T cell involvement in cutaneous drug eruptions

Background The most frequent side-effects of drug therapy are skin eruption s. Their pathomechanism is rather unclear. Objective In this prospective study we investigated the T cell activation a nd drug specificity in different forms of drug-induced exanthemas from 22 p atients. Methods During acute drug allergy, liver parameters and T cell subset activ ation in the circulation (up-regulation of CD25 and HLA-DR) were evaluated and skin biopsies of the acute lesion performed. After recovery, the causat ive drug was identified by lymphocyte transformation (LTT) and scratch-patc h 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 anti biotics, anti-epileptics and anti-hypertensives. Up-regulation of HLA-DR on circulating CD4(+) and/or CD8(+) T cells was detected in 17 patients, bein g most marked in patients with bullous reactions or hepatic involvement. Th e LTT was positive in 14/21 analysed and the patch test in 7/15. All patien ts 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 inv olvement. Conclusion Our data demonstrate activation and drug specificity of T cells in drug-induced skin eruptions. A predominant CD8(+) T cell activation lead s to more severe (bullous) skin symptoms or liver involvement, while predom inant activation of CD4(+) cells elicits mainly maculo-papular reactions.