULTS: Upon occurrence of both MPE and EM/SJS, Th2 cells outnumbered Th1 cells, whereas Tc1 and Tc2 cells differentially predominated in EM/SJS and MPE, respectively. An increase of HLA-DR+CD8+ cells in EM/SJS type provided another supportive evidence for Tc1 stimulation. In DIHS, during the development of the second wave of eruption and/or liver dysfunction associated with anti-HHV6 antibody elevation, CD4+ cells were gradually decreased, but CD8+ cells were inversely increased. Tc1 cells were increased as well as Th1 cells. Finally, in all the three groups, there existed a considerable number of CD25+CTLA-4-CD4+ T cells. CONCLUSION: Our study suggests that Th2/Tc2 and Th2/Tc1 cells mediate MPE and EM/SJS, respectively, and Tc1 cells are involved in the pathogenesis of DIHS at the late stage.
BACKGROUND: In the non-immediate type of drug eruptions, the populations of circulating T cells may be altered as a consequence of T cell responses to a culprit drug. OBJECTIVE: The aim of this study was to investigate differences among the types of drug eruptions in propagating T cell populations of the patients' peripheral blood. METHODS: The type of eruptions were divided into three categories: (1) generalized maculopapular eruption (MPE), (2) erythema multiforme (EM)/Stevens-Johnson syndrome (SJS), and (3) drug-induced hypersensitivity syndrome (DIHS) or drug rash with eosinophilia and systemic symptoms (DRESS). T cell populations were phenotypically analyzed by flow cytometry in the percentage of T helper (Th) 1 (CXCR3+CD4+), Th2 (CCR4+CD4+), Tc1 (CXCR3+CD8+), and Tc2 (CCR4+CD8+) subsets and their activation states as assessed by CD69, CD25 or HLA-DR positivity. RESULTS: Upon occurrence of both MPE and EM/SJS, Th2 cells outnumbered Th1 cells, whereas Tc1 and Tc2 cells differentially predominated in EM/SJS and MPE, respectively. An increase of HLA-DR+CD8+ cells in EM/SJS type provided another supportive evidence for Tc1 stimulation. In DIHS, during the development of the second wave of eruption and/or liver dysfunction associated with anti-HHV6 antibody elevation, CD4+ cells were gradually decreased, but CD8+ cells were inversely increased. Tc1 cells were increased as well as Th1 cells. Finally, in all the three groups, there existed a considerable number of CD25+CTLA-4-CD4+ T cells. CONCLUSION: Our study suggests that Th2/Tc2 and Th2/Tc1 cells mediate MPE and EM/SJS, respectively, and Tc1 cells are involved in the pathogenesis of DIHS at the late stage.
Authors: Sheena N Ramasamy; Cameron S Korb-Wells; Diluk R W Kannangara; Myles W H Smith; Nan Wang; Darren M Roberts; Garry G Graham; Kenneth M Williams; Richard O Day Journal: Drug Saf Date: 2013-10 Impact factor: 5.228