Fixed drug eruption. Expression of epidermal keratinocyte intercellular adhesion molecule-1 (ICAM-1).
The pathogenic mechanism of preferential localization to certain skin sites of fixed drug eruption lesions has remained unknown. Skin biopsy specimens were obtained from four patients with fixed drug eruptions at various time points after final exposure to the causative drug and were studied immunohistologically using monoclonal antibodies to intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1, and HLA-DR. The expression of ICAM-1 by keratinocytes was confined exactly to the involved epidermis. In contrast, the expression of HLA-DR by keratinocytes was observed not only in the involved epidermis but also in the uninvolved epidermis, although to a lesser extent. In general, the intensity of expression of ICAM-1 by keratinocytes correlated well with the degree of epidermal invasion of lymphocytes but not with the degree of dermal lymphocytic infiltration. Interestingly, in fixed drug eruption lesions, basal keratinocytes still showed intense reactivity for ICAM-1 6 to 10 days after final exposure to the causative drug, at which time the expression of HLA-DR was already down-modulated. Such a strong dissociation between the expression of ICAM-1 and HLA-DR on lesional keratinocytes was never observed at any time in the normal skin of control patients challenged with dinitrochlorobenzene. These results suggest that localized misregulated expression of ICAM-1 by the keratinocytes may be one factor that explains the preferential site-specificity characteristic of fixed drug eruptions.
Shiohara
T
T
Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
Nickoloff
B J
BJ
Sagawa
Y
Y
Gomi
T
T
Nagashima
M
M
D000328:Adult; D000368:Aged; D015815:Cell Adhesion Molecules / Q000032:analysis*; D003875:Drug Eruptions / Q000378:metabolism / Q000473:pathology*; D004817:Epidermis / Q000032:analysis / Q000473:pathology*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D015603:Keratinocytes / Q000032:analysis*; D008214:Lymphocytes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D013194:Staining and Labeling
D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens