Expression of the skin-homing receptor in peripheral blood lymphocytes from subjects with nonimmediate cutaneous allergic drug reactions

Abstract

Background: In nonimmediate cutaneous reactions to drugs, the skin is the organ most frequently involved, and T lymphocytes may play a relevant role. T cells related to skin immune responses express the cutaneous lymphocyte-associated antigen (CLA), the skin homing receptor. Methods: We studied the expression of the CLA in peripheral blood T lymphocytes from nine subjects with exanthematous reactions induced by betalactams (4), phenytoin (2), propyphenazone (1), spiramycin plus metronidazol (1) and captopril plus tiazide (1). The cutaneous symptoms appeared at least six hours after drug intake. CLA expression was evaluated by flow cytometry at the time of the reaction (T1) and one month later (T2). HLA-DR activation marker expression was also evaluated at T1. In four patients, it was necessary to readminister the culprit drug to establish a causal relationship, and sequential estimation of the markers was performed. Two control groups were included: healthy controls and subjects exposed to the culprit drugs with good tolerance. Values were compared by nonparametric statistics. Results: The expression of circulating CLA+ T cells at T1 was increased compared to healthy controls (median=20.4 vs 9.4) (P<0.001), and the patients also expressed increased levels of HLA-DR (median=3.8) (P <0.005). Comparison between T1 and T2 (median=11.2) also showed differences in levels of CLA+ T cells (P <0.01). The patients re-exposed to the culprit drug showed an increase followed by a decrease of circulating CLA+ T cells (P <0.05) and CLA+ HLA-DR+ (P <0.05) paralleling the symptoms. Conclusions: These data support the immunological nature of delayed skin reactions to drugs and suggest that these CLA+ T cells parallel the disease evolution and may participate in the pathophysiological mechanisms.