BACKGROUND: The most frequent side-effects of drug therapy are skin eruptions. Their pathomechanism is rather unclear. OBJECTIVE: In this prospective study we investigated the T cell activation and drug specificity in different forms of drug-induced exanthemas from 22 patients. METHODS: During acute drug allergy, liver parameters and T cell subset activation in the circulation (up-regulation of CD25 and HLA-DR) were evaluated and skin biopsies of the acute lesion performed. After recovery, the causative drug was identified by lymphocyte transformation (LTT) and scratch-patch tests. RESULTS: Seventeen of 22 (17/22) patients had maculo-papular exanthema, 4/22 bullous exanthema and 1/22 urticaria. The causative drugs were mainly antibiotics, anti-epileptics and anti-hypertensives. Up-regulation of HLA-DR on circulating CD4(+) and/or CD8(+) T cells was detected in 17 patients, being most marked in patients with bullous reactions or hepatic involvement. The LTT was positive in 14/21 analysed and the patch test in 7/15. All patients showed lymphocytic infiltration in the skin biopsy of the acute lesion. Generally CD4(+) T cells dominated; a higher percentage of circulating CD8(+) T cells was found in patients with bullous skin reactions or hepatic involvement. CONCLUSION: Our data demonstrate activation and drug specificity of T cells in drug-induced skin eruptions. A predominant CD8(+) T cell activation leads to more severe (bullous) skin symptoms or liver involvement, while predominant activation of CD4(+) cells elicits mainly maculo-papular reactions.
BACKGROUND: The most frequent side-effects of drug therapy are skin eruptions. Their pathomechanism is rather unclear. OBJECTIVE: In this prospective study we investigated the T cell activation and drug specificity in different forms of drug-induced exanthemas from 22 patients. METHODS: During acute drug allergy, liver parameters and T cell subset activation in the circulation (up-regulation of CD25 and HLA-DR) were evaluated and skin biopsies of the acute lesion performed. After recovery, the causative drug was identified by lymphocyte transformation (LTT) and scratch-patch tests. RESULTS: Seventeen of 22 (17/22) patients had maculo-papular exanthema, 4/22 bullous exanthema and 1/22 urticaria. The causative drugs were mainly antibiotics, anti-epileptics and anti-hypertensives. Up-regulation of HLA-DR on circulating CD4(+) and/or CD8(+) T cells was detected in 17 patients, being most marked in patients with bullous reactions or hepatic involvement. The LTT was positive in 14/21 analysed and the patch test in 7/15. All patients showed lymphocytic infiltration in the skin biopsy of the acute lesion. Generally CD4(+) T cells dominated; a higher percentage of circulating CD8(+) T cells was found in patients with bullous skin reactions or hepatic involvement. CONCLUSION: Our data demonstrate activation and drug specificity of T cells in drug-induced skin eruptions. A predominant CD8(+) T cell activation leads to more severe (bullous) skin symptoms or liver involvement, while predominant activation of CD4(+) cells elicits mainly maculo-papular reactions.
Authors: Simone Schmid; Petra C Kuechler; Markus Britschgi; Urs C Steiner; Nikhil Yawalkar; Alain Limat; Kurt Baltensperger; Lasse Braathen; Werner J Pichler Journal: Am J Pathol Date: 2002-12 Impact factor: 4.307
Authors: Abdelbaset A Elzagallaai; Sandra R Knowles; Michael J Rieder; John R Bend; Neil H Shear; Gideon Koren Journal: Mol Diagn Ther Date: 2009 Impact factor: 4.074
Authors: Abdelbaset A Elzagallaai; Sandra R Knowles; Michael J Rieder; John R Bend; Neil H Shear; Gideon Koren Journal: Drug Saf Date: 2009 Impact factor: 5.606