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


Miguel Blanca, Allergy Service
Hospital la Paz
Paseo de Castellana 261
28046, Madrid


Background: In nonimmediate cutaneous reactions to drugs, the skin is the organ most frequently involved, and T cells 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 cells from nine subjects with exanthematous reactions induced by β-lactams ( 4), phenytoin ( 2), propyphenazone ( 1), spiramycin plus metronidazol ( 1), and captopril plus tiazide ( 1). The cutaneous symptoms appeared at least 6 h after drug intake. CLA expression was evaluated by flow cytometry at the time of the reaction (T1) and 1 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 immunologic nature of delayed skin reactions to drugs, and suggest that these CLA+ T cells parallel the disease evolution and may participate in the pathophysiologic mechanisms.