Involvement of CCL27-CCR10 interactions in drug-induced cutaneous reactions

Background: Drug-induced skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, are severe buttons cutaneous diseases of uncertain etiology, although cytotoxic T cells seem to be involved. Cutaneous T cell-attracting chemokine (CTACK/CCL27) is selectively expressed in skin and attracts CCR10-expressing cells. Exclusive CTACK expression by keratinocytes; suggests its involvement in inflammatory skin diseases. Objective: We addressed whether CTACK/CCL27 production by the epidermis and CCR10(+) lymphocytes are involved in toxic epidermal necrolysis and Stevens-Johnson syndrome. Methods: We measured CTACK expression by epidermal cells in 2 patients with drug-induced buttons skin reactions and compared it to lesional skin from several drug-induced exanthemas. In parallel we measured CCR10 mRNA in peripheral blood mononuclear cells from the patients during the course of the disease and in lymphocytes infiltrating the skin. Results: CTACK expression levels in skin biopsies from the 2 patients with drug-induced buttons reactions were higher than those found in healthy subjects or in other drug-induced exanthemas. CCR10 mRNA levels were also elevated in peripheral blood lymphocytes and in lesional skin during the acute phase of the disease. Moreover, resolution was associated with a return to baseline of both CTACK and CCR10 receptor expression. Conclusion: CTACK-CCR10 interactions may be involved in the selective recruitment to the skin of cytotoxic lymphocytes in toxic epidermal necrolysis and Stevens-Johnson syndrome, as well as in less severe drug-induced cutaneous diseases.