Pathogenesis of drug-induced exanthema.
BACKGROUND
In vitro data derived from drug-specific T cell clones have revealed that heterogeneous T cell subsets with distinct phenotypes (CD4+ > CD8+) and cell functions (strong IL-5 production, cytotoxic potential) are generated. The aim of this study was to elaborate the relevance of these findings in vivo.


METHODS
Skin biopsy specimens from drug-induced maculopapular exanthema and normal skin were analyzed for CD4, CD8, CD25, HLA-DR, CD54, perforin, granzyme B, IL-5 and IFN-gamma using immunohistochemistry.


RESULTS
The majority of infiltrating lymphocytes in maculopapular drug eruptions were CD4+. Both CD4+ and CD8+ T cells expressed perforin and granzyme B and were partly located at the dermoepidermal junction and in the epidermis. In addition, strong immunoreactivity for IL-5 and moderate immunoreactivity for IFN-gamma were observed in the mononuclear cell infiltrate.


CONCLUSIONS
Our data indicate that skin infiltrating T cells with a cytotoxic potential and the ability to produce IL-5 and IFN-gamma may contribute to the damage of keratinocytes and the activation of eosinophils, which are typical features of drug-induced maculopapular exanthema.
Yawalkar
N
N
Clinic for Rheumatology and Clinical Immunology/Allergology, University of Bern, Switzerland.
Pichler
W J
WJ
D004342:Drug Hypersensitivity / Q000276:immunology*; D005076:Exanthema / Q000139:chemically induced* / Q000276:immunology*; D053804:Granzymes; D006801:Humans; D015848:Interleukin-5 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000096:biosynthesis; D012867:Skin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000145:classification; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015848:Interleukin-5; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases