LAUSR

Editor Anti-epileptic drugs (AEDs) are known to cause cutaneous adverse drug-induced reactions. The pathogenesis of these drug-induced reactions remains poorly understood. In our previous multicenter prospective study, we evidenced reactivation of Epstein–Barr virus (EBV), human herpes virus 6 (HHV-6) and/or human herpes virus 7 (HHV-7) in 76% of drug reaction with eosinophilia and systemic symptom (DRESS) patients. As a consequence of this increased viral antigen exposure, EBV-specific CD8+ T lymphocytes that expressed high levels of cutaneous lymphocyte-associated antigen (CLA) homing markers of skin were found both in blood and in involved organs including skin. To better understand drug-induced effects, we prospectively evaluated clinical and immunological features in 30 patients newly treated with anti-epileptic drugs (NCT02556320). This study has been approved by the Ethics Committee of the North West area II in France. Written informed consent was obtained from each patient. The clinical characteristics of patients are listed in Table 1. One patient developed a transient cutaneous eruption between visits on days 15 and 30. Treatment (lamotrigine) was, therefore, discontinued prematurely by decision of the investigator. During this eruption, the patient did not show abnormal biological characteristics. We first studied viral replication during the first 90 days of treatment. HHV-7 reactivation was detected in 14.3% of analysed clinically asymptomatic patients at baseline and in 30.8% at day 90 (Table 1). The HHV-7 reactivations belong to different patients at different time points and with the all AEDs studied. In contrast, no EBV or HHV-6 reactivation was detected during follow-up. These data are consistent with the ability of HHV-7 to spontaneously reactivate. Additionally we assessed the percentage evolution of peripheral blood lymphocyte subpopulations during AED therapy. No variation was observed in percentage of CD4+ or CD8+ T cells (Fig. 1a and d). A slight decrease in percentage of Treg (CD3 CD4 CD25) was observed between baseline (5.81 0.47%) and day 90 (4.07 0.62%), P = 0.039 (Fig. 1g). Similarly, a slight decrease in CLA+ CD4+ T-cell populations was also observed between baseline (5.05 1.11%) and day 90 (3.99 0.63%), P = 0.039 (Fig. 1a). Indeed number variations of lymphocyte