Up-regulated perforin expression of CD8(+) blood lymphocytes in generalized non-anaphylactic drug eruptions and exacerbated psoriasis

Perforin expressed in CD8(+) cytotoxic T cells is known to mediate the lysi s of target cells carrying microbial as well as tumor-associated antigens, and to be involved in autoimmune and transplant reactions. The aim of the p resent investigation was to study the role of perforin- and CD8-expressing effector lymphocytes from peripheral blood in patients with generalized inf lammatory skin diseases. Mononuclear cells were separated from peripheral v enous blood and permeabilized by 0.1% saponin. The co-expression of cytopla smatic perforin and cell membrane-residing CD8 was determined in lymphocyte s by immune-flow cytometry. Patients affected by generalized macular-papula r drug eruptions (n = 14), drug-unrelated acute urticaria (n = 10) and drug -independently exacerbated psoriasis (n = 11, PASI scores ranging from 25 t o 35), as well as control individuals not affected by any inflammatory skin disease (n = 10) were enrolled. Additionally, n = 5 patients with drug-ind uced Stevens-Johnson syndrome (SJS) were included. The average proportion o f CD8(+) peripheral lymphocytes co-expressing perforin in generalized drug eruptions (68.8 +/- 24.9%) and exacerbated psoriasis (67.2 +/- 17.1%) diffe red significantly from the controls (43.5 +/- 11.6%; p less than or equal t o 0.05), whereas no significant difference for acute urticaria (58.2 +/- 23 .1%) could be measured. In each of the 5 SJS patients treated by high dose systemic steroids the parameter substantially declined during the first 7 d ays after admission from an average value of 81.6% down to 33.0%. Thus, as compared to controls we observed an increased perforin(+) proportion of CD8 (+) lymphocytes in generalized drug eruptions and in exacerbated psoriasis but not in acute urticaria. Therefore the parameter showed some specificity as a marker of distinct inflammatory skin disorders, and proved to be usef ul in monitoring the disease activity of SJS under anti-inflammatory medica tion. Furthermore, the findings point to a possible crucial role of CD8(+) lymphocytes in the pathogenesis of psoriasis.