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

Abstract 

Background

Drug-induced skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, are severe bullous 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 bullous 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 bullous 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.

Keywords:  Stevens-Johnson syndrome, toxic epidermal necrolysis, drug allergy, chemokine, CTACK, CCL27, CCR10, exanthema

Abbreviations:  CLA, Cutaneous lymphocyte antigen, CTACK, Cutaneous T cell–attracting chemokine, GPR-2, G protein coupled receptor 2, ILC, IL-11 receptor α locus chemokine, PBMC, Peripheral blood mononuclear cell, PCR, Polymerase chain reaction, RT-PCR, Reverse transcriptase polymerase chain reaction, SJS, Stevens-Johnson syndrome, TEN, Toxic epidermal necrolysis, TNF, Tumor necrosis factor α